PHYSIOLOGY OF THE IMMUNE SYSTEM

CLASS 2: BODY DEFENSES & IMMUNITY

David T. OLUWOLE
Department of Physiology
College of Health Sciences, CUAB
 IMMUNITY
❖ However, many factors not directly related to our
❖ immunity = resistance to disease “immune system” affect an individual’s overall

❖ The immune system provides defence against ability to resist infections:

➢ Genetics: human diseases, zoonoses, etc
all the microorganisms and toxic cells to which
➢ Age: mainly an immune response
we are exposed ➢ Health: protein deficiency → less phagocytic

❖ without it we would not survive till adulthood activity

stress → lower resistance to disease
❖ our body has many ways to prevent or to slow
➢ Hormones: cortisone (a glucocorticoid) reduces
infections inflammatory response
➢ Microbiome: activate our immune system and
affect our susceptability to diseases 2
 THE IMMUNE SYSTEM
❖ Two (2) major kinds of mechanisms that protect the body:
❖ The immune system is a functional system
Non-specific Immunity
rather than a system with discrete organs
❖ an innate reaction that acts as a general response against
❖ parts of many organs contribute to body
all kinds of pathogens. It may be:
defense WITH almost all organs in body
a. physical and chemical barriers
play some role in immunity
b. internal cells and chemicals
❖ dispersed chemicals, cells and tissues
Specific Immunity
❖ dispersal and transport via circulatory and
❖ an adaptive system that fights specific individual
lymphatic systems
pathogens in customized ways
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 NON-SPECIFIC IMMUNITY
❖ The non-specific mechanisms for protecting the body 1. INTACT SKIN
❖ The skin is rarely, if ever, penetrated while intact, only a few
can be visualized as offering two distinct levels of
bacteria and parasitic worms (cercariae) can do this
protection
❖ However, if, staphs and streps are most likely to get in.
➢ Physical & Chemical barriers that work to prevent
❖ The intact skin can achieve this because:
entry of pathogens
➢ It consists of multiple layers of tightly packed dead cells
➢ Internal cells & Chemicals that attempt to remove filled with waxy keratin
pathogens if they get past the barriers ➢ It shed regularly to prevent build-up of bacterial
communities
PHYSICAL BARRIERS
➢ The sebaceous glands provides protective film over skin
❖ 1st major level of protection from invasion and infection ➢ The acidity of skin secretions ('acid mantle') inhibit bacterial
❖ Nonspecific, treats all potential pathogens the same way & fungal growth

❖ Attempt to prevent entry of pathogens into body ➢ The skin also contains bacteriocidal chemicals

❖ Includes: ➢ The Langerhans cells ( & Granstein cells) serve as antigen

presenting cells expose skin antigens to T-cells 4
 NON-SPECIFIC IMMUNITY
2. MUCOUS MEMBRANE INTERNAL CELLS & CHEMICALS
1. BLOOD
❖ They line all systems that open to outside of body
❖ has nonspecific, antimicrobial chemicals that help to fight
❖ The mucous membrane can achieve this because:
invaders. e.g transferrins – bind to Fe to inhibit bacterial
➢ Secretes mucus: thick, sticky, traps pathogens
growth.
➢ In the nose, the nasal hairs help trap pathogens
2. SIMPLE PHAGOCYTOSIS
➢ Many mucus membranes have cilia
❖ Many WBC’s travel through blood and tissues and gobble up
➢ The stomach lining secretes gastric juices, contains HCl bacteria and foreign material
and enzymes; and they are highly acidic ❖ Includes neutrophils and macrophages (formed from
➢ eye is protected by lacrimal apparatus. The continual blink monocytes)
flushes and wipes away pathogens ❖ migrate to area of infection
➢ The saliva in mouth allows continual flushing of bacteria ❖ Monocytes enlarge on the way to become macrophages
to stomach. Lysosome kills and dissolves some bacteria ❖ This engulf and destroy the circulating pathogens especially
➢ The urine provides continual flushing of bacteria entering bacteria
the urethra ❖ Some macrophages are “fixed macrophages” that screen the
➢ vaginal secretions flushes and trapping blood as it passes by. 5
 NON-SPECIFIC IMMUNITY
3. EOSINOPHILS c. repairs or replaces damaged tissues
❖ They can produce toxins and are most active against ❖ Inflammation occurs in three major stages viz:
parasitic worms a. Vasodilation
4. NATURAL KILLER CELLS b. Phagocyte migration and phagocytosis
❖ They are the “pit bulls” of the defense system c. Tissue repair
A. VASODILATION AND INCREASED PERMEABILITY
❖ A kind of WBC; not phagocytic
❖ Serves as police in the body in blood and lymph ❖ The damaged tissues release histamines and kinins causing the
❖ They promote cell lysis of virus infected or cancer cells
blood vessels to dilate in area of damage
5. INFLAMMATORY RESPONSE
❖ Hence, the blood flow to area increased causing swelling
❖ A larger response preventing the spread of infection from
localized area when there is damage to body’s tissues and (edema), redness and heat
causes: redness, pain, heat and swelling ❖ This then allows defensive chemicals and clotting factors and
❖ Overall, it has beneficial effect:
cells to move to the area
a. destroys injuring agent
b. removes it and its by-products or limits its effects ❖ Clot is forms around the area to prevent spread of infection 6
 NON-SPECIFIC IMMUNITY
B. PHAGOCYTE MIGRATION AND PHAGOCYTOSIS 6. FEVER
❖ Within an hour phagocytes begin to accumulate at the site ❖ Systemic rather than local response
❖ As the flow of blood decreases, phagocytes stick to lining ❖ It involves coordinated autonomic, neuroendocrine and
of blood vessels then squeeze out into tissue spaces behavioural response

