Bio 406 PDF Parasitology & Immunology

COURSE
GUIDE
BIO 406
PARASITOLOGY AND IMMUNOLOGY
Course Team Mr. Kofi O. Renner (Course Developer/Writer) –

Nigerian Institute for Oceanography and Marine
Research, Lagos
Dr. Adefunke M. Adesina (Course Editor) -
Ministry of Health
Yisa Abraham Gana (PhD) (Course Reviewer)
NATIONAL OPEN UNIVERSITY OF NIGERIA

BIO 406 COURSE GUIDE
© 2023 by NOUN Press

National Open University of Nigeria
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e-mail: centralinfo@nou.edu.ng
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All rights reserved. No part of this book may be reproduced, in any form
or by any means, without permission in writing from the publisher.
First Printed 2009
Reviewed 2021
Reprinted 2023
ISBN: 978-058-055-7
ii
CONTENTS PAGE
Introduction ……………………………………………………. iv
What You Will Learn In This Course …………………………. iv
Course Aims …………………………………………………… iv
Course Objectives ……………………………………………… v
Working through this Course …………………………………... v
Course Materials ……………………………………………….. vi
Study Units ……………………………………………………… vi
Presentation Schedule ………………………………………….. vii
Assessment ……………………………………………………… vii
Tutor-Marked Assignment ……………………………………… vii
Course Marking Scheme ………………………………………... viii
Facilitators/Tutors and Tutorials…………………………………. xiii
Summary ………………………………………………………… ix
iii
Introduction
Parasitology and Immunology (406) is a second semester course. It is a

two credit unit elective course which all students offering Bachelor of
Science (BSc) in Biology can take.
Parasitology and Immunology is an important area of study for scientists.

Immunity is a biological term that describes a state of having sufficient
biological defenses to avoid infection, disease, or other unwanted
biological invasion. Immunity involves both specific and non-specific
components. Since this course parasitology and immunology entails the
study of body defence mechanism, we will focus on the types of immunity
and their processes, hypersensitivity, interaction of antibody with
antigens. Also, immunology of tissue transplantation and infection will
explain further.
This course deals with parasitology and immunity with emphasis to

different types of immunity, defence mechanisms, processes, functions
and interaction of antibody to antigen.
What You Will Learn In This Course
In this course, you have the course units and a course guide. The course
guide will tell you briefly what the course is all about. It is a general
overview of the course materials you will be using and how to use those
materials. It also helps you to allocate the appropriate time to each unit so
that you can successfully complete the course within the stipulated time
limit.
The course guide also helps you to know how to go about your Tutor-
Marked-Assignment which will form part of your overall assessment at
the end of the course. Also, there will be tutorial classes that are related
to this course, where you can interact with your facilitators and other
students. Please I encourage you to attend these tutorial classes.
This course exposes you to parasitology and immunology, a sub-

discipline and very interesting field of Biology.
Course Aims
This course aims to enable you to know/understand the different types of

immunity, defence mechanisms, processes, functions and interaction of
antibody to antigen.
iv
Course Objectives
To achieve the aim set above, there are objectives. Each unit has a set of
objectives presented at the beginning of the unit. These objectives will
give you what to concentrate and focus on while studying the unit and
during your study to check your progress.
The Comprehensive Objectives of the Course are given below. At the end
of the course/after going through this course, you should be able to:
• Define immunity
• Describe the theories of immunity
• Have an understanding of types of immunity and their importance
to man
• Explain Infections and types
• Prevention and protection from infections
• Explain Immediate hypersensitivity
• Explain Type I, II, III and IV hypersensitivity
• Explain Low-level autoimmunity
• Identify Causes of autoimmunity
• Name and explain Genetic Factors
• Explain Environmental Factors affecting autoimmunity
Working Through the Course
a. To successfully complete this course. You are required to read

each study unit, read the textbooks and other materials provided by
the National Open University.
b. Reading the reference materials can also be of great assistance.
c. Each unit has self –assessment exercise which you are advised to
do. At certain periods during the course you will be required to
submit your assignments for the purpose of assessment.
d. There will be a final examination at the end of the course. The
course should take you about17 weeks to complete.
e. This course guide provides you with all the components of the
course, how to go about studying and how you should allocate your
time to each unit so as to finish on time and successfully.
The Course Materials
The main components of the course are:
1 The Study Guide

2 Study Units
3 Reference/ Further Readings
v
4 Assignments
5 Presentation Schedule
Study Units
The study units in this course are given below:
Module 1 Immunity
Unit 1 Immunity
Unit 2 Infection, immunity and protection
Unit 3 Antigen
Module 2 Hypersensitivity
Unit 1 Hypersensitivity
Unit 2 Autoimmunity
Unit 3 Immunology of Tissue Transplantation
In module one, unit one, two and three extensively explain different types
of immunity and protection, infection, and interaction of antibody with
antigen.
Module Two is concerned with hypersensitivity; inappropriate responds

of the immune system to the presence of antigen, autoimmunity; is the
failure of an organism to recognise its own constituent parts as self, which
allows an immune response against its own cells and tissues and
immunology of tissue transplantation.
Each unit will take a week or two lectures, will include an introduction,
objectives, reading materials, self-assessment question(s), conclusion,
summary, Tutor-Marked Assignments (TMAs), references and other
reading resources.
There are activities related to the lecture in each unit which will help your
progress and comprehension of the unit. You are required to work on
these exercises which together with the TMAs will enable you to achieve
the objective of each unit.
Presentation Schedule
There is a time-table prepared for the early and timely completion and
submissions of your TMAs as well as attending the tutorial classes. You
are required to submit all your assignments by the stipulated date and
time. Avoid falling behind the schedule time.
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Assessment
There are three aspects to the assessment of this course.
The first one is the self-assessment exercises. The second is the Tutor-
Marked Assignments and the third is the written examination or the
examination to be taken at the end of the course.
Do the exercises or activities in the unit applying the information and

knowledge you acquired during the course. The Tutor-Marked
Assignments must be submitted to your facilitator for formal assessment
in accordance with the deadlines stated in the presentation schedule and
the assignment file.
The work submitted to your tutor for assessment will account for 30% of
your total work.
At the end of this course you have to sit for a final or end of course
examination of about a three-hour duration which will account for 70%
of your total course mark.
Tutor -Marked Assignment
This is the continuous assessment component of this course and it

accounts for 30% of the total score. You will be given four (4) TMAs by
your facilitator to answer. Three of which must be answered before you
are allowed to sit for the end of the course examination.
These answered assignments must be returned to your facilitator.
You are expected to complete the assignments by using the information

and material in your reading references and study units.
Reading and researching into the references will give you a wider view
point and give you a deeper understanding of the subject.
Make sure that each assignment reaches your facilitator on or before the
deadline given in the presentation schedule and assignment file. If for any
reason you are not able to complete your assignment, make sure you
contact your facilitator before the assignment is due to discuss the
possibility of an extension. Request for extension will not be granted after
the due date unless there is an exceptional circumstance.
Make sure you revise the whole course content before sitting for
examination. The self-assessment activities and TMAs will be useful for
this purposes and if you have any comments please do before the
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examination. The end of course examination covers information from all

parts of the course.
Course Marking Scheme
Assignment Marks
Assignment 1-4 Four assignments, best three marks of the
four count at 10% each - 30% of
course marks.
End of course examination 70% of overall course marks
Total 100% of course materials
Facilitators/ Tutors and Tutorials
Sixteen (16) hours are provided for tutorials for this course. You will be
notified of the dates, times and location for these tutorial classes.
As soon as you are allocated a tutorial group, the name and phone number
of your facilitator will be given to you.
These are the duties of your facilitator:
• He or she will mark and comment on your assignment

• He will monitor your progress and provide any necessary
assistance you need.
• He or she will mark your TMAs and return to you as soon as
possible.
(You are expected to mail your tutored assignment to your facilitators at

least two days before the schedule date).
Do not delay to contact your facilitator by telephone or e-mail for

necessary assistance if:
• you do not understand any part of the study in the course material
• you have difficulty with the self-assessment activities
• you have a problem or question with an assignment or with the
grading of the assignment.
It is important and necessary you attend the tutorial classes because this
is the only chance to have face to face contact with your facilitator and to
ask questions which will be answered instantly. It is also a period where
you can point out any problem encountered in the course of your study.
viii
Summary
Parasitology and Immunology (406) is a course which explain the body

defence mechanism; how level of immunity in the organism can cause
infection and response of antibody and antigen to infection.
Also, the how natural or artificial, innate or acquired=adaptive and either

active or passive immunity function in organism.
On the completion of this course, you will have an understanding of basic

knowledge of different types of immunity, antibody-antigen interaction,
infection, immunity and protection, hypersensitivity and autoimmunity.
In addition, you will be able to answer the following questions:
• what do you understand by the term Immunity?

• explain innate immunity
• what is acquired immunity
• what is immunity?
• what is an infection?
• what are the types of resistance to infections?
• what are antigens
• differentiate between endogenous and exogenous antigens
• describe the interactions between antibodies and antigens
• state what antigens are composed of chemically.
• list 3 characteristics an antigen must have to be immunogenic
• briefly describe how the body recognises an antigen as foreign.
• what is autoimmunity
• discuss the pathogenesis of autoimmunity
• discuss on the genetic factors affecting autoimmunity
• the list of questions you are expected to answer is not limited to
the above list.
I believe you will agree with me that Mycology is a very interesting field
of biology.
I wish you success in this course.
ix
MAIN
COURSE
CONTENTS PAGE
Module 1 Immunity………………………………..
Unit 1 Immunity …………………………………

Unit 2 Infection, Immunity and Protection ……. 21
Unit 3 Antigen …………………………………. 31
Module 2 Hypersensitivity………………………. 44
Unit 1 Hypersensitivity ……………………….. 44

Unit 2 Autoimmunity …………………………. 59
Unit 3 Immunology of Tissue Transplantation … 70
BIO 406 MODULE 1
MODULE 1 IMMUNITY
Unit 1 Immunity
Unit 2 Infection, Immunity and ProtectionUnit 3 Antigen
UNIT 1 IMMUNITY
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Concept of Immunity
3.2 Passive Immunity
3.3 Active Immunity
3.4 Innate Immunity
3.5 Acquired Immunity
4.0 Conclusion
5.0 Summary
6.0 Tutor-Marked Assignment
7.0 References/Further Reading
1.0 INTRODUCTION
Immunity is a biological term that describes a state of having sufficient

biological defences to avoid infection, disease, or other unwanted
biological invasion. Immunity involves both specific and non-specific
components. The non-specific components act either as barriers or as
eliminators of a wide range of pathogens irrespective of antigenic
specificity. Other components of the immune system adapt themselves to
each new disease encountered and are able to generate pathogen- specific
immunity.
2.0 OBJECTIVES
At the end of this unit, you should be able to:
• define immunity
• describe the theories of immunity
• explain types of immunity and their importance to man.
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BIO 406 PARASITOLOGY AND IMMUNOLOGY
3.0 MAIN CONTENT
3.1 Concept of Immunity
The concept of immunity has intrigued mankind for thousands of years.

The prehistoric view of disease was that it was caused by supernatural
forces, and that illness was a form of theurgic punishment for evilthoughts
visited upon the soul by the gods or by one’s enemies. Betweenthe time
of Hippocrates and the 19th century, when the foundations of the
scientific method were laid, diseases were attributed to an alteration or
imbalance in one of the four humours. The modern word “immunity”
derives from the Latin immunis, meaning exemption from military
service, tax payments or other public services. The first written
descriptions of the concept of immunity may have been made by the
Athenian Thucydides who, in 430 BC, described that when the plague
hit Athens “the sick and the dying were tended by the pitying care of those
who had recovered, because they knew the course of the disease and were
themselves free from apprehensions. For no one was ever attacked a
second time, or not with a fatal result”. The term “immunes”, is also found
in the epic poem “Pharsalia” written around 60 B.C. by the poet Marcus
Annaeus Lucanus to describe a North African tribe’s resistance to snake
venom.
The first clinical description of immunity which arose from a specific

disease causing organism is probably Kitab fi al-jadari wa-al-hasbah (A
Treatise on Smallpox and Measles, translated 1848) written by the Islamic
physician Al-Razi in the 9th century. In the treatise, Al Razi describes the
clinical presentation of smallpox and measles and goes on to indicate that
that exposure to these specific agents confers lasting immunity. However,
it was with Louis Pasteur’s Germ theory of disease that the fledgling
science of immunology began to explain how bacteria caused disease, and
how, following infection, the human body gained the ability to resist
further infections.
The birth of active immunotherapy may have begun with Mithridates VI

of Pontus. To induce active immunity for snake venom, he recommended
using a method similar to modern toxoid serum therapy, by drinking the
blood of animals which fed on venomous snakes. According to Jean de
Maleissye, Mithridates assumed that animals feeding on venomous
snakes acquired some detoxifying property in theirbodies, and their blood
must contain attenuated or transformedcomponents of the snake venom.
The action of those components might be strengthening the body to resist
the venom instead of exerting toxic effect. Mithridates reasoned that, by
drinking the blood of these animals,he could acquire similar resistance to
the snake venom as the animals feeding on the snakes. Similarly, he
sought to harden himself against
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BIO 406 MODULE 1
poison, and took daily sub-lethal doses to build tolerance. Mithridates is

also said to have fashioned a 'universal antidote' to protect him from all
earthly poisons. For nearly 2000 years, poisons were thought to be the
proximate cause of disease, and a complicated mixture of ingredients,
called Mithridate, was used to cure poisoning during the Renaissance. An
updated version of this cure, Theriacum Andromachi, was used well into
the 19th century. In 1888 Emile Roux and Alexandre Yersin isolated
diphtheria toxin, and following the 1890 discovery by Behring and
Kitasato of antitoxin based immunity to diphtheria and tetanus, the
antitoxin became the first major success of modern therapeutic
Immunology.
In Europe, the induction of active immunity emerged in an attempt to

contain smallpox. Immunisation, however, had existed in various forms
for at least a thousand years. The earliest use of immunisation is unknown,
however, around 1000 A.D. the Chinese began practicing a form of
immunisation by drying and inhaling powders derived from the crusts of
smallpox lesions. Around the fifteenth century in India, the Ottoman
Empire, and east Africa, the practice of variolation (poking the skin with
powdered material derived from smallpox crusts) becamequite common.
Variolation was introduced to the west in the early 18th century by Lady
Mary Wortley Montagu. In 1796, Edward Jenner introduced the far safer
method of inoculation with the cowpox virus, a non-fatal virus that also
induced immunity to smallpox. The success and general acceptance of
Jenner's procedure would later drive the general nature of vaccination
developed by Pasteur and others towards the end of the 19th century.
3.2 Passive Immunity
Passive immunity is transmitted by antibodies or lymphocytes preformed

in another host. The passive administration of antibody against bacteria
makes immediately available excess antitoxin to neutralise the toxins.
Likewise, preformed antibodies to certain viruses can be injected during
the incubation period to limit viral multiplication. The main advantage of
passive immunisation with preformed antibodies is the prompt
availability of large amounts of antibody; disadvantages are the short life
span of these antibodies and possible sensitivity reactions if antibodies
from another species are administered.
Passive immunity is the transfer of active immunity, in the form of

readymade antibodies, from one individual to another. Passive immunity
can occur naturally, when maternal antibodies are transferred to the
foetus through the placenta, and can also be induced artificially, when
high levels of human (or horse) antibodies specific for a pathogen or toxin
are transferred to non-immune individuals. Passive immunisation
is used when there is a high risk of infection and insufficient time for the
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body to develop its own immune response, or to reduce the symptoms of

ongoing or immunosuppressive diseases. Passive immunity provides
immediate protection, but the body does not develop memory, therefore
the patient is at risk of being infected by the same pathogen later.
Naturally acquired passive immunity

