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IMUNOGEN-

ANTIGEN-HAPTEN
DEPARTEMEN MIKROBIOLOGI
FAKULTAS KEDOKTERAN USU
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SLO:
• Menjelaskan definisi Immunogen, Antigen &
Hapten
• Menjelaskan contoh-contoh Immunogen,
Antigen & Hapten
• Menjelaskan peranan Immunogen, Antigen &
Hapten
• Menjelaskan struktur Immunogen, Antigen &
Hapten
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KEPUSTAKAAN
• Levinson, W. 2004. Medical Microbiology &
Immunology: Examination & Board Review,
8th ed. McGraw-Hill.
• Roitt. 2001. Roitt's Essential Immunology, 8th
ed. Blackwell Science.
• Lehigh University, Text book based
Immunology, Spring 2003.
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SISTEM IMUM SECARA UMUM

Immune
System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Cell- Humoral


Components Components Mediated (Ab)
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DEFINISI
• Berdasarkan fungsi, Ag dibagi :
Immunogen & Hapten
• Immunogen : A substance that induces a
specific immune response
• A stimulus that produces a humoral or
cell-mediated immune response
• Bahan yang dapat menimbulkan respon
imun spesifik
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DEFINISI
• Hapten : A substance that is non-
immunogenic but which can react with
the products of a specific immune
response

• Molekul yg dapat bereaksi dgn Ab,


tetapi tidak dapat menstimulasi
pembentukan Ab secara langsung
IMMUNOGEN-ANTIGEN-
EPITOPE HAPTEN

• Seluruh imunogen adalah antigen tetapi


tidak semua antigen adalah imunogen

• Some very small molecules called haptens can


bind to Ab’s or TCR’s but they cannot initiate
an immune respons
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DEFINISI
• Hapten: a low molecular weight molecule that can be
made immunogenic by conjugation to a suitable
carrier

• Haptens are small molecules which could never induce an


immune response when administered by themselves but
which can when coupled to a carrier molecule

• Hapten hanya akan menjadi imunogenik jika diikat oleh


molekul yg besar (disebut carrier) yang dikenal sistem
imun dan baru dapat menstimulasi pembentukan Antibodi.
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DEFINISI
• Antigen (Ag) : A substance that reacts with
the products of a specific immune
response
• Any substance that binds specifically to an
antibody or a T-cell receptor
• Bahan yang dapat menstimulasi respon
imun spesifik atau bahan yang dapat
bereaksi dengan Antibodi (Ab) yang sudah
ada
Antigen (Ag)
• Substance that provokes an immune response in
specific lymphocytes
• Perceived as foreign, not a normal constituent of the
body
• Foreign cells & large complex molecules over 10,000
MW are most antigenic
• Foreign molecules <1,000 MW (haptens) are not
antigenic unless attached to a larger carrier
• Antigenic determinant, epitope – small molecular
group that is recognized by lymphocytes.
• An antigen has many epitopes.

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Antigens

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Antigens

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Special categories of antigens
• Autoantigens – molecules on self tissues for which
tolerance is inadequate
• Alloantigens – cell surface markers of one individual
that are antigens to another of that same species
• Heterophilic antigens – molecules from unrelated
species that bear similar antigenic determinants
• Superantigens – potent T cell stimulators, provoke an
overwhelming response
• Allergen – antigen that provokes allergy

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Bagian dari Antigen yang dikenali oleh
MHC

• Epitope: the portion of an antigen that is


recognized and bound by an Ab or TCR/MHC
complex (antigenic determinant)

• Paratope: “The site in the variable (V) domain of


an antibody or T-cell receptor that binds to an
epitope on an antigen
A processed antigen in an MHC is seen by a TCR
The key event
A processed antigen in an MHC is seen by a TCR.

The TCR asks the MHC, “Are you me?” and receives an
affirmative answer, “Yes.”

The TCR asks the processed antigen, “Are you me?”


and receives the negative answer, “No!”

