The document defines key immunological concepts such as antigen, immunogen, epitope, hapten, and different types of antigens. It describes the properties of immunogenicity and antigenicity. Antigens can induce immune responses and bind to antibodies/T-cell receptors. The size, structure, and foreignness of an antigen influence its immunogenicity. Antigens are classified as self, non-self, and superantigens based on their relationship to the host and ability to activate immune responses. Adjuvants can enhance antigen immunogenicity.

2. O ANTIGEN: Antigen is defined as any substance
that satisfies two distinct immunologic
properties – immunogenicity and antigenicity
O 1. Immunogenicity: it is the ability of an antigen
to induce immune response in the body ( both
humoral and / or cell mediated).
O B cells + antigen effector B cells (
plasma cells + memory B cells )
O T cells + antigens effector T cells (
helper T cells or cytotoxic cells + memory T
cells.

3. O 2. Antigenicity (immunological reactivity): it is
the ability of an antigen to combine specifically
with the final products of the above two
responses ( i.e. antibodies and / or T cell
surface receptors).
O The substance that satisfies the first property
i.e. immunogenicity (inducing specific immune
response) is more appropriately called “
immunogen” rather than using the word “
antigen”

4. O Epitope or antigenic determinant is the smallest
unit of antigenicity.
O It is defined as a small area present on the
antigen comprising of few (four or five) amino
acids or monosaccharide residues, that is
capable of sensitizing T and B cells and
reacting with specific site of T cell receptor or
an antibody.
O The specific site of an antibody that reacts with
the corresponding epitope of an antigen is
called paratope

5. O Epitope may be grouped into two types:
O 1. sequential or linear epitope: it presents as a
single linear sequence of few amino acid
residues.
O 2. conformational or non – sequential epitope:
are found on the flexible region of complex
antigens having tertiary structures.
O They are formed by brining together the
surface residues from different sites of the
peptide chain during its folding into tertiary
structure.

6. O Heptens are low molecular weight molecules
that lack immunogenicity (cannot induce
immune response) but retain antigenicity or
immunological reactivity ( i.e. can bind to their
specific antibody or T cell receptors).
O Heptens can become immunogenic when
combined with a large protein molecule called
carrier

7. O Haptens may be classified as complex or
simple.
O Complex haptens: contain two or more
epitope ; they can react with specific
antibodies and the hapten – antibody
complex can be visualized by various
methods such as precipitation reaction.
O Simple haptens: usually contains only one
epitope ( univalent).such haptens can bind to
the antibodies but the hapten antibody
complex cannot be visualized.

8. O Based on the antigen-host relationship,
antigens can be grouped into two groups as
follows:
O 1. Self or auto antigens: They belong to the
host itself; hence they are not immunogenic.
Hosts immune system does not react to its
own antigens, which is due to exhibiting a
mechanism called immunological tolerance.
However. sometimes. the self-antigens are
biologically altered (e.g. as in cancer cells) and
can become immunogenic.

9. O 2.Non-self or foreign antigens: they are
immunogenic and are of three types based on their
phylogenetic distance to the host.
O Alloantigens are species specific. Tissues of all
individuals in a species contain species-specific
antigens.
O lsoantigens are type of antigens which are present
only in subsets of a species, e.g. blood group
antigens and histocompatibility antigens. The
histocompatibility antigens are highly specific as
they are unique to every individual of a species.

10. O Heteroantigens: Antigens belonging to two
different species are called Heteroantigens,
e.g. antigens of plant or animal or
microorganism etc. A heterophile antigen is a
type of Heteroantigen that exists in unrelated
species.
O Heterophile antigens are type of heteroantigen
that are present in two different species; but
they share epitopes with each other .Antibody
produced against antigen of one species can
react with other and vice versa.

11. O There are various factors that influence
immunogenicity of an antigen.
O Size of the antigen: Larger is the size; more
potent is the molecule as an immunogen. It is
found that molecules of more than 10,000
Dalton molecular weight only can induce
immune response ( e.g. hemoglobin).
Substances of molecular weight between 5000-
10,000 Dalton are poor immunogens (e.g.
insulin).