Diapedesis ❖ It is used by all vertebrates as acute phase reaction to immune

❖ Chemical attractants, eg. kinins, draw WBC’s to site challenge

Chemotaxis ❖ hypothalamic thermostat is reset usually to 1-4 degrees above

❖ Neutrophils arrive first, monocytes then predominate normal eg. 102.2 ºF

during the later stages ❖ produced by pyrogens secreted by macrophages when exposed

❖ As the WBC’s die → pus accumulates to certain pathogens

❖ The fever symptoms:

C. TISSUE REPAIR ➢ blood vessels constrict

❖ This cannot be completed until all harmful substances ➢ metabolism increases

have been removed or neutralized ➢ shivering helps maintain high temp

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➢ skin remains cold – chills
 NON-SPECIFIC IMMUNITY
7. COMPLEMENT REACTIONS
The slight increase in temperature:
❖ foreign substance may trigger cascade which activates
❖ inhibits growth of some pathogens complement proteins = complement fixation

❖ speed metabolism for repair of body cells and to enhance ❖ ~5% of all blood proteins (20 different ones) are complement
proteins
phagocytosis
❖ they can operate non-specifically or specifically
❖ cause liver and spleen to store zinc and iron; both are ❖ complement proteins are formed from liver cells, lymphocytes,

nutrients needed by bacteria monocytes

❖ they trigger a cascade reaction (inactive → active) through
❖ intensifies effects of other chemicals eg interferon
initiation, amplification, effects
❖ However, very high temperatures (>40 ºC) may be life ❖ However, the effects of complement activation are short lived

threatening as they are quickly destroyed

❖ The malfunctions result in some hypersensitivity disorders
❖ Complement fixation can cause any of the following effects:
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 NON-SPECIFIC IMMUNITY
8. INTERFERON
a. Cell lysis (cytolysis)
❖ They are the antiviral chemical secreted by infected cells
❖ Here, the membrane attack complex forms
❖ Thus, they are host cell specific, not virus specific
“transmembrane channels” digests a hole in
❖ Hence, different tissues in same host produces different interferons
bacterial cell, killing it
❖ Meanwhile, all interferons are small proteins, stable at low pH and are
b. Opsonization
heat resistant
❖ This process makes pathogens stickier and easier
❖ They are produced by infected cells and spread to the uninfected cells
for the leukocytes to phagocytize
❖ They stimulate the synthesis of antiviral proteins that disrupt the
c. Enhances inflammatory response
various stages of viral multiplication
❖ This process will helps trigger the release of
❖ They are effective for only short periods i.e. good for acute, short term
histamine and chemical attractants for WBC’s
infections such as colds, influenza 9
 SPECIFIC IMMUNITY
❖ Functionally, it is the third line of defense against infections ANTIGENS
❖ It is non-innate, but adaptive as it: ❖ Any substance that can mobilize the immune system i.e.
provoke an immune response
1. carefully targeted
❖ it can be free molecules or attached to cells of bacteria,
❖ It recognizes a specific foreign substance and acts to fungi, etc
immobilize or neutralize it ❖ the ability of a molecule to act as an antigen depends on its
size and complexity
2. amplifies the immune response,
❖ Most are large complex organic molecules (MW >10,000),
❖ complement reactions, etc against specific pathogen not normally found in the body especially immunogenic:
➢ some lipids
3. is a systemic response effective throughout the entire body ➢ foreign proteins
➢ many large polysaccharides
➢ nucleic acids
4. Has memory
❖ But large simple molecules of many small repeating units
❖ It protects, even if one ever reinfected with same pathogen (e.g. plastics) have little or no immunogenicity
❖ resistance lasts a long time 10
 SPECIFIC IMMUNITY
❖ An must be foreign to the host as our body is programmed
to recognize our own proteins as “self” i.e. not ❖ But may become so by attaching to the body’s own

