This document discusses antigens and their role in stimulating immune responses. It defines antigens and immunogens as foreign substances that can induce antibody or T-cell responses. It describes different types of antigens including microbial, blood group, transplantation, and tumor antigens. It also discusses classification of antigens based on origin (exogenous or endogenous) and antigenicity (T cell dependent vs independent). The document further explains concepts such as epitopes, haptens, valency and determinants of antigenicity. It provides examples of heterophile antigens and superantigens and their diagnostic importance. Finally, it briefly introduces the concept of adjuvants and their mechanisms in enhancing immune responses.

1. Antigens
Dhruba Acharya
Lecturer/ Immunologist

2. Concept of Antigen and Immunogen
 The word, antigen, (antibody generation).
 Ag reacts specifically with corresponding Ab in detectable
way.
Immunogen or antigen:
* A foreign substance, when introduced into human
body, stimulate formation of specific antibodies or
sensitized lymphocytes (Immunogen)
* Antigens have the ability to combine specifically
with antibodies produced or sensitized T-
lymphocytes induced

3. TYPES OF ANTIGENS INVOLVED IN
PATHOGENESIS OF DISEASES
 Microbial antigens
 Blood group antigens
 Transplantation alloantigens
 Allergens
 Autoantigens
 Tumuor antigens
 Superantigens
 Heterophile antigen

4. Entrance of microbes (antigens) into the body:
 Through skin (by contact)
 The gastrointestinal tract (by ingestion)
 The respiratory tract (by inhalation)
 Injection into blood stream as a result of insect bites.

5. Classification of antigen: based on their origin
Exogenous Antigens
1- Bacterial antigens:
a- Antigens related to bacterial cells
- Somatic antigen (O): part of cell wall gm –ve bacteria.
- Capsular antigen (V): usually polysaccharide
- Flagellar Ag (H) : a protein made of flagellin
- Fimbrial Ag: surface antigens in fimbriated bacilli
b- Antigen secreted by bacteria:
- Exotoxins
- Enzymes
2- Viral antigens:
a- protein coat viral antigens
b- Soluble antigens (soluble nucleoproteins as in influenza)

6. Classification of antigen: based on their origin
Endogenous antigens
Human tissue antigens:
a- Blood group antigens:
A, B and Rh antigens
b- Histocompatibility antigens:
Glycoprotein molecules on all nucleated cells:
- Major histocompatibility complex antigens (MHC)
- Human leucocyte antigen (HLA)

7. • Complete antigen (Immunogen)
• Hapten (Incomplete antigen)
Complete antigen:
•Possess antigenic properties.
•Able to generate immune response by themselves.
•High molecular weight (>10,000) proteins.
•Some are polysaccharide.
Classification of antigen:
based on their antigenicity

8. Hapten:
•Low molecular weight (<10,000) substances.
•Non protein.
•Unable to induce immune response by themselves.
•Can become immunogenic when linked to proteins.
•Can react specifically with corresponding Ab.
TYPES: Complex haptens
Simple haptens

9. Complex haptens:
•Relatively large molecules.
•Can combine with specific Abs forming visible ppt.
•Polyvalent.
•Examples:
Capsular polysaccharide of Pneumococci,

10. Simple hapten:
•Low molecular wt. chemical substances.
•Combine with specific Ab, no ppt is produced.
•Univalent.
Examples of haptens:
•Bacterial:
•Polysaccharide C of beta hemolytic Streptococci

11. •Drugs & chemicals: Agents causing allergic dermatitis
and drug hypersensitivity.
•Blood group (ABO) substances: Glycoproteins
•Lipids: Forssman, transplantation and cardiolipin
antigens.

12. Biological classes of antigen
T cell dependent (TD) antigen
T cell independent (TI) antigen
•TD-Ag stimulate B cell to produce Ab with the help
of T cell.
• TD-Ag belong to protein
• Many kinds of determinants
• Stimulate B cell to produce :IgG, IgM, IgA
• Capable of inducing CMI
• Immune memory

13. TI-Ag can stimulate B cells to produce Ab without
the help of T cell
• Most are polysaccharide
•Same, repeating determinants
•Only induce B cell to produce IgM
•Can not induce CMI
•No immune memory

14. Antigenic epitopes:
Epitopes( Antigenic determinants):
Portions of antigen molecules that
physically interact with paratopes
(combining sites) of immune response
molecules and therefore actually
"determine" antigen specificity.
Three dimensional structure of
M. tuberculosis antigen 85B

15. Antigenic determinants:
•Antigen possess several epitopes, differ in specificity &
potency
•Size: (25-34)A.
•Molecular wt. : (400-1000)
•Three dimensional structure.
• Valency: number of antigenic determinants in Ag.

16. Valency: Total
Functional
•Total valency:
Sum of functional & nonfunctional (hidden) valency
•Complete antigen: two or more than two functional
valency.
•Hidden antigenic determinant: Epitope located in
unexposed region of Ag.

