Immune System

The protective system of human body to resist almost all

types of infectious organisms or toxins that tend to
damage is called the immune system.
AN OUTLINE OF THE IMMUNE SYSTEM

The immune system is a complex network of organs

containing of many interdependent cell types that

collectively protect the body from bacterial, parasitic,

fungal, and viral infections and from the growth of the

tumor cells.
Network of the organs of the immune system.
Organs of the Immune System

 Lymphoid Organs

 Bone Marrow

 Thymus

 Spleen

 Lymph Nodes
Lymphoid Organs

 Lymphoid organs are responsible for the production of

lymphocytes and antibodies.

 Anatomically, lymphoid organs are organized as

primary lymphoid organs and secondary lymphoid
organs.
 Primary lymphoid organs consist of bone marrow and

thymus.

 Stem cells in the bone marrow either differentiate to

give rise to B cells or they migrate to the thymus,

where their development into various types of T cell is

stimulated.
 Secondary lymphoid organs are of two types:

• Encapsulated, e.g. the lymph nodes and spleen

• Unencapsulated, e.g. mucosal associated

lymphoid tissue (MALT).

 Each of these secondary organs is concerned with a

different type of immune response.

• Lymph nodes deal with antigens in tissues

• Spleen deals with antigens in blood

• Mucosal associated lymphoid tissue (MALT)

system deals with antigens at mucosal surfaces

Bone Marrow

 All the cells of the immune system are initially derived

from the bone marrow by a process called
hematopoiesis.

 During hematopoiesis, bone marrow-derived stem cells

differentiate into either mature cells of immune system or
into precursors of cells that migrate out of the bone
marrow to continue their maturation elsewhere.
 In addition to red blood cells and platelets, the bone
marrow produces:

• B-lymphocytes

• Natural killer cells

• Granulocytes (neutrophils, eosinophils, and

basophils)

• Immature thymocytes (prothymocytes).

Thymus
 Immature thymocytes (prothymocytes) leave the bone
marrow and migrate into the thymus.
 The function of the thymus is to produce mature T
cells.
 After maturation process, T cells that are beneficial to
the immune system are spread, while those T cells that
might evoke a harmful autoimmune response are
eliminated.
Spleen
The spleen is an immunologic filter of the blood and
composed of:
• B cells
• T cells
• Macrophages
• Dendritic cells
• Natural killer cells
• Red blood cells.
 Macrophages and dendritic cells are called antigen-
presenting cells (APCs).

 An immune response is initiated when the macrophage

or dendritic cells present the antigen to the appropriate
B or T cells.

 In the spleen, B cells become activated and produce

large amounts of antibody.
Lymph Nodes

 The lymph nodes function as an immunologic filter

for the body fluid known as lymph.

 Lymph nodes are found throughout the body and

composed of:

• T cells

• B cells

• Dendritic cells
Cells of the Immune System
 Lymphocytes

 T Cells

 Natural Killer Cells

 B Cells

 Granulocytes or Polymorphonuclear (PMN)

Leukocytes

 Macrophages

 Dendritic Cells
 Lymphocytes are white blood cells and are one of the
body's main types of immune cells. They are made in
the bone marrow and found in the blood and lymph
tissue.
 T cell is a type of lymphocyte which develops in the
thymus gland and plays a central role in the immune
response. T cells can be distinguished from other
lymphocytes by the presence of a T-cell receptor on the
cell surface.
There are three major subtypes of T cells.

1. Helper T cells also called CD4+ T cells

(possesses CD4 protein)

2. Cytotoxic T cells or killer cells or CD8+ T cells

3. Suppressor T cells.
Natural Killer Cells
Natural killer cells often referred to as NK cells, are
similar to the killer T cells (CD8+ T cells). They can
recognize and destroy foreign cells, tumor cells, and
even some infected cells.
B Cells
The major function of B-lymphocytes is the production
of antibodies in response to foreign proteins of bacteria,
viruses, and tumor cells.
Granulocytes or Polymorphonuclear (PMN) Leukocytes

 Granulocytes or polymorphonuclear leukocytes (PMNs)

are a group of white blood cells.