immunogenic proteins (=Haptens) examples: chemicals in poison ivy,

❖ But, these same proteins may be strongly immunogenic to
animal dander, some detergents, cosmetics, etc
others as in transfusions and transplants reaction
❖ Microorganisms and pollen grains are immunogenic ❖ Actually, only certain parts of an entire antigen are

because their surface membranes have many such foreign immunogenic

molecules on them.
❖ Usually a small sequence of amino acids (~10) that
❖ Examples of antigen containing structures includes:
bacterial capsules; cell wall lipopolysaccharides of G- triggers an immune reactions

bacteria; glycoproteins in cell membranes; attachment sites ❖ i.e. the antigenic determinants (=epitopes)
for viruses; bacterial toxins and extracellular enzymes.
❖ most naturally occurring antigens have a variety of
❖ Small molecules such as peptides, nucleotides, and many
hormones are NOT immunogenic. antigenic determinants e.g. large proteins have 100’s
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 SPECIFIC IMMUNITY
ANTIGEN PROCESSING
❖ The immune surveillance is always in search for antigens ❖ The infected cells display major histocompatability

❖ It uses a large population of white blood cells mainly complex (MHC) molecules on their surface which bind to

lymphocytes and display small peptides or fragments of proteins that

❖ To control bacteria and large parasites, the immune system come from the parasite

deploys soluble antigen receptors called antibodies ❖ These MHC with foreign peptides form antigens that can be

❖ The antibodies bind directly to parasite and provide a focus recognized by antigen receptors on certain lymphocytes

for the immunologic molecules and cells. which identify and kill infected cells, leaving healthy cells

❖ Meanwhile, for viruses and other organisms that establish alone.

themselves within body cells, the immune system uses a

different process. 12
 SPECIFIC IMMUNITY
THE IMMUNE RESPONSE B-CELL DEVELOPMENT & ACTIVATION
❖ The immune response (specific immunity) involves the ❖ By the time an infant is a few months old B lymphocytes (B

interaction of two major processes in the body, directed by cells) have completed the 1st stage of their development

two different kinds of lymphocytes (WBC’s): ❖ They are manufactured in fetal liver

➢ Antibody Mediated Immunity (AMI) ❖ They synthesize up to 100,000 antibody molecules that they

➢ Cell Mediated Immunity (CMI;) hold in the cell membrane

❖ The next stage of development occurs in lymph nodes and

ANTIBODY MEDIATED IMMUNITY
spleen and only occurs if the B cell encounters an antigen it
❖ It is otherwise known as the Humoral Immunity.
recognizes.
❖ It is Mediated by B lymphocytes (B-cells)
➢ The specific B cells is activated by exposure to an antigen
❖ It involves the release of proteins called antibodies
➢ The antigen binds to antibodies on cell membrane of B cell
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 SPECIFIC IMMUNITY
B-CELL DEVELOPMENT & ACTIVATION ANTIBODIES
➢ This then triggers clonal selection and multiplication. ❖ Antibodies are proteins called immunoglobins (gamma

➢ Thus produces numerous copies of identical cells with globulin of plasma proteins)

identical antibodies on cell membranes ❖ Each of us has ~ a billion different kinds of antibodies and

❖ The differentiation into plasma cells and memory cells then each of these has a unique shape

occur ❖ Each immunoglobin molecule consists of 4 polypeptide

➢ The plasma cells secrete antibodies 2,000 Ab/sec over chains joined together to form a “Y” shaped molecule

few (4-5) days, then dies ➢ It antibody has 2 or more combining sites

➢ The memory cells do not secrete antibodies live for ➢ Small concave areas at tip of arms of “Y” that are

months or years uniquely shaped and complementary to the epitope

➢ if later the memory cells are exposed to same antigen ➢ Two long (=heavy, ~400 AA’s) chains and two short

they can develop into same kind of plasma cells and (=light, ~200 AA’s) chains linked by disulfide bonds.

