AUTOIMMUNITY

B Cell Tolerance
T Cell Tolerance
Clonal Deletion
Clonal Anergy
Immunogen vs Tolerogen
Mechanism of breaking B and T
Cell`Tolerance

B CELL TOLERANCE
Sel B menghasilkan antibodi untuk apa saja yang
tidak normal ada dalam tubuh
Mengenal antigen melalui resptor (IgM.IgD) yang
sudah ada pada sel B mature yang bisa
menangkap jutaan jenis antigen.
Bagaimana proses seleksi dalam BM waktu
pematangan sel B tidak jelas seperti pematangan
sel T di Timus.
Sel B tidak berespons terhadap antigen self
disebut tolerance (normal), tetapi B Cell
Tolerance dimaksudkan juga jika tidak berespon
terhadap antigen asing (abnormal)

B or T CELL TOLERANCE
is a process that involves the faillure of B or T cell to respond
to self antigens (normal) or foreign antigens (abnormal)
CLONAL DELETION
This process involved the elimination of immature B or
T cells after antigen binds to their receptor.
CLONAL ANERGY
This process involves the inability of mature B or T cells
to respond to antigen even after it binds to
its receptor.
IMMUNOGEN
The antigen is called an immunogen if it induces
activation of a B or T cell
TOLEROGEN
The antigen is called tolerogen if it does not activate
a B or T cell (Its induce B or T cell clonal anergy).

B CELL TOLERANCE

Stem Cell

Pro-B

Pre-B

Bone Marrow

Immature B Mature B Effector B

Peripheral lymphoid
organ or tissue

No antigen dependence
RAG-1 and RAG-2

Receptor Editing

IgM,IgD

Self antigen Foreign antigen

Selection

Clonal Deletion
(apoptosis)

CentralTolerance

Performance
effector
function.

Clonal anergy

Peripherial Tolerance

B CELL TOLERANCE
SELF ANTIGENS

IgM
B

IgD
Th

Immature

IgM
B

Th

Mature

CLONAL ANERGY
Polyclonal activation

CLONAL DELETION

ACTIVATED CLONE

DEATH
AUTOIMMUNE

SELECTION OF IMMATURE B CELLS

(CLONAL SELECTION)

IgM
B

AUTOIMMUNE DISEASE
IgD
B

Immature B cells

Self Antigen

IgM

IgM
Mature B cells

Self Antigen
IgM

IgD
B

Immature B cells

apoptosis
(Negative Selection)

Cell Activation
AUTOIMMUNE

Idiotype
(cdr)

Millions of proteins
(self & foreign)
H-Chain

Fab

Fc

Constan
portion
(merah)

Variable
portion
(biru)

L-Chain

papain

Antigen
Binding Site

-s-sRAG-1 & RAG-2

(Bone Marrow stage)

B CELL TOLERANCE IN BONE MARROW

Autoreactieve B Cells (Expression of chain)
Reactivate expression of RAG-1 & RAG-2
recombinese proteins. (rearranging light chain genes)
-deleting element
(sejumlah segmen gen hilang)
Assemble a new & gene
(Receptor Editing)

Fail of Receptor Editing

No autoreactivity
Release from Bone Marrow
to peripherial lymphoid organ

death
(apopthosis)

T CELLS TOLERANCE

TCR

Stem Cell Pro-T Pre-T Immature T Mature T Naive mature T

BM

Periphery

Thymus
No respon to antigen

Pos&Neg selection (self ant)

activation by
Foreign ant

RAG 1 & RAG 2 expression

Clonal Deletion
(apoptosis)

T cell regulator Clonal anergy

CentralTolerance

Peripherial Tolerance

T CELL ANERGY

CTLA-4

anergy

B CELL TOLERANCE
is a process that involves the faillure of B cell to respond to
self (normal) or foreign (abnormal) antigen.
CLONAL DELETION
This process involved the elimination of immature B cells
after antigen binds to their immunoglobulin receptor.
CLONAL ANERGY
This process involves the inability of mature cells
to respond to antigen even after it binds to
its immunoglobulin receptor.
IMMUNOGEN
The antigen is called an immunogen if it induces
activation of a B cells
TOLEROGEN
The antigen is called tolerogen if it does not activate
a B cell (Its induce B cell clonal anergy).

MECHANISM FOR BREAKING

B AND T CELL TOLERANCE

MOLECULAR MIMICRY
POLYCLONAL
B CELL ACTIVATION
POLYCLONAL
T CELL ACTIVATION
EXPOSURE OF HIDDEN
SELF ANTIGEN

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

MOLECULAR MIMICRY
IgD

IgM

Streptococcus
Antigen (epitop)

Streptococcus
antibody

Cross
Reaction

epitop on
heart cells

Destruction of heart tissue

RHEUMATIC FEVER

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

POLYCLONAL STIMULANT
LIPOPOLISACHARIDE (LPS)

IgD

IgM

IgD

Th

IgM
B

Self Antigen
(heart,Kidney,
Insulin,Lung)
ANERGIZED B CELLS

Stimulatory signal
Cytokine
ACTIVATED B CELLS
Anti heart Antibody
Anti kidney Antibody
Anti Insulin Antibody
Anti Lung Antibody