But what if the TCR asks the processed antigen,


“Are you me?” and receives the answer, “Yes.” TCR’s
which can see “self” are eliminated in a process called
clonal deletion.

Clonal deletion assures that TCR’s don’t see “self.”


Terdapat 2 jenis antigen

Exogenous: presented by Antigen


Presenting Cells (APC’s). These are
macrophages, B-cells, and some
dendritic cells

Endogenous: typically peptides derived


from any protein; an infected cell
displays “not-self” proteins and is, thus,
an “altered self cell”
Terdapat 2 jenis antigen

Exogenous: these antigens are


presented in MHC-II; they are seen
by T-cells with a TCR and an
associated protein called CD4

Endogenous: these antigens are


presented by MHC-I; they are seen
by T-cells with a TCR and an
associated protein called CD8
Terdapat 2 jenis T-cells

1. TH have CD4 which interacts with MHC-II;


thus, CD4+ T-cells are “MHC-II restricted.”

TH cells are “helper cells” that send signals (via


cytokines and surface proteins) to other cells of
the immune system.

The TH cells function as the “brain” of the


immune system.
Terdapat 2 jenis T-cells

2. TC have CD8 which interacts with MHC-I;


thus, CD8+ T-cells are “MHC-I restricted”

TC cells become cytotoxic T lymphocytes


(CTL’s) which attack “altered self-cells (e. g.,
infected cells.)
“Altered self-cells” are also called “target
cells.”
They are the targets for the CTL’s cytotoxicity.
• T-cell dependent antigens must be processed by
phagocytes called antigen presenting cells (APC).
• APC alters the antigen and attaches it to its MHC
receptor.
• Antigen presentation involves a direct collaboration
among an APC, T helper cell and an Ag-specific B or T
cell.
• Interleukin -1 is secreted by APC to activate TH cells
• Interleukin-2 is produced by TH to activate B & other T
cells

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Definisi
• Epitope /Antigenic Determinant :
that portion of an antigen that combines with
the products of specific immune response

• Bagian Antigen yg dapat menginduksi


pembentukan Ab & dapat diikat dengan
spesifik oleh bagian dari Ab atau reseptor
pada limfosit

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Determinants Recognized by the
Innate Immune System

• Adaptive Immune System – Discrete Determinants


– Reacts with a specific pathogen
• Innate Immune System – Broad Molecular Patterns
– Reacts with a variety of pathogens
• PAMPs – Pathogen Associated Molecular Patterns
• PRRs – Pattern Recognition Receptors

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Biological
PAMP PRR Consequence
of Interaction
Microbial cell wall Complement Opsonization;
components Complement
activation
Mannose- Mannose-binding Opsonization;
containing protein Complement
carbohydrates activation
Polyanions Scavenger Phagocytosis
receptors
Lipoproteins of TLR-2 (Toll-like Macrophage
Gram + bacteria receptor 2) activation;
Yeast cell wall Secretion of
components inflammatory
cytokines
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Biological
PAMP PRR Consequence
of Interaction
Double stranded TLR-3 Production of
RNA interferon
(antiviral)
LPS TLR-4 Macrophage
(lipopolysacchari activation;
de of Gram – Secretion of
bacteria inflammatory
cytokines
Flagellin TLR-5 Macrophage
(bacterial flagella) activation;
Secretion of
inflammatory
cytokines
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Biological
PAMP PRR Consequence of
Interaction

U-rich single TLR-7 Production of


stranded viral RNA interferon
(antiviral)

CpG containing TLR-9 Macrophage


DNA activation;
Secretion of
inflammatory
cytokines

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Hapten

• A low molecular-weight molecule that can be


made immunogenic by conjugation to a suitable
carrier
• A substance that is non-immunogenic but which can
react with the products of a specific immune
response
• Molekul yg dapat bereaksi dgn Ab, tetapi tidak dapat
menstimulasi pembentukan Ab secara langsung
Definisi
• Haptens are small molecules which could never
induce an immune response when administered
by themselves but which can when coupled to a
carrier molecule

• Hapten hanya akan menjadi imunogenik jika


diikat oleh molekul yg besar (disebut carrier)
yang dikenal sistem imun dan baru dapat
menstimulasi pembentukan Antibodi.

