Antigen
Antigen
1.
Introduction
2.
Antigenicity and specificity
3.
Requirements for immunogenicity
4.
Types of antigens
5.
Superantigen
6.
Adjuvant
Antigen
Introduction
1.Antigen (Ag) - the substances that induce a specific
immune response and subsequently react with the
products of a specific immune response.
2.Properties of Ag -immunogenicity
immunoreactivity
3. Immunogen - A substance that induces a specific
immune response.
Antigen
Introduction
4.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.
Haptens have the property of antigenicity but not
immunogenicity.
5. Tolerogen,allergen
Antigenicity and specificity
Hapten-carrier effect
Antigen
Antigenicity and specificity
Ⅰ. Foreignness
- The immune system normally discriminates
between self and non-self such that only foreign
molecules are immunogenic.
Antigen
Antigenicity and specificity
Ⅱ. specificity
1. Antigenic determinant (epitope)
- the portion of the antigen that binds
specifically with the binding site of an
antibody or a receptor on a lymphocyte.
- the size of an epitope is approximately
equivalent to 5-7 amino acids.
Antigen
Antigenicity and specificity
description
example
One epitope
haptens
Many epitopes of
Many
the same
polysaccharides,
specificity
homopolymers
Many epitopes of
different specificity
proteins
Reprensentation of some possible antigenic structures
Antigen
Antigenicity and specificity
2.structure of epitope
conformational
determinant
sequential determinant
Antigen and vaccine
3. Epitopes recognized by B cells
Epitopes recognized by T cells
B cell epitope
Antigenic peptide
Degradation
T cell epitope
T cell epitope
Natural protein
B cell epitope and T cell epitope
Antigen
T and B cell epitopes in a protein antigen
Antigen
Antigenicity and specificity
T cell epitope
B cell epitope
Receptor
TCR
BCR
MHC
necessary
non-necessary
Character linear short
natural polypeptide
peptide
polysaccharides
Size
8～12 aa(CD8+T)
5 ～15 aa
12～17aa(CD4+T)
5 ～7monosaccharides
Type
linear determinant
conformational
determinant ; linear
determinant
Location everywhere of Ag
surface of Ag
Antigen
Antigenicity and specificity
Ⅲ .common antigen and cross-reaction
Antigen
Factors influencing immunogenicity
A. Contribution of the Immunogen
1.Chemical Composition - In general, the more
complex the substance is chemically the more
immunogenic it will be.
2. Size - There is not absolute size above which a
substance will be immunogenic. In general, the larger
the molecule the more immunogenic it is likely to be.
Antigen
Factors influencing immunogenicity
3.Chemical Complexity- an increase in the chemical
complexity of a compound is accompanied by an
increase in its immunogenicity
4.Conformation and accessibility
5. Physical form - In general particulate antigens are
more immunogenic than soluble ones and denatured
antigens more immunogenic than the native form.
Antigen
Factors influencing immunogenicity
Antigen
Factors influencing immunogenicity
B. 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 nonresponders).
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.
Antigen
Factors influencing immunogenicity
C. Method of Administration
1. Dose - The dose of administration of an
immunogen can influence its immunogenicity.
2. Route - Generally the subcutaneous route is better
than the intravenous or intragastric routes.
The route of antigen administration can also alter
the nature of the response
3. Adjuvants
Antigen
Types of antigens
Th:Thymus-dependent antigen(TD-Ag)
Thymus-independent antigen(TI-Ag)
Relative:Xenogenic antigen
Allogenic antigen
Autoantigen
Heterophilic antigen
Idiotypic antigen
Antigen
Types of antigens
TD-Ag
T-dependent antigens are those that do not directly
stimulate the production of antibody without the help
of T cells. Proteins are T-dependent antigens.
Antigen
Types of antigens
TI-Ag
T-independent antigens are antigens which can directly
stimulate the B cells to produce antibody without the
requirement for T cell help In general,polysaccharides
are T-independent antigens. The responses to these
antigens differ from the responses to other antigens.
Antigen
Types of antigens
TI-Ag
T-independent antigens can be subdivided
into Type 1 and Type 2 based on their ability to
polyclonally activate B cells. Type 1 T independent
antigens are polyclonal activators while Type 2 are not.
Antigen
Types of antigens
Xenogenic Ag
-An antigen found in more than one species.
Antigen
Types of antigens
Allogenic Ag
-individuals of a species differ in alleles (are allogeneic)
and the antigenic diffences will cause an immune
response to allografts.
The antigens concerned are often of the MHC and are
referred to as alloantigens.
Antigen
Types of antigens
Autoantigen
-The antigens of an organisms own cells and cell
products are self antigens to the immune system of that
organisn.
- Clones of immune cells reactive with self antigens are
normally eliminated.
Antigen
Types of antigens
Heterophilic Ag(Forssman antigen)
- A cross-reacting antigen that appears in widely
ranging species such as humans and bacteria.
Antigen
Types of antigens
idiotypic Ag
- The combined antigenic determinants (idiotopes)
found on antibodies of an individual that are
directed at a particular antigen; such antigenic
determinants are found only in the variable region.
antigen
antibody
Antigen may
First antibody selected
Antigenic
be protein,
Mice
for high affinity for
determinant
idiotype1
immunized
carbohydrate,
immunizing antigen,
etc.
made monoclonal
Anti-idiotype antibodies
Raised against idiotype 1
Antiidiotype 1
like antigen
Antiidiotype 1
unlike antigen
Second antibodies
screened for similarity
to original antigen
Superantigen (SAg)
 When the immune system encounters a
conventional TD-Ag, only a small fraction (1 in
106 -104) of the T cell population is able to
recognize the antigen and become activated
(monoclonal/oligoclonal response). However,
there are some Ags which polyclonally activate
some subtypes of the T cells (up to 25%). These
Ags are called superantigens. Such as SEA~SEE,
Mls (minor lymphocyte stimulating Ag)
Types of SAgs
 T cell SAgs:
TCR SAgs: HSP
Endogenous:
TCR SAgs
Mls
Exogenous: SE, etc.
 B cell SAgs: SPA, gp120 (HIV)
bind BCR
Adjuvant
 It is a substance which, when mixed with an
immunogen, enhances the immune
response against the immunogen.
 The use of adjuvants, however, is often
hampered by undesirable side effects such
as fever and inflammation.
 CFA, IFA, BCG, LPS, CpG, etc.
Mitogen
 PHA (phytohemagglutinin, T, human)
 ConA (concanavalin A, T, mice)
 LPS (lipopolysaccharide, B,mice)
 SPA ( staphylococcus protein, B,human)
 PWM (pokeweed mitogen, T/B)