At the end of the lesson, students should be able to :

• Define antibody, antigen, cell-mediated immune

response and humoral immune response.

• Describe the cell-mediated immune response and

humoral immune response.

• Describe briefly the lymphatic system and how it

functions in immunity.
Antigen
any substances capable of stimulating an
immune response, usually a protein or a
large carbohydrate that is foreign to the
body.
Characteristics of antigens :

• Foreign to host – chemical groupings (markers) must be

different from those on host cells (receptors) – called
antigenic determinations or epitopes.

• Posesses two or more antigenic determinations ( 2 bivalent,

many multivalents).

• May be soluble, particular, cellular

• Examples :
– Soluble toxins, enzymes, venoms, plant extracts, medications, foreign
serums (proteins)
– Particulate – cell structures, (cell walls, flagella, capsules, pili),
viruses, mold spores, pollens, house dusts.
– Cellular – microorganism, viral infected host cells, foreign tissue cells,
neoplastic cells, altered hostcells.
• As antigens are foreign substance; they are not part of the
body’s chemistry.

• Most antigens are proteins, nucleoproteins, lipoproteins,

glycoproteins, or large polysaccharides with a molecular
weight greater than 10,000.
 Antibody
 Protein compounds (immunoglobulins)
produced by plasma cells in response to
specific antigens and having the capacity
to react against the antigens.
Structure of Antibody
• A single bivalent antibody unit is a
monomer.
• Most antibody monomers consists of
four polypeptide chains. Two are heavy
chains and two are light chains.
• Heavy chains – 2 chains – 400 amino
acids.
• Light chains – 2 chains – 200 amino
acids.
• Amino acid chains are held together by disulphide bonds.

• Within each chain is a variable (V) region, where antigen binding

occurs, and a constant (C) regions, which serves as a basis for
distinguishing the classes of antibodies.

• Antibody monomer is Y – or T-shaped; the variable regions from the

tips and the constant regions form the base and Fc fragment.

• The Fc region can attach to a host cell or complement.

 Immunoglobulin Classes
* Based on differences in structure of constant regions on
heavy chains, antibody can be divided into 5 classes :
IgG
• Most abundant (80% - 85% of total serum) – largely
responsible for immunity – are monomers

• Occurs primarily in plasma

• Smallest – crossing the placenta -> temporary protection

to newborn

• Longest lasting

• Provide naturally – acquired passive immunity

• Neutralize bacterial toxins

• Participate in complement fixation

• Enhance phagocytosis.
IgM
• Largest antibody – consists of 5 basic Y
molecules (monomers) held together by
a joining or J-chain and disulphide
bonds (pentameric structure)

• 5% - 10% of total serum Ig

• 10 combining sites – most reactive

• First to be produced

• Involved in agglutination and

complement fixation.
IgA
• 10% - 15% of total serum Ig – are
monomers

• Secretory antibody – primarily occurs

in secretions ( mucus, saliva,
gastrointestinal tract, human milk)

• Protects mucosal surfaces

(membranes) ; protect newborns,
from invasion by pathogens

• Consists of 2 basic Y molecules with 4

combining sites.
IgD
• Single Y molecule – less than 1%

• Binds to surface of B lymphocytes

(antigen receptor on B cells)

• Believe to function as immune

receptors – react with antigen
determinants which then initiates
development humoral immunity

• No known function in serum.

IgE
• ~0.002% of total serum Ig
• Y molecules with 2 sites

• Fc stem region binds to mast cells and

basophils

• Involved in allergic reactions resulting

in the release of histamine and other
chemical mediators

• Normally occurs in minute

concentrations but some individuals
produce abnormal higher levels.
Fig. 4 - Structure of immunoglobulin G

The polypeptide chains

making up the light and
heavy chains are here
drawn as cylinders. The
antigen binding site is at
the amino ends of the L
and H chains. Papain
digestion of IgG splits the
molecule into Fab, Fc,
and Fd fragments.
Due to the development of T Cells, Tc (CD8, T8) lymphocytes which
respond to intracellular antigens.

* Tc lymphs. Become sensitized to specific antigen.