Anti LPS Antibody

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

POLYCLONAL STIMULANT
SUPERANTIGEN OF BACTERIA

IgD
APC

Th

IgM
B

Self Antigen
(heart,Kidney,
Insulin,Lung)
ANERGIZED B CELLS

Stimulatory signal
Cytokine
ACTIVATED B CELLS
Anti heart Antibody
Anti kidney Antibody
Anti Insulin Antibody
Anti Lung Antibody

HLA link immunolgic

Disease
Disease
HLA allele RR
Rheumatoid Arthritis DR4
4
Insulin-Dep Diabetes DR3
5
DR4
5
DR3/DR4 25
Multiple sclerosis
DR2
4
SLE
DR2/DR3 5
Pemphigus vulgaris
DR4
14
Ankylosing Spondylitis B27
90-100

AUTOIMMUNITY
B Cell Tolerance
T Cell Tolerance
Clonal Deletion
Clonal Anergy
Immunogen vs Tolerogen
Mechanism of breaking B and T
Cell`Tolerance

B CELL TOLERANCE

Stem Cell

Pro-B

Pre-B

Bone Marrow

Immature B Mature B Effector B

Peripheral lymphoid
organ or tissue

No antigen dependence
RAG-1 and RAG-2

Receptor Editing

IgM,IgD

Self antigen Foreign antigen

Selection

Clonal Deletion
(apoptosis)

CentralTolerance

Performance
effector
function.

Clonal anergy

Peripherial Tolerance

B CELL TOLERANCE
SELF ANTIGENS

IgM
B

IgD
Th

Immature

IgM
B

Th

Mature

CLONAL ANERGY
Polyclonal activation

CLONAL DELETION

ACTIVATED CLONE

DEATH
AUTOIMMUNE

T CELLS TOLERANCE

TCR

Stem Cell Pro-T Pre-T Immature T Mature T Naive mature T

BM

Periphery

Thymus
No respon to antigen

Pos&Neg selection (self ant)

activation by
Foreign ant

RAG 1 & RAG 2 expression

Clonal Deletion
(apoptosis)

T cell regulator Clonal anergy

CentralTolerance

Peripherial Tolerance

T CELL ANERGY

CTLA-4

anergy

B CELL TOLERANCE
is a process that involves the faillure of B cell to respond to
self (normal) or foreign (abnormal) antigen.
CLONAL DELETION
This process involved the elimination of immature B cells
after antigen binds to their immunoglobulin receptor.
CLONAL ANERGY
This process involves the inability of mature cells
to respond to antigen even after it binds to
its immunoglobulin receptor.
IMMUNOGEN
The antigen is called an immunogen if it induces
activation of a B cells
TOLEROGEN
The antigen is called tolerogen if it does not activate
a B cell (Its induce B cell clonal anergy).

MECHANISM FOR BREAKING

B AND T CELL TOLERANCE

MOLECULAR MIMICRY
POLYCLONAL
B CELL ACTIVATION
POLYCLONAL
T CELL ACTIVATION
EXPOSURE OF HIDDEN
SELF ANTIGEN

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

MOLECULAR MIMICRY
IgD

IgM

Streptococcus
Antigen (epitop)

Streptococcus
antibody

Cross
Reaction

epitop on
heart cells

Destruction of heart tissue

RHEUMATIC FEVER

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

POLYCLONAL STIMULANT
LIPOPOLISACHARIDE (LPS)

IgD

IgM

IgD

Th

IgM
B

Self Antigen
(heart,Kidney,
Insulin,Lung)
ANERGIZED B CELLS

Stimulatory signal
Cytokine
ACTIVATED B CELLS
Anti heart Antibody
Anti kidney Antibody
Anti Insulin Antibody
Anti Lung Antibody

Anti LPS Antibody

THE ROLE OF INFECTION IN THE

DEVELOPMENT OF AUTOIMMUNITY :

POLYCLONAL STIMULANT
SUPERANTIGEN OF BACTERIA

IgD
APC

Th

IgM
B

Self Antigen
(heart,Kidney,
Insulin,Lung)
ANERGIZED B CELLS

Stimulatory signal
Cytokine
ACTIVATED B CELLS
Anti heart Antibody
Anti kidney Antibody
Anti Insulin Antibody
Anti Lung Antibody

HLA link immunolgic

Disease
Disease
HLA allele RR
Rheumatoid Arthritis DR4
4
Insulin-Dep Diabetes DR3
5
DR4
5
DR3/DR4 25
Multiple sclerosis
DR2
4
SLE
DR2/DR3 5
Pemphigus vulgaris
DR4
14
Ankylosing Spondylitis B27
90-100

AUTOIMMUNE DISEASES
Rheumatoid Arthritis (antinuclear antibody)
Rheumatic Fever (antistreptococcus antibody)
Goiter(antibody against thyroid epithelial cells)
Diabetes Mellitus type I (antibody against
materials of cytoplasm/cell membrane of
pancreas cell, cytotoxicity of T cell to cell).
Chronic Thyroiditis (Hashimoto), (B and T cell
infiltration)
Scleroderma (antinuclear antibody)

Contoh-contoh penyakit otoimun

Artritis reumatoid (antinuclear antibody)
Demam Reuma (antibodi thd streptococcus)
Goiter (antibodi terhadap epitel tiroid)
Diabetes Mellitus tipe I (antibodi terhadap
bahan sitoplasma dan membran sel Beta
Pankreas dan sitotoksitas sel T terhadap el
Beta Pankreas).
Tiroiditis kronis(Hashimoto) (infiltrasi sel T&B)
Scleroderma (antinuclear antibody)