Tolerance and immunity-Central Tolerance, Importance and Factors Influence Tolerance Induction

Tolerance and immunity-Central Tolerance, Importance and Factors Influence Tolerance Induction


Tolerance


* It is a specific immunologic unresponsiveness that is the absence of specific immune responses to a particular antigen in a fully immunocompetent person
* Unresponsiveness to self antigens is known as auto tolerance and it is a normal physiological condition.
* Both B-cells and T-cells participate in tolerance
* But T-cells play the primary role

Central Tolerance


Clonal–deletion:
* It is the process by which T-cells acquire the ability to distinguish self from non self, in fetal thymus
* This involves the killing of T-cells that react against antigens present in the fetus at that time
* Clonal deletion is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes.

Peripheral Tolerance


T-cell tolerance (clonal anergy):
* Some self-reactive T cells are not killed in thymus and enter periphery
* Functional inactivation of surviving self-reactive T cells
* B-cells become tolerant to self by two mechanisms:
1) Clonal deletion
Self reactive B cells are destroyed in the bone marrow. Therefore, mature self reacted B cells are not formed.tolerance
2) Clonal anergy
In normal cases, B cells in the periphery are unable to induce an immune response against self antigen. This process is called clonal anergy.
* Tolerance in B-cells is less complete than in T-cells
*  That’s why, most of the autoimmune diseases are mediated by antibodies and defect in B cells is responsible for them.

Factors Influencing The Induction Tolerance


1) Immunologic maturity of the host:
Neonates are immunologically immature and well
accept allograft that would be rejected by mature host
2) Structure and dose of antigen:
a- Simple molecules induce tolerance more readily than
complex ones
b- Very high and very low doses of antigen may result
in tolerance
3) T-cells become tolerant more readily and remain
tolerant longer than B-cells
4) The continuous presence of antigen helps to
maintain tolerance
5) Administration of immunosuppressive drugs enhances tolerance as in transplantation

Clinical Importance of Tolerance


1) Organ transplantation:
Introduction of tolerance may help in prevention of rejection
2) Tumor development:
Tolerance to tumor antigen results in growth of the
tumor without being detected by the immune mechanisms
3) Autoimmune disorders:
Disturbance of self-tolerance results in autoimmune disease.
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