secrete antibodies i.e. they “remember” an earlier ➢ A constant region → same AA sequence for all in same

encounter with the antigen class

➢ A variable region → antigen binding sites (tips of Y) 14
 SPECIFIC IMMUNITY
❖ The body uses ~300 gene “pieces” to make >1 Billion
different kinds of antibody molecules
❖ The amino acid sequence determines the specific shape of
these polypeptide chains
❖ This unique shape allows a specific antibody to combine
with specific antigen.
CLASSES OF ANTIBODY MOLECULES
IgG
❖ The most abundant antibody in plasma 75-80% of gamma
globulin also found in internal secretions (synovial fluid,
spinal fluid, peritoneal fluid)
❖ It is effective against bacteria, viruses, and toxins
❖ The plasma levels increase dramatically during secondary
responses
STRUCTURE OF ANTIBODIES
❖ It is the only Ig that can cross placenta 15
 SPECIFIC IMMUNITY
Ig M
Ig E
❖ The largest of the antibodies
❖ It is only found in blood (5-10% of plasma immunoglobins)
❖ It is associated with allergies

❖ The 1st antibody released to blood by plasma cells during primary ❖ It causes certain WBC’s to release histamine, dilates
response capillaries and constricts bronchi
❖ It attacks specific toxins e.g. diptheria, tetanus, botulism toxin Ig D
❖ The blood group antibodies belong to this group → cause ❖ It is very low in concentrations in serum and the levels
agglutination
increase during chronic infections
Ig A
❖ Responsible for the formation of the antigen/antibody
❖ It is Dimer
complex by B-cell activity does not generally destroy the
❖ 10-25% in serum, also found in body secretions: mucus, saliva,
invader
urine, milk, tears
❖ It is active against bacterial and viral infections
❖ it prepares the antigen for the destruction by the non-specific

❖ It inhibits attachment of parasites in gut phagocytosis (WBC’s) triggering complement fixation CMI
❖ The 1st to encounter bacteria in GI tract (T-cell activity)
❖ It can passed to nursing child through the mothers milk
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 SPECIFIC IMMUNITY
Antibodies bind to antigens to cause a variety of possible effects including:

1. Agglutination: bind to antigens on cells to cause them to 5. Stimulates Natural Killer Cells: antibodies coat and
clump together makes it easier for WBC’s to remove mark a cell for destruction by the NK cells = antibody
dependent cell mediated cytotoxicity
2. Precipitation: binds soluble antigens together causing
them to precipitate out of solution thus makes it easier for 6. Complement Fixation: triggers complement reactions
WBC’s to remove them especially against cellular antigens. The cascade reactions
can cause cell lysis, opsonization and inflammatory
3. Neutralization: binds to bacterial toxins (esp. exotoxins) enhancement
and causes them to be non-toxic

4. Prevents viral attachment: binds to viral receptor sites

to prevent viral invasion of cells (doesn’t work for latent
viruses)
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 SPECIFIC IMMUNITY
Primary and Secondary Response Active and Passive Immunity
Primary Response
Active Immunity:
❖ The persons initial exposure to an antigen
❖ The exposure triggers body’s own immune response including
❖ It lag of several days before antibodies begin being
memory cells
produced
Passive Immunity:
❖ The peak production in ~10 days
❖ The subject receives antibodies from another person or animal,
Secondary Response
rather than making them himself
❖ The re-exposure to same pathogen triggers memory cell
❖ This offers immediate protection,
response
❖ It is short term
❖ Memory cells can persist for 20 years or more
❖ There is no active antibody production is stimulated
❖ It has much quicker response much stronger response
Natural and Artificial Immunity ❖ There is no memory develops
Natural: The immune response is triggered due to natural ❖ e.g.
exposure to a pathogen ➢ The foetus gets antibodies from mom
Artificial (acquired): The immune response is triggered by ➢ gamma globulin to treat hepatitis, botulism, snake bites, etc
a medical procedure, e.g vaccination 18
 CELL MEDIATED IMMUNITY
a. specific T cells activated by exposure to a specific antigen
❖ This type of immunity is mediated by T lymphocytes (T-
(on a cell)
cells)
T-cells cannot recognize free antigens in the blood
❖ It involves a more diverse group of cells than for AMI
generally, it need cell to cell contact to work e.g. viral
❖ It is usually, slower to respond
infected cell, cancer cell, bacterial cell
❖ The antigens are usually larger than in AMI
b. initiate clonal selection and multiplication of specific kind
❖ It is most active in: bacterial infections destruction of
of T-cell
malignant tumor cells transplant rejections
c. differentiation into several cell types
❖ T-cells also contain antigen receptors on their cell
Helper T-cells (esp. CD4 cells)
membranes
T-Cell Development and Activation ➢ The most prevalent of all kinds of T cells, 65%
1. It’s probably also first develop in fetal liver from stem cells ➢ Its directly helps T and B cells to function
2. Then move to thymus where they develop and proliferate ➢ Its releases lymphokines: recruit lymphocytes; stimulate
3. And move into lymph nodes and spleen as T- cells differentiation of lymphocytes; help B cells recognize
4. The next stage of development occurs only if T cell antigens.
encounters an antigen it recognizes: ➢ There can be no immune response without them 19
 CELL MEDIATED IMMUNITY
Cytotoxic T- cells (CD8 cells) Cytokines are soluble chemical messengers by which cells of the
➢ It directly kill specific target cells by lysis immune system communicate with each other
➢ It is especially effective against foreign cells, They directs the activities of both B and T cells and phagocytes
cancer cells, fungi, some protozoa and helminths KINDS OF CYTOKINES

