ANTIGEN

Yoes Prijatna Dachlan

Fakultas Kedokteran
Universitas Airlangga

microbe

antigen
Ag-binding site

epitope

Fab region

Antibody (Ab)

Fc region

Fc receptor

phagocyte
(Yoes Prijatna Dachlan, 2011)

(Male, Brostoff, Roth, Roitt, 2006)

Bacterial Pathogen
S. pneumoniae

C1s

C1r

collagen
region

C1q
(Yoes Prijatna Dachlan, 2014)

Ag can bind in pockets or

grooves or on extended
surfaces in the binding sites of
Abs

(Janeway, CA., 2001)

(Yoes Prijatna Dachlan, 2010)

CRO CDN

S. pneumoniae

C1q

C3b CRP

SAP

Opsonization

S. pneumoniae

FcR

C3bR Receptor for

CRP SAP

Phagocytosis

(Yoes Prijatna Dachlan, 2014)

ANTIBODIES RECOGNIZE EPITOPES

epitope
rekognisi
Ag 1

Ag 2

Ag 3

(Yoes Prijatna Dachlan, 2011)

Ab 1

Ab 2

Ab 3

(Male, Brostoff, Roth, Roitt, 2006)

Ag

Immunogenicity, Specificity
&
Clonal selection theory

Ag

B cell

B cell

ONE CELL ONE SPECIFICITY

Activation

Plasma cell

B cell

Ab

Ag
(Yoes Prijatna Dachlan 2011)

Lymphocyte clones matures

in the absence of Ags

In generative
lymphoid organs

Clones of mature
lymphocytes
specific for diverse Ags

Ags enter
lymphoid tissues

Ag-specific clones are

activated (selected)
by Ags
Ag-specific immune
responses occur

The Clonal Selection

Theory
(Yoes Prijatna Dachlan,2015)

(Abbas, 2015)

ANTIGEN :
Molecules that are
specifically recognized by
antigen receptors either B
cells or T cells

Ag
Receptor

Ag

B cell

MHC
molecule

Molecules that initiate

adaptive immune
responses

TCR

T cell

APC

Antigen
(Yoes Prijatna Dachlan, 2011)

(Male, Brostoff, Roth, Roitt, 2006)

(Yoes Prijatna Dachlan 2010)

(Yoes Prijatna Dachlan

(Abbas, 2010)

Peptide binding to MHC molecules

In recognition
by T cells
P2(Tyr53)
P5(Le56)
P8(Asn59)

(Abbas, 2010)
(Yoes Prijatna Dachlan

Involved in binding to MHC molecules

P1(Asp52)
P4(Ile55)
P6(Gln57)
P7(Ile58)
P9(Ser60)

ANTIGENS are any substances that are capable, under appropriate

conditions, of inducing the formation of antibodies and reacting
specifically with the antibodies so produced. They react with both Tcell recognition receptors and antibodies (Zabriskie,JB., 2009; Ess Clin
Imm)

IMMUNOGEN

EPITOPE

More recently, the term

immunogen has been
designated to refer to
molecules that induce the
activation of T or B cells
in
the presence of
appropriate costimulatory
molecules

The B and T-cell

antigen
receptors recognize a
unique region of the
antigen
= Antigenic
determinant
Complex Ags contain
several epitopes
(Gorczynski,R., 1999; Clin Imm)
(Yoes Prijatna Dachlan 2011)

Antigens:
Immunogenicity & Antigenicity
Immunogenicity is the
ability to induce a humoral
and/or CM immune
responses
B + Ag Eff-B + Memory B

Plasma cells Ab
T + Ag Eff-T + Memory T

CTL, Th

Antigenicity is
the ability to
combine
specifically with
the final product
of the immune
responses

(Yoes Prijatna Dachlan 2011)

Immunogen &
immunogenicity

1. Particular
ofof
anan
infectious
macromolecules
1.Particular
Particularmacromolecules
macromolecules
of an
agent
: proteins
or: proteins
polysaccharides
infectious
agent
infectious agent : proteinsor
or
2.polysaccharides
Immunogenicity
polysaccharidesrather depends on a
of properties
of the
particular
2.2.number
Immunogenicity
rather
depends
on
aa
Immunogenicity
rather
depends
on
biological
system
that the
Ag encounters
number
of
properties
of
the
particular
number
of
properties
of
the
particular
3.biological
Nature : foreignness,
chemical
system
that
the
Ag
encounters
biological
system
that
the
Ag
complexity, accessibility, susceptibility to
3. Nature
: foreignness, chemical
encounters
the Ag processing and presentation
complexity,
accessibility,
susceptibility to
3.
Nature
:
foreignness,
chemical
4.the
TheAg
biological
system
: genotype,
dosage
processing
and
presentation
accessibility,
susceptibility
&complexity,
route administration,
adjuvants
4. The
biological
system : genotype,
to the
Ag: B
processing
presentation
5. Epitopes
and T cell and
epitopes,
&
route
administration,
adjuvants
4.dosage
The
biological
system
:
genotype,
sequential and conformational (non5.sequential)
Epitopes
B andadministration,
T cell epitopes,
dosage &: route
epitopes
sequential
adjuvants and conformational (non(Yoes Prijatna Dachlan 2010)
sequential) epitopes