* Associated with tissues.
Develops in response to :
* Antigen on whole (intact) cells.
* Antigen usually introduced directly into tissues
* Example : intracellular bacteria, system is fungi,
protozoans, helminths, viral infected host cells, neoplastic
cells, foreign (transplanted) tissue cells, altered host tissue
cells.
3. Chemical Messengers of Immune Cells : Cytokines

* Cells of the immune system communicate with each other

by means of chemicals called cytokines.
* Interleukins (IL) are cytokines that serves as
communicators between leukocytes.
* Interferens are cytokines that protect against viruses.
* Chemokines cause leukocytes to move to the site of
infections.
* Cytokines may be useful in treating tumors.
* found in body fluids.

* involves antibodies produced by B cells (B-lymphocytes) in

response to a specific antigen.

* Antibodies primarily defend against bacteria, viruses, and toxins

in blood plasma and lymph.

* Bone marrow stem cells give rise to B cells.

* Mature B cells migrate to lymphoid organs.

* Mature B cells recognizes an antigen with antigen receptors.

 Fig 5 - Life history of T cells and B cells
In the development of T cells and B cells in there is a pogression from an
antigen-independent to an antigen-dependent state. Macrophages play a
critical role in the functions of both lymphocyte types.
1. Lymph system is closely associated with cardiovascular
system.

2. Functions

a. Takes up excess tissues fluid and retuns it to

bloodstream.

b. Absorbs fats in intestinal villi and transports them to

bloodstream.

c. Helps defend body against disease.

3. Lymphatic Vessels Transport One Way
* Most body regions richly supplied with lymphatic capillaries.
* Structure of larger lymph vessels similar to veins including presence
of valves.
* Movement of lymphs depends upon skeletal muscle contraction,
similar to veins.
* Lymph capillaries take up unabsorbed tissue fluid.
* Edema is local accumulation of fluid in tissue causing swelling.
* Once within lymph vessels, fluid is termed lymph.
* Lymphatic capillaries join to form two ducts:
i. Right lymphatic duct serves right arm, right side of
head and neck, and right thoracic area.
ii. Larger thoracic duct serves left arm and thoracic
area, abdomen and lower body.
h. Both ducts drain into the subclavian veins in the thorax.
Lymph Nodes
• Small (1- 25 mm) round structures.
• Found at points along lymphatic vessels.
• Have fibrous connective tissue capsule with incoming
and outgoing lymphatic vessels.
• Each nodule contains sinus filled with lymphocytes and
macrophages.
• Occurs singly or in groups of nodules :
– Tonsils are located in back of mouth on either side
– Adenoids on posterior wall above border of soft palate
– Peyer’s patches found within intestinal wall.

* Lymph nodes occur in regions : axillary nodes in armpits

and inguinal nodes in groin.
Spleen
• Located in upper left abdominal cavity just beneath diaphragm.
• Structure similar to lymph node; outer connective tissue divides organ
into lobules with sinuses.
• Lobules contain sinuses filled with blood.
• Blood vessels of spleen can expand; therefore spleen functions as blood
reservoir; makes blood available in times of low pressure or oxygen
need.
• Spleen has red pulp containing RBCs,
lymphocytes, and macrophages; functions to
remove bacteria and worn-out blood cells.
• White pulp contains mostly lymphocytes. Both
help to purify the blood.
Thymus
• Located along trachea
behind sternum in upper
throax.
• Larger in children;
disapears in old age.
• Divided into lobules
where T lymphocytes
mature.
• Interior (medulla) of
lobule secretes thymosin
thought to aid T cells to
mature.
Red Bone Marrow
• Site of origin of all types of blood
cells.
• Five types of white blood cells
(WBCs) function in immunity.
• Stem cells continuously divide to
produce cells that differentiate into
various blood cells.
• Most bones of children have red
blood marrow.
• In adult, red marrow is found in the
skull, sternum, ribs, clavicle, spinal
column, femur, and humerus.
• Red blood marrow has network of
connective tissue where reticular
cells produce reticular fibers; these
plus stem cells fill sinuses;
differentiated blood cells enter
bloodstream at these sinuses.
Helper T cell

virus

© UPP Kolej MARA Seremban

At the end of the lesson, students should be able to :
• Describe the cell-mediated immune response and
humoral immune response.
• Describe self and non-self recognition,
autoimmunity and its significance in medicine.
E.g., tissue grafting.
 (What do antibodies do?)

