1. • NATURE OF ANTIGEN AND THE MAJOR
HISTOCOMPATIBILITY COMPLEX

2. INTRODUCTION
Antigen refers to macromolecules that are
capable of eliciting formation of antibodies or
sensitized T cells in an immunocompetent host.
Means any agent which can generate antibody.
Immunogens refer to macromolecule capable
of triggering an adaptive immune response.

3. • All immunogens are antigens but not all antigens are
immunogens.
• All antigen are recognized by specific antibodies or T
cell receptor not all antigen can evoke immune
response.
• Those antigen that are capable of inducing immune
response are called immunogens.

4. This response is actually caused by combination of factors:
 Nature of immunogens itself.
 Genetic coding of major histocompatibility complex (MHC)
that combine with an immunogen before T cells are able to
respond.
 Immunogen processing and presentation

5. Factors influencing immune response
• Factors influencing immune response

6. b) Health of an individual
Healthy individuals normally respond fully to
the immunogens while malnourished,
fatigued or stressed ones are less likely to
have a successful immune response

7. ) Dose of immunogens
Generally, the larger the dose one is exposed
to, the greater the immune response.
However, very large doses may result in T- and
B-cell tolerance.

8. Route of inoculation
Immunogen entrance routes to the body
determine the cell populations which will be
involved in the response and how much will
be needed to trigger a response.
Such routes are intravenous, intradermal,
subcutaneous and oral.

9. ) Genetic capacity
The stronger the genes involved in allowing
the individuals to respond to the
immunogens, the greater the ability to
influence the immune response.

10. TRAITS OF IMMUNOGENS
• Immunogens: are molecules that elicits
immune
response, It triggers an immune response.
e.g. incase of the humoral response or the B-
cells.
The ability of immunogen to stimulate a host
response depends on the following
characteristics.

11. • A: Properties of immunogecity
• 1)Molecular size
• 2) Chemical composition and molecular
complexity.
• 3) Foreignness
• 4) The ability to be processed and presented
with MHC molecules.

12. • B: Contribution of biological system.
• 1) Genotype of the recipient animal.
• 2) Immunogen dosage and route of
administration.
• Usually immunogen has the molecular weight
between 10000- 100000 Daltons to recognized by
immune system

13. • Immunogenicity is also determined by a
substance chemical composition and
molecular complexity.
• Protein and polysaccharides are the best
immunogens .
• Protein are powerful immunogens because
they are made up of a variety of units known
as amino acid .

14. NATURE OF EPITOPES
Epitopes are smaller molecular shaped parts
of the immunogen that is recognized by the
immune system.
For proteins there is evidence that,amino
acids epitopes recognized by B- cells may
consist of 6-15 amino acids.

15. In other hand the large molecules may have
numerous epitopes, where by each one tends
to be capable of triggering specific antibody
production or a T-cell response.
Epitopes may be repeating copies or may tend
to have have different specificities.They can be
sequential/linear or conformational.

16. CLASSIFICATION OF EPITOPES
Epitopes are classified into two categories:-
Linear/sequential epitopes- are formed by a
specific sequence as amino acids are following
one another in a single chain.
Confirmational epitope- are formed due to the
folding of one or multiple chain bringing certain
amino acids from different segment of linear
sequence/sequences into proximity with each
other to be recognized.

17. Epitopes recognized by the B-cells differ from
those recognized with T-cells.
Fore instance surface antibodies of B-cells may
react with both linear and the conformational
epitope.
But for T-cells recognizes only as a part of a
complex formed with MHC proteins on the
surface of an antigen presenting cells.

18. HAPTENS
• Are non immunogenic material that when
combine with a carrier creat a new antigenic
determinant.
• Once antibody production is initiated, the
hapten is capable of reacting with antibody
even when the haptens is not complexed to a
carrier molecule

19. • However precipitation or agglutination
reaction will not occur because the haptens
has a single determinant site and can not form
a cross link with more than one antibody
molecule that are necessary for agglutination
or precipitation

20. • A good example of haptens is an allergic
reaction to poison called “ivy” containing a
chemical substance called catechols which are
haptens.
• Once in contact with the skin this can couple
with tissue protein to form immunogens that
give rise to contact dermatitis.

21. Characteristics of Haptens

22. RELATIONSHIP OF ANTIGENS TO THE
HOST
 Antigens can be placed in broad categories
according to their relationship to the host.
 Autoantigens are those antigens that belongs
to the host.
-These do not evoke an immune response under
normal circumstances.

23.  Alloantigens are those from other member s
of the host’s species , and these are capable
of eliciting an immune responses.
-They are importance in tissue transplantations
and blood transfusions.

24.  Heteroantigens are those antigens from other
species such are other animals, plants or
microorganisms.
 Heterophile antigens are heteroantigens that
exists in unrelated plants or animals but are
either identical or closely related in structure
so that antibody to one will cross reacted with
antigen of the other

25. • Example of heterophile antigen is blood group
A and B antigens of human related to bacterial
polysaccharides.

