ANTIGEN, HAPTEN, ALL TYPES OF ANTIGENS, IMMUNOGEN , ATTRIBUTES OF ANTIGENICITY, DETERMINANTS OF ANTIGENICITY, IMMUNOLOGY KUBY, MEDICAL MICROBIOLOGY & IMMUNOLOGY OF PANIKER , LIPPINCOTT'S IMMUNOLOGY, OTHER SOURCES.

1. ANTIGEN
-BY SURAJ DHARA
(MMCH)

2. IMMUNOGENICITY & ANTIGENICITY
 Immunogenicity :- The ability of a substance to induce the
immune response either humoral or cell mediated in the
body.
. B cells + Ag Plasma cells + Memory cells
. T cells + Ag T helper / T cytotoxic + Memory cells
 Antigenicity :- The ability of an antigen to combine
specifically with the final products of the immune response.
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3. ANTIGEN
 Antigen can be defined as any substance which, when
introduced into the body, evokes the immune system &
reacts with the products of immune system in a specific &
observable manner.
 It satisfies two distinct immunologic properties :-
1. Immunogenicity
2. Antigenicity (immunological reactivity)
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4. IMMUNOGEN
 A substance which induces a detectable immune response
(either cell-mediated or humoral) are appropriately called
immunogen .
 An immunogen can trigger an immune response & acts as
an antigen in that response.
 All molecules having immunogenicity also show antigenicity.
So, all immunogens are antigens.
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5. Contd…
 Despite the fact that all antigens are recognised by specific
lymphocytes or antibodies, not every antigen can evoke an
immune response.
 Antigens those are capable of inducing an immune response
are said to be immunogenic & are called immunogens.
So, all antigens are not immunogens.
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6. CONFUSED TILL ??...Ha Ha Ha..
 Let’s discuss the whole thing by taking an example, that is :
 HAPTEN :- They are low molecular weight substances,
incapable of inducing antibody formation by themselves but
can react specifically with antibodies.
 So they are :- 1. Non-immunogenic
2. Antegenic
 They can become immunogenic when combined with a
larger protein molecule as a carrier.
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7. HAPTEN-CARRIER COMPLEX
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8. TYPES OF HAPTEN
 Complex Hapten :- 1. Polyvalent
2. Hapten – antibody complex can be
visualized as precipitate.
 Simple Hapten :- 1. Univalent
2. Hapten – antibody complex can’t be
visualized, as it is believed that polyvalency (more than one
epitope) is required for precipitation reaction.
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9. EPITOPE
1. Smallest unit of antigenicity, called antigenic determinant.
2. Consisting of 4 or 5 amino acids or monosaccharide residues.
3. Having specific chemical structure, electric charge & steric configuration.
4. Capable of sensitizing T & B cells and reacting with the specific site of
TCRs or an antibody.
5. Combining area on antibody corresponding to epitope is known as
paratope.
6. Epitopes & paratopes determine the specificity of immune reactions.
7. Antigenic mosaic – Antigens such as bacteria or viruses carry many
different types of epitopes.
8. Presence of similar epitopes on different antigens are responsible for
antigenic cross-reaction.
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10. TYPES OF EPITOPE
 Sequential or linear – Epitopes may be present as a single
linear sequence of primary configuration.
 They are recognised by T cells.
 Non-sequential or Conformational – Epitopes are found on
the flexible region of a tertiary antigen formed by bringing
together the surface residues from different sites of peptide
chain during folding.
 They are recognised by B cells.
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11. EPITOPE (Contd…)
 Linear epitopes on digestion of antigen maintain the
sequence.
 On digestion of antigen the conformational epitopes loses
their sequence.
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12. EPITOPES BINDING WITH PARATOPES
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13. TYPES OF ANTIGEN
Based on ability to
carry immunogenicity &
antigenicity :
Complete
antigen
Hapten
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Complex Simple

14. TYPES OF ANTIGEN
.
• Based on origin
Type - i
• Microbial
• Tissue
Type - ii
• Exogenous
• Endogenous
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Autologous /
Self
Xenogenic /
Heterophile
Allogenic /
Iso /
Homologous

