Antigen,its types, epitope, Hapten and cross reactions

1. By,
Dr. Prashanth Kumar K.S
PhD Scholar

2. What is an Antigen?
 Any substance or a molecule against which an immune
response is generated is called Antigen
 Anti- Against Gen- generation
 Molecules vary in their ability to act as antigens (their
antigenicity)

3.  Immunogenicity is the ability to induce a humoral and/or
cell mediated immune response
 Antigenicity is the ability to combine specifically with
the final products of the above responses (i.e., antibodies
and/or cell-surface receptors)
 All immunogens are antigens but not all antigens are
immunogens.

4. What makes a good antigen
 Molecules vary in their ability to act as antigens (their
antigenicity)
 Factors affecting the ability of a substance to act as antigen are
 Size
 Chemical nature
 Complexity
 Structural stability
 Foreignness
 Dosage and route of administration of antigen
 Genetic makeup of the immunized animal

5. Antigen
Size
Stability
Complexity
Foreignness

6.  The best antigens are large, complex, and foreign
 In general, foreign proteins make the best antigens,
especially if they are big (greater than 1000 Da is best)

7. Size
 Large molecules are better antigens than small molecules
 Hemocyanin, a very large protein from invertebrate blood
(670 kDa)
 Serum albumin from other mammals (69 kDa)
 The small peptide hormone angiotensin (1031 Da) is a poor
antigen

8. The relative sizes of
several significant
antigens.
Size does matter!
Big molecules are
generally much more
antigenic than small
molecules. Molecules
as small as angiotensin
are poor antigens.

9. Chemical nature
 Carbohydrates
 Simple polysaccharides, such as starch or glycogen, are not
good antigens
 More complex carbohydrates may be effective antigens,
especially if bound to proteins
 Lipids
Lipids tend to be poor antigens
When linked to proteins or polysaccharides, lipids can trigger
immune responses

10.  Mammalian nucleic acids are very poor antigens
 Microbial nucleic acids, on the other hand, have a
structure very different from that found in eukaryotes with
many unmethylated CpG sequences
 Protiens
 Proteins are the most effective antigens
 Adaptive immune system has evolved to trap, process,
and then recognize foreign proteins

11. Complexity
 The more complex an antigen is, better is the immune
response
 Starch and other simple repeating polymers are poor
antigens, but complex bacterial lipopolysaccharides are
good.

12. Structural stability
 To bind to a foreign molecule, the cell surface receptors of
the adaptive immune system must recognize its shape
 Gelatin, a protein well known for its structural instability
 Flagella, is a flexible, weak antigen

13. Foreignness
 The cells that respond to antigens (antigen-sensitive cells)
are selected so that their receptors do not normally bind to
molecules originating within an animal (self-antigens).
 The greater the difference in molecular structure between a
foreign antigen and an animal’s own antigens, the greater
will be the intensity of the immune response

14.  Kidney graft from an identical twin –Accepted readily
 A kidney graft from an unrelated animal of the same
species will be rejected
 A kidney graft between different species such as from a
pig to a dog will be rejected

15. Dose and route of
administration
 Some combination of optimal dosage and route of
administration will induce a peak immune response in a given
animal
 Experimental immunogens are generally administered
parenterally (para, around; enteric, gut)
 The administration route strongly influences which immune
organs and cell populations will be involved in the response

16. Genotype of the animal
 The genetic constitution (genotype) of an immunized
animal influences the type of immune response the animal
manifests, as well as the degree of the response
 Genes that encode B-cell and T-cell receptors and by genes
that encode various proteins involved in immune
regulatory mechanisms

17. Types of antigens
 Microbial antigens
Bacterial
Viral
Other Microbial Antigens
 Non microbial antigens
 Cell Surface Antigens
 Autoantigens

