The document discusses various properties of antigens that determine their antigenicity including molecular size, foreignness, chemical complexity, stability, and more. It also describes different types of antigenic determinants recognized by B cells and T cells as well as factors like dosage, route of administration, and adjuvants that influence immunogenicity. Finally, it covers antigen specificity and different types of antigens such as haptens, superantigens, and isoantigens.
4. ANTIGEN
Molecules that can be
recognized by
Immunoglobulin receptors of
B cells or
T cell receptors (when
complexed with MHC)
are called as ANTIGENS
5. DEFINITION..
ANTI - GEN
Contd..
‘ANTI’body ‘GEN’erator
Substances that react with
antibodies
IMMUNO - GEN
‘IMMUN’E response
‘GEN’erator
6. DEFINITION..contd.
IMMUNOGENICITY
.
– ability of an Ag to elicit an
immune reaction in the form
of a B cell or T cell response
ANTIGENICITY
– just the ability to combine
with the products of the
above responses
7. DEFINITION..contd..
All molecules that are
immunogenic are antigenic
All molecules that are
antigenic are not
immunogenic
Antigens that are not
immunogenic, but can take
part in immune response
9. Determinants Of
Antigenicity
The important
determinants….
Molecular size
Foreignness
Chemical & Structural
Complexity
Stability
10. MOLECULAR SIZE
Protein molecules with
large molecular weight -
Highly Antigenic
Substances with mol wt >
1,00,000 Da highly
immunogenic
Substances with mol wt <
11. MOLECULAR
This property is used in some
SIZE..contd..
of the experimental studies
High molecular wt proteins like
BOVINE GAMMA GLOBULIN (MW
1,50,000 da)
- used to induce immune
reaction
Substances with Low Mol Wt can
be made antigenic by adsorbing
these LMW molecules on
12. FOREIGNNESS
A molecule should be
recognized as non-self
(foreign) to be more
immunogenic
Self or nonself
decided by the immune
system,
Depending on whether or not
13. FOREIGNNESS
Body has the ability to tolerate
the self antigens
Tolerance to self-antigens
develops by contact with them
in the initial phases of the
development of the immune
system,
- particularly during the
14. Foreignness
Immunogenicity of a molecule in a
contd… a species
species is greater when
is distantly related to another
species
Immunogenicity of a molecule in a
species is lesser when a species is
closely related to another species
Severity of immunogenicity of a
molecule is dependent on the
15. Foreignness
For example- a graft from a Human
contd…
to Human will be rejected within
two weeks, if immunosuppressive
drugs are not used, but a graft
from a Chimpanzee to Human is
rejected, even if
immunosuppressive drugs are
used
Bovine Serum Albumin - more
16. Chemical & Structural
Complexity
Proteins – most potent
immunogens
Polysaccharides
– Immunogenicity less
than proteins
Nucleic acids & Lipids
– not efficient in eliciting
an good immune reaction
17. Chemical & Structural
Complexity
In Proteins, the
immunogenicity is dependent
on its structural complexity –
i.e
if the structure is simple (like
chains of single amino acid or
simple sugar,) it is less
immunogenic.
if the structure is complex (like a
18. Chemical & Structural
Complexity Contd..
In CMI, response of T cells to
proteins, depends on how peptide
is recognised & presented by MHC
cells
The structure of protein, plays an
impt role in its immunogenicity,
especially in CMI
Since lipids are not efficient in
eliciting a good immune response,
19. Chemical & Structural
Complexity. Contd..
However these Lipid-specific
Antibodies (LSAb) have a role in
measurement of certain lipid-
based molecules & drugs
LSAb are produced by following
process
First treat the lipid with hapten
Then conjugate the lipid-hapten with
suitable carrier molecule such as
20. STABILITY
Highly stable and non-
degradable substances are
not immunogenic.
example:- some platics,
metals, or chains of D-
aminoacids
B’se Internalization,
21. STABILITY
Very stable substances
such as silicone have been
successfully used as non-
immunogenic substances
for implants in breast
reconstructive surgery.