Antibodies do not directly destroy an antigenic

pathogen. The antibody binds to the antigen to form
an antigen-antibody complex, which tags the invader
for destruction by one of several effector mechanisms.
In complement fixation,
• antibodies combine with complement proteins;
• this combination activates the complement proteins,
• which produce lesions in the foreign cell’s membrane that
result in cell lysis.
Graph showing antibody formation in repeated infection

© UPP Kolej MARA Seremban

1. When a person is exposed to an antigen for the first time, there is
a lag of several days before specific antibody becomes detectable.
This antibody is IgM.
2. After a short time, the antibody level declines. These are main
characteristics of the primary response.
3. If, at a later date he or she is re-exposed to the same antigen,
there is a far more rapid appearance of antibody, and in greater
amount. It is of the IgG class and remains detectable for months
or years. These are the features of the secondary response.
4. If, at the same time that he is re-exposed to an antigen, he is
exposed to a different antigen for the first time, the properties of
the specific response to this antigen are those of the primary
response.
 10 Immune Response
1. Following the first exposure to a
foreign antigen, a lag phase occurs in
which no antibody is produced, but
activated B cells are differentiating
into plasma cells. The lag phase can
be as short as 2-3 days, but often is
longer, sometimes as long as weeks or
months.
2. The amount of antibody produced is
usually relatively low.
3. Over time, antibody level declines to
the point where it may be
undetectable.
4. The first antibody produced is mainly
IgM (although small amounts of IgG
are usually also produced).
20 Immune Response
• If a second dose of the same antigen
is given days or even years later, an
accelerated 20 or anamnestic
immune response (IR) occurs. This
lag phase is usually very short (e.g. 3
or 4 days) due to the presence of
memory cells.
2. The amount of antibody produced
rises to a high level.
3. Antibody level tends to remain high
for longer.
4. The main type of antibody produced
is IgG (although small amounts of
IgM are sometimes produced).
1. Macrophage – antigen processing cells

a. Phagocytosis – engulfs and digests antigen

b. Antigenic determinants presented on cell membrane
c. Secrets Interleukin I – attracts additional macrophages
and lymphocytes

2. TH Lymphocytes (TH = helper T)

a. Secrete Interleukin II
b. Stimulates proliferation and differentiation B lymphocytes

Picture
3. B Lymphocytes

a. React with antigenic determinants

b. Proliferate forming clone identical immature B
lymphocytes
c. Differentiate into plasma cells and memory cells

4. Memory Cells

a. Secrete antibodies
b. Antibodies react specifically with anigen
5. Memory Cells

• Some of immature B lymphocytes. Develop into memory

cells.
• React specifically with the same antigen upon subsequent
exposure (subsequent contact with the same antigen
results in a very high antibody titer and is called the
secondary, anamnestic, or memory response. The
antibodies involved are primarily IgG).
• Proliferate rapidly forming plasma cells and memory cells.
• Plasma cells produced same antibodies  react
specifically with antigen.
• T cells and B cells that react with self antigens are
destroyed during fatal development; this is called clonal
deletion. Picture
 Produced in response to antigen

• The amount of antibody in serum is called the antibody

titer.
• Following a primary exposure - no antibody produced for
approximately one wek.
• Gradual increase in antibody level, in 2nd week peaks and
level off.
• Eventually antibody level decreases.
• Antibody level remains low till next exposure to the same
antigen.
• Anamnestic response- following subsequent exposure 
immediate increase in antibody to even higher level; 1 to 3
days. (Refer Primary response)
• T – dependent antigens
- require TH
lymphocytes

• T – independent antigens
- do not
require TH lymphocytes react
directly with B lymphocytes.

© UPP Kolej MARA Seremban

 (Cell – mediated Immunity)

1. Macrophage – antigen processing cells

a. Phagocytosis – cells engulfs and

digests antigen
b. Antigenic determinants
presented on cell membrane
c. Secrets Interleukin I ( IL1) –
attracts macrophages and
lymphocytes

2. TH Lymphocytes
• React with antigenic determinants on cell membrane
• Secrete Interleukin II - stimulates proliferation and
differentiation TC lymphocytes

© UPPK Kolej MARA Seremban

 (Cell – mediated Immunity)

3. TC Lymphocytes

• React with antigenic determinants

• Profilerate forming clone identical immature TC

• Differentiate into “activated” TC lymphocytes and memory

cells
• “Activated” TC lymphocytes react specifically with antigen
• Secrete perforin – causes lysis of cell membrane