Foreignness
The immune system normally discriminates
between self and nonself
Only molecules that are foreign to the host
are immunogenic
The greater the phylogenetic distance
between two species, the greater the
structure and antigenic disparity between
them

(Yoes Prijatna Dachlan 2010)

Foreignness
Cow
Not immunogenic

Rabbit

Strongly immunogenic

BSA
Bovine serum albumin

Human

Strongly immunogenic

(Yoes Prijatna Dachlan 2010)

Molecular size
1.The most potent immunogens are
macromolecular
proteins
with
molecular weights > 100,000 Da
2. Generally, substances with a MW <
5000 10,000 Da are poor
immunogens
3. In a few instances, substances with
a MW of < 1000 have proved to be
immunogenic
(Yoes Prijatna Dachlan 2010)

Mode of contact
An insufficient (low) dose of Ag
Low-zone tolerance (immunologic
unresponsiveness)
Excessive doses of Ag High-zone
tolerance
Boosters the clonal proliferation
of Ag-specific T and B cells
Route of contact can influence the
qualitative nature of a response
(iv,id,sc,im,ip)
(Yoes Prijatna Dachlan 2010)

Chemical complexity
Homopolymer : repeating units of a single amino acids

Poor immunogen
Copolymers of 2 or even better 3 AAs are more
immunogenic

Aromatic AAs (e.g. tyrosine) contribute
immunogenicity than nonaromatic residues

more

to

The protein organizational structure (conformational and

linear epitopes)

(Yoes Prijatna Dachlan 2010)

Accessibility
YEYEYEAAAAA

AAAAAYEYEYE

YEYEYEAAAAA

AAAAAYEYEYE

YEYEYEAAAAA

AAAAAYEYEYE

A-specific
antibodies

Y and E-specific
antibodies

(Yoes Prijatna Dachlan 2011)

The protein organizational

structure (1)

(Kuby, 2006)

(Yoes Prijatna Dachlan 2010)

The protein organizational

structure (2)

(Kuby, 2006)

(Yoes Prijatna Dachlan 2010)

2010
(Yoes Prijatna Dachlan 2010)

2010
Yoes Prijatna Dachlan 2010

Genetic constitution of the host

Two different inbred strains of mice
responded very differently to
synthetic polypeptide immunogen
MHC gene products play a central
role in determining the degree to
which an animal responds to an
immunogen
(Yoes Prijatna Dachlan 2010)

ADJUVANTS

Ag persistence is prolonged
Co-stimulatory signals are enhanced
Local inflammation is increased
The non-specific proliferation of
lymphocytes is stimulated

(Yoes Prijatna Dachlan 2010)

The capacity of the drugs to

induce allergic reactions
In the body, formation of hapten carrier
conjugates is the basis of allergic responses
to drugs such as penicillin
Penicilloyl-protein derivative = H-C-Conjugates

(Yoes Prijatna Dachlan 2010)

Hapten is an Ag, not

immunogen

(Yoes Prijatna Dachlan 2010)

Kuby, 2006
(Yoes Prijatna Dachlan 2010)

Ags :
Protein, Polysaccharide, Lipids
T-dependent antigens

T-independent antigens

Particularly protein
antigens,
B cell activation occurs
only
in the presence of T-cell
cytokines, and cognate
interaction with
activated T
cells

Polysaccharide molecules
can activate B cells in the
absence of T cell help
Type I : Pneumococcal
polysacharide, non
mitogenic
Type II : LPS, a cell wall
component ofn Gram ve
bacteria, mitogenic

(Yoes Prijatna Dachlan 2011) (Gorczynski,R., 1999; Clin Imm)

Abs

CD8+ T cell
Hepatic stage

Sporozoite

LSA
SALSA

CSP
TRAP
STARP

Abs
Merozoite
AMA-1
EBA175
Pf RH1/2/3/4
MSP1/2/3
RAP1/2
GLURP

Ring trophozoite
RESA

~Species specific immunity

~Stage specific immunity
~Antigenic diversity
~Geographic origin
~Polyclonal B cell activation

NK and
CD4+ T cell

Schizonts
PfEMP-1
Rifins
STEVOR
HRP-2

Abs

(Yoes Prijatna Dachlan 2013)

Gametocyte
Pfg27
Pfg230
Pfg48/45

(Kinyanjui, 2012)