ANTIGENS

Are simple or complex foreign substances which maybe

organic, inorganic or biological agents and they:
o Enhance
o Provoke
o Elicit
The immune response when they enter in the body
parenterally/circulation
Originally from the term antibody generator
When foreign bodies or substances enter the system or body,
it mediates:
o Immediate
o Delayed type of immune response
Various events of defense mechanism will be taking place to
remove the antigen. Humoral and cell mediated will take
place last

CLASSIFICATION OF ANTIGENS
1. Complete antigen
-when these antigen evokes the immune response without
any assistant or carrier molecule
-they possess both qualities:
>immunogenicity
>antigenicity
2. Incomplete antigen
-foreign substances requires carrier molecule
-examples: haptens

HAPTENS
A tiny molecule that has low molecular weight and antigenic
property but lacks immunogenic property

*Immunogenic property- production of antibodies is governed
by carrier molecule
*Carrier molecule- non-antigenic and helps in provoking
immune property
*chemically reactive side chains- azide, sulphonates, arsenate,
carboxylate

ADJUVANTS
Chemical suspension or liquid substances with antigen
(proteineous, exhibit a maximum antigenicity) are dissolved
Used as a carrier compound for haptens making it complete
Chemically which when administered with antigen, enhances
or provokes immunity
Enhances the activation of B-lymphocyte, T-lymphocyte and
macrophages

ADJUVANTS ARE COMMONLY USED AS:
Freuds complete adjuvant
- A water-in-oil emulsion containing killed mycobacteria
Freuds incomplete adjuvant
- Alum (aluminum hydroxide) suspension without any
mycobacteria

Adjuvants can react in several ways:
1. Alter the distribution and persistence of antigen within the
presence of host
2. Stimulate lymphocyte production: non-specific
3. Activate macrophages
4. Alter traffic of circulating lymphocytes

Types of antigens (processed by macrophages):
1. Exogenous antigen
-are trapped by APCs (antigen Processing cells) such as
macrophages, dendritic cells; indicated by phagocytosis
-enters the body or system start circulating in the body
fluid

2. Endogenous antigen
-these are bodys own cell or sub fragments or
compounds, antigenic products that are produced
-classified into:
a.) Autoantigen- synthesized by the body (ex.
Nucleoproteins, nucleic acids)
b.) Alloantigen- same set of molecules with the
genetic variation (ex. Blood group antigen,
HLA)
-processsed by the macrophages which are accepted by
cytotoxic T-cells

Chemical nature of antigen
1. Proteins
-vast majority of antigens and pure proteins/ glycoproteins/
lipoproteins are very good antigen
2. Polysaccharides
-pure polysaccharides and lipopolysaccharides
3. Nucleic acid
-poorly antigenic/immunogenic which is when single stranded
or when complexed with proteins
4. Lipids
-non-immunogenic although they maybe haptens

Factors of immunogenicity
1. Molecular mass
-smaller molecules do not provoke immune system
-MW: 1,000-10,000
-should possess optimum molecular mass or large molecule
which then binds with the receptors and provoke immune
response
-the larger the more immunogenic
2. Antigenic determinant
-antigenic determinant or epitopes are the regions of antigen
which specially binds with the antibody molecule
-the bigger the more immunogenic
3. Foreignness
-the immune system normally discriminates between self and
non-self components such that only foreign molecules are
immunogenic
4. Chemical composition
-the more complex the substance is chemically the more
immunogenic it will be
5. Physical composition
-particulate Ag are more immunogenic than soluble ones/and
denatured Ag more immunogenic than the native form
*particulate- agglutination
*soluble- precipitation
6. Rigidity
-maintenance of the conformational structure of protein Ag:
any alteration leads to loss of reactivity