Picture

© UPP Kolej MARA Seremban

 (Cell – mediated Immunity)
5. Memory Cells

• Some of immature TC lymphs. Develop into memory cells

• React specifically with the same antigen upon subsequent
exposure
• Proliferate rapidly forming “activated” TC lymphocytes
and memory cells.
• Activated” TC lymphocytes react specifically with antigen
 secrete perforin  causes lysis of cell membrane
6. Time

a. Following primary exposure – 2 to 3 weeks

b. Following subsequent exposure – 3 to 5 days

© UPP Kolej MARA Seremban

© UPP Kolej MARA Seremban
Is the simplest mechanism. The antibody blocks
viral attachment sites or coats bacterial toxins,
making them ineffective. Phagocytic cells
eventually destroy the complex.

© UPPK Kolej MARA Seremban

 In opsonization, bound antibodies enhance
macrophages attachment to and phagocytosis of
microbes.
© UPP Kolej MARA Seremban
 Antibody-mediated agglutination neutralizes
and opsonizes the microbes. Each antibody has
two or more antigen-binding sites and can cross-
link adjacent antigens. The cross-linking can
result in clumps of bacteria being held together
by the antibodies, making it easier for phagocytes
to engulf the mass.
© UPP Kolej MARA Seremban
 Precipitation is similar to agglutination but
involves the cross-linking of soluble antigen
molecules instead of cells; these immobile
precipitates are easily engulfed by phagocytes.

© UPP Kolej MARA Seremban

© UPP Kolej MARA Seremban
An Overview of The Immune Response

© UPP Kolej MARA Seremban

© UPP Kolej MARA Seremban
© UPP Kolej MARA Seremban
 Self
&
non-self recognition
 OBJECTIVES:
Students should be able to:

3. Describe what is major histocompatibility

complex(MHC).

5. Differentiate self and non-self recognition.

7. Describe autoimmunity and its significance in

medicine.
• Major histocompatibility
complex ( MHC )

• Autoimmunity
 MAJOR
HISTOCOMPATIBILITY
COMPLEX (MHC)
• Sometimes referred as human leukocyte
antigens ( HLA ) in humans.

• What is MHC?
A group of glycoproteins embedded
in the plasma membrane of the cells.
An important “ self-makers” coded by a
family of genes.

There are at least 20 MHC genes, at least 100

alleles for each genes.

The probability that two individuals will have

matching MHC sets is virtually zero unless
they are identical twins.
 TWO MAIN CLASSES OF
MHC MOLECULES
• Class I MHC molecules -
located on all nucleated cells
of the body.

• Class II MHC molecules –

found only on specialized cells,
such as macrophages, B cells
and activated T cell.
• MHC’s function in antigen presentation by
binding to an antigen, thereby facilitating
antigen binding to a T cell

• Class MHC I molecules facilititate antigen

binding to cytotoxic T cells.

• Class MHC II molecules facilitate antigen

binding to helper T cells.
• The body’s immune defenses do not normally
attack tissues that carry a “self-marker”.
Rather, immune cells and other body cells
coexist peaceably in a state known as self-
tolerance.

• But when immune defenders encounter cells

or organism carrying molecule that say
‘foreign’, the immune troops move quickly to
eliminate intruders.
• Non-self
includes
pathogens and
cells from
other
individuals of
the same
spesies.
Tissue grafts and organ
transplantation
Tissue grafts and organ transplantation

1. The MHC is responsible for stimulating

the rejection of tissue grafts and organ
transplants.

Because MHC creates a unique protein

fingerprint for each individual, foreign
MHC molecules are antigenic, inducing
immune responses against the donated
tissue or organ.
To minimize rejection, attempts are
made to match MHC of tissue donor
and recipient as closely as possible.

In the absence of identical twins,

siblings usually provide the closest
tissue-type match.
1. In addition to MHC matching, various
medicines are necessary to suppress
the immune response to the
transplant.
However, this strategy leaves the
recipient more susceptible to
infection and cancer during the
course of treatment.
More selective drugs, which
suppress helper T cell
activation without crippling
nonspecific defense or T-
independent humoral responses,
have greatly improved the
success of organ transplant.
1. In bone marrow transplants, it is the
graft itself, rather than the host,
that is the source of potential
immune rejection.
Bone marrow transplants are used
to treat leukemia and other
cancers as well as various
hematological diseases.
 Prior marrow transplants, the
recipient is typically treated with
irradiation to eliminate the
recipient’s immune system, leaving
little chance of graft rejection.