 Granulocytes are composed of three cell types:

Neutrophils, eosinophils, and basophils.

 These cells are predominantly important in the removal

of bacteria and parasites from the body.
Macrophages

 Monocytes become macrophages when they move from the

circulation into the tissue. When they enter the tissues they
begin to swell, increasing their diameter, these cells are now
called macrophages.

 They are often referred to as scavengers or antigen

presenting cell (APC).

 The macrophages secrete a special activating substance,

interleukin-1 which promotes still further growth and
reproduction of the specific lymphocytes.
Dendritic Cells

 Dendritic cells which also originate in the bone marrow

function as APCs.

 These are more efficient APCs than macrophages

 Dendritic cells are phagocytes in tissues that are in

contact with the external environment; therefore, they are
located mainly in the skin, nose, lungs, stomach, and
intestine.
Innate And Adaptive Immune System
 The immune system protects organisms from infection
with layered defenses of increasing specificity.

 Most simply physical barriers prevent pathogens such

as bacteria and viruses from entering the organism.

 If a pathogen ruptures these barriers, the innate

(natural) immune system provides an immediate, but
nonspecific response.
 However, if pathogens successfully avoid the innate
response, a third layer of protection, the adaptive
immune system, is activated by the innate response.

 The immune system or body defense mechanism is

classified into two types:

1. Innate immunity also called natural or native

immunity which is non-specific.

2. Adaptive immunity also called acquired immunity

which is specific.
Innate Immunity (Natural or Native Immunity)

 It refers to defense mechanisms that are present even

before infection (preexisting) and hence provides
immediate protection against exposure to a new
pathogen.

 Such innate responses are not specific to a particular

pathogen but it is nonspecific, i.e. it is not directed
against specific invaders but against any pathogens that
enter the body.
Innate immunity is the first line of defense. This system
does not confer long-lasting immunity against a pathogen.

These defense mechanisms include the barrier formed by:

• Skin
• Chemicals in perspiration
• Skin oil
• Saliva
• Tears
• Hair in our nostrils
• cilia and mucus that clean out debris from our
lungs and trachea
 Inflammatory response which is the dilation of blood
vessels and accumulation of WBCs at the site of an
injury is one of the first responses of the immune system
to infection.

 The symptoms of inflammation are redness and swelling,

which are caused by increased blood flow into a tissue

 Fever, a raised body temperature to inhibit the growth of

pathogens.
Types of Innate Immunity

Innate immunity has two types of defense mechanisms:

1. Innate humoral immune system.

2. Innate cellular or cell-mediated immune system.

Innate Humoral Immune System

It involves a variety of substances found in the humor

(the body fluid used to be called humorous) which
protects against extracellular microbes and their
toxins.

It consists of
 Certain natural chemical compounds present in the blood
that destroy foreign organisms, e.g.

• Skin and respiratory tract secrete antimicrobial

peptides such as the β-defensins
• Enzymes such as lysozyme and phospholipase A2
in saliva, tears and breast milk are also
antibacterial.
• In the stomach, gastric acid and proteases serve as
powerful chemical defense against ingested
pathogens.
Plasma proteins (proteins of the complement system).

 It contains about 20 different proteins and is named for

its ability to “complement” the killing of pathogens by
antibodies.

 Other circulating proteins of the innate humoral

immunity are mannose-binding lectin and C-reactive
protein, both of which coat microbes for phagocytosis
and complement activation.
Lung surfactant is also a component of innate humoral

immunity, providing protection against inhaled

microbes.
Innate Cellular or Cell-mediated Immune System

It is carried out by cells and is responsible for defense

against intracellular microbes. It consists of :

• Epithelial barriers that resist entry of environmental microbes.