12. O Chemical nature of the antigen: Proteins are
stronger immunogens than carbohydrates
followed by lipids and nucleic acids.
O Susceptibility of antigen to tissue enzymes:
Only substances that are susceptible to the
action of tissue enzymes are immunogenic.
O Degradation of the antigen by the tissue
enzymes produces several immunogenic
fragments having more number of epitopes
exposed.

13. O Molecules that are not susceptible to tissue
enzymes such as polystyrene latex or
synthetic polypeptides composed of D-amino
acids are not antigenic; while polypeptides
consisting of L-amino acids are antigenic as
they are degradable by tissue enzymes.
O However, substances very rapidly broken
down by tissue enzymes may not be
immunogenic as that may denature the
epitopes.

14. O Structural complexity: Simple homopolymers
made up of single amino acid lack
immunogenicity. Polymers made up of two or
more amino acids are immunogenic.
O Addition of aromatic amino acids increases
immunogenicity.
O Complex proteins containing 20 amino acids
and with four level of structural organization
are strongly immunogenic; e.g. hemoglobin.

15. O Foreignness to the host: one of the key factor
which determines immunogenicity.
O Higher is the phylogenetic distance between
the antigen and the host; more is the
immunogenicity.
O Self-antigens are not immunogenic; whereas,
Heteroantigens and Alloantigens are
immunogenic; the degree of immunogenicity
increases with the distance.

16. O Plant antigens are more immunogenic than
animal antigens to humans.
O Bovine serum albumin is more immunogenic
to chicken than to goat.
O lsoantigens are not immunogenic to those
individuals who possess these antigens; but
for other individuals they are immunogenic.

17. O Genetic factor: Different individuals of a given
species show different types of immune responses
towards the same antigen.
O This is believed to be due to the genetic differences
between the individuals.
O Responders are the individuals who produce
antibody faster.
O Slow responders are the individuals who produce
antibody slowly and may need repeated antigenic
exposures.
O Non-responders are the individuals who do not
produce antibody in spite of repeated antigenic
exposures.

18. O Optimal dose of antigen: An antigen is
immunologically active only in the optimal dose
range. A too little dose fails to elicit immune
response and a too large dose leads to
development of immunological tolerance.
O A phenomenon previously designated by Felton
as immunological paralysis.

19. O Route of antigen administration: the immune
response is better induced following parenteral
administration of an antigen; however it also
depends on the type of antibody produced.
O Immunoglobulin A (IgA) are better induced
following oral administration of antigens.
O Inhalation of pollen antigens induces IgE
synthesis; whereas the same antigens given
parenterally lead to formation of IgG antibodies.

20. O Site of injection may influence
immunogenicity The hepatitis B vaccine is
more immunogenic following deltoid
injection than gluteal injection.
O This may be due to the paucity of antigen
presenting cells (APCs) in gluteal fat.

21. O Repeated doses of antigens: Repeated doses of
antigens over a period of time are needed to
generate an adequate immune response.
O This is due to the role of memory cells in
secondary immune response.
O However, after a certain doses of antigens, no
further increase in antibody response is seen.

22. O Multiple antigens: When two or more antigens
are administered simultaneously, the effects
may vary.
O The antibody response to one or the other
antigen may be equal or diminished (due to
antigenic competition) or enhanced ( due to
adjuvant like action).

23. O The term "adjuvant" refers to any substance that
enhances the immunogencity of an antigen. They are
usually added to vaccines to increase the
immunogenicity of the vaccine antigen.
O Examples of Adjuvant Activity
O Alum (aluminium hydroxide or phosphate)
O Mineral oil (liquid paraffin)
O Freund's incomplete adjuvant It is a water-in-oil
emulsion containing a protein antigen in the aqueous
phase.

24. O Examples of Adjuvant Activity
O Freund's complete adjuvant is the mixture of
Freund’s incomplete adjuvant and suspension
of killed tubercle bacilli in the oil phase.
O Lipopolysaccharide (LPS) fraction of gram-
negative bacilli e.g. LPs of Bordetella
pertussis acts as an excellent adjuvant for
diphtheria and tetanus toxoids. This explains
the reason for using combined immunization
for diphtheria, pertussis and tetanus in the
form of DPT vaccine.