15. TYPES OF ANTIGEN
 Microbial antigen : These are structural antigens of microbes.
e.g. – Somatic O, Flagellar H, Capsular K, Fimbrilar antigen
 Tissue antigen :Blood group antigen, Transplantation antigen
 Exogenous antigen : Antigens present outside the cell.
e.g. – allergens (pollen, dust), parts of microbes, drugs,
pollutants.
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16. TYPES OF ANTIGEN
 Endogenous antigen : They are generated within normal
cells as a result of normal cell metabolism or because of
viral & bacterial infection.
• Autologous antigen : They belong to the host itself; hence
they are ordinarily non-antigenic.
 Horror auto – toxicus ( fear of self poisoning) : An individual
doesn’t normally mount an immune response against
his/her own antigens .
 Immunological tolerance of self antigens is conditioned by
contact with them during the development of immune
system at embryological period.
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17. TYPES OF ANTIGEN
 Autoimmunity : It can be developed when exposure of the
1. Sequestrated antigens, normally not found in circulation or
tissue fluid.
 Eye lens protein normally confined within a capsule.
2. Antigens those are not present at embryonic life & develop
later.
 Sperm protein.
• Allogenic antigen : A genetically determined antigen present
in some but not all individuals of a species.
e.g. Human erythrocyte antigens based on which
individuals are classified into different blood groups.
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18. TYPES OF ANTIGEN
• Heterophile antigen : The same or closely related antigens
may sometimes occur in different biological species .
 Forssman antigen – A lipid carbohydrate complex widely
distributed among bacteria, animals, birds, plants. Anti-
Forssman antibody can be prepared in rabbits as they have
no such antigen.
o Heterophile antigens having diagnostic application :
Antibody against one antigen can be detected in patient’s
serum by employing a different antigen which is heterophile
(cross reactive) to 1st antigen.
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19. Diagnostic application of Heterophile Antigen
 Weil-Felix reaction : Done for typhus fever. Proteus antigens
act as heterophile to the antibodies against rickettsial
antigens.
 Paul-Bunnell test : Done for infectious mononucleosis. Sheep
RBC antigens are used to detect cross reacting antibodies
against Epstein-Barr virus in patient’s serum.
 Cold agglutination test : In primary atypical pneumonia. Using
human O blood group antigen detection of antibody against
Mycoplasma.
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20. TYPES OF ANTIGEN
Based on immune
response
T cell dependent antigen
(TD)
T cell independent antigen
(TI)
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 TI type I
 TI type II

21. TD ANTIGENS
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Here B cells can’t respond to these antigens without a co-stimulatory signal from T-helper cells.
Ags bind to surface Ig on B cells.
They are internalised & processed to smaller peptides.
Expressed on surface of B cells complexed with MHC-II.
Presented to the T cells.
Recognised by helper T cells.
T cells secrete cytokines & express CD40 ligand.
CD40 ligand binds with that receptor on B cell.
T-B interaction & released cytokines bring stimulus for B-cell activation.

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Signal-1
Signal-2Signal-3

23. TYPE-I TI ANTIGENS
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24. TYPE-II TI ANTIGENS
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 If a neighbouring cell produces cytokines (like dendritic cell
produces BAFF) B cells can class switch & produce IgG.

25. TD VS TI
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Property T cell dependent T cell independent
T cell involvement Yes No
Antigenic interaction Tertiary complex
• TCRs
• MHC-II
• Ag
Binary complex
• Membrane Ig of B cell
• Ag
Chemical nature Mostly soluble protein Type-1 : LPS
Type-2 : Polymeric protein & polysaccharide
Memory cell Yes No
Antigen processing by Mø Yes No
Isotype switching Yes No (type-1) ; Limited (type-2)
Complement activation No Yes ( type-2)
Polyclonal activation No Yes (type-1; in high dose)
Type of B cell activated Mature only Both mature & immature
Antibody production All classes : IgM, IgG,
IgA & IgE
Restricted to IgM & IgG3