• Phagocytic cells, mainly neutrophils and macrophages. These

phagocytic cells destroy bacteria and other invaders.

• Natural killer (NK) lymphocytes that can recognize and

destroy foreign cells, tumor cells, and even some infected cells.
Adaptive Immunity (Acquired Immunity)
 It consists of mechanisms that are stimulated by
microbes (pathogens) and are also capable of
recognizing non-microbial substances (toxins) called
antigen.

 Adaptive immunity develops later after exposure to

microbes and is even more powerful in fighting infections.

Types of Adaptive Immunity

1. Humoral immunity

2. Cellular or cell-mediated immunity.

Adaptive/Acquired Humoral Immune System

 When an antigen presenting cells (APCs) presents an

antigen to a B cell, the B cell is signaled to proliferate
and produce antibodies that specifically bind to that
antigen.

 If antibodies bind to antigens (bacteria or parasites), it

acts as a signal for polymorphonuclear (PMN)
leukocytes or macrophages to engulf and kill them.
 Adaptive (Acquired) Cellular or Cell-mediated

Immune System

 T-lymphocytes that are specifically made in the lymph

nodes are responsible for acquired cellular immunity.

 If the antigen presenting cells (APCs) present the

antigen to T cells, the T cells become activated.
Activated T cells proliferate to form CD4 T cells
+

(helper T cells), CD8 T cells (cytotoxic T cells), or

+

killer T cells.
B Cell Development And Formation Of Antibodies

 The B-lymphocytes, is responsible for forming

antibodies that provide acquired humoral immunity.

 Early development of B-lymphocytes occurs in the bone

marrow.

 In the first step, stem cells develop into pro-B cells. In

response to a signal (interleukin-7) received from
stromal cells in the bone marrow promotes
differentiation of pro-B cells into pre-B cells.
 These pre-B cells undergo extensive proliferation. This
gives rise to B cells with monomeric IgM and IgD
molecules on their surface.

 These monomeric immunoglobulins are called surface

immunoglobulins (sIgs).
 Surface immunoglobulins (IgM and IgD), present on
the surface of all native B cells, constitute the antigen
binding component of the B cell receptor (BCR).

 B cells recognize antigen via the B cell antigen

receptor.
 In addition to membrane immunoglobulin, the B cells
also express several other molecules that are essential
for B cell function. These include:

–– Complement receptors (CD21).

–– Fc receptors

–– CD40.
 When virgin B cells reach secondary lymphoid tissues,
they may be activated by protein and non-protein
antigens.

 Activation of B cells require help from helper T

(CD4+T) cells.

 Helper T cells activate B cells by binding to CD40

expressed on B cells and by secreting cytokines.
 This interaction is essential for B cell maturation.
Different cytokines stimulate B cells to produce
different antibody producing cells.

 The end result of B cell activation is their

differentiation into antibody secreting cells,
called plasma cells.
Development of B and T-lymphocytes.
(TCR: T cell receptor)
B Cell Stimulation and Secretion of Specific Antibody

 B cell is triggered when the antigen binds to a B cell.

Then the B cell engulfs the antigen by endocytosis and

digests it into fragments of peptides.

 These degraded pieces of antigen bound to its unique

class II MHC (major histocompatibility complex)

molecules are displayed on the cell surface with the

formation of antibody producing activated B cells.

In human, MHC molecules are called human leukocyte
associated (HLA) antigens.
Activation of native B cell for production of plasma cell
 The activated B cell then binds to a helper T (CD4+T)
cell, which possesses the CD4 protein.

 When this happens, cytokines are secreted by the helper

T cell and help the B cell to multiply and mature into
antibody producing plasma cells.

 Plasma cell then secretes the soluble antibody

corresponding to the surface immunoglobulin found on
the stimulated parent cell..
Production of antibodies from activated B cell.
 Each antibody is specific for a particular antigen
because of its unique structural organization of amino
acids in the variable portions of both the light and
heavy chains.