Maternal passive immunity is a type of naturally acquired passive
immunity, and refers to antibody-mediated immunity conveyed to afoetus
by its mother during pregnancy. Maternal antibodies (MatAb) are passed
through the placenta to the foetus by an FcRn receptor on placental cells.
This occurs around the third month of gestation. IgG is the only antibody
isotype that can pass through the placenta. Passive immunity is also
provided through the transfer of IgA antibodies found in breast milk that
are transferred to the gut of the infant, protecting against bacterial
infections, until the newborn can synthesise its own antibodies.
Artificially acquired passive immunity

Artificially acquired passive immunity is a short-term immunisation
induced by the transfer of antibodies, which can be administered in
several forms; as human or animal blood plasma, as pooled human
immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and
in the form of monoclonal antibodies (MAb). Passive transfer is used
prophylactically in the case of immunodeficiency diseases, such as hypo-
gammaglobulinemia. It is also used in the treatment of several types of
acute infection, and to treat poisoning. Immunity derived from passive
immunisation lasts for only a short period of time, and there is also a
potential risk for hypersensitivity reactions, and serum sickness,
especially from gamma globulin of non-human origin.
The artificial induction of passive immunity has been used for over a
century to treat infectious disease, and prior to the advent of antibiotics,
was often the only specific treatment for certain infections.
Immunoglobulin therapy continued to be a first line therapy in the
treatment of severe respiratory diseases until the 1930’s, even after
sulfonamide lot antibiotics were introduced.
Passive transfer of cell-mediated immunity

Passive or "adoptive transfer" of cell-mediated immunity, is conferredby
the transfer of "sensitised" or activated T-cells from one individual into
another. It is rarely used in humans because it requires histocompatible
donors, which are often difficult to find. In unmatched donors this type of
transfer carries severe risks of graft versus host disease. It has, however,
been used to treat certain diseases including some types of cancer and
immunodeficiency. This type of transfer
differs from a bone marrow transplant, in which hematopoietic stem
cells are transferred.
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BIO 406 MODULE 1
IN TEXT QUESTION
What is passive immunity?
Passive immunity is the transfer of active immunity, in the form of
readymade antibodies, from one individual to another.
3.3 Active Immunity
Active immunity is induced after contact with foreign antigens. This

contact may consist of clinical or subclinical infection, immunisation with
live or killed infectious agents or their antigens, exposure to microbial
products or transplantation of foreign cells. In all these instances, the host
actively produces antibodies and lymphoid cells acquire the ability to
respond to the antigens. Advantages of active immunity include long-term
resistance –based on memory of prior contact with antigen and the
capacity to respond faster and to a greater extent on subsequent contact
with the same antigen, disadvantages include the slow onset of resistance
and the need for prolonged orrepeated contact with the antigen.
Fig. 1: The Time Course of an Immune Response. Due to the

formation of immunological memory, re-infection atlater time points
leads to a rapid increase in antibody production and Effector T cell
Activity. These laterinfections can be mild or even inapparent.
When B cells and T cells are activated by a pathogen, memory B-cells
and T- cells develop. Throughout the lifetime of an animal these memory
cells will “remember” each specific pathogen encountered, and are able
to mount a strong response if the pathogen is detected again. This type of
immunity is both active and adaptive because the body's immune system
prepares itself for future challenges. Active immunity often involves both
the cell-mediated and humoral aspects of immunity as well as input from
the innate immune system. The innate system is
present from birth and protects an individual from pathogens regardless
5
of experiences, whereas adaptive immunity arises only after an infection

or immunisation and hence is "acquired" during life.
Innate Immunity
Naturally acquired active immunity occurs when a person is exposed to
a live pathogen, and develops a primary immune response, which leads to
immunological memory. This type of immunity is “natural” because itis
not induced by deliberate exposure. Many disorders of immune system
function such as immunodeficiency and immuno-suppression can affect
the formation of active immunity.
Artificially acquired active immunity

Artificially acquired active immunity can be induced by a vaccine; a
substance that contains antigen. A vaccine stimulates a primary response
against an antigen without causing symptoms of the disease. The term
vaccination was coined by Edward Jenner and adapted by Louis Pasteur
for his pioneering work in vaccination. The method Pasteur used entailed
treating the infectious agents for those diseases so they lost the ability to
cause serious disease. Pasteur adopted the name vaccine as a generic term
in honour of Jenner's discovery, which Pasteur's work built upon.
In 1807, the Bavarians became the first group to require that theirmilitary
recruits be vaccinated against smallpox, as the spread of smallpox was
linked to combat. Subsequently the practice of vaccination would increase
with the spread of war.
There are four types of traditional vaccines:
a. Inactivated vaccines are composed of micro-organisms that have

been killed with chemicals and/or heat and are no longer infectious.
Examples are vaccines against flu, cholera, plague, and hepatitis A. Most
vaccines of this type are likely to require booster shots.
b. Live, attenuated vaccines are composed of micro-organisms that
have been cultivated under conditions which disable their ability to induce
disease. These responses are more durable and do not generally require
booster shots. Examples include yellow fever, measles, rubella, and
mumps.
c. Toxoids are inactivated toxic compounds from micro-organisms in
cases where these (rather than the micro-organism itself) cause illness,
used prior to an encounter with the toxin of the micro- organism.
Examples of toxoid-based vaccines include tetanus anddiphtheria.
d. Subunit -vaccines are composed of small fragments of disease
causing organisms. A characteristic example is the subunit vaccine
against Hepatitis B virus.
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BIO 406 MODULE 1
Most vaccines are given by hypodermic injection as they are not absorbed
reliably through the gut. Live attenuated polio and some typhoid and
cholera vaccines are given orally in order to produce immunity based in
the bowel.
IN TEXT QUESTIONS
How is active immunity acquired?
Answers
Active immunity is induced after contact with foreign antigens.
3.3 Innate Immunity
The innate immunity system is what we are born with and it is

nonspecific; all antigens are attacked pretty much equally. It is genetically
based and we pass it on to our offspring.
Surface Barriers or Mucosal Immunity
a. The first and, arguably, most important barrier is the skin. The skin
cannot be penetrated by most organisms unless it already hasan opening,
such as a scratch, or cut.
b. Mechanically, pathogens are expelled from the lungs by ciliary
action as the tiny hairs move in an upward motion; coughing and sneezing
abruptly eject both living and nonliving things from the respiratory
system; the flushing action of tears, saliva, and urine also force out
pathogens, as does the sloughing off of skin.
c. Sticky mucus in respiratory and gastrointestinal tracts traps many
microorganisms.
d. Acid pH (< 7.0) of skin secretions inhibits bacterial growth. Hair
follicles secrete sebum that contains lactic acid and fatty acids both of
which inhibit the growth of some pathogenic bacteria and fungi. Areas of
the skin not covered with hair, such as the palms and soles of the feet, are
most susceptible to fungal infections. Think athlete's foot.
e. Saliva, tears, nasal secretions, and perspiration contain lysozyme,
an enzyme that destroys Gram positive bacterial cell walls causing cell
lysis. Vaginal secretions are also slightly acidic (after the onset of
menses). Spermine and zinc in semen destroy some pathogens.
Lactoperoxidase is a powerful enzyme found in mother's milk.
f. The stomach is a formidable obstacle insofar as its mucosa secrete
hydrochloric acid (0.9 < pH < 3.0, very acidic) and protein-digesting
enzymes that kill many pathogens. The stomachcan even destroy drugs
and other chemicals.
Normal flora are the microbes, mostly bacteria, that live in and on our
bodies with, usually, no harmful effects to us. We have about 1013 cells
in our bodies and 1014 bacteria, most of which live in the large intestine.
There are 103–104 microbes per cm2 on the skin (Staphylococcus aureus,
7
Staph. epidermidis, diphtheroids, streptococci, Candida, etc.). Various

bacteria live in the nose and mouth. Lactobacilli live in the stomach and
small intestine. The upper intestine has about 104 bacteria per gram; the
large bowel has 1011 per gram, of which 95–99% are anaerobes (An
anaerobe is a microorganism that can live without oxygen, while an
aerobe requires oxygen.) or bacteroides. The urogenitary tract is lightly
colonized by various bacteria and diphtheroids. After puberty, the vagina
is colonized by Lactobacillus aerophilus that ferment glycogen to
maintain an acidic pH level. Normal flora fill almost all of the available
ecological niches in the body and produce bacteriocidins, defensins,
cationic proteins, and lactoferrin all of which work to destroy other
bacteria that compete for their niche in the body. The resident bacteria can
become problematic when they invade spaces in which theyare not meant
to be. As examples: (a) staphylococcus living on the skin can gain entry
to the body through small cuts. (b) Some antibiotics, in particular
clindamycin, kill some of the bacteria in our intestinal tract.
This causes an overgrowth of Clostridium difficile, which results in

pseudomembranous colitis, a rather painful condition wherein the inner
lining of the intestine cracks and bleeds. A phagocyte is a cell that attracts
(by chemotaxis), adheres to, engulfs, and ingests foreign bodies.
Promonocytes are made in the bone marrow, after which they are released
into the blood, they are called circulating monocytes, which eventually
mature into macrophages (meaning "big eaters", see below).
Fig. 2: Some macrophages are concentrated in the lungs, liver

(Kupffer cells), lining of the lymph nodes and spleen, brain microglia,
kidney mesoangial cells, synovial A cells, and osteoclasts. They are
long-lived, depend on mitochondria for energy, and are best at
attacking dead cells and pathogens capable of living within cells.
Once a macrophage phagocytises a cell, it places some of its proteins,
called epitopes, on its surface—much like a fighter plane displaying
its hits. These surface markers serve as an alarm to other immune
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BIO 406 MODULE 1
cells that then infer the form of the invader. All cells that do this are
called antigen presenting cells (APCs).
Fig. 3: The non-fixed or wandering macrophages roam the blood

vessels and can even leave them to go to an infection site where they
destroy dead tissue and pathogens. Emigration by squeezing through
the capillary walls to the tissue is called diapedesis or extravasation.
The presence of histamines at theinfection site attracts the cells to
their source.
Fig. 4: Natural killer cells move in the blood and lymph to lyse(cause
to burst) cancer cells and virus-infected body cells. They are large
granular lymphocytes that attach to the glycoproteins on the
surfaces of infected cellsand kill them.
Polymorphonuclear neutrophils, also called polys for short, are

phagocytes that have no mitochondria and get their energy from stored
glycogen. They are nondividing, short-lived (half-life of 6–8 hours, 1–4
9
day lifespan), and have a segmented nucleus. [The picture below shows
the neutrophil phagocytising bacteria, in yellow.] They constitute 50–
75% of all leukocytes. The neutrophils provide the major defence against
pyogenic (pus-forming) bacteria and are the first on the scene to fight
infection. They are followed by the wandering macrophages about three
to four hours later.
Fig. 5: The complement system is a major triggered enzymeplasma

system. It coats microbes with molecules that make them more
susceptible to engulfment by phagocytes. Vascular permeability
mediators increase the permeability of the capillaries to allow more
plasma and complement fluid to flow to the site ofinfection. They also
encourage polys to adhere to the walls of capillaries (margination)
from which they can squeeze through in a matter of minutes to arrive
at a damaged area. Once phagocytes do their job, they die and their
"corpses," pockets of damaged tissue, and fluid form pus.
Fig. 6: Eosinophils are attracted to cells coated withcomplement C3B,

where they release major basic protein (MBP), cationic protein,
perforins, and oxygen metabolites, all of which work together to burn
holes incells and helminths (worms). About 13% of the WBCs are
eosinophils. Their lifespan is about 8–12 days. Neutrophils,
eosinophils, and macrophages are all phagocytes.
Dendritic cells are covered with a maze of membranous processes that

look like nerve cell dendrites. Most of them are highly efficient antigen
presenting cells. There are four basic types: Langerhans cells, interstitial
dendritic cells, interdigitating dendritic cells, and circulating dendritic
cells. Our major concern will be Langerhans cells, which are found in the
epidermis and mucous membranes, especially in the anal, vaginal, and
oral cavities. These cells make a point of attracting antigen and
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BIO 406 MODULE 1
efficiently presenting it to T helper cells for their activation. [This

accounts, in part, for the transmission of HIV via sexual contact.]
Fig. 7: Each of the cells in the innate immune system bind toantigen
using pattern-recognition receptors. Thesereceptors are encoded in
the line of each person. This immunity is passed from generation to
generation. Over the course of human development these receptors
for pathogen-associated molecular patterns have evolved via natural
selection to be specific to certain characteristics of broad classes of
infectious organisms. There are several hundred of these receptors
and they recognise patterns of bacterial lipopolysaccharide,
peptidoglycan, bacterial DNA, dsRNA, and othersubstances. Clearly,
they are set to target both Gram- negative and Gram-positive
bacteria.
11
3.5 Acquired Immunity
Lymphocytes come in two major types: B cells and T cells. The peripheral
blood contains 20–50% of circulating lymphocytes; the rest move in the
lymph system. Roughly 80% of them are T cells, 15% B cells and
remainder are null or undifferentiated cells. Lymphocytes constitute 20–
40% of the body's WBCs. Their total mass is about the same as that of
the brain or liver. B cells are produced in the stem cellsof the bone
marrow; they produce antibody and oversee humoral immunity. T cells
are nonantibody-producing lymphocytes which are also produced in the
bone marrow but sensitised in the thymus and constitute the basis of cell-
mediated immunity. The production of these cells is diagrammed below.
Parts of the immune system are changeable and can adapt to better attack
an invading antigen. There are two fundamental adaptive mechanisms:
cell-mediated immunity and humoral immunity.
Cell-mediated immunity
Macrophages engulf antigens, process them internally, then display parts
of them on their surface together with some of their own proteins. This
sensitises the T cells to recognise these antigens. All cells are coated
with various substances. CD stands for cluster of differentiation and there
are more than one hundred and sixty clusters, each of which is a different
chemical molecule that coats the surface. CD8+ is read "CD8 positive."
Every T and B cell has about 105 = 100,000 molecules on its surface. B
cells are coated with CD21, CD35, CD40, and CD45 inaddition to
other non-CD molecules. T cells have CD2, CD3, CD4, CD28, CD45R,
and other non-CD molecules on their surfaces.
The large number of molecules on the surfaces of lymphocytes allows

huge variability in the forms of the receptors. They are produced with
random configurations on their surfaces. There are some 1018 different
structurally different receptors. Essentially, an antigen may find a near-
perfect fit with a very small number of lymphocytes, perhaps as few as
one.
T cells are primed in the thymus, where they undergo two selection
processes. The first positive selection process weeds out only those T
cells with the correct set of receptors that can recognise the MHC
molecules responsible for self-recognition. Then a negative selection
process begins whereby T cells that can recognize MHC molecules
complexed with foreign peptides are allowed to pass out of the thymus.
Cytotoxic or killer T cells (CD8+) do their work by releasing
lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as
managers, directing the immune response. They secrete chemicals called
lymphokines that stimulate cytotoxic T cells and B cells to grow and
divide, attract neutrophils, and enhance the ability of macrophages to
12
BIO 406 MODULE 1
engulf and destroy microbes. Suppressor T cells inhibit the production of

cytotoxic T cells once they are unneeded, lest they cause more damage
than necessary. Memory T cells are programmed to recognise and respond
to a pathogen once it has invaded and been repelled.
Humoral immunity
An immunocompetent but as yet immature B-lymphocyte is stimulated to
maturity when an antigen binds to its surface receptors and there is aT
helper cell nearby (to release a cytokine). This sensitises or primes the B
cell and it undergoes clonal selection, which means it reproduces
asexually by mitosis. Most of the family of clones becomes plasma cells.
These cells, after an initial lag, produce highly specific antibodies at a rate
of as many as 2000 molecules per second for four to five days. The other
B cells become long-lived memory cells. Antibodies, also called
immunoglobulins or Igs, constitute the gamma globulin part ofthe
blood proteins. They are soluble proteins secreted by the plasma offspring
(clones) of primed B cells. The antibodies inactivate antigens by, (a)
complement fixation (proteins attach to antigen surface and causeholes to
form, i.e., cell lysis), (b) neutralisation (binding to specific sites to prevent
attachment—this is the same as taking up a parking space),
(c) agglutination (clumping), (d) precipitation (forcing insolubility and
settling out of solution), and other more arcane methods.
Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-