➢ It recognizes virally infected cells by viral antigens Chemotactic Factor: attracts macrophages to invaders
on the cells surface Macrophage Activating Factor: tells macrophages to destroy antigen,

Suppressor T-cells (CD8 cells) gives them enhanced antibacterial activity; increased metabolic activity;

➢ They restricts rampant uncontrolled immune more lysosomes and increased phagocytosis
response Lymphotoxin: poison which kills any cell it contacts, but requires direct

➢ They dampens activity of T and B cells cell contact

➢ They brings immune response to an end Migration Inhibition Factor: halts macrophage migration

Delayed Hypersensitivity Cells Interleukin 1: stimulates helper T-cells in presence of antigen; attracts

Memory Cells macrophages in inflammatory response

5. Each T-cells secrete specific kinds of immuno- Interleukin 2: proliferation of TH cells; proliferation and differentiation
active chemicals = cytokines (lymphokines) of B-cells; and activation of Tc and NK cells 20
 CELL MEDIATED IMMUNITY
INTERACTIONS OF AMI AND CMI SYSTEMS
Alpha Interferon: inhibits intracellular viral replication;
❖ Both systems work together to increase the immune response
increases activity of macrophages against microbes and
against specific foreign antigens
tumor cells
❖ as in
Tumor Necrosis Factor: toxic to tumor cells; enhances
➢ The production of antibodies by B-cells often requires
activity of phagocytic cells
helper T-cells
GM-CSF (Granulocyte Macrophage-Colony Stimulating
➢ especially “T-dependent antigens” – proteins such as
Factor): stimulates the formation of RBC’s and WBC’s from
viruses, bacteria, foreign RBC’s, hapten – carrier
stem cells
combinations

➢ It stimulate B-cells to differentiate into plasma cells and

produce antibodies
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 DISORDERS OF IMMUNE SYSTEM
❖ Most immune disorders can be categorized as: Hypersensitivities

1) Autoimmune diseases ❖ An example is allergies

2) Hypersensitivities ❖ Ig E mistakes a harmless foreign substance for a dangerous invader

3) Immunodeficiencies and triggers runny nose, tears, itching, swelling

Autoimmune Diseases ❖ It can be immediate (Acute) mediated by B-cells (IGE → mast cells →

❖ A normal state of self tolerance breaks down due to: histamine and may cause anaphylactic shock or delayed mediated by

➢ self reactive lymphocytes are normally silenced T-cells

during development , in this case some escape Immunodeficiencies

and attack body ❖ The failure of immune system to respond adequately to a pathogen

➢ new self antigens appear due to gene mutation ❖ As in SCID (Severe Combined Immunodeficiency Disease)
or hapten binding congenital (A child born without functional immune system)

➢ foreign antigens resembling self antigens ❖ AIDS (Acquired Immunodeficiency Syndrome) results from infection
trigger antibodies that not only attack foreign with HIV virus

antigens but self antigens as well ❖ usually acquired by sexual contact or drug injections.
❖ HIV targets helper-T (CD4) cells 22
I like to prepare for war and pray for peace
MA DIRA!!!