7. Spatial accessibility of determinant groups
-tertiary structure of protein
-epitopes must be exposed & accessible to the receptor to react
-the more accessible epitope the more immunogenic
8. Insolubility
-refers to the physical state of the Ag
-it must be insoluble and particulate to the immunogenic
9. Ability to be processed & presented with MHC
10. Genetic factors
-Some substances that are immunogenic in one species but not
in another. Similarly, some substances are immunogenic in one
individual but not in others
-The species or individual may lack or have altered genes that
code for the receptor for antigen on B-cell & T-cell
-They may not have

11. Age
-Can also influence immunogenicity usually the very young
and the very old have a diminished ability to elicit & immune
response to an immunogen

CLASSIFICATIONS:
Accdg. To RELATIONSHIP to the host
1. Autologous
-found within the same individual
2. Syngeneic
-antigen found individuals of an inbred strain
(Identical twins)
3. Allogeneic or homologous
-found within the same species but Ag is supplied by
different individuals
*alloantigen/ isoantigen
-occur in certain members of the species but not in others
4. Xenogeneic or heterologous
-antigen found across species boundaries
*heterophil
- Ag that occur in different species
Accdg to its PRESENCE in the host
1. Sequestered Antigen
-autologous substance that do not come in contact
smawith Ab-producing cells since they are in accessible
2. Blood group Antigen
-found in the surface of RBC & in some instances in
secretions
3. Tissue-type Antigen
-genetically endowed & naturally present in the tissue
-examples: HLA Ag,
A & B Ag of the ABO system
4. Tissue-specific Antigen
-Ags that are unique and common to specific organs
-examples: thyroglobulin-thyroid gland
Basic protein- brain
PSA- prostate
Accdg. to ABILITY TO STIMULATE immune response
1. Thymus dependent Antigen
-Antigen is processed by the macrophage and presented
to the T-helper cell
-It provokes immunogenic memory
2. Thymus-independent Antigen
-Antigen that can activate B-cells directly without
intervention of T-helper only IgM Ab and

Accdg. to SEROLOGIC BEHAVIOR
1. Agglutination
-particulate & becomes aggregated or clumped
-example: RBC Ag in BT
2. Hemagglutinogen
-can cause the clumping of RBC
3. Precipitinogen
-soluble & are precipitated or settled out
-example: CRP
Factors contributing to immune responsiveness of a host
1. Dosage of the Ag
2. Frequency of encounter
3. Route of introduction into host
4. Gender
5. Genetic endowment
6. Underlying disease
7. Medication
8. Age

ANTIBODIES
IMMUNOGLOBULIN
Ag receptors on the surface of B-cells
With specific structure, which recognize and bind the antigen
in vivo
Ability of the host to produce immunoglobulin is genetically
endowed
The property of specific recognition of theses Ag in vivo is
determined by genes
The expression of immunoglobulin on a B-cell surface
requires the presence of transmembrane sequence that permit
insertion into a cell membrane
In the absence of this transmembrane sequence occurs in
plasma cells, the Ab become secreted into the plasma

2 HALLMARK PROPERTIES OF ANTIBODY
1. SPECIFICITY
-the Ab is able to recognize and bind its particular Ag
-there is complementariness of the antigenic epitope and
Ab combining site in the recognition and binding
-it is based on physical and chemical interaction
2. DIVERSITY & HETEROGENICITY
-the Ab is able to recognize and respond to vast array of
Ag
-this property derives from the extensive gene
rearrangement with genetic immunoglobulin capable of
recognizing many different Ag
DISTRIBUTION
Plasma (serum in-vitro)
Saliva
Tears
Mucous secretions
Other body fluids(sanctuaries that do not contain Ab)

BIOLOGICAL ACTIVITIES OF ANTIBODY
PRIMARY
o To bind atigens specifically
SECONDARY
o Opsonization
o Neutralization of toxin and viruses
o Complement fixation- lysis of cell(end)