1%, and IgE-0.002% (responsible for autoimmune responses, such as
allergies and diseases like arthritis, multiple sclerosis, and systemic
lupus). IgG is the only antibody that can cross the placental barrier to the
foetus and it is responsible for the 3 to 6 month immune protection of
newborns that is conferred by the mother.
13
Fig. 8: IgM is the dominant antibody produced in primaryimmune

responses, while IgG dominates in secondary immune responses. IgM
is physically much larger than the other immunoglobulins.
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BIO 406 MODULE 1
Fig. 9: Notice the many degrees of flexibility of the antibody

molecule. This freedom of movement allows it to more easily conform
to the nooks and crannies on an antigen. The upper part or Fab
(antigen binding) portion of the antibody molecule (physically and
not necessarily chemically) attaches to specific proteins [called
epitopes] on the antigen. Thus, antibody recognises the epitope and
not the entire antigen. The Fc region is crystallisable and is
responsible for effector functions, i.e., the end to which immune cells
can attach.
Lest you think that these are the only forms of antibody produced, you
should realise that the B cells can produce as many as 1014
conformationally different forms.
The process by which T cells and B cells interact with antigens is

summarised in the diagram below.
15
In the ABO blood typing system, when an A antigen is present (in a

person of blood type A), the body produces an anti-B antibody, and
similarly for a B antigen. The blood of someone of type AB, has both
antigens, hence has neither antibody. Thus that person can be transfused
16
BIO 406 MODULE 1
with any type of blood, since there is no antibody to attack foreign blood
antigens. A person of blood type O has neither antigen but both antibodies
and cannot receive AB, A, or B type blood, but they can donate blood for
use by anybody. If someone with blood type A received blood of type B,
the body's anti-B antibodies would attack the new blood cells and death
would be imminent.
All of these of these mechanisms hinge on the attachment of antigen and

cell receptors. Since there are many, many receptor shapes available,
WBCs seek to optimise the degree of confluence between the two
receptors. The number of these "best fit" receptors may be quite small,
even as few as a single cell. This attests to the specificity of the
interaction. Nevertheless, cells can bind to receptors whose fit is less than
optimal when required. This is referred to as cross-reactivity. Cross-
reactivity has its limits. There are many receptors to which virions cannot
possibly bind. Very few viruses can bind to skin cells.
The design of immunising vaccines hinges on the specificity and cross-

reactivity of these bonds. The more specific the bond, the more effective
and long-lived the vaccine. The smallpox vaccine, which is made from
the vaccinia virus that causes cowpox, is a very good match for the
smallpox receptors. Hence, that vaccine is 100% effective and provides
immunity for about 20 years. Vaccines for cholera have a relatively poor
fit so they do not protect against all forms of the disease and protect for
less than a year.
The goal of all vaccines is promote a primary immune reaction so that

when the organism is again exposed to the antigen, a much stronger
secondary immune response will be elicited. Any subsequent immune
response to an antigen is called a secondary response and it has
• a shorter lag time

• more rapid buildup
• a higher overall level of response
• a more specific or better "fit" to the invading antigen
• utilises IgG instead of the large multipurpose antibody IgM.
IN TEXT QUESTION
What are the types of lymphocytes?
Answer
Lymphocytes come in two major types: B cells and T cells.
17
4.0 CONCLUSION
The student should be able to discuss on the following topics:
• Theories of immunity
• Passive and Active Immunity
• Innate and Acquired Immunity.
5.0 SUMMARY
Immunity can be natural or artificial, innate or acquired=adaptive, and

either active or passive.
• Active natural (contact with infection): develops slowly, is long

term, and antigen specific.
• Active artificial (immunisation): develops slowly, lasts for several
years, and is specific to the antigen for which the immunisation
was given.
• Passive natural (transplacental -mother to child): develops
immediately, is temporary, and affects all antigens to which the
mother has immunity.
• Passive artificial (injection of gamma globulin): develops
immediately, is temporary, and affects all antigens to which the
donor has immunity.
6.0 TUTOR-MARKED ASSIGNMENT
i. What do you understand by the term immunity?

ii. Explain innate immunity.
iii. What is acquired immunity.
7.0 REFERENCES/FURTHER READING
A "al-Razi" (2003). The Columbia Electronic Encyclopedia. Sixth

Edition. Columbia University Press.
Coico, R., Sunshine, G., & Benjamin, E. (2003). “Immunology: A Short

Course.” Pg. 48.
Geo. F.B, Janet, S.B.& Stephen, A. M. (2001). Medical Microbiology.
Gherardi, E. The Concept of Immunity. History and Applications.
Immunology Course Medical School, University of Pavia.
Janeway, Charles; Paul Travers, Mark Walport, & Mark Shlomchik

(2001). Immunobiology. Fifth Edition. New York and London: Garland
Science. ISBN 0-8153-4101-6.
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BIO 406 MODULE 1
Keller, Margaret A. & Richard, Stiehm E. (Oct 2000). "Passive Immunity

in Prevention and Treatment of Infectious Diseases." Clinical
Microbiology Reviews 13 (4): 602–614.
Lindquester, Gary J. (2006). Introduction to the History of Disease.

Disease and Immunity, Rhodes College.
Microbiology and Immunology On-Line Textbook: USC School of
Medicine.
Silverstein, Arthur M. (1989). History of Immunology. Academic Press.
19
UNIT 2 INFECTION, IMMUNITY AND PROTECTION
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Infection
3.2 Examples of Infections
3.3 Prevention as a means of Protection
3.4 Non-Specific Resistance
3.5 Specific Immune Response to Infection
4.0 Conclusion
5.0 Summary
7.0 Reference/Further Reading
1.0 INTRODUCTION
In the previous unit you learnt about the different types of immunity. In
this unit you will learn more deeply on the immune system. The immune
system is the body's defence against infectious organisms and other
invaders. Through a series of steps called the immune response, the
immune system attacks organisms and substances that invade body
systems and cause disease.
The immune system is made up of a network of cells, tissues, and organs

that work together to protect the body. The cells involved are white blood
cells, or leukocytes, which come in two basic types that combine to seek
out and destroy disease-causing organisms or substances.
Leukocytes are produced or stored in many locations in the body,

including the thymus, spleen, and bone marrow. For this reason, they are
called the lymphoid organs. There are also clumps of lymphoid tissue
throughout the body, primarily as lymph nodes, that house the leukocytes.
The leukocytes circulate through the body between the organs and nodes
via lymphatic vessels and blood vessels. In this way, the immune system
works in a coordinated manner to monitor the body for germs or
substances that might cause problems.
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BIO 406 MODULE 1
2.0 OBJECTIVES
• define the immune system

• define infections and state types of infections and
• specify how to prevent infections.
3.0 MAIN CONTENT
3.1 Infection
An infection is the colonisation of a host organism by parasite species.

Infecting parasites seek to use the host's resources to reproduce, often
resulting in disease. Colloquially, infections are usually considered to be
caused by microscopic organisms or microparasites like viruses, prions,
bacteria, and viroids, though larger organisms like macroparasites and
fungi can also infect.
Hosts normally fight infections themselves via their immune system.

Mammalian hosts react to infections with an innate response, often
involving inflammation, followed by an adaptive response.
Pharmaceuticals also help fight infections.
Diagnosis of infections can be difficult as specific signs and symptoms

are rare. If an infection is suspected, blood, urine and sputum culture tests
are usually the first step. Chest x-rays and stool analysis may also aid
diagnosis. Spinal fluid can be tested to ensure that there is no brain
infection.
In children the presence of cyanosis, rapid breathing, poor peripheral

perfusion, or a petechial rash increases the risk of a serious infection by
greater than 5 fold. Other important indicators include parental concern,
clinical instinct, and temperature greater than 40 °C.
Infections could be as a result of bacteria or a virus. Bacterial and viral

infections can both cause symptoms such as malaise, fever, and chills. It
can be difficult to distinguish between bacterial and viral infection but it
is important to do so, because viral infections cannot be cured by
antibiotics.
There is a general chain of events that applies for infections to occur. The
chain of events involves several steps which include infectious agent,
reservoir, entering a susceptible host, and exit and transmission to new
hosts. Each of the links must be present in a chronological order for an
infection to develop and understanding these steps helps health care
21
workers target the infection and prevent it from occurring in the first
place.
Infection begins when an organism successfully colonises a host by

entering the body, growing and multiplying. Most humans are not easily
infected but those who are weak, sick, and malnourished, have cancer or
are diabetic have increased susceptibility to chronic or persistent
infections. Individuals who have a suppressed immune system are
particularly susceptible to opportunistic infections. Invasion of the host
generally occurs through the mucosa in orifices like the oral cavity, nose,
eyes, genitalia, anus, or open wounds. While a few organisms can grow
at the initial site of entry, many migrate and cause systemic infection in
different organs. Some pathogens grow within the host cells
(intracellular) whereas others grow freely in bodily fluids.
Wound colonisation refers to nonreplicating microorganisms within the

wound, while in infected wounds replicating organisms exist and tissue is
injured. All multicellular organisms are colonised to some degree by
extrinsic organisms, and the vast majority of these exist in either a
mutualistic or commensal relationship with the host. An example of the
former would be the anaerobic bacteria species which colonise the
mammalian colon, and an example of the latter would be the various
species of staphylococcus which exist on human skin. Neither of these
colonisations would be considered infections. The difference between an
infection and a colonisation is often only a matter of circumstance.
Organisms which are non-pathogenic can become pathogenic given
specific conditions, and even the most virulent organism requires certain
circumstances to cause a compromising infection. Some colonising
bacteria, such as Corynebacteria sp. and viridans streptococci, prevent
the adhesion and colonisation of pathogenic bacteria and thus have a
symbiotic relationship with the host, preventing infection and speeding
wound healing.
The variables involved in the outcome of a host becoming inoculated by

a pathogen and the ultimate outcome include the:
• route of entry of the pathogen and the access to host regions that
it gains
• intrinsic virulence of the particular organism
• quantity or load of the initial inoculant
• immune status of the host being colonised.
As an example, the staphylococcus species present on skin remain
harmless on the skin, but, when present in a normally sterile space, such
as in the capsule of a joint or the peritoneum, will multiply without
resistance and create a huge burden on the host.
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BIO 406 MODULE 1
Infections result in diseases. Disease can arise if the host's protective

immune mechanisms are compromised and the organism inflicts damage
on the host. Microrganisms can cause tissue damage by releasing avariety
of toxins or destructive enzymes. For example, Clostridium tetani
releases a toxin which can paralyze muscles, or staphylococcus releases
toxins which can produce shock and sepsis. Not all infectious agents
cause disease in all hosts. For example less than 5% of individuals
infected with polio develop the disease. On the other hand, some
infectious agents are highly virulent. The prion causing mad cow disease
and Creutzfeldt–Jakob disease kills almost all animals and people that
are infected.
Persistent infections occur because the body is unable to clear the

organism after the initial infection. Persistent infections are characterised
by the continual presence of the infectious organism often as latent
infection with occasional recurrent relapses of active infection. There are
some viruses that can maintain a persistent infection by infecting different
cells of the body. Some viruses once acquired never leave the body. A
typical example is the herpes virus which tends tohide in nerves and
become reactivated when specific circumstances arise. Persistent
infections cause millions of deaths globally each year. Chronic infections
by parasites account for high morbidity and mortality in many
underdeveloped countries.
In order for infecting organisms to survive and repeat the cycle of

infection in other hosts, they (or their progeny) must leave an existing
reservoir and cause infection elsewhere. Transmission of infections can
take place via many potential routes. Infectious organisms may be
transmitted either by direct or indirect contact. Direct contact occurs
when an individual comes into contact with the reservoir. This may
mean touching infected bodily fluids or drinking contaminated water or
being bitten by the deer tick. Direct contact infections can also result
from inhalation of infectious organisms found in aerosol particles
emitted by sneezing or coughing. Another common means of direct
contact transmission involves sexual activity - oral, vaginal, or anal sex.
Indirect contact occurs when the organism is able to withstand the harsh
environment outside the host for long periods of time and still remain
infective when specific opportunity arises. Inanimate objects that are
frequently contaminated include toys, furniture, door knobs, tissue wipes
or personal care products from an infected individual. Consuming food
products and fluid which have been contaminated by contact with an
infecting organism is another case of disease transmission by indirect
contact.
A common method of transmission in under developed countries isfecal-

oral transmission. In such cases, sewage water is used to wash food or is
23
consumed. This results in food poisoning. Common pathogens which are

transmitted by the fecal-oral route include Vibrio cholerae, Giardia
species, rotaviruses, Entameba histolytica, Escherichia coli, and tape
worms. Most of these pathogens cause gastroenteritis.
All the above modes are examples of horizontal transmission because

the infecting organism is transmitted from person to person in the same
generation. There are also a variety of infections transmitted vertically -
that is from mother to child during the birthing process or fetal
development. Common disorders transmitted this way include AIDs,
hepatitis, herpes, and cytomegalovirus
IN TEXT QUESTION
What is infection?
Answer.
An infection is the colonisation of a host organism by parasite species.
3.2 Examples of Infections
Specific bacterial infections