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Hapten
Hapten
Faktor-faktor yang mempengaruhi Immunogen

• Sifat dari Immunogen:


1. Foreigness /Asing
2. Size/Ukuran
3. Chemical Composition/Kompleksitas
4. Physical form/Bentuk fisik
5. Degradabilitas
 Faktor Biologik : Genetik & Umur
 Cara Immunogen masuk ke dalam tubuh

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1. Foreigness /Asing

• Sistem Imun dapat membedakan ‘self’ atau


‘non self’ antigen
• Pada keadaan normal, tubuh akan melakukan
toleransi terhadap komponen diri /’self’ dan
tidak membentuk respon imun terhadap sel
tubuh sendiri
• Jika molekul menjadi ‘non self’ maka akan
bersifat asing/immunogen  respon imun

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2. Size/Ukuran
• Immunogen yang poten biasanya memiliki BM>10.000 (Cth:
protein dg BM yg besar)
• Molekul dengan BM<10.000 bersifat kurang immunogenik. Asam
amino atau monosakarida biasanya tidak bersifat antigenik
• Kecuali: hapten (protein dg BM kecil), tp jk berikatan dg molekul
carrier  Antigenik
• Chemical Composition
– Primary Structure Sequence determinants

– Secondary Structure
Conformational determinants
– Tertiary Structure
– Quarternary Structure
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3.Chemical Composition/ Kompleksitas
• Bentuk polipeptida linear & protein globular
dapat menstimulasi terjadinya respon imun

• Semakin kompleks zat yang membentuk


molekul  sifat imunogen molekul akan
semakin tinggi

– Particulate > Soluble


– Denatured > Native
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4.Physical form/Bentuk fisik

• Antigen dalam bentuk partikel lebih


bersifat imunogen dibandingkan dengan
yang bersifat larut
• Antigen yang telah mengalami
denaturasi juga lebih bersifat imunogen
dibandingkan dengan bentuk aslinya.

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5.Degradibilitas
• Antigen yang mudah difagositosis lebih
bersifat imunogen
• Hal ini karena kebanyakan jenis Ag (spt: T-
dependent Ag), jika akan membentuk imun
respon, terlebih dahulu harus dikenal,
kemudian diproses, baru dipresentasikan
kepada T-helper oleh APC (Antigen Presenting
Cell)
• Ag processing by Ag Presenting Cells (APC)

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Faktor Genetik & Umur

• Faktor Genetik: ada bbrp jenis zat yg


bersifat imunogen pd 1 individu, tp tidak
pada individu yg lain.
• Umur : usia yang sangat muda ataupun
usia yang sangat tua, kurang mampu
menimbulkan respon imun akibat suatu
imunogen

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Cara Masuk Imunogen ke Dalam Tubuh

• Dosis : respon imun menjadi tidak optimal dapat


disebabkan oleh dosis Ag yang terlalu besar ataupun
yang terlalu kecil
• Cara masuk: secara umum, melalui cara Sub
Cutaneus (SC) adalah lebih baik dibandingkan dgn
cara Intra Venous (IV) ataupun intra gastric.
• Subcutaneous > Intravenous > Intragastric
• Adjuvan : zat yang digabungkan dengan imunogen
untuk memperbesar respon imun
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Adjuvants
• A substance that non-specifically enhances the
immune response to an antigen

1. Prolong the presence of the antigen


2. Enhance production of “co-stimulatory”
signals
3. Induce granuloma formation (i.e., an
accumulation of macrophages)
4. Non-specifically stimulate lymphocytes
THANK YOU

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