Tolerance And Immunity-Central Tolerance-Peripheral 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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