H pylori is associated with inflammation of the stomach and is a common
cause of stomach ulcers and gastritis. At least 10 percent of individuals
infected with h pylori develop an ulcer. Moreover, there isan increased
risk of stomach cancer after an infection with this organism.
Methicillin-resistant staphylococcus aureus predominantly affects theskin

and is considered to be a super bug as it is very resistant to antibiotics.
This bacterium is known to generate a variety of toxic enzymes which can
lead to vomiting, diarrhoea, shock and sepsis. MRSA is quite common in
hospitals and today there is great cause for concern about its spread.
Chronic ear infections

Chronic ear infections are a common problem in childhood. These
infections may be due to bacteria or the common cold virus. The disorder
often presents with persistent blockage of the ear, hearing loss, chronic
ear drainage, balance problems, deep ear pain, headache, fever, excess
sleepiness or confusion. Chronic ear infections usually develop slowly
over many years in patients who have had ear problems. The treatment of
persistent ear infections is complex and requires a combination of
antibiotics, corticosteroids, and/or placement of tubes. When this fails
surgery is required to control the infection.
Osteomyelitis
Osteomyelitis is a bone infection caused by various bacteria and can occur
in both children and adults. When bone gets infected, there is continuous
pain, fever and it is painful to move the extremity. Bone infections are
24
BIO 406 MODULE 1
acquired from infections elsewhere in the body, from trauma or are spread
from adjacent infected tissues. The diagnosis of bone infection requires a
bone scan, blood cultures and x rays. Sometimes the bone marrow is
aspirated to discover the specific organism. Osteomyelitis is a serious
infection and carries a high complication rate if not treated promptly. If
the infection is diagnosed rapidly, the prognosis is good. However chronic
Osteomyelitis can take years to heal and can keep on recurring.
Individuals at risk of Osteomyelitis include those who have artificial
joints or metal components in their joint.
Lyme disease
Lyme is a tick borne disease that can cause a skin rash, fever, chills, body
aches, and joint pain. Some infected individuals develop severe weakness
and temporary paralysis. Lyme disease is caused by at least three species
of bacteria belonging to the genus Borrelia, which are carried by deer
ticks. Infections are more common during summer,especially if the host
spends time in grassy woodlands where ticksbreed. When the infection
is diagnosed promptly, most people do recover fully. However, there are
some individuals who keep on having recurring or lingering symptoms
long after the infection has been treated. When it becomes chronic, Lyme
Disease can present with a variety of symptoms including migrating joint
pains, headaches, confusion, excess fatigue, inability to sleep, paralysis
of one side of the face, and difficulty concentrating. Even though there
are reliable tests available they are not one hundred percent sensitive.
While most individuals do respond to a 14 day course of antibiotics, some
individuals take considerably longer.
3.3 Prevention as a Means of Protection
Viable treatment and prevention strategies will disrupt the infectioncycle.

For example, direct transmission can be diminished by adequate hygiene,
maintaining a sanitary environment, and health education.
When infection attacks the body, anti-infective drugs can suppress the
infection. Four types of anti-infective or drugs exist: antibacterial
(antibiotic), antiviral, antitubercular, and antifungal. Depending on the
severity and the type of infection, the antibiotic may be given by mouth,
injection or may be applied topically. Severe infections of the brain are
usually treated with intravenous antibiotics. Sometimes, multiple
antibiotics are used to decrease the risk of resistance and increase
efficacy. Antibiotics only work for bacteria and do not affect viruses.
Antibiotics work by slowing down the multiplication of bacteria or by
killing the bacteria. The most common classes of antibiotics used in
medicine include penicillin, cephalosporins, aminoglycosides,
macrolides, quinolones and tetracyclines.
25
Techniques like hand washing, wearing gowns, and wearing face masks
can help prevent infections from being passed from the surgeon to the
patient or vice versa. Frequent hand washing remains the most important
defence against the spread of unwanted organisms. Nutrition has to be
improved and one has to make changes in life style- such as avoiding the
use of illicit drugs, using a condom, and entering an exercise programme.
Cooking foods well and avoiding eating foods which have been left
outside for a long time is also important. Do not take antibiotics for longer
than needed. Long term use of antibiotics leads to resistance and chances
of developing opportunistic infections like clostridium difficile colitis.
Vaccination is another means of preventing infections by facilitating the
development of immune resistance in vaccinated hosts.
3.4 Non-Specific Resistance
Innate or non-specific resistance is the mechanism by which the host

eliminates most invading micro-organism by non-specific
immunological means. There are three major mechanisms of non- specific
immunity to infection:
• Surface/ Mechanism barriers

• Action of phagocytic cells
• The role of complement.
Surface/Mechanism Barriers
The skin is the most obvious mechanical barrier preventing micro-
organisms from gaining access to the body. Fatty acids and lysozyme
contained in sweat lower the pH and render the skin uninhabitable to most
bacteria or immobilise the micro-organisms. The mucociliary action of
cells lining the respiratory tract is another non-specific mechanical
protective mechanism, as is the acid produced in the stomach which
renders the gastrointestinal environment hostile to infectious agents. The
mucociliary lining of the lungs, tears and saliva all provide some
protection against infection.
Action of Phagocytic Cells

Once micro-organisms penetrate surface barriers, it becomes exposed to
the action of phagocytic cells. Phagocytosis of micro-organisms and
their killing intracellularly by prteolytic and other enzymes is the most
primitive of defences against microbes which manage to gain access into
the body. Three main cells involved in non specific immune responses to
infection include; macrophages, polymorphonuclear neutrophilis (PMN)
and eosinophils.
Macrophages are found in abundance in the liver, spleen, lymph, nodes,

the lungs and sub-epithelial tissues of the skin. Their main function is to
26
BIO 406 MODULE 1
phagocytose particulate matter including bacteria, viruses and

antigen/antibody complexes. The larger the substances, the more readily
it is phagocytosed by macrophages and this action is independent of any
specific immunological mechanism.
Polymorphs reside in the bone marrow where they are plentiful and
although they are normally short-lived, prolonged infection leads to
polymorphonuclear leucocytosis in the peripheral blood. Polymorphs
may also accumulate in the lymph nodes causing lymphadenopathy.
Phagocytic cells are attracted to the site of infection by chemotactic
factors, the most powerful of which are the complement breakdown
products C3a and C5a. A variety of other serum substances such as
prostaglandin E1 and tuftsin produced by the spleen also serve as
chemotactic agents and some bacteria possess low molecular weight
substances which serve to attract them to the site of infection. Broadly,
the same chemotactic factors are responsible for attracting PMN and
monocytes to the site of inflammation but in addition to Ca5, immune
complexes are active monocyte chemotactic factors. Lymphokines attract
macrophages to the site of immune reaction and immobilise them there.
The phagocytic cells form pseudopodia around the microbe eventually
engulfing it to form a phagosome. The phagosome is lined byits own wall
and is therefore effectively extracellular. The cytoplasm of the phagocytic
cells contains granules full of powerful bactericidal substances and when
these granules fuse with the phagosome, they formthe vaculole, killing
the microbes.
3.5 Specific Immune Response to Infection
Specific humoral immunity is based on antibodies directed against the

invading micro-organism. There are two main phases in antibody
production. After initial contact with the antigen a few days or weeks
elapse before antibodies are produced. First IgM then IgG antibodies are
produced but the titres of both are low in this phase, known as the primary
antibody response. Subsequent exposure to the same antigen evokes a
much faster and more sustained antibody production. This
secondary response resulting in a persistence of the antibody is
responsible for resistance to infection. Antibodies can also directly
neutralise the effects of micro-organisms by combining with their toxins,
thus preventing the appearance of illness. Antibodies also act in concert
with complement to cause bacterial lysis. Antibody-dependent parasite
killing is best exemplified by schistosome in a cyotoxic manner that is
independent of complement.
Cell –mediated Immunity

This important in those infections where the organisms are intracellular
because they are inaccessible to humoral antibody. Specific cell-
27
mediated immunity to infection is the function mainly of T lymphocytes

and macrophages. Contact between antigen, macrophages and
lymphocytes leads to the production of lymphokines, memory T
lymphocytes and killer cells. Such killer cells attack and destroy infected
cells bearing the antigen in question releasing the microbes in them which
now become exposed to humoral antibody capable of neutralisingthem or
their effects. The lymphocyte killing of the target cell does not require
antibody or complement. Lymphokines are soluble factors released by T
lymphocytes as a result of contact with antigen. Thelymphokines enhance
the phagocytic activity of macrophages. Macrophages are activitated by
the lymphokines. Such activated macrophages exhibit greatly enhanced
cytotoxicity to infectious agents as well as tumour cells. Macrophage
activation is important in controlling infections such as leprosy,
tuberculosis and a number of viralinfections.
IN TEXT QUESTION
What is the function of T lymphocytes?
Answer:
Specific cell- mediated immunity to infection is the function mainly
of
T lymphocytes and macrophages.
4.0 CONCLUSION
The student has learnt the following:
• Infections
• Immunity
• Prevention of infections.
5.0 SUMMARY
With the huge array of infectious micro-organisms in the environment,

the host has to develop the ability to mount appropriate defence
mechanisms in order to prevent recurrent infections and survive. Nature
has endowed mankind with just that ability. Several different mechanisms
have been evolved by living organism including man to counter the
effects of invasion by pathogens.
i. What is immunity?
ii. What is an infection?
iii. What are the types of resistance to infections?
7.0 REFERENCE/FURTHER READING
Koh, GCKW, van der Poll T.& Peacock, S.J. (2011). "The Impact of
Diabetes on the Pathogenesis of Sepsis". Eur J Clin Microbiol & Infect
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BIO 406 MODULE 1
Dis. doi:10.1007/s10096-011-1337-4.
Nursing Pharmacology Made Incredibly Easy. Lippincott Williams &

Wilkins. 2009.p.483.
Prudhomme, S. Bonnaud, B. & Mallet, F. (2005). Endogenous

Retroviruses and animal reproduction. Cytogenet Genome Res, 110: 353-
364.doi:10.1159/000084967.
Salimonu, L.S.(2004). Basic Immunology for Students of Medicine and

Biology. College Press and Publishers Limited.
29
UNIT 3 ANTIGEN
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Specific Terminology
3.2 Origin of Antigens
3.3 Interaction of Antibody with Antigens.
4.0 Conclusion
5.0 Summary
1.0 INTRODUCTION
In this unit, you will learn about antigen. An antigen is defined as a

substance that reacts with antibody molecules and antigen receptors on
lymphocytes. An immunogen is an antigen thatis recognised by the body
as non-self and stimulates an adaptive immuneresponse. For simplicity,
both antigens and immunogens are usuallyreferred to as antigens. An
antigen is any substance that causes your immune system to produce
antibodies against it. An antigen may be a foreign substance from the
environment such as chemicals, bacteria, viruses, or pollen. An antigen
may also be formed within the body, as with bacterial toxins or tissue
cells.
2.0 OBJECTIVES
• explain antigens, immunogen and epitope

• mention the characteristics of antigens and what substances may
act as antigens
• identify how antigens are recognised as foreign.
3.0 MAIN CONTENT
3.1 Specific Terminology
To be immunogenic, an antigen must possess three characteristics:
• be of high molecular weight

• exhibit chemical complexity, and
• exhibit foreignness (recognised as non-self by the body).
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BIO 406 MODULE 1
Antigens are macromolecules that elicit an immune response in thebody.

Antigens can be proteins, polysaccharides, conjugates of lipids with,
proteins (lipoproteins) and polysaccharides (glycolipids).
It will be helpful to distinguish between

• antigens that enter the body from the environment; these would
include
• inhaled macromolecules (e.g., proteins on cat hairs thatcan
trigger an attack of asthma in susceptible people)
• ingested macromolecules (e.g., shellfish proteins thattrigger an
allergic response in susceptible people)
• molecules that are introduced beneath the skin (e.g., on asplinter
or in an injected vaccine)
• antigens that are generated within the cells of the body; these
would include:
• proteins encoded by the genes of viruses that have infecteda cell
• aberrant proteins that are encoded by mutant genes; such as
mutated genes in cancer cells.
In all cases, however, the initial immune response to any antigen

absolutely requires that the antigen be recognised by a T lymphocyte ("T
cell"). The truth of this rule is clearly demonstrated in AIDS: the
infections (viral or fungal or bacterial) that so often claim the life of AIDS
patients do so when the patient has lost virtually all of his or her CD4+ T
cells.
The two categories of antigens are processed and presented to T cells by

quite different mechanisms.
31
3.2 Origin of Antigens
Antigens can be classified in order of their class.
Exogenous antigens
Exogenous antigens are antigens that have entered the body from the
outside, for example by inhalation, ingestion, or injection. The immune
system's response to exogenous antigens is often subclinical. By
endocytosis or phagocytosis, exogenous antigens are taken into the
antigen-presenting cells (APCs) and processed into fragments. APCs then
present the fragments to T helper cells (CD4+) by the use of class II
histocompatibility molecules on their surface. Some T cells are specific
for the peptide:MHC complex. They become activated and start to secrete
cytokines. Cytokines are substances that can activate cytotoxic T
lymphocytes (CTL), antibody-secreting B cells, macrophages, and other
particles.
Some antigens start out as exogenous antigens, and later become

endogenous (for example, intracellular viruses). Intracellular antigens can
be released back into circulation upon the destruction of the infectedcell.
Antigen-presenting cells
• An antigen–presenting cell engulfs the antigen by endocytosis.
• The endosome fuses with a lysosome where the antigen is
degraded into fragments (e.g. short peptides).
32
BIO 406 MODULE 1
• These antigenic peptides are then displayed at the surface of the

cell nestled within a class II histocompatibility molecule.
• Here they may be recognised by CD4+ T cells.
Endogenous antigens
Antigens that are generated within a cell (e.g., viral proteins in any
infected cell) are:
• degraded into fragments (e.g., peptides) within the cell and then
• displayed at the surface of the cell nestled within a class I
histocompatibility molecule.
• Here they may be recognised by CD8+ T cells.
• Most CD8+ T cells are cytotoxic and have the machinery to destroy
the infected cell (often before it is able to release a fresh crop of viruses
to spread the infection).
Endogenous antigens are antigens that have been generated within

previously-normal cells as a result of normal cell metabolism, or because
of viral or intracellular bacterial infection. The fragments are then
presented on the cell surface in the complex with MHC class I
molecules and activated cytotoxic CD8+ T cells recognise them. When
recognised, the T cells begin to secrete various toxins that cause the lysis
or apoptosis of the infected cell. In order to keep the cytotoxic cells from
33
killing cells just for presenting self-proteins, self-reactive T cells are

deleted from the repertoire as a result of tolerance (also known as negative
selection). Endogenous antigens include xenogenic (heterologous),
autologous and idiotypic or allogenic (homologous) antigens.
Autoantigens
An autoantigen is usually a normal protein or complex of proteins (and
sometimes DNA or RNA) that is recognised by the immune system of
patients suffering from a specific autoimmune disease. These antigens
should, under normal conditions, not be the target of the immune system,
but, due to mainly genetic and environmental factors, the normal
immunological tolerance for such an antigen has been lost in these
patients.
Tumour antigens
Tumour antigens or neoantigens are those antigens that are presented by
MHC I or MHC II molecules on the surface of tumour cells. These
antigens can sometimes be presented by tumour cells and never by the
normal ones. In this case, they are called tumour-specific antigens (TSAs)
and, in general, result from a tumour-specific mutation. More common
are antigens that are presented by tumour cells and normalcells, and
they are called tumour-associated antigens (TAAs). Cytotoxic T
lymphocytes that recognise these antigens may be able to destroy the
tumour cells before they proliferate or metastasize.
Tumour antigens can also be on the surface of the tumour in the form of,
for example, a mutated receptor, in which case they will be recognised by
B cells.
Nativity
A native antigen is an antigen that is not yet processed by an APC to
smaller parts. T cells cannot bind native antigens, but require that they
be processed by APCs, whereas B cells can be activated by native ones.
Antigenic specificity
Antigen(ic) specificity is the ability of the host cells to recognise an

antigen specifically as a unique molecular entity and distinguish it from
another with exquisite precision. Antigen specificity is due primarily to
the side-chain conformations of the antigen. It is a measurement, although
the degree of specificity may not be easy to measure, and need not be
linear or of the nature of a rate-limited step or equation.
34
BIO 406 MODULE 1
3.3 Interaction of Antibody with Antigens
NATURE OF ANTIGEN-ANTIBODY REACTIONS