17. Types of epitope:
Linear (sequential) epitope:
•Continuous and found in polysaccharide as well as in both
native (nondenatured) and denatured proteins.
Confirmational epitope:
•Discontinuous

19. Determinants of antigenicity:
Size:
•Large molecules (haemocyanin mol. wt. 6.75 million):
highly antigenic.
•Low mol. Wt. substances (less than 10,000) :
non antigenic/weakly antigenic.
Chemical nature:
• Protein/polysaccharide.
•Lipids and nuclic acids: less antigenic, antigenicity
increased by combination with proteins.
•Gelatin, histones and protamines are protein but
nonantigenic.

20. Foreignness:
•Ag foreign to the individual induce immune response.
• Antigenicity related to the degree of foreignness.
Susceptibility to tissue enzymes:
•Ag are degraded by host into fragments of appropriate size
containing Ag determinants.
•Phagocytosis & intracellular enzymes play important role.
•Substances unsusceptible to tissue enzymes are non antigenic.

22. Antigenic specificity:
•Depends on antigenic determinants.
•Antigenic specificity is not absolute, cross reaction can occur with
similar antigens.
Species specificity:
•Tissues of all individuals in a species contain species specific
antigen.
•Some degree of cross reaction can occur.
•Forensic application: Identification of species.

23. Isospecificity:
•Isoantigens (Alloantigens): present in some but not all
members of a species.
•Can produce isoantibodies.
•Example: human erythrocyte antigen.
•Importance: blood transfusion.
Organ specificity:
•Confined to a particular organ/tissue.
•Certain organs like brain, kidney, lens protein of one species
share specificity with another species.
•Example: Sharing of brain specific antigen by man and sheep.

24. Histocompatibility antigen:
• Major histocompatibility antigen: HLA.
• Graft rejection.
Autospecificity:
•Self Ag (Autologous antigens): generally non immunogenic.
•Examples: lens protein, thyroglobulin.
•Normally do not come in contact with general blood circulation & are
not reconized as self antigen.
•Antigen absent during embryonic life but appear later(sperm)
•May produce autoimmune diseases.

25. Heterophile antigen
Antigens of similar nature (if not identical), present in different
tissues of more than one species.
Composition: Lipoprotein polysaccharide complex.
Examples:
Forssman antigen:
Lipopolysaccharide complex, described by Forssman.
Present in red cells and other tissues of many animals.
Bacteria with Forssman antigen: Salmonella, Shigella.
Human RBC of blood group B share Ag with E-Coli.

26. Diagnostic importance of heterophile antigen:
Weil-Felix reaction:
Heterophile Ag present on Rickettsiae are shared by certain
strains of Proteus(OX2, OX19, OXK).
Diagnosis of typhus fever.
Paul-Bunnel reaction:
Heterophile Ag present on EB virus are shared by
Sheep & Ox RBCs.
Diagnosis of infectious mononucleosis.

27. Superantigens
•Certain protein molecules activate very large number of
T cells irrespective of their antigenic specificities.
•Normal Ag stimulate about 0.001% of circulating T cell,
Superantigens stimulate 20% of circulating T cell.
•Exaggerated T cell activation leads to massive outpouring
of cytokines causing multisystem dysfunction.
Examples:
•Staphylococcal enterotoxin (food poisoning)
•Exofoliative toxin (scalded skin syndrome)
•Streptococcal pyrogenic exotoxin (shock)

28. Tumour antigens
•Present in malignant cells, absent in normal cells.
•Induce immune response when transplanted into animals,
•Such antigens are called tumour specific transplantation Ag.
Tumour specific Ag (TSA):
•EB virus ---B cell lymphoma, HPV-cervical carcinoma.

29. Tumor associated Ag (TAA)
•Highly expressed on tumor cells but in low level
expressed on normal cells, such as AFP, CEA
AFP (alpha-fetoprotein): over-expression in liver cancer
CEA (carcinoembryonic antigen): over-expression in
carcinoma of colon , pancreas, stomach and breast.

30. Adjuvant
The Latin “adjuvans” means to help, particularly to
reach a goal.
•Substance that helps to enhance the pharmacological
effect of drug or increases the
ability of an Ag to stimulate the immune system.
•When injected with Ag, enhances Ab production.
•Increases both cellular and humoral immunity.

31. Classification of adjuvant
•Freund’s adjuvant:
Complete Freund’s adjuvant (CFA)
Incomplete Freund’s adjuvant (IFA)
•Liposomes
•Inorganic compounds
•Cytokines

32. Types:
Bacterial adjuvant:
Freund’s adjuvant: consist of mineral oil which acts as
emulsifier, when it contains suspension of killed tubercle
bacilli, called Freund’s complete adjuvant.
Develop delayed hypersensitivity.
•Adjuvant effect of tubercle bacilii: muramyl dipeptide.
•Produces local granuloma, not suitable for human use.
•GNB show adjuvant effect due to their lipopolysaccharide .

33. Chemical adjuvant: Silica particles, Berrilium sulphate,
Calcium alginate, Bantonite.
MECHANISM OF ADJUVANT:
•Prolonged persistance of immunogen at the site of injection.
•Liberation of lymphocyte activating factor.
•Induction of granuloma formation.
•Stimulation of lymphocyte proliferation in non specific manner
Antitumor effect by stimulating specific CMI.
USE: Vaccination

34. Lets take a break!