Antigen

Antigen (Ag)
 It is a substance that reacts with the

products of a specific immune
response.
 Epitope or Antigenic Determinant

That portion of an antigen that
combines with the products of a
specific immune response.
Immunogenicity versus Antigenicity
Immunogen
A substance that induces a specific immune response.
B cells + Ag –--- Effector B cells +Memory B cells

Plasma cells (secretes Ab)
T cells + Ag ---- Effector T cells + Memory T cells

CTL’s, T(H) etc secretes cytokines
cytotoxic factors
 All molecules that have the property
of immunogenicity also have the
property of antigenicity, the reverse
is not true.
 Eg: Haptens
Hapten
 A substance that is non-immunogenic but
which can react with the products of a
specific immune response. Haptens are
small molecules which could never induce
an immune response when administered
by themselves but which can when
coupled to a carrier molecule.
Free haptens, however, can react
with products of the immune response
after such products have been elicited.
Haptens have the property of antigenicity
but not immunogenicity.
Haptens are valuable research and
diagnostic tools
Contribution of the Immunogen
1. Foreignness
2. Molecular Size
There is not absolute size above which a substance will be
immunogenic. However, in general, the larger the molecule the more
immunogenic it is likely to be.
3. Chemical Composition
In general, the more complex the substance is chemically the more
immunogenic it will be. The antigenic determinants are created by
the primary sequence of residues in the polymer and/or by the
secondary, tertiary or quaternary structure of the molecule.
 Physical form
In general particulate antigens are more immunogenic than soluble
ones and denatured antigens more immunogenic than the native
form.
 Degradability
Antigens that are easily phagocytosed are generally more
immunogenic. This is because for most antigens (T-dependant
antigens) the development of an immune response requires that the
antigen be phagocytosed, processed and presented to helper T cells
by an antigen presenting cell (APC).
Contribution of the Biological System
 1. Genetic Factors
Some substances are immunogenic in one species but not
in another. Similarly, some substances are immunogenic in
one individual but not in others (i.e. responders and non-
responders). The species or individuals may lack or have
altered genes that code for the receptors for antigen on B
cells and T cells or they may not have the appropriate
genes needed for the APC to present antigen to the helper
T cells.
 2. Age
Age can also influence immunogenicity. Usually the very
young and the very old have a diminished ability to mount
and immune response in response to an immunogen.
Method of Administration
 1. Dose
The dose of administration of an immunogen can
influence its immunogenicity. There is a dose of
antigen above or below which the immune
response will not be optimal.
 2. Route
Generally the subcutaneous route (to a local
lymph node) is better than the intravenous (to
spleen) or intramuscular routes. The route of
antigen administration can also alter the nature
of the response
Adjuvants
(to help)
 Substances that can enhance the
immune response to an immunogen
are called adjuvants. The use of
adjuvants, however, is often
hampered by undesirable side effects
such as fever and inflammation.
Adjuvants exert following effects:
 Antigen persistence is prolonged
 Costimulatory signals are enhanced
 Local inflammation is increased
 The nonspecific proliferation of

lymphocytes is stimulated
Examples of adjuvants
 Aluminium potassium sulphate (Alum) only
adjuvant used for human use
 Freund’s incomplete adjuvant contains Ag in

aqueous solution, mineral oil and an emulsifying
agent.
 Freund’s complete adjuvant contains heat killed

Mycobacterium
Properties of B cell epitopes

- Usually
dependent on the native, tertiary conformation
of the antigen (PROTEIN FOLDING)
 - Must be accessible - tend to be on the “surface” of the

antigen (hydrophilic)
 - May be made of sequential or non-sequential amino acid

sequences (epitopes made up of non-sequential amino
acid sequences are called “conformational epitopes”).
 - Binds to soluble antigen, No MHC molecule requirement
 - Large antigens contain multiple, overlapping B cell

epitopes some of which are immunodominant.
 Some epitopes,called immunodominant,induce a more pronounced

immune response in a particular animal than other epitopes.
Properties of T cell epitopes
 - Involves a tertiary complex: T cell receptor,
antigen, and MHC molecule
 - Internal linear peptides (hydrophobic) produced

by processing and bound to MHC molecules
 - Does not bind to soluble antigen, APC

processing
 - Recognize mostly proteins but some lipids and

glycolipids can be presented on MHC-like
molecules
Pattern-Recognition Receptors (PRR)
 - Receptors of the innate immune system