However, the donated marrow,

containing lymphocytes, may react
against the recipient, producing graft
versus host reaction, unless well
matched.
AUTOIMMUNE DISEASES
The Body Attacks Itself
• Autoimmunity arises when the ‘immune’
system fails to distinguish between ‘self’
and ‘non-self’ (foreign) cells, and attacks
‘self’, or body tissues.

• Causes generally not known, but may

involve genetic, viral and environmental
factors or after recovery from infection.
• Some bacteria produce toxic
product that cause T cells to
bind to macrophages; perhaps
this is how T cells learn to
recognize the body’s own
tissues, which they now attack.
e.g. Autoimmune diseases

1. Myasthenia gravis
2. Multiple sclerosis
3. Rheumatoid arthritis
4. Systemic lupus
erythematosus
5. Heart damage
following rheumatic
fever & Type I
diabetes.
Rheumatoid Arthritis of the Hands
Rheumatoid arthritis can result in severe
deformation of the hands, wrists, feet,
ankles, hips, and shoulders. The
characteristic swelling, pain, and restricted
movement
 Multiple sclerosis
In this illness the myelin sheath covering
the spinal cord is destroyed, leading to
difficulty in walking and other movements.
The damage in multiple sclerosis is not
produced by an auto antibody but by a
lymphocyte that reacts directly with the
protective sheath.
 Myasthenia gravis
Myasthenia gravis is a neuromuscular disease
that causes weakness and fatigue, most
commonly in the muscles of the eyes, face,
throat and limbs. MG is an acquired disease,
meaning it isn't inherited as a genetic
disease.

The word "myasthenia" means muscle

weakness.
Systemic lupus erythematosus
 OBJECTIVES

At the end of presentation, students should be able to:

 Defined AIDS

 Explain the causative agents

 Explain the process of infection

 Explain the process of virus replication virus

 Dictate the symptoms, disease and its prevention

Definition of AIDS

• Acquired Immune
Deficiency Syndrome
(AIDS )

• Causes the depression of

the immune response

• Due to HIV (Human

Immunodifiency Virus)
• Individual with AIDS are highly susceptible to
opportunistic diseases and cancer

• Mortality rate approaches 100%

• A person having HIV can be a carrier and not

manifest AIDS sympthom
 HIV Infection
• HIV infests cells, including
TH cells, which carry the
CD4 receptor on their
surface.

• After entry, HIV RNA is

reversed-transcribed

• The product DNA is

integrated into the host cell
genome

• The viral genome directs

the production of new virus
particles
HIV is not eliminated from the body for several
reasons :

 The latent virus is invisible to the immune system

 The virus undergoes rapid mutation

The population of T-cells eventually declines to
the point where cell mediated immunity collapses

 Secondary infection characteristics of HIV

infection develop ( Pneumocystis pneumonia and
Karposi’s carcoma )
Vertical Unprotected
transmission from Injection drug use sexual
mother to child intercourse
in utero with infected
during delivery partners
breastmilk

HIV Transmmission
 Symptoms
• Nausea • Easy bruising
• Diarrhea • Pink and purple
• Unexplained weight blotches, flat and
loss/ fatique raised, usually ainless
• Swollen glands found beneath the
skin or mucous
• Fever membranes such as
• Shaking/chills lasting nose,mouth, eyes and
several weeks rectum
• Blurred vision • Lung infection or
cancer
Diagnosis
HIV antibody test (although
not a test for AIDS), it can be
used to to test the presence
of antibodies
For conclusive results,
testing for HIV must take 6
months after possible
exposure
Retesting is necessary in
case of negative results after
3 months
 Prevention
• Do not engaged yourself in any oral,anal or vaginal
intercourse with one or multiple sexual partners who is
infected with AIDS

• If intending so, practise safe sex

• Reduce the number of sexual partners

• Avoid exchange of bodily fluids

• Ask health status of your partners

• Avoid sexual contact with mind altering substances

• Maintain a healthy lifestyle

End of this chapter