 There are two variable sites on the illustrated antibody

for attachment of antigens, making antibody bivalent
IgM which consists of 10 light and 10 heavy chains has
as many as 10 binding sites.
Binding of antigen molecules to one another by bivalent antibody.
Mechanism of Action of Antibodies
Antibodies act mainly in two ways:

1. Direct action: By direct attack on the invader.

2. Indirect action: By activation of the complement

system
Direct action:

Because of the bivalent nature of the antibodies, the

antibodies can inactivate the invading agent in one of
several ways, by binding of antigen (the invader) via
antigen binding region (Fab) of antibody.
This can lead to any one of the following methods:

Agglutination, in which multiple large particles with

antigens on their surfaces, such as bacteria or red cells,

are bound by cross-linking together into a clump.

Precipitation, in which the molecular complex of

soluble antigen and antibody becomes so large that it

is rendered insoluble and precipitates.

Neutralization, by blocking of the attachment of

viruses or bacterial toxins to membrane receptor

by covering the toxic sites of the antigenic agent by

antibodies.

Lysis, in which some potent antibodies are occasionally

capable of directly attacking membranes of cellular

agents and thereby cause rupture of the agent.

Indirect action:

Most of the protection comes through indirect action by

activating the complement system. The activation of the

complement system is initiated by the binding of one of the

complement molecules to the Fc portion of the antibody

molecules.
 Development Of T-lymphocytes

 T-lymphocytes are derived from stem cells of the

embryo.

 These stem cells themselves are incapable of forming

directly activated T-lymphocytes.

 They are further differentiated in the thymus.

 Lymphoid stem cells after formation in the bone marrow

are first transported to the thymus gland (Pro-T cell).
 In the thymus gland, they divide rapidly (immature T
cell) and at the same time develop extreme diversity
for reacting against different specific antigens.

 These different types of preprocessed T-lymphocytes

then leave the thymus and distributed via blood
throughout the body and stored in the secondary
lymphoid tissue everywhere.
 Millions of specific T-lymphocytes are stored in the
lymphoid tissue.

 When specific antigens come in contact with T

lymphocytes in the lymphoid tissue, specific T
lymphocytes become activated to form activated maturen
T cells.

 These T cells are then distributed throughout the body. T

cells), or killer T cells.
There are major three types of T cells with distinct function

• CD4+T cells (helper T cells),

• CD8+T cells (cytotoxic cells)

• T cells), or killer T cells.

Role of Helper T cells (CD4+ T Cells)

 As their name implies, they help in the functions of the

immune system by several ways.

 The activation of helper T cells causes it to release

number of proteins called lymphokines or cytokines or
more specifically interleukins and other stimulatory
signals that stimulate the activity of macrophages, killer
T cells, and B cells.
 Helper T cells express TCR that recognizes antigen
bound to class II MHC molecules.

 Helper T cells have no cytotoxic activity and do not kill

infected cells or clear pathogens directly.

 They instead control the immune response through

lymphokines by directing other cells to perform these
tasks.
 Lymphokines act as the regulator of immune
functions by acting on other cells of the immune
system and bone marrow and help determine which
type of immune responses the body will make to
particular pathogens.

 In the absence of them lymphokines, the immune

system is almost paralyzed.
Role of helper T cell in regulation of the immune system.
Role of Cytotoxic T Cells/Killer Cells/CD8+T Cells

 Cytotoxic T cells are also called killer cells because

these cells are capable of killing directly certain tumor
cells, viral infected cells, and sometimes parasites and
at times even some of the body’s own cells.

 Cytotoxic T cells directly attack cells carrying certain

foreign or abnormal molecules on their surfaces.
 Cytotoxic T cells recognize small fragments of these
viral proteins carried on the surface of an infected cell
by body’s own class I MHC (major histocompatibility
complex) protein molecules.

