Antigen

ANTIGEN
Dr. N.RAJKUMAR,
MD.MICROBIOLOGY,
ASSISTANT PROFESSOR,
DEPT OF MICROBIOLOGY,
DSMCH

ANTIGEN
 Molecules that can be
recognized by
 Immunoglobulin receptors of
B cells or
 T cell receptors (when
complexed with MHC)
are called as ANTIGENS

DEFINITION..
 ANTI - GEN
Contd..
 ‘ANTI’body ‘GEN’erator
 Substances that react with
antibodies
 IMMUNO - GEN
 ‘IMMUN’E response
‘GEN’erator

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

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

Determinants Of
Antigenicity
 The important
determinants….
 Molecular size
 Foreignness
 Chemical & Structural
Complexity
 Stability

MOLECULAR SIZE
 Protein molecules with
large molecular weight -
Highly Antigenic
 Substances with mol wt >
1,00,000 Da  highly
immunogenic
 Substances with mol wt <

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

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

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

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

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

Chemical & Structural
Complexity
 Proteins – most potent
immunogens
 Polysaccharides
– Immunogenicity less
than proteins
 Nucleic acids & Lipids
– not efficient in eliciting
an good immune reaction

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

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,

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

STABILITY
 Highly stable and non-
degradable substances are
not immunogenic.
 example:- some platics,
metals, or chains of D-
aminoacids
 B’se Internalization,

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,

Other factors of Antigenic
Determinant
 Biological systems
 Dosage
 Route
 Adjuvants

BIOLOGICAL
SYSTEMS
 Play an important role in
determining the
Immunological Efficiency of
an Ag
 Some substances
- immunogenic in one
species

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

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

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.

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

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

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

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

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

ANTIGENIC SPECIFICITY
Antigenic
specificity of an
antigen depends
on
EPITOPES or

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 &

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

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

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

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

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

SUPERANTIGENS
 Examples
 Staphylococcal
enterotoxins,
 TSS toxin,
 Efoliative toxins &
 some viral proteins.

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

Antigen

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