18. Bacterial antigens
 The cell wall of Gram-positive organisms is largely
composed of peptidoglycan (chains of alternating N-acetyl
glucosamine and N-acetyl muramic acid cross-linked by
short peptide side chains)
 The cell wall in Gram-negative organisms, in contrast
consists of a thin layer of peptidoglycan covered by an
outer membrane consisting of a lipopolysaccharide

20.  Capsular antigens are collectively called K antigens.
 Pili and fimbriae are short projections that cover the surfaces
of some Gram-negative bacteria; they are classified as F or
K antigens
 Flagellar antigens are collectively called H antigens
 Bacterial nucleic acids rich in unmethylated CpG sequences
serve both as effective antigens for the adaptive immune
system and as potent stimulators of innate immunity acting
through TLRs

21. Viral Antigens
 “Obligate” intracellular parasites
 Capsid proteins are good antigens, highly capable of
Stimulating antibody formation

23. Other microbial antigens
 Fungi, protozoan parasites, arthropods, and even parasitic
worms (helminths)

24. Nonmicrobial Antigens
 Food contains many foreign molecules- Allergic
 Inhaled dusts can contain antigenic particles such as
pollen grains
 Organ grafts are an effective way of administering a large
amount of foreign material to an animal.

25. Cell Surface Antigens
 Outer membrane of every mammalian cell consists of a fluid
lipid bilayer with a complex mixture of protein molecules
embedded in it
 Glycoproteins known as blood-group antigens are found on the
surface of red blood cells
 Nucleated cells, such as leukocytes, possess hundreds of
different protein molecules on their surface
 The cell surface proteins that trigger graft rejection are called
histocompatibility antigens

26. Autoantigens
 Autoimmune responses
 Hormones, such as thyroglobulin
 Structural components, such as basement membranes
 Complex lipids, such as myelin
 Intracellular components, such as the mitochondrial proteins,
 Nucleic acids, or nucleoproteins
 Cell surface proteins, such as hormone receptors

27. Epitopes
 Large molecules have specific regions against which immune
responses are directed- Antigenic determinants
 In a large, complex protein molecule, many different epitopes
may be recognized by the immune system, but some are much
more immunogenic than others.
 Directly related to its size and there is usually about one epitope
for each 5 kDa of a protein

28. Haptens
 Small molecules that can function as epitopes only when bound to other
larger molecules are called haptens (in Greek, haptein means “to grasp
or fasten”)
 Landsteiner employed various haptens, small organic molecules that are
antigenic but not immunogenic.Chemical coupling of a hapten to a large
protein,called a carrier, yields an immunogenic hapten-carrier
conjugate.
 Even very minor modifications to the shape of a hapten may influence
its ability to be bound by an antigen receptor or by an antibody

30.  Penicillin -penicilloyl-serum proteins such as albumin -
penicilloyl-albumin complexes
 Poison of ivy plant (Rhus radicans)-allergic contact
dermatitis


31. Adjuvants
 Adjuvants(from Latin adjuvare,to help) are substances
that, when mixed with an antigen and injected with
it,enhance the immunogenicity of that antigen
 Antigen persistence is prolonged
 Co-stimulatory signals are enhanced
 Local inflammation is increased
 The nonspecific proliferation of lymphocytes is
stimulated.

33.  Water-in-oil adjuvants also prolong the persistence of
antigen. A preparation known as Freund’s incomplete
adjuvant
 Freund’s complete adjuvant- containing heat-killed
Mycobacteria as an additional ingredient

34. Cross-Reactions
 Identical or similar epitopes may sometimes be found on
apparently unrelated molecules
 In another situation, the epitopes on a protein may differ
in only minor respects from those on the same protein
obtained from an animal of a related species

35. Food or bacterial antigens encountered in the diet carry epitopes that cross-react with
blood group glycoprotein A. As a result, pigs of blood group O make antibodies to
the A epitope despite never having received group A red cells. Should these animals
be inadvertently transfused with group A blood, they will suffer an immediate and
severe transfusion reaction

36. References
 Tizard, Ian R. Veterinary immunology , 9th ed.
 Immunology by Kuby