 The protein of the infecting virus is processed into

fragments which combine with class I MHC protein
molecule and brought to the surface of the infected cell.
There the complex is recognized by a killer cell
 Killer T cells are activated when their TCR binds to
this specific antigen in a complex with the class-I
MHC molecule of another cell.

 Recognition of this MHC antigen complex is aided by

CD8 receptor on the killer T cell. The killer T cell
then travels throughout the body in search of cells
where the MHC-I receptor bear this antigen.

 After binding, the killer (cytotoxic) T cell secretes

hole forming proteins called perforins.
 Perforins make hole in the plasma membrane of the
attacked cell through which fluid from interstitial
space flows rapidly into the attacked cell. The
attacked cells then become swollen and it dissolves
shortly thereafter.

 Killer T cell activation is tightly controlled and

requires activation signals provided by helper T cells
Direct attack on invading cell by cytotoxic T cell.
Role of Suppressor Cells

As their name implies, they are capable of suppressing

the function of both cytotoxic T cells and helper T cells
and prevent the excessive immune reactions that may
cause damage to the body’s own tissue.
IMMUNOLOGICAL MEMORY
 When B cells and T cells are activated and begin to
reproduce duplicate cells, some of their offspring will
become long lived memory cells.
 Throughout the lifetime of an animal these memory cells will
remember each specific pathogen encountered and can mount
a strong response if the pathogen is detected again.
 This is “adaptive” because it occurs during the lifetime of an
individual as an adaptation to infection with that pathogen
and prepares the immune system for future challenges.
 Immunological memory is the ability to “remember”
foreign substance previously encountered and react
again promptly if the pathogen is detected again.
There are two kinds of immunological memory.

1. Passive short-term memory.

2. Active long-term memory.

Passive Short-Term Memory

 In passive immunity, antibodies come from outside the

person’s body. Passive immunity is usually short term,
lasting from a few days up to several months. Several
layers of passive protection are provided by the mother.
 During pregnancy, antibody IgG, is transported from
mother to baby directly across the placenta so human
babies have high levels of antibodies even at birth, with
the same range of antigen specifies as their mother.

 Breast milk also contains antibodies that are transferred

to the gut of the infant and protect against bacterial
infections until the newborn can synthesize its own
antibodies.
Active Long-Term Memory

 Long term active memory is acquired following

infections by activation of B and T cells.

 When a clone of T-lymphocytes is activated by an

antigen, many of the newly formed lymphocytes are
preserved in the lymphoid tissue to become additional T-
lymphocytes of that specific clone which are called
memory cells.
 These memory cells even spread throughout the
lymphoid tissue of the entire body.

 On subsequent exposure to the same antigen anywhere in

the body, release of activated T cells occurs far more
rapidly and much more powerfully than had first
exposure.

 A few of the activated B lymphocytes do not go on to

form plasma cells but instead form some new B
lymphocytes similar to those of the original clone.
 Thus the new lymphocytes are added to the original
lymphocytes of the same clone.
 They also circulate throughout the body to all the
lymphoid tissue.
 However, they remain dormant until activated once
again by a new quantity of the same antigen. These
lymphocytes are called memory cells.
 Subsequent exposure to the same antigen will cause a
much rapid, and much more potent antibody response
this second time.
 THE IMMUNE SYSTEM AND VACCINE

 A host organism needs time, often days, to mount an

immune response against a new antigen, but memory

cells permit a rapid response to pathogens previously

encountered.

 Active immunity can also be generated artificially,

through vaccination.
 The principle behind vaccination (also called
immunization) is to introduce an antigen from a
pathogen in order to stimulate the immune system and
develop specific immunity against that particular
pathogen without causing disease associated with that
organism.

 The active component of a vaccine that is responsible to

protect against a particular viral/bacterial infection can
often consists of many forms.
 Killed or inactivated vaccines contain pathogens that
have been rendered harmless by treatment with
chemicals or high heat.

