tolerance in our immune system , types of immune tolerance ,causes of loss of tolerance and autoimmunity

1. BY :NIDA MAQSOOD

2.  The state of inactivation of immune system to antigens
 Unresponsiveness of immune system to self antigens is
self-tolerance
 No immune response
 Healthy tissues and organs shed low levels of component
protein and cell undergo apoptosis are source of self
antigen

3. There are two types
1) Central Tolerance
2) Peripheral Tolerance

4. Central Tolerance
 Refers to primary or
central lymphoid organs
i.e thymus and bone
marrow
 Induce during early
development of
lymphocytes
 Eliminate most auto-
reactive T and B cells
 Refers to peripheral or
secondary lymphoid
organs i.e spleen ,lymph
nodes
 Induced in mature
lymphocytes
 Prevent auto-reactive
mature lymphocytes from
attacking self-antigen
Peripheral Tolerance

5.  Induce during early development of lymphocytes
 Thymic epithelial express MHCI molecule
 Bone marrow derived dendritic cells and macrophages
in thymus express MHCII molecule
 Immature T cells react with self MHC molecules

6.  Moderate binding of immature T cells and MHC
molecule
 Survival of T cells and T cells further proliferate
 Migrate to peripheral lymphoid organs
Moderate
binding
Immature
T cells
MHC
molecule
Survival
of T cells

7.  Very strong bonding of T cells and MHC molecule
 Death of cell occur due to apoptosis
 Remove all reactive T cells that recognize self
antigens
Very
strong
binding of
Immature
T cell
MHC
molecule
Cell
death

8.  Induce in mature lymphocytes
 Control or eliminate auto reactive B and T cells after
they exit bone marrow and thymus
 Its mechanism involve induction of anergy ,immune
deviation deletio, suppression

9. • Binding of TCR’s to MHC on surface of APC’s provide
first signal for activation of T cells
• But T cells must also receive second signal from APC’s
• CD8 T cells bind to the self MHC I on non APC’s this
binding provide first signal and block the second
• absence of second signal causes inactivation of T cells
known as anergy

10.  Tolerance also induce by regulatory cells
 CD4+ CD25+T cells diminish the activity of T cells
stimulated by variety of T cells
 CD8+ T cells inhibit activation and proliferation of
CD4+T cells

11.  Potentially harmful immune response in
converted to less harmful immune response

12.  List possible causes for lack of self tolerance
 Cross reactivity between similar antigens
 alteration of self antigens
 abnormal exposure to self antigens

13. Self tolerance if fails (start
responding to self-antigens)
Autoimmunity immune system
attack self
Autoimmune diseases
individuals own molecules,
tissues, cells and organs damaged