Lock and Key Concept
The combining site of an antibody is located in the Fab portion of the

molecule and is constructed from the hypervariable regions of the heavy
and light chains. X-Ray crystallography studies of antigen-antibody
interactions show that the antigenic determinant nestles in a cleft formed
by the combining site of the antibody as illustrated above.
Fig. 1: Mariuzza, R.A., Biochemistry 39, 6296, 2000Source: Li,

Y., Li., Smith-Gill, S.J.
35
Thus, our concept of antigen-antibody reactions is one of a key (i.e.the

antigen) which fits into a lock (i.e. the antibody).
Non-covalent Bonds
The bonds that hold the antigen to the antibody combining site are all non-
covalent in nature. These include hydrogen bonds, electrostatic bonds,
Van der Waals forces and hydrophobic bonds. Multiple bonding between
the antigen and the antibody ensures that the antigen will be bound tightly
to the antibody.
Reversibility
Since antigen-antibody reactions occur via non-covalent bonds, they are
by their nature reversible.
AFFINITY AND AVIDITY
Affinity
Antibody affinity is the strength of the reaction between a single antigenic
determinant and a single combining site on the antibody. It is the sum of
the attractive and repulsive forces operating between the antigenic
determinant and the combining site of the antibody as illustrated in Figure
2.
Fig. 2
Affinity is the equilibrium constant that describes the antigen-antibody

reaction as illustrated in Figure 3. Most antibodies have a high affinity for
their antigens.
36
BIO 406 MODULE 1
Fig. 3
Avidity
Avidity is a measure of the overall strength of binding of an antigen with
many antigenic determinants and multivalent antibodies. Avidity is
influenced by both the valence of the antibody and the valence of the
antigen. Avidity is more than the sum of the individual affinities. This is
illustrated in Figure 4.
Fig. 4
To repeat, affinity refers to the strength of binding between a single

antigenic determinant and an individual antibody combining site whereas
avidity refers to the overall strength of binding between multivalent
antigens and antibodies.
SPECIFICITY AND CROSS REACTIVITY
Specificity
Specificity refers to the ability of an individual antibody combining site
to react with only one antigenic determinant or the ability of a population
of antibody molecules to react with only one antigen. In general, there is
a high degree of specificity in antigen-antibody reactions. Antibodies can
distinguish differences in:
• The primary structure of an antigen

• Isomeric forms of an antigen
37
• Secondary and tertiary structure of an antigen
Cross reactivity
Cross reactivity refers to the ability of an individual antibody combining
site to react with more than one antigenic determinant or the ability of a
population of antibody molecules to react with more than one antigen.
Figure 5 illustrates how cross reactions can arise. Cross reactions arise
because the cross reacting antigen shares an epitope in common with the
immunising antigen or because it has an epitope which is structurally
similar to one on the immunising antigen (multispecificity).
Fig. 5
TESTS FOR ANTIGEN-ANTIBODY REACTIONS
Factors affecting measurement of antigen-antibody reactions

The only way that one knows that an antigen-antibody reaction has
occurred is to have some means of directly or indirectly detecting the
complexes formed between the antigen and antibody. The ease with
which one can detect antigen-antibody reactions will depend on a number
of factors.
Affinity
The higher the affinity of the antibody for the antigen, the more stable
will be the interaction. Thus, the ease with which one can detect the
interaction is enhanced.
Avidity
Reactions between multivalent antigens and multivalent antibodies are
more stable and thus easier to detect.
Antigen to antibody ratio

The ratio between the antigen and antibody influences the detection of
antigen-antibody complexes because the size of the complexes formed is
related to the concentration of the antigen and antibody. This is depicted
in Figure 6.
38
BIO 406 MODULE 1
Fig. 6
Physical form of the antigen

The physical form of the antigen influences how one detects its reaction
with an antibody. If the antigen is a particulate, one generally looks for
agglutination of the antigen by the antibody. If the antigen is soluble one
generally looks for the precipitation of the antigen after the production of
large insoluble antigen-antibody complexes.
Agglutination Tests Agglutination/Hemagglutination
When the antigen is particulate, the reaction of an antibody with the
antigen can be detected by agglutination (clumping) of the antigen. The
general term agglutinin is used to describe antibodies that agglutinate
particulate antigens. When the antigen is an erythrocyte the term
hemagglutination is used. All antibodies can theoretically agglutinate
particulate antigens but IgM, due to its high valence, is particularly good
agglutinin and one sometimes infers that an antibody may be of the IgM
class if it is a good agglutinating antibody.
Qualitative agglutination test
Agglutination tests can be used in a qualitative manner to assay for the

presence of an antigen or an antibody. The antibody is mixed with the
particulate antigen and a positive test is indicated by the agglutination of
the particulate antigen (Figure 7).
39
Fig. 7
For example, a patient's red blood cells can be mixed with antibody to a
blood group antigen to determine a person's blood type. In a second
example, a patient's serum is mixed with red blood cells of a known blood
type to assay for the presence of antibodies to that blood type in the
patient's serum.
Quantitative agglutination test
Agglutination tests can also be used to measure the level of antibodies to

particulate antigens. In this test, serial dilutions are made of a sample to
be tested for antibody and then a fixed number of red blood cells or
bacteria or other such particulate antigen is added. Then the maximum
dilution that gives agglutination is determined. The maximum dilution
that gives visible agglutination is called the titer. The results are reported
as the reciprocal of the maximal dilution that gives visible agglutination.
Figure 8 illustrates a quantitative hemagglutination test.
Fig. 8
Prozone effect - Occasionally, it is observed that when the concentration

of antibody is high (i.e. lower dilutions), there is no agglutination and
then, as the sample is diluted, agglutination occurs. The lack of
agglutination at high concentrations of antibodies is called the prozone
effect. Lack of agglutination in the prozone is due to antibody excess
resulting in very small complexes that do not clump to form visible
agglutination.
40
BIO 406 MODULE 1
Applications of agglutination tests
i. Determination of blood types or antibodies to blood group

antigens.
ii. To assess bacterial infections
e.g. A rise in titre of an antibody to a particular bacterium indicates an
infection with that bacterial type. N.B. a fourfold risein titre is generally
taken as a significant rise in antibody titre.
Practical considerations
Although the test is easy to perform, it is only semi-quantitative.
IN TEXT QUESTION
What is agglutination?
Answer
The general term agglutinin is used to describe antibodies that agglutinate
particulate antigens.
4.0 CONCLUSION
• The definition of antigens

• The importance of antigens to man
• Origin of antigens
• Interaction of antibody with antigens
5.0 SUMMARY
An antigen is a foreign molecule that, when introduced into the body,

triggers the production of an antibody by the immune system. Theimmune
system will then kill or neutralise the antigen that is recognised as a
foreign and potentially harmful invader. These invaders can be molecules
such as pollen or cells such as bacteria. The term originally came from
antibody generator and was a molecule that binds specifically to an
antibody, but the term now also refers to any molecule or molecular
fragment that can be bound by a major histocompatibility complex
(MHC) and presented to a T-cell receptor. "Self" antigens are usually
tolerated by the immune system; whereas "Non-self" antigens are
identified as invaders and attacked by the immune system.
41
i. What are antigens?

ii. Differentiate between endogenous and exogenous antigens.
iii. Describe the interactions between antibodies and antigens.
iv. State what antigens are composed of chemically.
v. List 3 characteristics an antigen must have to be immunogenic
vi. Briefly describe how the body recognises an antigen
as foreign.
Antigens. http://biology-pages.info/
Guyton & Hall (2006). Textbook of Medical Physiology. 11th Edition.

Page 440. Philadelphia: Elsevier, Inc. PA.
Parham, Peter (2009). The Immune System. 3rd Edition. pg. G:2,
Garland Science, Taylor and Francis Group, LLC.
Parham, Peter (2009). The Immune System. 3rd Edition. pg. G:11,
Garland Science, Taylor and Francis Group, LLC.
"Kuby Immunology." 6th Edition. Macmillan. 2006, pg. 77 ISBN

1429202114, 9781429202114.
Lindenmann, Jean (1984). "Origin of the Terms 'Antibody' and

'Antigen.'" Scand. J. Immunol. 19 (4): 281–5.
42
BIO 406 MODULE 2
MODULE 2 HYPERSENSITIVITY
Unit 1 Hypersensitivity
Unit 2 Autoimmunity
Unit 3 Immunology of Tissue Transplantation
UNIT 1 HYPERSENSITIVITY
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Hypersensitivity
3.2 Type I Hypersensitivity
3.3 Type II Hypersensitivity
3.4 Type III Hypersensitivity
3.5 Type IV Hypersensitivity
4.0 Conclusion
5.0 Summary
1.0 INTRODUCTION
The immune system is an integral part of human protection against

disease, but the normally protective immune mechanisms can sometimes
cause detrimental reactions in the host. Such reactions are known as
hypersensitivity reactions, and the study of these is termed
immunopathology. The traditional classification for hypersensitivity
reactions is that of Gell and Coombs and is currently the most commonly
known classification system. It divides the hypersensitivity reactions into
the following 4 types:
a. Type I reactions (ie, immediate hypersensitivity reactions)involve

immunoglobulin E (IgE)–mediated release of histamine and other
mediators from mast cells and basophils.
b. Type II reactions (ie, cytotoxic hypersensitivity reactions)involve
immunoglobulin G or immunoglobulin M antibodies bound to cell
surface antigens, with subsequent complement fixation.
c. Type III reactions (ie, immune-complex reactions) involve
circulating antigen-antibody immune complexes that deposit in
postcapillary venules, with subsequent complement fixation.
d. Type IV reactions (ie, delayed hypersensitivity reactions, cell-
mediated immunity) are mediated by T cells rather than by antibodies.
43
2.0 OBJECTIVES
• describe immediate hypersensitivity

• differentiate Types I,II, III and IV hypersensitivity.
3.0 MAIN CONTENT
3.1 Hypersensitivity
Occasionally, the immune system responds inappropriately to the

presence of antigen. These responses are referred to as hypersensitivities.
There are four different types of hypersensitivities that result from
different alterations of the immune system. These types are classified as:
a. Type I: Immediate Hypersensitivity

b. Type II: Cytotoxic Hypersensitivity
c. Type III: Immune Complex Hypersensitivity
d. Type IV: Delayed Hypersensitivity
3.2 Type I Hypersensitivity
Type I hypersensitivity is also known as immediate or anaphylactic

hypersensitivity. The reaction may involve skin (urticaria and eczema),
eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis),
bronchopulmonary tissues (asthma) and gastrointestinal tract
(gastroenteritis). The reaction may cause a range of symptoms from minor
inconvenience to death. The reaction usually takes 15 - 30 minutes from
the time of exposure to the antigen, although sometimes it may have a
delayed onset (10 - 12 hours).
Immediate hypersensitivity is mediated by IgE. The primary cellular

component in this hypersensitivity is the mast cell or basophil. The
reaction is amplified and/or modified by platelets, neutrophils and
eosinophils. A biopsy of the reaction site demonstrates mainly mast cells
and eosinophils.
The mechanism of reaction involves preferential production of IgE, in

response to certain antigens (often called allergens). The precise
mechanism as to why some individuals are more prone to type-I
hypersensitivity is not clear. However, it has been shown that such
individuals preferentially produce more of TH2 cells that secrete IL-4, IL-
5 and IL-13 which in turn favour IgE class switch. IgE has very high
affinity for its receptor (Fcε; CD23) on mast cells and basophils.
44
BIO 406 MODULE 2
A subsequent exposure to the same allergen cross links the cell-bound IgE
and triggers the release of various pharmacologically active substances
(figure 1).
Fig. 1: Induction and Effector Mechanisms in Type 1

Hypersensitivity
Cross-linking of IgE Fc-receptor is important in mast cell triggering. Mast

cell degranulation is preceded by increased Ca++ influx, which is a
crucial process; ionophores which increase cytoplasmic Ca++ also
promote degranulation, whereas, agents which deplete cytoplasmic Ca++
suppress degranulation.
The agents released from mast cells and their effects are listed in Table
1. Mast cells may be triggered by other stimuli such as exercise, emotional
stress, chemicals (e.g., photographic developing medium, calcium
ionophores, codeine, etc.), anaphylotoxins (e.g., C4a, C3a, C5a, etc.).
These reactions, mediated by agents without IgE-allergen
interaction, are not hypersensitivity reactions, although they produce the
same symptoms.
45
Table 1: Pharmacologic Mediators of Immediate

Hypersensitivity
MEDIATOR
Preformed mediators in granules
bronchoconstriction, mucus secretion,

Histamine vasodilatation, vascular permeability
Tryptase Proteolysis
kinins and vasodilatation, vascular

kininogenase permeability, edema
ECF-A attract eosinophil and neutrophils

(tetrapeptides)
Newly formed mediators
leukotriene B4 basophil attractant
leukotrieneC4, D4 same as histamine but 1000x morepotent
prostaglandinsD2
edema and pain
platelet aggregation and heparin release:

PAF microthrombi
The reaction is amplified by PAF (platelet activation factor) which causes

platelet aggregation and release of histamine, heparin and vasoactive
amines. Eosinophil chemotactic factor of anaphylaxis (ECF- A) and
neutrophil chemotactic factors attract eosinophils and neutrophils,
respectively, which release various hydrolytic enzymes that cause
necrosis. Eosinophils may also control the local reaction by releasing
arylsulphatase, histaminase, phospholipase-D and prostaglandin-E,
although this role of eosinophils is now in question.
Cyclic nucleotides appear to play a significant role in the modulation of

immediate hypersensitivity reaction, although their exact function is ill
understood. Substances which alter cAMP and cGMP levels significantly
alter the allergic symptoms. Thus, substances that increase intracellular
46
BIO 406 MODULE 2
cAMP seem to relieve allergic symptoms, particularly broncho-

pulmonary ones, and are used therapeutically (Table 2). Conversely,
agents which decrease cAMP or stimulate cGMP aggravate these allergic
conditions.
Table 2 : Relationship between Allergic Symptoms and Cyclic-

nucleotides
Lowering of cyclic-AMP Elevation of cyclic-AMP

stimulation of α-adrenergicreceptor stimulation of β-adrenergicreceptor
(nor-epinephrin, phenyl- (epinephrine, isoproterenol)
epinephrin) blocking of α-adrenergic
or receptor (phenoxybenzamine)
blocking of β-adrenergic inhibition of
receptor phosphodiesterase(theophylline)
(propanolol) binding of histamine-2 or PGE to
their receptors
elevation of cyclic-GMP
stimulation of γ-
cholinergic receptor (acetyl
choline, carbacol)
WORSENING OF IMPROVEMENT OF
SYMPTOMS SYMPTOMS
Diagnostic tests for immediate hypersensitivity include skin (prick and

intradermal) tests (fig. 1A), measurement of total IgE and specific IgE
antibodies against the suspected allergens.
47
Fig. 1 : A Close-up View of Intradermal Skin Test with

Multiple Positive Allergen Responses
Total IgE and specific IgE antibodies are measured by a modification of

enzyme immunoassay (ELISA). Increased IgE levels are indicative of
an atopic condition, although IgE may be elevated in some non-atopic
diseases (e.g., myelomas, helminthic infection, etc.).
There appears to be a genetic predisposition for atopic diseases and there

is evidence for HLA (A2) association.
Symptomatic treatment is achieved with anti-histamines which block

histamine receptors. Chromolyn sodium inhibits mast cell degranulation,
probably, by inhibiting Ca++ influx. Late onset allergic symptoms,
particularly bronchoconstriction which is mediated by leukotrienes, are
treated with leukotriene receptor blockers (Singulair, Accolate) or
inhibitors of the cyclooxygenase pathway (Zileutoin). Symptomatic,
although short term, relief from bronchoconstriction is provided by
bronchodilators (inhalants) such as isoproterenol derivatives(Terbutaline,
Albuterol). Thophylline elevates cAMP by inhibiting cAMP-
phosphodiesterase and inhibits intracellular Ca++ release is also used to
relieve bronchopulmonary symptoms.
The use of IgG antibodies against the Fc portions of IgE that binds to mast
cells has been approved for treatment of certain allergies, as it can block
48
BIO 406 MODULE 2
mast cell sensitisation.
Hyposensitisation (immunotherapy or desensitisation) is another

treatment modality which is successful in a number of allergies,
particularly to insect venoms and, to some extent, pollens. The
mechanism is not clear, but there is a correlation between appearance of
IgG (blocking) antibodies and relief from symptoms. Suppressor T cells
that specifically inhibit IgE antibodies may play a role.
3.3 Type II Hypersensitivity
Type II hypersensitivity is also known as cytotoxic hypersensitivity and

may affect a variety of organs and tissues. The antigens are normally
endogenous, although exogenous chemicals (haptens) which can attach to
cell membranes can also lead to type II hypersensitivity. Drug- induced
hemolytic anemia, granulocytopenia and thrombocytopenia are such
examples. The reaction time range from minutes to hours. Type II
hypersensitivity is primarily mediated by antibodies of the IgM or IgG
classes and complement (Figure 2).
Fig. 2: Type II Cytotoxicity Mechanism

Phagocytes and K cells may also play a role.
The lesion contains antibody, complement and neutrophils. Diagnostic
tests include detection of circulating antibody against the tissues involved
and the presence of antibody and complement in the lesion (biopsy) by
immunofluorescence. The staining pattern is normally smooth and linear,
49
such as that seen in Goodpasture's nephritis (renaland lung basement

membrane) (figure 3A) and pemphigus (skin intercellular protein,
desmosome) (figure 3B).
Fig. 3A: Immunofluorescent Stain of Immunoglobulin G (IgG)

Showing Linear Pattern in Goodpasture's Syndrome
50
BIO 406 MODULE 2
Fig. 3B: Pemphigus vulgaris - immunofluorescence
Treatment involves anti-inflammatory and immunosuppressive agents. In

type II hypersensitivity (or cytotoxic hypersensitivity) the antibodies
produced by the immune response bind to antigens on the patient's own
cell surfaces. The antigens recognised in this way may either be intrinsic
("self" antigen, innately part of the patient's cells) or extrinsic (adsorbed
onto the cells during exposure to some foreign antigen, possibly as part
of infection with a pathogen). These cells are
recognized bymacrophages or dendritic cells, which act as
antigen-presenting cells. This causes a B cell response, wherein
antibodies are produced againstthe foreign antigen.
An example of type II hypersensitivity is the reaction to penicillinwherein

the drug can bind to red blood cells, causing them to berecognised as
different; B cell proliferation will take place andantibodies to the drug
are produced. IgG and IgM antibodies bind tothese antigens to form
complexes that activate the classical pathway ofcomplement activation
to eliminate cells presenting foreign antigens(which are usually, but not
in this case, pathogens). That is, mediators of acute inflammation are
generated at the site and membrane attackcomplexes cause cell lysis and
death. The reaction takes hours to a day. Another form of type II
hypersensitivity is called antibody-dependentcell-mediated cytotoxicity
(ADCC). Here, cells exhibiting the foreign
51
antigen are tagged with antibodies (IgG or IgM). These tagged cells are
then recognised by natural killer (NK) cells and macrophages (recognised
via IgG bound (via the Fc region) to the effector cell surface receptor,
CD16 (FcγRIII)), which in turn kill these tagged cells.
3.4 Type III Hypersensitivity
Type III hypersensitivity is also known as immune complex

hypersensitivity. The reaction may be general (e.g., serum sickness) or
may involve individual organs including skin (e.g., systemic lupus
erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs
(e.g., aspergillosis), blood vessels (e.g., polyarteritis), joints (e.g.,
rheumatoid arthritis) or other organs. This reaction may be the pathogenic
mechanism of diseases caused by many microorganisms.
The reaction may take 3 - 10 hours after exposure to the antigen (as in
Arthus reaction). It is mediated by soluble immune complexes. They are
mostly of the IgG class, although IgM may also be involved. The antigen
may be exogenous (chronic bacterial, viral or parasitic infections), or
endogenous (non-organ specific autoimmunity: e.g., systemic lupus
erythematosus, SLE). The antigen is soluble and not attached to the organ
involved. The damage is caused by platelets and neutrophils (Figure 4).
52
BIO 406 MODULE 2
Fig. 4: Mechanism of Damage in Immune Complex

Hypersensitivity
The lesion contains primarily neutrophils and deposits of immune

complexes and complement. Macrophages infiltrating in later stagesmay
be involved in the healing process.
The affinity of antibody and size of immune complexes are important in

production of disease and determining the tissue involved. Diagnosis
involves examination of tissue biopsies for deposits of immunoglobulin
and is complemented by immunofluorescence microscopy. The
immunofluorescent staining in type III hypersensitivity is granular (as
opposed to linear in type II such as seen in Goodpasture's syndrome). The
presence of immune complexes in serum and depletion in the level of
complement are also diagnostic. Polyethylene glycol-mediated turbidity
(nephelometry) binding of C1q and Raji cell test are utilised to detect
immune complexes. Treatment includes anti-inflammatory agents.
3.5 Type IV Hypersensitivity
Type IV hypersensitivity is also known as cell -mediated or delayed type

hypersensitivity. The classical example of this hypersensitivity is
tuberculin (Montoux) reaction (Figure 5) which peaks 48 hours after the
injection of antigen (PPD or old tuberculin).
53
Fig. 5: Mantoux Intradermal Tuberculin Skin Test for

Tuberculosis
The lesion is characterised by induration and erythema.
Table 3 : Delayed Hypersensitivity Reactions
Reaction Clinical Antigen and

Type time appearance Histology site
epidermal (
lymphocytes, organic
contact 48-72 hr eczema followed by chemicals,
macrophages; poison ivy,
edema of heavy metals,
epidermis etc.)
intradermal
tuberculin 48-72 hr local lymphocytes, (tuberculin,
induration monocytes, lepromin, etc.)
macrophages
persistent
macrophages, antigen or
granuloma 21-28 hardening epitheloid and foreign body
days giant presence
cells, fibrosis (tuberculosis,
leprosy, etc.)
Type IV hypersensitivity is involved in the pathogenesis of many

autoimmune and infectious diseases (tuberculosis, leprosy,
blastomycosis, histoplasmosis, toxoplasmosis, leishmaniasis, etc.) and
granulomas due to infections and foreign antigens. Another form of
delayed hypersensitivity is contact dermatitis (poison ivy (figure 6),
chemicals, heavy metals, etc.) in which the lesions are more papular.
54
BIO 406 MODULE 2
Fig. 6: Poison Ivy CDC
Type IV hypersensitivity can be classified into three categoriesdepending

on the time of onset and clinical and histological presentation(Table 3).
Mechanisms of damage in delayed hypersensitivity include T

lymphocytes and monocytes and/or macrophages. Cytotoxic T cells (Tc)
cause direct damage whereas helper T (TH1) cells secrete cytokines
which activate cytotoxic T cells and recruit and activate monocytes and
macrophages, which cause the bulk of the damage (figure 4). The delayed
hypersensitivity lesions mainly contain monocytes and a few T cells.
Major lymphokines involved in delayed hypersensitivity reactioninclude

monocyte chemotactic factor, interleukin-2, interferon-gamma, TNF
alpha/beta, etc.
Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux

test (figure 5)) and patch test (for contact dermatitis). In vitro tests for
delayed hypersensitivity include mitogenic response, lympho-
cytotoxicity and IL-2 production.
Corticosteroids and other immunosuppressive agents are used in
treatment.
55
Table 5 : Comparison of different Types of Hypersensitivity
type-I type-III type-IV

characteristi (anaphylact type-II (immune (delayed
cs ic) (cytotoxic) complex) type)
antibody IgE IgG, IgM IgG, IgM None
tissues &
antigen exogenous cell surface soluble organs
responsetime 15-30 minutes-hours 48-72

minutes 3-8 hours hours
erythema
appearance weal & flare lysis and and edema, erythema and
necrosis necrosis induration
compleme monocytes
histology basophils and antibody and nt and and
eosinophil complement neutrophil s lymphocytes
transferred
with antibody Antibody antibody T-cells
erythroblasto SLE,
allergic sis farmer's tuberculin
examples asthma, fetalis, lung disease test, poison
hay Goodpasture' s ivy,
fever nephritis granuloma
IN TEXT QUESTION
What is Type I hypersensitivity?
Answer
Type I hypersensitivity is also known as immediate or anaphylactic
hypersensitivity.
4.0 CONCLUSION
• Hypersensitivity
• Types of hypersensitivity
• Examples of each type of hypersensitivity.
56
BIO 406 MODULE 2
5.0 SUMMARY
Hypersensitivity refers to excessive, undesirable (damaging, discomfort-

producing and sometimes fatal) reactions produced by the normal
immune system. Hypersensitivity reactions require a pre-sensitised
(immune) state of the host. Hypersensitivity reactions can be divided into
four types: type I, type II, type III and type IV, based on the
mechanisms involved and time taken for the reaction. Frequently, a
particular clinical condition (disease) may involve more than one type of
reaction. It is a series of undesirable reactions produced by the normal
immune system, including allergies and autoimmunity. These reactions
may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity
reactions require a pre-sensitised (immune) state of the host. The four-
group classification was expounded by P. H. G. Gell and Robin Coombs
in 1963. Hypersensitivity denotes immunologic sensitivity to antigens
that manifest itself by tissue reactions that can cause injury. They appear
much later. There are 4types of these hypersensitivity states or reactions.
Three are immediate and one is delayed. Apart from differences in time
intervals, there are also other differences in the mode of transfer of
hypersensitivity from a sensitised to a non-sensitised subject.
i. What is hypersensitivity?
ii. Explain immune complex hypersensitivity
iii. What is delayed hypersensitivity?
Abdul Ghaffar (2010). Microbiology and Immunogy. Hypersensitivity

Reactions.
Gell PGH, Coombs RRA, eds. Clinical Aspects of Immunology. 1st ed.
Oxford, England: Blackwell; 1963.
Salimonu, L.S. (2004). Basic Immunology for Students of Medicine and

Miriam, K Anand, MD, FAAAAI, FACAAI; Chief Editor: Michael A

Kaliner, MD (2012). Immediate Hypersensitivity Reactions .
medscape.com
http://www.cehs.siu.edu/fix/medmicro.com (2011). Hypersensitivity
57
UNIT 2 AUTOIMMUNITY
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Causes of Autoimmunity
3.2 Low level Autoimmunity
3.3 Immunological Tolerance
3.4 Genetic Factors
3.5 Environmental Factors
3.6 Pathogenesis of Autoimmunity
4.0 Conclusion
5.0 Summary
7.0 Reference/Further Reading
1.0 INTRODUCTION
Autoimmunity and autoimmune diseases are consequences of

immunological destruction of body’s own tissue following loss of
recognition by lymphoid organs of the self-cells as self. During
differentiation and speciation of lymphoid stem cells in primary organs,
most of the cells that are capable of causing autoimmunity are deleted.
Yet, the body contains large numbers of lymphocytes that are self-
reacting.
2.0 OBJECTIVES
• describe low-level autoimmunity