25. O Other bacteria or their products:
O Mycobacterium bovis
O Toxoid (diphtheria toxoid and tetanus toxoid
act as adjuvant for Haemophilus influenzae -
type b vaccine)
O Nonbacterial products: Such as silica
particle beryllium sulfate;, squalene and
thiomersal

26. O Adjuvants act through the following steps:
O Delaying the release of antigen: Adjuvant on
mixing, precipitate the antigen which is then
released slowly from the site of administration
thus prolonging the antigenic exposure.
O By activating phagocytosis: The adjuvant-
antigen precipitate is of larger size, thus
increases the likelihood of phagocytosis. The
MDP (muramyl di peptide) component of
tubercle bacilli can activate the macrophages
directly.

27. O By activating TH cells: Activated macrophages
release interleukin-11 (1L-11) and express
higher level of MHC-II; thus promoting helper T
(TH) cell activation which in turn activates B
cells to produce specific antibodies.
O By granuloma formation: Certain adjuvants
such as Freund's complete adjuvant causes
chronic inflammation and granuloma formation
at the inoculation site (hence not suitable for
human use). Activated phagocytes in granuloma
continue to enhance TH cell activation.

28. O Depending on the mechanisms of inducing
antibody formation, antigens are classified as
T cell dependent (TD) and T cell independent
(TI) antigens
O T Dependent (TD) Antigens Most of the normal
antigens are T cell dependent, they are
processed and presented by antigen-
presenting cells (APCs) to T cells which leads
to T cell activation. The activated T cells
secrete cytokines that in turn stimulate the B
cells to produce antibodies.

29. O T Independent (TI) Antigens There are a few
antigens such as bacterial capsule, flagella and
LPS (lipopolysaccharide) that do not need the
help of T cells and APCs. They directly bind to
immunoglobulin receptors present on B cells
and stimulate B cells polyclonally.
O lt leads to increased secretion of non-specific
antibodies hypergammaglobulinemia.

30. O TI antigens can activate both mature and
immature B cells. B cells can only differentiate
into activated cells. there is no memory cells
formation.
O Activated B cells do not undergo affinity
maturation and class switch over (both
properties are unique to TD antigen stimulated
B cells); thus such an activated B cell can
produce only limited classes of antibodies
such as lgM and IgG3.

31. O Superantigens are the third variety of biological
class of antigens. the unique feature of
Superantigens is, they can activate T cells
directly without being processed by antigen-
presenting cells (APCs).
O the variable β region of T cell receptor (vβ of
TCR) appears to be the receptor for
Superantigens.
O they directly bridge non-specifically between
major histocompatibility complex (MHC)-II of
APCs and T cells

32. O Non-specific activation of T cells leads to
massive release of cytokines which can
activate B cell polyclonally, which leads co
increased secretion of non-specific antibodies
(hypergammaglobulinemia ).
O Examples of Superantigens
O Various products of microorganisms behave as
Superantigens; the most important being
staphylococcal and streptococcal toxins.

33. O Bacterial Superantigens
O Staphylococcal toxin:
O Toxic shock .syndrome toxin-1 (TSST·1}
O Exfoliative toxin
O Enterotoxins
O Streptococcal pyrogenic exotoxin (SPE)·A
and C Mycoplasma orthritidis mitogen-I
O Yersinia enterocolitica
O Yersinia pseudotuberculosis

34. O Viral Superantigens
O Epstein Barr virus associated superantigen
O Cytomegalovirus associated superantigen
O Rabies nucleocapsid
O HIV encoded superantigen (nef- negative
regulatory factor)
O Fungal superantigen
O Malassezia furfur

35. O Disease Associated with Superantigens
Superantigens can cause a number of
diseases.
O Toxic shock syndrome
O Food poisoning
O Scalded skin syndrome
O Rare conditions such as- atopic dermatitis,
O Kawasaki syndrome,
O Psoriasis,
O Acute disseminated encephalomyelitis.