Mekanisme kontrol pada

respons imun
Respons imun sbg suatu sistem yg
fisiologik signal on : respons imun
(+) signal off : tak terjadi respons imun
Ag spesifik + limfosit respons imun (+):
imuno-kompeten.
Ag spesifik + limfosit respons imun (-) :
imuno-toleran.

Immunologic
Tolerance

Contents

Part Introduction
Part Development of Immunologic Tolerance
Part Mechanism of Immunologic Tolerance
Part Immunologic Tolerance and Clinic
Medicine

Part Introduction
Definition: A type of specific unresponsiveness
to an antigen induced by the exposure of
specific lymphocytes to that antigen, but
response to other antigens normally.
(= state of unresponsiveness to particular
antigenic epitope)
Tolerogens: antigens that induce tolerance
As a concequence of inactivation by antigen,
lymphocytes deleted or anergic

General features of Immunologic tolerance

Tolerance is antigenic specific and results from the
recognition of antigens by specific lymphocytes.
Normal individuals are tolerant of their own
antigens(self antigen)----- Self-tolerance.
Foreign antigens may be administered in ways that
preferentially inhibit immune response by inducing
tolerance in specific lymphocytes---antigen
induction.

Immunologic
Immunologic features
features of
of tolerance
tolerance

ItIt is
is an
an antigen-induced,
antigen-induced, active
active process
process

Like
Like immunologic
immunologic memory,
memory,itit is
is antigen
antigen specific
specific

Like
Like immunologic
immunologic memory,
memory,itit can
can exist
exist in
in BB cells,
cells,
TT cells
cells or
or both
both

Like
Like immunologic
immunologic memory,
memory,its
its easier
easier to
to induce
induce
and
and lasts
lasts longer
longer in
in TT cells
cells than
than in
in BB cell
cell

Difference of Immunologic tolerance &

immunodeficiency, immunosuppression
Immunodeficiency: any condition in which
there is deficiency in the production of
humoral and /or cell-mediated immunity--non-specificity to Ag
Immunosuppression: The suppression of
immune responses to antigens. This can be
achieved by various means, including
physical, chemical----non-specificity to Ag

Part Development of Immunologic

Tolerance

1. Induction of immunologic tolerance to

antigen in fetal period and neonate period
Owen first observed
immunologic
tolerance to
allogenic antigen in
fetal period in 1945

Experiment of Medawar on immunologic tolerance

2. Induction of immunologic tolerance to

antigen in adult
Antigen and immunologic tolerance:
Concentration of antigens
Type of antigen: monomer, aggregates
Pathway of antigen entering body
Features of determinant: tolerogenic epitope
Variation of antigen

High
High and
and low
low dose
dose tolerance
tolerance

Tolerance
Tolerance in
in TT and
and B
B cells
cells

Factors
Factors affecting
affecting tolerance
tolerance
role
role of
of antigen
antigen
Favor immune
response

Favor tolerance

Physical form of
antigen

Large, aggregated,
complex molecules,
properly processed

soluble, aggregate-free,
simple small molecules,
not processed

Route of injection

Subcutaneous or
intramuscular

Oral or, sometimes,

intravenous

Dose of antigen

Optimal dose

Very large or very small

dose

Factors which
affect response

Individual and immunologic tolerance:

Heredity, Age, Gender, Health

Factors
Factors affecting
affecting tolerance
tolerance
the
the role
role of
of host
host
Factors that
affect response

Favor immune
response

Favor tolerance

Age of responding
animal

Fully differentiated;
memory T & B cells

Newborn (mice), immunologically immature

Differentiation
state of cells

Older, immunologically mature

Relative undifferentiated B
cell with only IgM, T cells
in the thymic cortex

Host
Host age
age and
and antigen
antigen dose
dose affect
affect
tolerance
tolerance

newborn

adult

Part Mechanism of Immunologic

Tolerance

1. Central tolerance:
Central tolerance occurs in the central
lymphoid organs as a consequence of
immature self-reactive lymphocytes
recognizing ubiquitous self-antigen.
2. Peripheral tolerance:
tolerance was induced in peripheral organs
as a result of mature self-reactive
lymphocytes encountering tissue-specific
self antigens under particular conditions

1. Central tolerance
Clonal deletion (apoptotic cell death)
During maturation of lymphocytes in the
thymus for T cell or in the bone marrow for B
maturation, immature lymphocytes that
recognize ubiquitous self-antigen with high
affinity are deleted by negative selection

Clonal
Clonal deletion:
deletion:

negative
negative selection
selection of
of TT cells
cells in
in the
the thymus
thymus

Negative
Negative selection
selection of
of BB cells
cells in
in
bone
bone marrow
marrow

2. Peripheral tolerance
clonal deletion and clonal ignorance:
large tissue specific antigen delete specific T cells.
self-reactive lymphocytes remain viable and
functional but do not react to the self antigens in
any detectable way.
Clonal anergy and inactivation:
functional inactivation without cell death: lack costimulatory signal

Clonal
Clonal anergy
anergy in
in TT cells
cells

Clonal
Clonal anergy
anergy in
in B
B cells
cells

 Action of Suppressor lymphocyte (Ts)

- CD8+ cells have cytotoxic activity toward T
and B cells

Action of cytokines:
-TGF- supressant of T and B
proliferation,
mediated

- IL-10, IFN-gamma prevent IL4

switching of B cell.

Part Immunologic Tolerance and

Clinic Medicine

1. To induce immunologic tolerance

Prevent the rejection of organ allografts

and xenografts
Treat autoimmune diseases
Treat allergic diseases

2. To terminate immunologic
tolerance
To treat tumor :
enhance first signal or second signal
To treat infection diseases

Summary
Definition of immunologic tolerance
Features of immunologic tolerance
Induction of immunologic tolerance
Mechanism of immunologic tolerance
Clinical application of immunologic tolerance