• name causes of autoimmunity
• explain genetic factors
• list environmental factors affecting autoimmunity.
3.0 MAIN CONTENT
3.1 Causes of Autoimmunity
Controlling factors that restrain the development of autoimmune

responses include Ts cells, cytokines and products of macrophages.
However, these regulatory mechanisms may be evaded by:
• Release of normally sequestered auto-antigen which is then taken
up by antigen presenting cells and hence stimulation of TH cells.
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BIO 406 MODULE 2
• Inappropriate expression of MHC class II and inability of auto-

reactive TH cell to recognise potential autoantigens on cells, which do not
normally express MHC class II genes.
• Defects in the generation of Ts cells with hyperactivity of TH. This
may overstimulate B-cells for excessive production of antibody that may
include auto-reactive ones. In thyroxicosis, antibody to thyroid
stimulating hormone TSH receptors combines with TSH receptors as if it
is TSH, therefore autoantibodies to hormone receptors mimic the function
of the normal hormone concerned.
• Deletion of self-antigen recognising T- and B-lymphocytes during
maturation process. In pernicious anaemia, autoantibody isformed against
intrinsic factor. This autoantibody combines with intrinsic factor to
disrupt the uptake of Vitamin B12. This is transported across the intestinal
mucosa when it combines with intrinsic factor. In systemic lupus
erythematosus, immune complexes containg auto-antigens and
autoantibodies are deposited in the kidney to cause hypersensitivity,
glomerulonephritis and proteinuria.
3.2 Low Level Autoimmunity
While a high level of autoimmunity is unhealthy, a low level of

autoimmunity may actually be beneficial. First, low-level autoimmunity
might aid in the recognition of neoplastic cells by CD8+ T cells, and thus
reduce the incidence of cancer.
Second, autoimmunity may play a role in allowing a rapid immune

response in the early stages of an infection when the availability of foreign
antigens limits the response (i.e., when there are few pathogens present).
In their study, Stefanova et al. (2002) injected an anti-MHC Class II
antibody into mice expressing a single type of MHC Class II molecule
(H-2b) to temporarily prevent CD4+ T cell-MHC interaction. Naive CD4+
T cells (those that have not encountered any antigensbefore) recovered
from these mice 36 hours post-anti-MHC administration showed
decreased responsiveness to the antigen pigeon cytochrome C peptide, as
determined by Zap-70 phosphorylation, proliferation, and Interleukin-2
production. Thus Stefanova et al. (2002) demonstrated that self-MHC
recognition (which, if too strong may contribute to autoimmune disease)
maintains the responsiveness of CD4+ T cells when foreign antigens are
absent. This idea ofautoimmunity is conceptually similar to play-fighting.
The play-fighting of young cubs (TCR and self-MHC) may result in a
few scratches or
scars (low-level-autoimmunity), but is beneficial in the long-term as it
primes the young cub for proper fights in the future.
59
3.3 Immunological Tolerance
Pioneering work by Noel Rose and Witebsky in New York, and Roitt and
Doniach at University College London provided clear evidence that, at
least in terms of antibody-producing B lymphocytes, diseases such as
rheumatoid arthritis and thyrotoxicosis are associated with loss of
immunological tolerance, which is the ability of an individual to ignore
'self', while reacting to 'non-self'. This breakage leads to the immune
system's mounting an effective and specific immune response against self
determinants. The exact genesis of immunological tolerance is still
elusive, but several theories have been proposed since the mid-twentieth
century to explain its origin.
Three hypotheses have gained widespread attention among

immunologists:
a. Clonal Deletion theory, proposed by Burnet, according to which

self-reactive lymphoid cells are destroyed during the development of the
immune system in an individual. For their work Frank M. Burnet and
Peter B. Medawar were awarded the 1960 Nobel Prize in Physiology or
Medicine "for discovery of acquired immunological tolerance".
b. Clonal Anergy theory, proposed by Nossal, in which self-
reactive T- or B-cells become inactivated in the normal individual and
cannot amplify the immune response.
c. Idiotype Network theory, proposed by Jerne, wherein a network
of antibodies capable of neutralising self-reactive antibodies exists
naturally within the body.
In addition, two other theories are under intense investigation:
• The so-called "Clonal Ignorance" theory, according to which host

immune responses are directed to ignore self-antigens
• The "Suppressor population" or "Regulatory T cell" theories,
wherein regulatory T-lymphocytes (commonly CD4+FoxP3+cells, among
others) function to prevent, downregulate, or limit autoaggressive
immune responses in the immune system.
Tolerance can also be differentiated into 'Central' and 'Peripheral'

tolerance, on whether or not the above-stated checking mechanisms
operate in the central lymphoid organs (Thymus and Bone Marrow) or the
peripheral lymphoid organs (lymph node, spleen, etc., where self- reactive
B-cells may be destroyed). It must be emphasised that these
theories are not mutually exclusive, and evidence has been mounting
suggesting that all of these mechanisms may actively contribute to
vertebrate immunological tolerance.
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BIO 406 MODULE 2
A puzzling feature of the documented loss of tolerance seen in

spontaneous human autoimmunity is that it is almost entirely restricted
to the autoantibody responses produced by B lymphocytes. Loss of
tolerance by T cells has been extremely hard to demonstrate, and where
there is evidence for an abnormal T cell response it is usually not for the
antigen recognised by autoantibodies. Thus, in rheumatoid arthritis there
are autoantibodies to IgG Fc but apparently no corresponding T cell
response. In systemic lupus there are autoantibodies to DNA, which
cannot evoke a T cell response, and limited evidence for T cell responses
implicates nucleoprotein antigens. In Celiac disease there are
autoantibodies to tissue transglutaminase but the T cell response is to the
foreign protein gliadin. This disparity has led to the idea that human
autoimmune disease is in most cases (with probable exceptions including
type I diabetes) based on a loss of B cell tolerance which makes use of
normal T cell responses to foreign antigens in a variety of aberrant ways.
3.4 Genetic Factors
Certain individuals are genetically susceptible to developing autoimmune

diseases. This susceptibility is associated with multiplegenes plus other
risk factors. Genetically predisposed individuals do not always develop
autoimmune diseases.
Three main sets of genes are suspected in many autoimmune diseases.

These genes are related to:
a. Immunoglobulins
b. T-cell receptors
c. The major histocompatibility complexes (MHC).
The first two, which are involved in the recognition of antigens, are
inherently variable and susceptible to recombination. These variations
enable the immune system to respond to a very wide variety of invaders,
but may also give rise to lymphocytes capable of self-reactivity.
Scientists such as H. McDevitt, G. Nepom, J. Bell and J. Todd have also

provided strong evidence to suggest that certain MHC class II allotypes
are strongly correlated with:
• HLA DR2 is strongly positively correlated with Systemic Lupus
Erythematosus, narcolepsy and multiple sclerosis, and negatively
correlated with DM Type 1.
• HLA DR3 is correlated strongly with Sjögren's syndrome,
myasthenia gravis, SLE, and DM Type 1.
• HLA DR4 is correlated with the genesis of rheumatoid arthritis,
Type 1 diabetes mellitus, and pemphigus vulgaris.
61
Fewer correlations exist with MHC class I molecules. The most notable
and consistent is the association between HLA B27 and ankylosing
spondylitis. Correlations may exist between polymorphisms within class
II MHC promoters and autoimmune disease.
The contributions of genes outside the MHC complex remain the subject
of research, in animal models of disease (Linda Wicker's extensivegenetic
studies of diabetes in the NOD mouse), and in patients (Brian Kotzin's
linkage analysis of susceptibility to SLE).
Recently, PTPN22 has been associated with multiple autoimmune

diseases including Type I diabetes, rheumatoid arthritis, systemic lupus
erythematosis, Hashimoto’s thyroiditis, Graves’ disease, Addison’s
disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile
idiopathic arthritis, and psoriatic arthritis.
Sex
A person's sex also seems to have some role in the development of
autoimmunity, classifying most autoimmune diseases as sex-related
diseases. Nearly 75% of the more than 23.5 million Americans who suffer
from autoimmune disease are women, although it is less- frequently
acknowledged that millions of men also suffer from these diseases.
According to the American Autoimmune Related Diseases Association
(AARDA), autoimmune diseases that develop in men tendto be more
severe. A few autoimmune diseases that men are just as, or more likely
to develop as women, include: ankylosing spondylitis, type1 diabetes
mellitus, Wegener's granulomatosis, Crohn's disease and psoriasis.
The reasons for the sex role in autoimmunity are unclear. Women appear
to generally mount larger inflammatory responses than men when their
immune systems are triggered, increasing the risk of autoimmunity.
Involvement of sex steroids is indicated by that many autoimmune
diseases tend to fluctuate in accordance with hormonal changes, for
example, during pregnancy, in the menstrual cycle, or when using oral
contraception. A history of pregnancy also appears to leave a persistent
increased risk for autoimmune disease. It has been suggested that the
slight exchange of cells between mothers and their children
during pregnancy may induce autoimmunity. This would tip the gender
balance in the direction of the female.
Another theory suggests the females high tendency to get autoimmunity

is due to an imbalanced X chromosome inactivation. The X-inactivation
skew theory, proposed by Princeton University's Jeff Stewart, has
recently been confirmed experimentally in scleroderma and autoimmune
thyroiditis. Other complex X-linked genetic susceptibility mechanisms
are proposed and under investigation.
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BIO 406 MODULE 2
3.5 Environmental Factors
An interesting inverse relationship exists between infectious diseases

and autoimmune diseases. In areas where multiple infectious diseases are
endemic, autoimmune diseases are quite rarely seen. The reverse, to some
extent, seems to hold true. The hygiene hypothesis attributes these
correlations to the immune manipulating strategies of pathogens. Whilst
such an observation has been variously termed as spurious and
ineffective, according to some studies, parasite infection is associated
with reduced activity of autoimmune disease.
The putative mechanism is that the parasite attenuates the host immune
response in order to protect itself. This may provide a serendipitous
benefit to a host that also suffers from autoimmune disease. The details
of parasite immune modulation are not yet known, but may include
secretion of anti-inflammatory agents or interference with the host
immune signalling mechanism.
A paradoxical observation has been the strong association of certain

microbial organisms with autoimmune diseases. For example, Klebsiella
pneumoniae and coxsackievirus B have been strongly correlated with
ankylosing spondylitis and diabetes mellitus type 1, respectively. This has
been explained by the tendency of the infecting organism to produce
super-antigens that are capable of polyclonal activation of B-
lymphocytes, and production of large amounts of antibodies of varying
specificities, some of which may be self-reactive.
Certain chemical agents and drugs can also be associated with the genesis
of autoimmune conditions, or conditions that simulate autoimmune
diseases. The most striking of these is the drug-induced lupus
erythematosus. Usually, withdrawal of the offending drug cures the
symptoms in a patient.
Cigarette smoking is now established as a major risk factor for both

incidence and severity of rheumatoid arthritis. This may relate to
abnormal citrullination of proteins, since the effects of smoking correlate
with the presence of antibodies to citrullinated peptides.
3.6 Pathogenesis of Autoimmunity
Several mechanisms are thought to be operative in the pathogenesis of

autoimmune diseases, against a backdrop of genetic predisposition and
environmental modulation. It is beyond the scope of this article to discuss
each of these mechanisms exhaustively, but a summary of some of the
important mechanisms have been described:
63
• T-Cell Bypass - A normal immune system requires the activation

of B-cells by T-cells before the former can produce antibodies in large
quantities. This requirement of a T-cell can be bypassed in rare instances,
such as infection by organisms producing super- antigens, which are
capable of initiating polyclonal activation of B-cells, or even of T-cells,
by directly binding to the β-subunit of T-cell receptors in a non-specific
fashion.
• T-Cell-B-Cell discordance - A normal immune response is
assumed to involve B and T cell responses to the same antigen, even if
we know that B cells and T cells recognise very different things:
conformations on the surface of a molecule for B cells and pre-processed
peptide fragments of proteins for T cells. However,there is nothing as far
as we know that requires this. All that is required is that a B cell
recognising antigen X endocytoses and processes a protein Y (normally
=X) and presents it to a T cell. Roosnek and Lanzavecchia showed that B
cells recognising IgGFc could get help from any T cell responding to an
antigen co-endocytosed with IgG by the B cell as part of an immune
complex. In coeliac disease it seems likely that B cellsrecognising tissue
transglutamine are helped by T cells recognising gliadin.
• Aberrant B cell receptor-mediated feedback - A feature of human
autoimmune disease is that it is largely restricted to a small group of
antigens, several of which have known signaling roles in the immune
response (DNA, C1q, IgGFc, Ro, Con. A receptor, Peanut agglutinin
receptor (PNAR)). This fact gave rise to the idea that spontaneous
autoimmunity may result when the binding of antibody to certain antigens
leads to aberrant signals being fed back to parent B cells through
membrane bound ligands. These ligands include B cell receptor (for
antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-
like receptors 9 and 7 (which can bind DNA and nucleoproteins) and
PNAR. Moreindirect aberrant activation of B cells can also be envisaged
with autoantibodies to acetyl choline receptor (on thymic myoid cells) and
hormone and hormone binding proteins. Together with the
concept of T-cell-B-cell discordance this idea forms the basis of the
hypothesis of self-perpetuating autoreactive B cells. Autoreactive B cells
in spontaneous autoimmunity are seen as surviving because of subversion
both of the T cell help pathway and of the feedback signal through B cell
receptor, thereby overcoming the negative signals responsible for B cell
self- tolerance without necessarily requiring loss of T cell self- tolerance.
• Molecular Mimicry - An exogenous antigen may share structural
similarities with certain host antigens; thus, any antibody produced
against this antigen (which mimics the self-antigens) can also, in theory,
bind to the host antigens, and amplify the immune response. The idea of
molecular mimicry arose in the context of Rheumatic Fever, which
follows infection with Group A beta-haemolytic streptococci. Although
rheumatic fever has been attributed to molecular mimicry for half a
century no antigen has been formally identified (if anything too many
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BIO 406 MODULE 2
have been proposed). Moreover, the complex tissue distribution of the

disease (heart, joint, skin, basal ganglia) argues against a cardiac specific
antigen. It remains entirely possible that the disease isdue to e.g. an
unusual interaction between immune complexes, complement
components and endothelium.
• Idiotype Cross-Reaction - Idiotypes are antigenic epitopes found
in the antigen-binding portion (Fab) of the immunoglobulin molecule.
Plotz and Oldstone presented evidence that autoimmunity can arise as a
result of a cross-reaction between theidiotype on an antiviral antibody and
a host cell receptor for the virus in question. In this case, the host-cell
receptor is envisioned as an internal image of the virus, and the anti-
idiotype antibodies can react with the host cells.
• Cytokine Dysregulation - Cytokines have been recently divided
into two groups according to the population of cells whose functions they
promote: Helper T-cells type 1 or type 2. The second category of
cytokines, which include IL-4, IL-10 andTGF-β (to name a few), seem to
have a role in prevention of exaggeration of pro-inflammatory immune
responses.
• Dendritic cell apoptosis - immune system cells called dendritic
cells present antigens to active lymphocytes. Dendritic cells that are
defective in apoptosis can lead to inappropriate systemic lymphocyte
activation and consequent decline in self-tolerance.
• Epitope spreading or epitope drift - when the immune reaction
changes from targeting the primary epitope to also targeting other
epitopes. In contrast to molecular mimicry, the other epitopes need not be
structurally similar to the primary one.
• Epitope modification or Cryptic epitope exposure – this
mechanism of autoimmune disease is unique in that it does not
result from a defect in the hematopoietic system. Instead, disease results
from the exposure of cryptic N-glycan (polysaccharide) linkages common
to lower eukaryotes and prokaryotes on the glycoproteins of mammalian
non-hematopoietic cells and organs. This exposure of phylogenically
primitive glycans activates one or more mammalian innate immune cell
receptors to induce a chronic sterile inflammatory state. In the presence
of chronic and inflammatory cell damage, the adaptive immune system is
recruited and self–tolerance is lost with increased autoantibody
production. In this form of the disease, the absence of lymphocytes can
accelerate organ damage, and intravenous IgG administration can be
therapeutic. Although this route to autoimmune disease may underlie
various degenerative disease states, no diagnostics for this disease
mechanism exist at present, and thus its role in human autoimmunity is
currently unknown.
65
4.0 CONCLUSION
• Autoimmunity
• Causes of autoimmunity
• Genetic factors affecting autoimmunity
• The pathogenesis of autoimmunity.
5.0 SUMMARY
Autoimmunity is the failure of an organism to recognise its own

constituent parts as self, which allows an immune response against its
own cells and tissues. Any disease that results from such an aberrant
immune response is termed an autoimmune disease. Autoimmunity is
often caused by a lack of germ development of a target body and as such
the immune response acts against its own cells and tissues. Prominent
examples include Coeliac disease, diabetes mellitus type 1 (IDDM),
systemic lupus erythematosus (SLE), Sjögren's syndrome, Churg- Strauss
Syndrome, Hashimoto's thyroiditis, Graves' disease, idiopathic
thrombocytopenic purpura, rheumatoid arthritis (RA), lupus and allergies.
Autoimmune diseases are very often treated with steroids.
i. What is autoimmunity?
ii. Discuss the pathogenesis of autoimmnity.
iii. Discuss on the genetic factors affecting autoimmunity.
7.0 REFERENCE/FURTHER READING
Ainsworth, Claire (Nov. 15, 2003). The Stranger Within. New Scientist
(subscription).
Edwards, J.C., Cambridge, G. (2006). "B-cell Targeting in Rheumatoid

Arthritis and other Autoimmune Diseases." Nature Reviews Immunology,
6 (5): 394–403. doi:10.1038/nri1838.
PMID 16622478.
Edwards, J.C., Cambridge, G.& Abrahams, V.M. (1999). "Do self

Perpetuating B Lymphocytes Drive Human Autoimmune Disease?".
Immunology, 97: 1868–1876.
Everyday Health > Women and Autoimmune Disorders By Krisha

McCoy. Medically Reviewed by Lindsey Marcellin, MD, MPH. Last
Updated: 12/02/2009
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Green, R.S.et al 2007). "Mammalian N-glycan Branching Protects

against Innate Immune Self-recognition and Inflammation in
Autoimmune Disease Pathogenesis" Immunity 27: 308-320.
Induction of Autoantibodies against Tyrosinase-Related proteins

following DNA Vaccination: Unexpected Reactivity to a Protein
Paralogue Roopa Srinivasan, Alan N. Houghton, & Jedd D. Wolchok.
Jerne, N. (1974). "Towards a Network Theory of the Immune System".

