REGULASI SISTEM IMUN

Ratna Kusumawati

Fakultas Kedokteran
Universitas Sebelas Maret
Surakarta
ANATOMY OF THE IMMUNE SYSTEM
CELLS OF THE IMMUNE SYSTEM
FUNCTIONING OF THE IMMUNE SYSTEM
HUMORAL (ANTIBODY MEDIATED) IMMUNE RESPONSE CELL MEDIATED IMMUNE RESPONSE
ANTIGEN (1ST EXPOSURE)
ENGULFED BY

MACROPHAGE ANTIGENS
FREE
DISPLAYED
ANTIGENS BECOMES BY
DIRECTLY
INFECTED
ACTIVATE APC CELLS
ACTIVATE
STIMULATES

HELPER CYTOTOXIC
B CELLS T CELLS
STIMULATES STIMULATES T CELL

MEMORY
GIVES RISE TO HELPER T GIVES RISE TO
CELLS
STIMULATES STIMULATES
STIMULATES

ANTIGEN (2nd EXPOSURE)

PLASMA MEMORY STIMULATES ACTIVE
MEMORY
CELLS B CELLS T CELLS CYTOTOXIC T
CELL

SECRETE ANTIBODIES
SISTEM KOMPLEMEN
Dua aspek penting dalam
regulasi respons imun:

1. Pada saat terbentuknya imunokompetensi.

2. Pengendalian respon limfosit yang matang

terhadap Ag.
Secara umum respons imun dipengaruhi oleh:

• Genetik
• Umur
• Nutrisi
• Molekul MHC
• Efek sitokin
• Antigen
• Antibodi
Pengaturan oleh Ag

Dosis besar Dosis kecil

diberikan berulang diberikan berulang

Toleransi Toleransi

Dosis sedang Imunitas

Pengaturan oleh Ag

Sifat Ag:
Makin kompleks

Makin banyak epitop

Memperbesar interaksi antar sel

Merangsang respons imun

Pengaturan oleh Ag

Metabolisme Ag:

Substansi yang tidak dapat dimetabolis

Resisten terhadap digesti enzimatik

Tidak dapat diproses oleh APC

Pengaturan oleh Ag

Ag sequestration: • protein lensa

• protein sperma
• Ag tulang rawan

Terlindung barrier anatomik

Tidak terpapar pada sistem imun

 Cytokines

B Th
Antigen Cytokines Tc LG
presentation
Activation
Cytotoxicity

APC

Intracellular Virally infected

Organism in Cells & some
macrophage tumor cells
Antibody production
 MODEL DIFERENSIASI SEL MEMORY
Ag
+
costimulation

Activated cells + factor / Effector cells

environment X
Ag

Activated cells + factor

Memory cells
environment Y
 MODEL DIFERENSIASI SEL MEMORY (3)

Ag
+ Apoptotic death
costimulation Ag >95%

Naieve cell Activated cell Effector cell

Memory cell
Pengaturan oleh Ab

Feedback inhibition
Produksi Ab
• produksi Ab

Produksi IgG

Menghambat produksi IgM

CYTOKINE
SOURCE

REC CELLS

AUTOCRINE

ENDO BIOLOGIC
ACTION CYTOKINE
CRINE EFFECTS

PARACRINE

REC CELLS
TARGET
 SOURCE

• MACROPHAGE
• T LYMPHOCYTE
• EPITHELIAL CELL
• DENDRITIC CELL
• FIBROBLAST
 CELLS

ANTIGEN MITOGEN

CYTOKINE

• LYMPHOKINE
• MONOKINE
• INTERLEUKIN
MEDIATE
and
REGULATE

IMMUNE & INFLAMMATORY

REACTION
CYTOKINE
 CD4+ T cells
• T cells with CD4 marker (glycoprotein)
• 70% of T cells in the periphery
• T helper cells
• Play central role in modulating cellular immunity
via secretion of cytokines that modulate:
– B cell activation
– Immunoglobulin secretion (quality)
– Macrophage and dendritic cell activation
– Cellular chemotaxis and inflammation
• Th1 versus Th2 cells
 Th1 and Th2 cells
CD4+ T helper cells can be classified into two
based on their cytokine profiles: T helper cell type
1 (Th1) and T helper cell type 2 (Th2).
 Cytokine profile is influenced by several factors:
Nature and dose of antigen
Route of infection
Initial cytokine environment
Type of antigen presenting cell/costimulation
Genetic background

 The cytokine profile determines the effector function of

the helper cell
Differences b/w Th1 and Th2 cells

Th1 cell Th2 cell

Produces type 1 Produces type 2
cytokines cytokines
 IL-2, IFN-g, TNF-a,  IL-4, IL-5, IL-10, IL-

TNF-b 13
Activates macrophages Provides help to B cells
and DCs for intracellular in antibody response
killing of pathogens Mediates allergy and
Mediates CMI immunity to
extracellular pathogens,
including parasites
Fungsi efektor
Sel T helper 1

Fungsi efektor
Sel T helper 2
Peranan sitokin
MEDIATOR & REGULATOR

INNATE
IMMNUNITY
TNF, IL-1, IL-12, IFN a, b
IL-10. IL-6, IL-15, IL-18

ADAPTIVE
IMMNUNITY

IL-2, IL-4, IL-5, IFN 

LT, TGF b, IL-13
29
 ACTIVATED MN PHAGOCYTE
ANTIGEN STIMULATED T CELL
NK CELL
MAST CELL

LPS (GRAM NEG) MICROBES

TNF a

• POTENTIAL MEDIATOR OF ACUTE

INFLAMMATORY RESPONSE
• RESPONSIBLE FOR SYSTEMIC
COMPLICATION OF SEVERE INFECTION
 CLASSIFICATION OF IFN

SOURCE
LEUCOCYTE IFN IFN a
TYPE I
FIBROBLAST IFN IFN b
TYPE II IMMUNE IFN IFN g
BIOLOGIC ACTION OF IFN a & b
BIOLOGIC ACTION OF IFN g
BIOLOGIC EFFECT OF TNF a
Cytokines imbalance between effector and T regulatory cells in Autoimmune disease
ROLE OF CYTOKINE
IN HEMATOPOIESIS
 CELLS

INFLAMMATORY
STIMULI

CHEMOKINE

CHEMOTACTIC CYTOKINE

• STIMULATE LEUCOCYTE MOVEMENT

• REGULATE MIGRATION LEUCOCYTE
FROM BLOOD TO TISSUE

RECRUIT LEUCOCYTES TO THE SITE OF INFLAMMATION

 TISSUE

NORMALLY/INJURY

CHEMOKINE

PROMOTING MIGRATION LYMPHOCYTE

TO DIFFERENT REGION OF PERIPHERAL
LYMPHOID ORGAN
REGULATE THE TRAFFIC OF LYMPHOCYTES
THROUGH PERIPHERAL LYMPHOID TISSUE
 REGULASI DALAM
TOLERANSI IMUNOLOGIK
Sistem imun normal
 membedakan self dari nonself

self tissue/ self tissue/

antigen antigen

immune
tolerance response autoimmune

SISTEM IMUN
 Sentral
diinduksi oleh pengenalan
self-Ag oleh limfosit immature
di organ limfoid generative.
Self tolerance
Perifer
diinduksi oleh pengenalan
self-Ag oleh limfosit mature
di organ limfoid perifer.
Toleransi Limfosit T
ANERGI
Akibat pengenalan Ag tanpa adanya
ko-stimulasi yang adekuat.
Delesi

apoptosis
Supresi oleh sel T regulator
KOOPERASI ANTAR SEL
Complex network