26. ADJUVANTS
• An adjuvant is a substance administered with an
immunogen that increases the immune response.
• It acts by producing local inflammatory response
that attracts a large number immune system cells
to the injection site.
• Example aluminum salts and Freund’s complete
adjuvants.

27. Adjuvant are thought to enhance the immune
response by:
Prolonging the existence of immunogen in the
area
Increasing the effective size of the immunogen
Increasing the number of macrophages involved
in antigen processing.

28. MAJOR HISTOCOMPATIBILITY
COMPLEX (MHC
• Genetic capability to mount an immune response
is linked to a group of molecule originally reffered
to as human leukocyte antigen (HLA)
• These antigen are also known as MHC molecule
because they determine whether transplanted
tissue is histocompatible and thus accepted or
recognized as foreign and rejected.

29. • MHC molecules are actually found on all
nucleated cells in the body, and they play a
role in the development of both humoral and
cellular immunity
• They are relevant clinically because they
may be involved in transfusion reaction, graft
rejection, and autoimmune disease

30. GENES CODING FOR MHC MOLECULES
(HLA ANTIGEN)
• MHC is a polymophic system in human, this
is because it comprises so many possible
alleles at each location
• Polymorphism is essential to our survival
because MHC molecule play a vital role in
triggering immune response to diverse
immugen

31. • Gene coding for the MHC found in
chromosome 6 and are divided into three
categories or classes
• Class I molecules are coded for a three
different location or loci, termed A, B and C

32. • Class II gene are situated in the D region and
there are several different loci known as DR, DQ
and DP
• In class II there is a gene that codes for alpha
chain and one or more gene for the beta chain
• Between class I and class II region on
chromosome 6 is the area for class III gene
which code for complement protein and
cytokines

33. • Class III are not expressed on cell surface, but
have immune response, class I and class II are
responsible in antigen recognition
• Haplotype is the package of inherited MHC
gene
or is the group of gene within an organism
that was inherited together from a single parent

34. • Thus each inherited chromosomal region
consists of a package of gene for A, B, C, DR,
DP, and DQ
• Full genotype would consist of two of each
gene at a particular locus because there are
numerous allele or variant forms at each locus

35. • An individual MHC type is about as unique as
a fingerprint
figure; MHC location for the class I, II and III gene on
chromosomes 6

36. STRUCTURE OF CLASS I MOLECULES
 Class I molecules are expressed in all
nucleated cells.
 Expressed more in lymphocytes and weakly
expressed in liver hepatocytes, neuronal cells,
muscle cells and sperm.

37.  Each class I is a glycoprotein dimer made up of
two noncovalently linked polypeptide chains, a
and β2-microglobulin
α- chain is folded into three domains α1, α2and
α3 and it has molecular weight of 45,000daltons
 β2-microglobulin is the lighter chain has
molecular weight of 12000daltons

38.  β2-microglobulin chain does not penetrate
the cell membrane while α-chain penetrates
via transmembrane segment
 α1 and α2 forms the deep groove at the top
of the molecule that acts as the peptide-
binding site in antigen recogniction

39. α3 region of a-chain reacts with CD8 on
cytotoxic cells
 Another group of called non-classical class I
molecules are not expressed on the surface of
cells and are not used in antigen recognition.

40. STRUCTURE OF CLASS II MHC
MOLECULES
The occurrence of class II MHC molecules is
much more restricted than class I.
 Class II MHC molecules are primarly found in
antigen presenting cells which include B-
lymphocytes, monocytes, macrophages and
dentritic cells.

41. The MHC class II molecules consist of two
non-covalently bound polypeptide chains that
are both encoded by genes in the MHC
complex
 α-chain has molecular weight of
33,000daltons and b-chain has molecular
weight of 27,000daltons

43. Each chain has two domains in which α1 and
β1 domains come together to form peptide-
binding site.
 The main role of class I and class II MHC
molecules is to bind peptide inside the cells
and transport them to the plasma membrane
where T cells can recognize them in process
known as antigen presentation

44.  Class I molecules mainly present peptides that have
been synthesized inside the cell to CD8(cytotoxic) cells.
 Class II molecules present exogenous antigen to CD4
(helper) cells
 Class I are thus watchdogs of viral, tumor and certain
parasitic antigens synthesized inside the cell, while
class II stimulate CD4 in case of bacterial nfections or
presence of other material that is endocytosed by the
cell.

45. Roles of class I molecule.
MHC class 1 synthesized in the rough
endoplasmic reticulum.
It bind peptide within the cell (endogenous
peptide) and transport them to the plasma
membrane where it recognized by CD8+ T
cell.
CD8+ T cell produce cytokines that cause lysis
of the target cell .

46. CD8+ T cell recognizes antigen

47. Roles of class II molecule
It transported from endoplasmic reticulum to
an endosomal compartment before they can
bind peptide.
Due to invariant chain class II molecule bind
with exogenous peptide that favored by low
PH of endosomal compartment

48. Cont…
On the cell surface class II molecule
recognized by CD4 (T helper) cell
CD4+ T cell trigger the B cell for the formation
of antibody.

49. CD4+ T cell recognizes antigen