Ann Immunol (Paris) 125C (1–2): 373–89. PMID 4142565.
Klein, J. Sato, A. (September 2000). "The HLA System. Second of two

Parts". N. Engl. J. Med. 343 (11): 782–6.
doi:10.1056/NEJM200009143431106. PMID 10984567.
Kubach, J. & et al (2005). "Dendritic Cells: Sentinels of Immunity and

Tolerance". Int J Hematol. 81 (3): 197–203.
doi:10.1532/IJH97.04165. PMID 15814330.
Pike, B. Boyd, A. & Nossal, G. (1982). "Clonal Anergy: the Universally

Anergic B lymphocyte". Proc Natl Acad Sci USA, 79 (6): 2013–7.
doi:10.1073/pnas.79.6.2013. PMC 346112.
PMID 6804951.
Salimonu, L.S.(2004). Basic Immunology for Students of Medicine And

Stefanova I., Dorfman J. R. & Germain, R. N. (2002). "Self-Recognition
Promotes the Foreign Antigen Sensitivity of Naive T Lymphocytes."
Nature, 420 (6914): 429–434.
doi:10.1038/nature01146. PMID 12459785.
Theory: High autoimmunity in Females due to Imbalanced X

Chromosome Inactivation: Tolerance and Autoimmunity
67
UNIT 3 IMMUNOLOGY OF TISSUE

TRANSPLANTATION
CONTENTS
1.0 Introduction
2.0 Objectives
3.0 Main Content
3.1 Types of Transplant
3.2 Evidence that Graft Rejection is Immunological
3.3 Mechanism of Graft Rejection
4.0 Conclusion
5.0 Summary
1.0 INTRODUCTION
Organ transplantation is the moving of an organ from one body toanother

or from a donor site on the patient's own body, for the purpose of
replacing the recipient's damaged or absent organ. The emerging field of
regenerative medicine is allowing scientists and engineers to create
organs to be re-grown from the patient's own cells (stem cells, or cells
extracted from the failing organs). Organs and/or tissues that are
transplanted within the same person's body are called autografts.
Transplants that are performed between two subjects of the same species
are called allografts. Allografts can either be from a living or cadaveric
source. Replacement of diseased organs by transplants of healthy tissues
has long been an objective in science. This has been frustrated by the
uncooperative attempts by the body to reject grafts from other individuals.
2.0 OBJECTIVES
• identify types of transplants

• describe mechanism of graft rejection
• evanluate immunology of graft rejection
• mention how to recognise prevention of graft rejection
3.0 MAIN CONTENT
3.1 Types of Transplant
Autograft
Autograft is the transplant of tissue to the same person. Sometimes this
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BIO 406 MODULE 2
is done with surplus tissue, or tissue that can regenerate, or tissues more
desperately needed elsewhere (examples include skin grafts, vein
extraction for CABG, etc.) Sometimes an autograft is done to remove the
tissue and then treat it or the person, before returning it (examples include
stem cell autograft and storing blood in advance of surgery). In a
rotationplasty a distal joint is used to replace a more proximal one,
typically a foot and ankle joint is used to replace a knee joint. The patient's
foot is severed and reversed, the knee removed, and the tibia joined with
the femur.
Allograft and allotransplantation

An allograft is a transplant of an organ or tissue between two genetically
non-identical members of the same species. Most human tissue andorgan
transplants are allografts. Due to the genetic difference between the organ
and the recipient, the recipient's immune system will identify the organ as
foreign and attempt to destroy it, causing transplant rejection.
A subset of allografts is the case in which organs or tissues are

transplanted from a donor to a genetically identical recipient (such as an
identical twin). Isografts are differentiated from other types of transplants
because while they are anatomically identical to allografts, they do not
trigger an immune response.
Xenograft and xenotransplantation

A transplant of organs or tissue from one species to another is called a
xenograft. An example is porcine heart valve transplants, which is quite
common and successful. Another example is attempted piscine-primate
(fish to non-human primate) transplant of islet (i.e. pancreatic or insular
tissue) tissue. The latter research study was intended to pave the way for
potential human use, if successful. Xenotransplantion however is often an
extremely dangerous type of transplant because of the increased risk of
non-compatibility, rejection, and disease carried in the tissue of the donor
and transplanted to the recipient.
Split transplants
Sometimes a deceased-donor organ, usually a liver, may be divided
between two recipients, especially an adult and a child. This is not usually
a preferred option because the transplantation of a whole organ is more
successful.
Domino transplants
This operation is performed on patients with cystic fibrosis because both
lungs need to be replaced and it is a technically easier operation to replace
the heart and lungs at the same time. As the recipient's native heart is
usually healthy, it can be transplanted into someone else needing a heart
transplant. This term is also used for a special form of liver transplant in
69
which the recipient suffers from familial amyloidotic polyneuropathy, a

disease where the liver slowly produces a protein that damages other
organs. This patient's liver can be transplanted into an older patient who
is likely to die from other causes before a problem arises.
This term also refers to a series of living donor transplants in which one
donor donates to the highest recipient on the waiting list and the transplant
centre utilises that donation to facilitate multiple transplants. These other
transplants are otherwise impossible due to blood type or antibody
barriers to transplantation. The "Good Samaritan" kidney is transplanted
into one of the other recipients, whose donor in turn donates his or her
kidney to an unrelated recipient. Depending on the patients on the waiting
list, this may sometimes be repeated for up to six pairs, with the final
donor donating to the patient at the top of the list.
This method allows all organ recipients to get a transplant even if their
living donor is not a match to them. This further benefits patients below
any of the recipients on waiting lists, as they move closer to the top of the
list for a deceased-donor organ. Johns Hopkins Medical Centre in
Baltimore and Northwestern University's Northwestern Memorial
Hospital have received significant attention for pioneering transplants of
this kind.
3.2 Evidence that Graft Rejection is Immunological
First and Second Set Reactions

Usually the second contact with an antigen represents a more explosive
event than the first contact. Rejection of a second graft from the same
donor is also more accelerated than the first. Initial vascularisation is poor
and may not occur. There is rapid invasion by polymorphs and lymphoid
cells including plasma cells. Thrombosis and acute destructioncan be seen
by 3 – 4 days.
Role of the Lymphocyte

Neonatally, the thymectomised organism finds it difficult to reject skin
grafts. This difficulty can be removed by injection of lymphocytes from
syngenic normal donors. Recipient of T cells from a donor who already
rejected will give accelerated rejection of a further graft of the same type.
Production of Antibodies
After rejection, humoral substances with specificity for graft donor
antigens may be recognised. An example in man is lymphocytotoxin. The
specificity of the antigens involved in graft rejection is under genetic
control. Genetically identical individuals such as uniovular twins have
identical transplantation antigens and grafts can be freely exchanged
between them.
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3.3 Mechanism of Graft Rejection
Lymphocyte – mediated Rejection

Whereas passive transfer of serum from an animal which has rejected a
skin allograft cannot usually accelerate the rejection of a similar graft on
the recipient animal, injection of lymphoid cells shorten graft survival.
A primary role of lymphoid cells in first set rejection is consistent with
the histology of the early reaction which shows infiltration by
mononuclear cells with very few polymorphs. Neonatal thymectomy
prolongs the survival of skin transplants. Also, there is a long survival of
grafts on children with thymic deficiencies. T cells are implicated in these
regions.
The role of antibody

While earlier experience with skin and solid tumour grafts suggest that
they were not readily susceptibile to cytotoxic antibodies, it is not true for
all organ transplants. For example although acute early rejection of kidney
allograft occurring up to 10days or so after transplantation is characterised
by a dense cellular infiltration likely to be cell-mediated immunity,
hyperacute rejection occurs within minutes of transplantation in
individuals with pre-existing antibodies. Such antibodies arise from blood
group incompatibility or pre-sensitisation to class 1 MHC molecules
through blood transfusion. The complexity of action and interaction of
cellular and humoral factors in graft rejection is considerable.
Circumstances exist when grafts are protected from destruction by
antibodies, ie., enhancement.
Prevention of Graft RejectionTissue Typing
Since MHC differences provoke the most vicious rejection of grafts, these
antigen specificities are being defined in an attempt to minimise rejection
by matching graft and recipient in a similar way individuals are cross-
matched for blood transfusion where ABO groups provide strong
transplantation antigens. Alleles at the three class I loci are identified by
C’ dependent cytotoxic reactions using monospecific sera. Typing is done
by setting up lymphocytes against a panel of such sera in the presence of
complement. Class II locus (HLA-D) is defined by the
mixed lymphocyte reaction (MLR) using homozygous stimulating cells
for typing. Failure to respond to a given typing cell means that the
lymphocytes bear that specificity. HLA alleles are now defined by their
gene sequences employing the polymerase chain reaction (PCR)
technique. Different HLA antigens are arbitrarily assigned numerical
specificities.
Use of Immunosuppressants
The use of agents producing general immunosuppressants can prevent
graft rejection. However, because they are non-specific, patients on
immunosuppressive therapy tend to be susceptible to infections and are
71
more prone to develop lymphoreticular cancers, particularly of viral

aetiology. Lymphoid cell abltion can be produced through injections of
anti-lymphocyte globulin or of monoclonal anti-CD3. For total lymphoid
irradiation, fractional irradiation is focused on lymphoid tissues while
shielding the bone marrow, lungs and other vital non- lymphoid tissues.
Many immunosuppressive drugs now in use were first employed in cancer
chemotherapy because of their toxicity to dividing cells. These anti-
mitotic drugs are especially toxic for cells of the bone marrow and small
intestine and must be used with great care.
IN TEXT QUESTION
What is an allograft?
Answer
An allograft is a transplant of an organ or tissue between two genetically
non-identical members of the same species.
4.0 CONCLUSION
1. Types of transplants
2. Mechanisms of graft rejection
5.0 SUMMARY
The importance of pathology and immunology in transplantation is

increasing with the widespread use of organ and tissue transplantation
for the treatment of end-stage diseases. Recently, the end points for
clinical trials in organ transplantation have been based on pathology, not
graft failure. Organ and tissue transplantation has advanced from an
experimental procedure used only in life-threatening, emergency
procedures to the treatment of choice for a wide range of clinical
conditions. Organs are transplanted to rectify an irreversible functional
deficit but, unless donor and recipient are genetically identical, graft
antigens will trigger a rejection response by the recipient. In the early part
of this century, experiments on transplantation of tumours showed that
there were strict limitations on the ability of tumour grafts to survive.
i. What do you understand by the term autograft?

ii. What evidence is there to show that graft
rejection isimmunological?
72
BIO 406 MODULE 2
Frohn, C, Fricke, L., Puchta, J.C., Kirchner, H. (February 2001). "The

effect of HLA-C matching on acute renal transplant rejection". Nephrol.
Dial. Transplant, 16 (2): 355–60.
Salimonu, L.S.(2004). Basic Immunology for Students of Medicine and

See WHO Guiding Principles on Human Cell, Tissue and Organ

Transplantation, Annexed to World Health Organisation, 2008.
73

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COURSE

Course Team Mr. Kofi O. Renner (Course Developer/Writer) –

NATIONAL OPEN UNIVERSITY OF NIGERIA

© 2023 by NOUN Press

First Printed 2009

Parasitology and Immunology (406) is a second semester course. It is a

Parasitology and Immunology is an important area of study for scientists.

This course deals with parasitology and immunity with emphasis to

What You Will Learn In This Course

This course exposes you to parasitology and immunology, a sub-

This course aims to enable you to know/understand the different types of

Working Through the Course

a. To successfully complete this course. You are required to read

The Course Materials

The main components of the course are:

1 The Study Guide

The study units in this course are given below:

Module Two is concerned with hypersensitivity; inappropriate responds

There are three aspects to the assessment of this course.

Do the exercises or activities in the unit applying the information and

Tutor -Marked Assignment

This is the continuous assessment component of this course and it

These answered assignments must be returned to your facilitator.

You are expected to complete the assignments by using the information

examination. The end of course examination covers information from all

Course Marking Scheme

Facilitators/ Tutors and Tutorials

These are the duties of your facilitator:

• He or she will mark and comment on your assignment

(You are expected to mail your tutored assignment to your facilitators at

Do not delay to contact your facilitator by telephone or e-mail for

Parasitology and Immunology (406) is a course which explain the body

Also, the how natural or artificial, innate or acquired=adaptive and either

On the completion of this course, you will have an understanding of basic

• what do you understand by the term Immunity?

I wish you success in this course.

Unit 1 Immunity …………………………………

Unit 1 Hypersensitivity ……………………….. 44

Immunity is a biological term that describes a state of having sufficient

At the end of this unit, you should be able to:

3.0 MAIN CONTENT

3.1 Concept of Immunity

The concept of immunity has intrigued mankind for thousands of years.

The first clinical description of immunity which arose from a specific

The birth of active immunotherapy may have begun with Mithridates VI

poison, and took daily sub-lethal doses to build tolerance. Mithridates is

In Europe, the induction of active immunity emerged in an attempt to

3.2 Passive Immunity

Passive immunity is transmitted by antibodies or lymphocytes preformed

Passive immunity is the transfer of active immunity, in the form of

body to develop its own immune response, or to reduce the symptoms of

Naturally acquired passive immunity

Artificially acquired passive immunity

Passive transfer of cell-mediated immunity

Active immunity is induced after contact with foreign antigens. This

Fig. 1: The Time Course of an Immune Response. Due to the

of experiences, whereas adaptive immunity arises only after an infection

Artificially acquired active immunity

There are four types of traditional vaccines: