IMMUNE SYSTEM

Cells of the Immune System

• Lymphocytes – B cell
- T cell
- large granular lymphocyte
• Phagocytes – mononuclear phagocytes
- neutrophils
- eosinophils
• Auxillary cells – basophils
- mast cells
- platelets
• Tissue cells
 Components of the Immune
System
• ADAPTIVE IMMUNE RESPONSE
1. Cell mediated immunity
2. Humoral or Antibody mediated immunity

Features
1. Specificity
2. Diversity
3. Memory
• LYMPHOCYTES
- responsible for the specific immune
response
- initiate adaptive immune response
- derived from stem cell
- T cells (Thymus); B cells (Marrow)
• B cells
- recognizes a particular antigen using
receptor molecules on its surface
- differentiate into plasma cell
- produce large amount of soluble
receptor molecules (antibody)
- antibodies help activate other parts of
the immune system
• T cells
- recognize antigen in association with markers
on host cells (T cell antigen receptor/TCR)
Types (function)
1. interacts with B cells and help them divide,
differentiate and form antibodies (T Helper cells)
2. interacts with phagocytes and help them
destroy pathogen (T Helper cells)
3. responsible for the destruction of host cells
infected by virus and intracellular pathogens (T
Cytotoxic cells)
 ANTIGEN
• an organism, a molecule, or part of a molecule
that is recognized by the immune system
• foreign molecules
• may be simple/complex, protein, carbohydrate or
synthetic origin

Immunogen – causes an immune response

Hapten – simple, usually non-biologic, can bind to
immune receptors but cannot cause an immune
response
Tolerogens – in normal, healthy state,
tolerance to self molecules develop;
induce adaptive immune
unresponsiveness; exposure results in
diminished response
Epitope / Antigenic Determinants
- refers to an area on an antibody with
which an antibody can react
- discrete regions or the smallest part of
an antigen recognized by somatically
generated B and T cells
Lymphocytes may recognize multiple
epitopes in one antigen
Adjuvant
- substances that provide a variety of
stimuli to the immune system
- enhance the amount of immune
response when given along with an
antigen
- increases the magnitude of the response
 Immunogenicity
Factors
1. Size: greater than 10KDa are more
immunogenic
2. complexity: complex proteins have
numerous and diverse epitopes (more
epitopes)
3. conformation and accessability: epitopes
must be “seen” and accessible to the
immune system
Chemical properties: proteins are more
immunogenic than carbohydrates, steroid
and lipids; amino acids and haptens are
generally not immunogenic
RECOGNITION OF FOREIGN ANTIGEN IS
THE HALLMARK OF THE SPECIFIC
ADAPTIVE IMMUNE RESPONSE

Molecules involved
1. Immunoglobulins
2. T-cell antigen receptors(TCR)
 ANTIBODIES
• synthesized by B lymphocytes (B cells)
• secreted by plasma cells (differentiated B
cells)
• applied to immunoglobulin molecules with
specificity for an epitope (antigen)
• immobilize antigen and render them
harmless
• “tag” antigen for destruction and removal
by other components of the immune
system
BASIC STRUCTURE
• four polypeptides
• 2 identical light chains
and 2 identical heavy
chains linked by
disulfide bonds
forming a monomeric
unit
• LIGHT CHAINS • HEAVY CHAINS
- L chains - H chains
- has both a variable - has 1 variable
domain & constant domain & 3 constant
domain domain
- made up of amino
acids and disulfide
bonds
- variations in amino
acid
sequence(variable)
 Antigen-binding sites
• formed by the • concerned with the
variable domains of binding to the antigen
both the light and • specific
heavy chains – forms
a pocket
Classification of Antibodies
IgG IgM
- major Ig in the normal - 10% of Ig pool
human serum - has a pentameric
- 70 to 75% structure
- single molecule with 4 - largely confined to the
subclasses intravascular pool
- distributed evenly - predominant “early” Ig
between the intravascular during immune response
and extravacular pool
- major antibody of the
secondary immune
response
IgA
- 15 to 20% of Ig pool
- mainly a monomer in
humans
- predominant in mucous
secretions such as saliva,
colostrum,
tracheobronchial and
genitourinary secretions
- 3 subclass
IgD
- less than 1% of total
plasma Ig
- present on membranes
of B cells
- precise biological
function is unknown
- play a role in antigen-
triggered lymphocyte
differentiation
IgE
- scarce in serum
- found on the surface
membrane of
basophils and mast
cells
- associated with
helminthic parasites
and with allergic
diseases
 Functional Properties
Fab region Fc region
- binds to antigen - binds the Ig to host
tissue and various
cells of the immune
system (phagocytic
cells and components
of the complement
system)
 Enzymatic Fragmentation
• Papain
3 fragments
2 bound to specific Ag (Fab:
fragment antigen binding)
1 crystallized in soln (Fc: fragment
crystallizable)
• Pepsin
1 fragment which bound 2 antigen
F(ab)2
Fd – heavy chain portion of the Fab
Theories of Antibody Formation
• Instructive Hypothesis
suggested that a flexible antibody
molecule is acted by an antigen to form a
complementary part
• Selective Theory
put forward the idea of clonal selection –
each lymphocyte produce one type of Ig
only and the antigen selects and
stimulates cells of the Ig type
 MAJOR HISTOCOMPATIBILITY
COMPLEX
• MHC
• also called Human Leukocyte Antigen
• segment of chromosome 6 containing several
genes that are critical to immune function
• include genes encoding a variety of enzymes and
structural molecules needed for the activation and
function of B and T cells.
• a region of DNA that encodes a group of molecules
that recognize antigens
 Major Classes
• HLA Class 1
HLA – A; HLA – B; HLA - C
• HLA Class 2
HLA – DR; HLA – DQ; HLA - DP
• HLA Class 3
• LOCI
- different alleles can be inherited
- recognition by antibodies to specific HLA
antigen or by DNA probes
` - (antibody) 26 HLA-A; 59 HLA-B; 10HLA-
C; 22HLA-DR; 9HLA-DQ; 6HLA-DP
 Histocompatibility Testing

Histocompatibility Testing
1. HLA antigen typing (tissue typing)
2. screening recipient for anti-HLA
antibodies (antibody screen)
3. lymphocyte crossmatch (compatibility
test)
 HLA Antigen Typing
• identifies antigens on the WBC’s that
determine tissue compatibility for organ
transplant
• serological and DNA methods
Purpose
1. provide evidence of tissue compatibility
(antigens on the surface of leukocytes of
the recipient matched with those from
donor)
2. determine parentage (paternity testing)
 Antibody Screen
• performed in order to detect antibodies in
the recipient’s serum that reacts with HLA
antigen
• microcytotoxicity test
• reported as the percentage of panel
reactive antibodies (PRA) – number of
wells reactive with patient’s serum
 Crossmatch Test
• peripheral lymphocytes from the donor are
separated into B and T lymphocytes
• serum from recipient is mixed with T-cells
or B-cells from donor
• positive findings – presence of preformed
antibodies in the recipient that are active
against the donor tissue
• reported as compatible or incompatible