On the other hand, if a
substance is very unstable,
22. Other factors of Antigenic
Determinant
Biological systems
Dosage
Route
Adjuvants
23. BIOLOGICAL
SYSTEMS
Play an important role in
determining the
Immunological Efficiency of
an Ag
Some substances
- immunogenic in one
species
24. BIOLOGICAL SYSTEMS
Some substances
contd.
immunogenic in one individual ,
but not in others individual
Species or individuals may lack
or have altered genes that code
for receptors for Ag on B&T cells.
They may not have appropriate
genes needed to code for APC to
25. Other Factors – Dosage &
Dose of Route of Ag by
Ag & the route
which Ag comes into contact
with the immune system also
influences immunogenicity of
Ag
Very low dose of Ag – do not
stimulate immune response
B’se too few lymphocytes are
contacted
26. Other Factors – Dosage &
Route of Ag
Repeated administration of Ag –
Booster dose
Required to enhance immune
response of host to certain Ags
Particularly important in case of
vaccines – to get the needed
prerequisite immune level.
Hence the Booster doses of
vaccines such as DPT, DT, etc.
27. Other Factors – Dosage & Route
of Ag
Generally Ags are administered by
parenteral route to produce good level
of Antibodies
Can be given by
Intravenous - IV,
Subcutaneous - SC,
Intradermal - ID,
Intramuscular - IM,
Intraperitoneal - IP, &
Mucosal routes
SC route – better than IV route at
28. Other Factors –
Adjuvants
Substances that boost /
increase the
immunogenicity of the Ag,
when mixed with that Ag &
injected.
Increase both the strength
& duration of immune
29. ADJUVANTS CONTD…
Boosts immunogenicity in
several ways, eg:- by
forming depot at injection
site & prolongs persistence
of Ag at the site
ALUM (aluminum potassium
sulfate)
precipitates Ag, releases
30. ADJUVANTS
CONTD…
Freund’s complete adjuvant
in addition to emulsifying
factors, contains heat killed
mycobacteria
Bacterial component activates
macrophages & increases
production of IL-1 & B7
membrane molecules enhance
immune response
31. ADJUVANTS..
B7 molecules on APC binds to
contd..
CD28, a cell-surface protein on
TH cells triggers co-
stimulation an enhancement
of T cell immune response
Some adjuvants like synthetic
polyribo-nucleotides & bacterial
lipo-polysaccarides stimulate
33. EPITOPE
Immunologically active region of
an Immunogen
Binds to Ag specific membrane
receptors on lymphocytes or
secreted antibodies
Determines the complexity of any
antigen
2 types & each have different
properties
37. Antigenic Specificity – B Cell
Epitopes
Antigenic determinant
recognized by B cell
Can combine with its receptor
only if the antigen molecule is
in its native state
Complementary surfaces of the
Ab & Ag molecules appear to
be relatively flat
39. Antigenic Specificity – B Cell
Epitopes
About 6 or 7 sugar residues
or AA long
Hydrophilic
Located at bends in protein
structure
Found in regions of protein
that have a higher mobility
41. Antigenic Specificity – T Cell
Epitopes
T cells recognize AA in proteins
T dependent Ags
T cells do not recognize
Polysaccharide Ag or Nucleic
Acid Ag T independent Ags
Primary sequence of AA in
proteins determines antigenic
determinants recognized by T
42. Antigenic Specificity – T Cell
Epitopes
Free peptides are not
recognised by the T cells,
but they recognize peptides
complexed with MHC
molecules
Thus for a T cell response, it
should recognize both
43. Antigenic specificity – T cell
epitopes
T cell epitopes - small &
only 8-15 AA
Epitopes are restricted to
those parts of Ag that can
bind to MHC molecules
There can be difference
among individuals in their T
cell response to same
44. Antigenic specificity – T
cell epitopes
Each MHC molecule can bind
several peptides, but not all
peptides.
Therefore for a peptide to be
immunogenic, in a particular
individual, that individual must
have the required MHC
molecule that can bind to that
peptide
45. Antigenic specificity – T cell
epitopesprepares a
2 types of processing
protein Ag for Ag presentation. They
are
‘Externally derived antigens’
processing
Phagocytosed bacteria are killed &
lysed by phagocytic cells
(macrophages). Pieces of bacteria
are processed & presented by class II
MHC mol
46. Species specificity
Tissues of all individuals in a
species possess certain species
specific Ag.
