Antigen by Dr. Rakesh

1. Antigen
Dr. Rakesh Prasad Sah
Associate Professor, Microbiology

2. Introduction
• Antigens are substance  introduced into body  evokes an
immune response (humoral and cell mediated) either by sensitizing
T cell or B cells or both  has ability to combine with final products
of two immune responses i.e. Abs of humoral response and T-
lymphocytes surface receptors in CMI.

3. Introduction
Antigen
Humoral Immunity Cell Mediated Immunity
Ag + B lymphocytes Ag + T lymphocytes
Effector B lymphocyte
(Plasma cells)
Effector T lymphocytes
(Helper T lymphocytes/
Cytotoxic T lymphocytes)
Antibodies

4. • Defined as any substance that satisfies two distinct immunologic
properties-
 Immunogenicity
 Antigenicity.
Immunogenicity
• Ability of an antigen to induce immune response in the body
(both humoral and/or cell mediated).
 B cells + antigen → effector B cells (plasma cell) + memory B
cells
 T cells + antigen → effector T cells (helper T cell or cytotoxic
T cell) + memory T cells

5. • Substance that satisfies immunogenicity - more appropriately
called as ‘immunogen’ rather than ‘antigen’.
Antigenicity (immunological reactivity)
• Ability of an antigen to combine specifically with the final
products antibodies and/or T cell-surface receptors.
• All molecules having immunogenicity property, also show
antigenicity, but the reverse is not true.
 E.g. Haptens- which are antigenic but not immunogenic.

6. Epitope or antigenic determinant
• Smallest unit of antigenicity on antigen is called Epitope or
antigenic determinant.
• Specific site of an antibody that reacts with the
corresponding epitope of an antigen is called as Paratope.

7. Types of Antigen
• Complete Antigen
• Incomplete Antigen/Hapten
• Complete Antigen
– Ags  which can induce Ab formation by themselves  can react
specifically with these antibodies.
• Incomplete Antigen/Haptens
– Substances  unable to induce antibody formation own it’s own  but
can become immunogenic (capable of producing antibodies)  when
covalently linked to proteins, called carrier proteins.
– These Abs  produced not only against hapten but also against the
carrier protein.

8. Classification
• Complex haptens - contain two or more epitopes.
• Simple haptens - contain only one epitope.

9. ANTIGEN-HOST RELATIONSHIP
• Based on the antigen-host relationship, antigens can be grouped into
two groups:
 Self or auto antigens
 Non-self or foreign antigens
Self or auto antigens:
• Belong to the host itself - not immunogenic.
• Hosts  do not react to their own antigens by exhibiting a
mechanism called  immunological tolerance.
• Sometimes, the self-antigens are biologically altered (e.g. as in
cancer cells) and can become immunogenic.

10. Non-self or foreign antigens
• Immunogenic and are of three types based on their phylogenetic
distance to the host.
 Alloantigens : are species specific. Tissues of all individuals in
a species contain species-specific antigens.
 Isoantigens : Ags present in subsets of species, e.g. blood
group Ags and histocompatibility Ags.
 Heteroantigens: Ags belonging to two different species are
called heteroantigens. E.g. Ag of plant or animal or
microorganisms.

11. Heterophile Antigens
• Type of heteroantigens that are present in two different species; but
they share epitopes with each other.
• Antibody produced against antigen of one species can react with the
other and vice versa.
Diagnostic Application
• Heterophile antigens can be used in various serological tests.
• Antibody against one antigen can be detected in patient’s serum by
employing a different antigen which is heterophile (cross reactive) to
the first antigen. Examples:
 Weil-Felix reaction
 Paul-Bunnell test
 Cold agglutination test and Streptococcus MG test

12. Factors of Antigenicity
• Foreignness
• Size
• Chemical Nature
• Susceptibility to Tissue Enzymes
• Adjuvant
• Species specificity
• Isospecificity
• Autospecificity
• Organ specificity
• Heterophile specificity

13. Factors of Antigenicity
• Foreignness
• Size
– large molecules  highly Antigenic
– Low mol wt. (less than 10,000) either non-antigenic or weakly antigenic.
• Chemical Nature
– Natually occuring Ags are either proteins or polysaccharides
– Protein are more effective Ags.
– Exception is gelatin (low tyrosine content) (aromatic radical).
– Lipids and nucleic acids are less antigenic but become more antigenic
when combines to proteins.