26. OTHER ANTIGENS
Super antigen
Histocompatibility
antigen
Tumor antigen
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27. SUPER ANTIGENS
Antigens that activate very large number of T cells directly irrespective of their antigenic
specificity, without being processed by APCs .
Highly resistance to proteases & to denaturation by CD4+ T cells.
They bind to lateral aspect of variable part of β chain (Vβ) of TCRs.
They directly bridge non-specifically between MHC-II of APCs & TCRs.
Normal Ag binds to αβ heterodimer groove of the MHC molecule through the V region of α &
β chains of TCRs.
Release of cytokines (IL-2) causes massive proliferation of T-lymphocytes.
That leads to further release of variety of cytokines.
Bring profound effect on immune system.
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28. EXAMPLE OF SUPERANTIGENS
Organisms Superantigen Disease
Staphylococcus aureus Enterotoxin, TSST-1  Food poisoning
 Toxic shock syndrome
 Scalded skin syndrome
Group A Streptococci Pyogenic exotoxins  Shock
 Psoriasis
 Rheumatic heart disease
Epstein-Barr virus Associated superantigen  B cell lymphoma
Rabies virus Nucleocapsid protein  Rabies
HIV Nef (negative regulatory factor)  AIDS
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29. SUPERANTIGEN BINDING
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30. HISTOCOMPATIBILITY ANTIGENS
 Ags specific to each individual of a species.
 They are encoded by genes known as histicompatibility
genes which collectively constitute MHC.
 Cause immune response to the graft & determine the
survival of the graft.
 They are alloantigens specific for each individual.
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31. DETERMINANTS OF ANTIGENICITY
 SIZE
 CHEMICAL NATURE
 SUSCEPTIBILITY TO TISSUE ENZYMES
 FOREIGNNESS
 ANTIGENIC SPECIFICITY
 SPECIES SPECIFICITY
 ISO-SPECIFICITY
 AUTO-SPECIFICITY
 ORGAN-SPECIFICITY
 HETEROGENIC SPECIFICITY
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32. SIZE
Higher the molecular weight higher will be the antigenicity.
MW > 10,000 D are mainly antigenic.
Hemocyanins (MW 6.75 million) is highly antigenic.
Adsorption with bentonite or kaolin make the low MW substances
antigenic.
Some substances bind with the tissue protein & become antigenic
(penicillin, formaldehyde & picryl chloride)
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33. CHEMICAL NATURE
Higher the structural diversity higher will be the antigenicity.
Protein > Polysaccharide >> Lipids, Nucleic acids.
So, Proteins (composed of permutation-combination of about 20
amino acids) are more antigenic than polysaccharides ( p/c of 4-5
monosaccharides).
Gelatin, being structurally unstable, is non-immunogenic.
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34. SUSCEPTIBILITY TO TISSUE ENZYMES
Higher the exposure to tissue enzymes higher will be antigenicity.
Phagocytosis & intracellular enzymes break the antigen into
immunogenic fragments.
D amino acids are not antigenic (not metabolised) while polypeptides
consisting L amino acids are antigenic.
But rapid destruction of the substances may lead to non-antigenicity.
Substances unsusceptible to those enzymes are not antigenic.
Eg: Polystyrene latex.
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35. FOREIGNNESS
 Antigens foreign to the body (non-self) induce an immune
response.
 Normally immune response does not develop against self-
antigen due to self tolerance.
 Sometimes auto-immunity develops due to breakdown of
the homeostatic mechanism.
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36. ANTIGENIC SPECIFICITY
 Depends on the position of the antigenic determinant group
in antigen molecule.
 It is determined by single chemical groupings & even by a
single acid redical.
 Antigens bearing the stereochemical similarities may cross
react.
 Sometimes cross reaction occurs due to sharing of identical
epitopes by different Ags.
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37. SPECIES SPECIFICITY
 Tissues of all individuals in a species contain species
specific Ags.
 Helps in
Tracing of evolutionary relationship.
Forensic application for identification of the species from
blood & seminal stain.
 An individual sensitised to horse serum will react with
serum from other equines but may not do the same with
bovine serum.
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38. ISO-SPECIFICITY
 They are genetically determined antigen present in some
but not all individuals of a species.
 Human erythrocyte antigens based on which individuals
are classified into different blood groups.
 Clinical importance
Blood transfusion.
Iso-immunisation during pregnancy.
Determining disputed paternity cases.
Blood grouping in anthropology.
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39. AUTO-SPECIFICITY
 Autologous or self antigens are non-antigenic except some
exceptions.
 Lens protein & sperm protein exposure to circulation
leading to auto-immunity.
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40. ORGAN-SPECIFICITY
 Some organs of different species share the same antigen.
 Organs like brain, kidney, lens protein share specificity with
that of another species.
The neuroparalytic complications following anti-rabic
vaccination using sheep brain vaccines are a consequence
of brain specific antigens shared by sheep & human beings.
 The sheep brain Ags induce immunological response in the
vaccine, damaging their nervous tissue.
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41. HETEROGENIC SPECIFICITY
 The same or closely related antigens may sometimes occur
in different biological species, classes or kingdoms.
Forssman antigen – A lipid carbohydrate complex widely
distributed among bacteria, animals, birds, plants.
o Heterophile antigens having diagnostic application :
 Weil-Felix reaction : Done for typhus fever.
 Paul-Bunnell test : Done for infectious mononucleosis.
 Cold agglutination test : In primary atypical pneumonia.
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