Some degree of cross-reaction
occurs between Ag from related
species
Species Specificity shows
phylogenetic relationship – useful
in tracing evolutionary relationship
48. Isospecificity
Determined by the presence of
ISOANTIGENS
Ag found in some members of
species, but not all.
A species can be grouped
depending on the presence of
different isoantigens in its members
These are genetically determined
Two examples of isoantigens are
49. Isoantigens- Blood Group
Ag
Based on human erythrocyte
antigens, the individuals are
classified into different blood group
– best example of isoAntigen
Blood groups are of primary
importance in transfusion of blood
& blood products and in
isoimmunization during pregnancy
Blood groups provide valuable
50. Isoantigens -
The Histocompatibility Ag
cellular determinants specific
for each individual of a species
Associated with plasma membrane
of tissue cells
HLA – Human Leukocyte Antigen –
the major histocompatibility Ag that
determines homograft rejection
HLA typing - absolutely essential
before carrying out transplantation
51. Auto-specificity
Self-antigens are generally non-
antigenic
Sequestrated Ag are not
recognised as selfAg
Eye lens protein
sperm
B’se corneal tissue & sperm are
never encountered by the immune
system during development of
52. Organ specificity
Ag characteristics of an
organ/tissue
– organ specific Ag
Found in brain, kidney & lens
tissues
Even different animal species share
same Ag
Brain specific Ag - shared by human
brain & sheep
53. Heterophile
specificity
Determined by the presence of
heterophile Ag
Same Ag or closely related Ag
present in tissues of different
species, classes, or kingdom are
known as Heterophile Ag
Antibodies against the heterophile
Ag produced by one of the species
cross-react with the Ag of other
54. Heterophile
specificity..contd..
Ex: of serological tests that use
heterophile Ag
Weil-felix reaction
Paul-bunnell test
Cold agglutination tests
Weil –Felix Reaction diag of
Rickettsial Inf
The strains of Proteus species such
as OX-19, OX-2, OX-K are used to
55. Heterophile specificity..
contd.. diag of IM-
Paul-Bunnell test
Infectious Mononucleosis -
caused by Epstein-Barr virus –
demonstration of heterophile
antibodies that agglutinate
sheep RBCs.
Cold Agglutinin Test diag of
Primary Atypical Pneumonia
56. HAPTENS
Small organic mol that are
Antigenic
Not immunogenic, b’se they
cannot activate helper T cells
Failure to activate helper T
cells is due to their inability
to bind to MHC proteins –
b’se they are not proteins &
57. HAPTENS
Haptens are univalent, hence
cannot activate B cells by
themselves – can activate when
covalently bound to a ‘carrier
protein’ – form an immunogenic
hapten-carrier-conj
Haptens (in hapten-carrier
complex) combine with an IgM
58. HAPTENS
A peptide of the carrier
protein is presented in asso
with class II MHC protein to
the helper T cells.
The activated helper T cells
then produce interleukins,
which stimulates the B cells
59. HAPTENS
Animals immunized with such
a conjugate produce
antibodies specific for
The hapten determinant
Unaltered epitopes on the carrier
protein, &
New epitopes formed by
combined parts of both the
hapten & carrier
60. HAPTENS
Hapten – carrier molecule is
then taken in, processed, &
pieces of the carrier are
presented by these B cells &
helper T cells
In our body, the formation of
hapten-carrier conjugates is
the basis for development of
61. SUPERANTIGEN
Class of molecules that can
S
interact with APCs & T cells in a
nonspecific way
Act differently by interacting
with MHC class II mol of the
APC & the Vb domain of the T
cell receptor results in
activation of a large number of T
63. ANTIGEN
SUPERANTIGEN
Antigen presenting cell
CHO α2 β2 CHO α2 β2
MHC Class II
CHO α1 β1 CHO CHO α1 β1 CHO
Super
Antigen antigen
CHO CHO CHO CHO
αV βV αV βV
T cell receptor
CHO CHO CHO CHO
αC βC αC βC
T lymphocyte