 Live attenuated (weakened) vaccines contain live

pathogens that have accumulated mutations so that they
are no longer virulent to human cells. These vaccines
are most commonly generated by reaped infection of
the pathogen in cultured cells until its virulence is lost.
 Subunit vaccines contain a purified protein component of the
pathogen. Such proteins can be either isolated from infected
material (such as blood from chronically infected patients) or
generated by recombinant methods.

 Toxide vaccines (toxin produced by certain bacteria e.g.

tetanus or diphtheria) are used against pathogens that employ
an extracellular toxin to cause disease. These vaccines contain
a form of the toxin that has been inactivated by treatment with
chemicals or high heat.
PRIMARY AND SECONDARY RESPONSE

 The formation of antibodies that occurs on first

exposure to a specific antigen is called primary
response.

 The formation of antibodies that occurs after second

exposure to the same antigen is secondary response.
 The potency of primary response is weak and short life
(only few weeks).

 The secondary response by contrast, begins rapidly after

exposure to the antigen (often within hours), is far more
potent and forms antibodies for many months rather
than for only a few weeks.
Differences between primary response
and secondary response.
HISTOCOMPATIBILITY MOLECULES

Histocompatibility molecules originally identified as

antigens that stimulate rejection of transplanted organs,

which are now known to be extremely important for the

induction and regulation of the immune response. These

are present on the surface of antigen presenting cells.

 Physiologic function of cell surface histocompatibility
molecules is to bind peptide fragments of foreign proteins
for presentation to antigen specific T cells.

 In human histocompatibility proteins are encoded by a

large group of genes called the major histocompatibility
complex (MHC) or the human leukocyte antigen
(HLA) complex, so named because MHC encoded
antigens were initially detected on leukocytes.
In human, the major histocompatibility proteins or the
human leukocyte antigen, on the basis of their chemical
structure, tissue distribution and function are classified
into three categories:

1. Class I MHC proteins

2. Class II MHC proteins

3. Class III MHC proteins
DISORDERS OF HUMAN IMMUNITY

Failures of host defense causes:

 Immunodeficiency

 Autoimmunity

 Hypersensitivity
Immunodeficiency
 Immunodeficiency occur when one or more of the
component of the immune system is inactive.

 In developed countries, obesity, alcoholism and drug

use are common causes of poor immune function.

 However, malnutrition is the most common cause of

immunodeficiency in undeveloping countries
Autoimmunity

 Failure to differentiate host cells from a foreign

invader can trigger an autoimmune response in which
the body’s immune system attacks its own tissues and
organs.

 The resulting damage may be cumulative, such as

occurs in rheumatoid arthritis and multiple sclerosis, or
acute, such as the complete destruction of pancreatic
islets cells that occurs in type 1dibetes.
Hypersensitivity

 Hypersensitivity is an immune response that damages

the body’s own tissues.

 They are divided into four classes (Type I to IV) based

on the mechanisms involved and the time course of the
hypersensitive reaction.
 Type I hypersensitivity is an immediate or anaphylactic
reaction, often associated with allergy. Symptoms can
range from mild discomfort to death. Type I
hypersensitivity is mediated by IgE released from mast
cells and basophils.

 Type II hypersensitivity occurs when antibodies bind to

antigen on the patient’s own cells, marking them for
destruction. This is also called antibody-dependent (or
cytotoxic) hypersensitivity and is mediated by IgG and
IgM antibodies.
 In Type III immune complexes (aggregations of antigens,

complement proteins and IgG and IgM antibodies)

deposited in various tissues trigger Type III

hypersensitivity reactions.

 Type IV hypersensitivity (also known as cell mediated or

delayed type sensitivity) usually takes between two three

days to develop. Type IV reactions are involved in many

autoimmune and infectious diseases, but may also involve

contact dermatitis. These reactions are mediated by T cells,

monocytes, and macrophages.

Thank you