BASIS OF STRUCTURE
4 POLYPEPTIDE CHAIN UNITS
2 heavy chains
-5kinds (IgG, IgM, IgA, IgD, IgE)
2 light chains
-2 types
Disulfide bonds
-interchain
-intrachain
2 IDENTICAL LIGHT CHAINS
MW: approx. 23,000
About 200 amino acids
2 types based on structure differences
o Kappa
o Lambda
A given Ig contain either identical kappa or lambda but never
both
Example: BJP- from malignant plasma cells are lambda

2 IDENTICAL HEAVY CHAINS
MW: approx. 50,000-75,000
Five antigenically distinct isotype of heavy chains based on
structural differences in the carboxy terminal
The heavy chain isotype from the basis of 5 classes of Ig:
IgG, IgM, IgA,IgD, IgE
The carboxy determinants gives the differentiation between
immunoglobulins
Heavy chain classes are subdivided into subclasses of
molecules based on greater degree of amino acids sequence
relatedness
o IgG- IgG
1
, IgG
2
, IgG
3
, IgG
4

o IgA- IgA
1
, IgA
2

o IgM- IgM
1
, IgM
2

o No subclasses for IgE, IgD

DISULFIDE BONDS
S-S binds hold together the 4 polypeptide chains
2 types:
o Interchain S-S bonds
between:
-heavy chains (H-H);
-heavy and light chains (H-L);
-light chains (L-L)
H-H bonds occur primarily at the hinge region and the
carboxy portion of Ig
o Intrachain S-S bond
Occur within the individual chain type
The number of bonds vary depending on the type:
-Light Chain (LC) - 2
-Gamma chain (GC) 4
-Alpha chain 4
-Delta chain 4
-Mu & Epsilon - 5
Stronger that interchain bond
The distribution forms the basis for diversion of
immunoglobulins into domains

REGIONS
Each heavy and light chains consist of 2 segments
1. Variable region
-shows wide variation in amino acid sequence in the
amino terminant portion of the Ig
-the areas of variability in the region are called
hypervariable regions or hot spots
-hypervariable region are involved in the formation of
Ag binding site
-there are atleast 3 hypervariable region in both VH and
VL chains



2. Constant regions
-shows an unvarying amino acid sequence in the
carboxyl or C-terminal portion of the molecule except
for minor inherent difference
-the sections that make up the tips of the Ys arms
vary greatly from one antibody to another, this is called
the variable region

DOMAINS
Each Ig chain consist of series of globular homology regions
enclosed by disulfide bonds
IgA, IgD, IgG chains- 3 constant
Each light chains consist of 2 domains-
o 1 variable
o 1 constant
Domain consists of about 10 amino acid residue

BASIC STRUCTURES
Domains
o VL and CL
o VH and CH
1,
CH
2,
CH
3,
or CH
4

Functional properties
o VL, HL -bind to Ag
o CL CH
1
genetic marker
o CH
2
complement binding site;
Placental transfer (IgG)
o CH
3
or CH
4
binding to FcR complement binding site
(IgM)

FRAGMENTS
Products of enzyme action (cleavage) of papain and pepsin at
the hinge region
1. Fab(fragment Antigen binding)
-entire light chain and the VH and CH
1

-monovalent, can bind Antigen but cannot precipitate

2. Fd fragment
-VH and CH1 of the heavy chain within the Fab
-provides the bulk of the fab

3. Fc (fragment crystallizable)
-contains the carboxy terminal portion of the heavy chain
-binds the carbohydrate moiety
-dictates whether a given Ig can cross the placenta

HINGE REGION
Portion of the heavy chain between CH1 and CH2
Considered aspartate domain because it is not homologous to
any other known domain
Provides the susceptibility to fragmentation by enzymatic
attack

VALENCE AND AVIDITY
VALENCE
-maximum number of antigenic determinant with which Ab
can react
-examples: IgG : 2, Fab: 1
AVIDITY
-the firmness of association between a multideterminant Ab
& Ag produced against it
-the higher the binding site the more firm it is