14. Factors of Antigenicity
• Susceptibility to Tissue Enzymes
– Only substances that are susceptible to the action of tissue enzymes are
immunogenic.
– Degradation of the antigen by the tissue enzymes produces several
immunogenic fragments having more number of epitopes exposed.
• Adjuvant
– Any substance that enhances the immunogenicity of an Ag  is called
Adjuvant.
• Species specificity
• Isospecificity

15. Factors of Antigenicity
• Autospecificity
– Self Ag are  non-antigenic  exceptions (lens protein and sperm)
 not recognized as self Ags.
– Lens protein  confined within capsule  does not come in contact with
immune system  therefore not recognized.
– Similarly, Ag (sperm)  absent during embryonic life and develop later,
 also not recognized by immune system.
– When these Ag  released into tissue after injury  Abs produced
against them  leading to autoimmune diseases.

16. Factors of Antigenicity
• Organ specificity
– Confined to particular organ.
– Like brain, kidney and lens proteins of one species  shares specificity
with that of another species.
– As brain specific Ags  shared by man and sheep  antirabies
vaccines (Sheep brain vaccines)  may cause neuroparalytic
complications in man.
• Heterophile specificity

17. BIOLOGICAL CLASSES OF ANTIGENS
• Depending on the mechanisms of inducing antibody formation,
antigens are classified as:
 T cell dependent (TD) antigens.
 T cell independent (TI) antigens.

18. T cell dependent (TD) antigens.
• Most of the normal antigens are T cell dependent, they are
processed and presented by APCs to T cells which leads to T
cell activation.
• Activated T cells secrete cytokines that in turn stimulate the B
cells to produce antibodies.

19. T cell independent (TI) antigens
• Antigens such as bacterial capsule, flagella and LPS
(lipopolysaccharide) that do not need the help of T cells and APCs.
• Directly bind to immunoglobulin receptors present on B cells and
stimulate B cells polyclonally.
• Leads to increased secretion of non-specific antibodies
(hypergamma-globulinemia).

20. Differences between T-independent antigens and T-
dependent antigen
T Independent Antigen T dependent Antigen
Structurally simple- LPS, capsular
polysaccharide, flagella
Structurally complex- protein in nature
Dose dependent Immunogenicity Immunogenic over wide range of dose
No memory Memory present
No antigen processing Antigen processing step is needed
Slowly metabolized Rapidly metabolized
Activate B cells polyclonally Activate B cells monoclonally
Activate both mature and immature B
cells
Activate mature B cells only
B cells stimulated against T
independent antigen do not undergo-
 Affinity maturation
 Class switch over
B cells stimulated against T dependent
antigen undergo
 Affinity maturation
 Class switch over
Antibody response is restricted to IgM
and IgG3
Antibodies of all classes can be
produced

21. Superantigens
• Superantigens are the third variety of biological class of antigens,
recently described in the last decade.
• Unique feature of superantigens is, they can activate T cells directly
without being processed by antigen presenting cells (APCs).
• The variable β region of T cell receptor (vβ of TCR) appears to be the
receptor for superantigens.

22. Superantigens
• Directly bridge non-specifically between major histocompatibility
complex (MHC)-II of APCs and T cells.
• Non-specific activation of T cells leads to massive release of
cytokines which can activate B cell polyclonally, which leads to
increased secretion of non- specific antibodies
(hypergammaglobulinemia)

24. Bacterial superantigen
Staphylococcal toxin-
 Toxic shock syndrome toxin-1(TSST-1); Exfoliative toxin; Enterotoxins
Streptococcal toxin- Streptococcal pyrogenic exotoxin (SPE)-A and C
Mycoplasma arthritidis mitogen-I
Yersinia enterocolitica
Yersinia pseudotuberculosis
Viral superantigen
Epstein-Barr virus associated superantigen
Cytomegalovirus associated superantigen
Rabies nucleocapsid
HIV encoded superantigen (nef- negative regulatory factor)
Fungal superantigen
Malassezia furfur

25. Diseases Associated with Superantigens
• Conditions associated with staphylococcal toxins are as follows-
 Toxic shock syndrome
 Food poisoning
 Scalded skin syndrome
 Rare conditions such as-
Atopic dermatitis
Kawasaki syndrome
Psoriasis
Acute disseminated encephalomyelitis.