 - Recognize unique antigens (motifs) in
microorganisms (Danger Signals!!!)
 - These antigens are absent in the host
(nonself)
 - Several Pattern-Recognition Receptors
(PRRs) identified
 - BIO401: Toll-like receptors (TLRs)
Properties of antigen and antibody
reaction
 Specificity and diversity
 Affinity Constants: Because Ab/Ag binding is reversible

(on/off) it follows the Law of Mass Action and you can
determine an Equilibrium Constant (K) or a Dissociation
Constant (Kd).
 Ab Affinity vs. Ab Avidity:

• The affinity of an Ab is the pure measure of the on/off rate
between Ag and Ab combining site
• In the real world, Abs have 2-10 combining sites, and some
Ags have multiple epitopes to which the Abs might bind (multi-
valency both ways).Avidity is the term for the true, overall
strength of attachment of an Ab to its Ag.
Immunoglobulin(Ig)
 Ig can recognize almost every kind of biologic
molecule including simple compound such as
sugars, lipids, autacoids and hormones as well as
macromolecules such as complex carbohydrates,
phospholipids, nucleic acids and proteins.
 Two forms of Igs:

 membrane-bound form(BCR)
 secreted form(Antibodies)
 Membrane and Secreted Forms of Ig Heavy

Chains differ in AA seq of COOH end of their
Heavy Chains.
Immunoglobulin(Ig)
 The secreted forms of IgG and IgE are
monomers
 The membrane forms of all isotypes are
monomers
 The secreted forms of IgA and IgM are
covalently bound multimers, joined
through the "tail pieces" at the carboxy
ends of H chains
 IgM and IgA also have a "J piece" which is
S-S bonded to the tail ends.(stablizing)
Classes of antibodies
 IgG - provides long-term immunity or protection

 IgM - first antibody produced in response to an antigenic
stimulus
 IgA - found in secretions. Protects against infections in

urinary, GI, and respiratory tracts
 IgE - involved in allergic reactions
 IgD - not much known about it. Surface receptor of B

lymphocytes
 Most important classes of antibodies in blood banking are

IgM and IgG, and to a certain extent IgA
https://www.youtube.com/watch?v=AERyetmR7FY
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Antigen (Ag)

 It is a substance that reacts with the

 Epitope or Antigenic Determinant

B cells + Ag –--- Effector B cells +Memory B cells

T cells + Ag ---- Effector T cells + Memory T cells

 Costimulatory signals are enhanced

 Local inflammation is increased

 The nonspecific proliferation of

 Freund’s incomplete adjuvant contains Ag in

 Freund’s complete adjuvant contains heat killed

 - Must be accessible - tend to be on the “surface” of the

 - May be made of sequential or non-sequential amino acid

 - Binds to soluble antigen, No MHC molecule requirement

 - Large antigens contain multiple, overlapping B cell

 Some epitopes,called immunodominant,induce a more pronounced

 - Internal linear peptides (hydrophobic) produced

 - Does not bind to soluble antigen, APC

 - Recognize mostly proteins but some lipids and

 - Receptors of the innate immune system

 Specificity and diversity

 Affinity Constants: Because Ab/Ag binding is reversible

 Ab Affinity vs. Ab Avidity:

 Two forms of Igs:

 Membrane and Secreted Forms of Ig Heavy

 IgG - provides long-term immunity or protection

 IgA - found in secretions. Protects against infections in

 IgE - involved in allergic reactions

 IgD - not much known about it. Surface receptor of B

 Most important classes of antibodies in blood banking are

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