Immune tolerance

1. IMMUNE TOLERANCE
BY AGI FAITHFULL AND OJOKOJO OYINDOUBRA
BU/22B/BMS/6829 AND BU/22A/BMS/6577

2. TABLE OF CONTENT
◦DEFINITION
◦SELF TOLERANCE
◦CENTRAL TOLERANCE
◦PERIPHERAL TOLERANCE
◦CONCLUSION

3. .
DEFINITION
Immune tolerance or immunological tolerance is the process by which the
immune system does not attack an antigen. It can be either 'natural' or 'self
tolerance', in which the body does not mount an immune response to self
antigens, or 'induced tolerance', in which tolerance to external antigens created
by manipulating the immune system.
Immunological tolerance is a state of unresponsiveness of an individual to a
particular
antigen. It is induced by prior exposure of that antigen. The antigen which causes
the
tolerance is called tolerogen.
it occurs in three forms:
Central tolerance,
Peripheral tolerance

4. SELF TOLERANCE
The normal lack of the ability to produce an immunological response to
autologous (self) antigens. A breakdown of self tolerance leads to autoimmune
diseases. The ability to recognise the difference between self and non-self is
the prime function of the immune system.
Genetic defects in these processes lead to autoimmunity, such as in
Autoimmune
polyendocrine syndrome type 1 (APS-1) and immunodysregulation
polyendocrinopathy
enteropathy X-linked syndrome (IPEX).

5. MECHANISMS OF IMMUNOLOGICAL TOLERANCE
A. T-CELL TOLERANCE
1. Central Tolerance
T cells develop in the thymus. As they mature, recombination of gene segments create
the
two chains that make up the T-cell receptor for antigen (TCR). Although the receptors
on a
single T cell are all alike, there is a virtually unlimited repertoire of receptor specificities
created in the population of T cells within the thymus.
T cells whose receptors bind these epitopes so tightly that they could attack the cell
displaying them are deleted by apoptosis. The T cells that survive this negative
selection
leave the thymus and migrate throughout the immune system (lymph nodes, spleen,
etc.).
It turns out that antigen-presenting cells in the medulla of the thymus express a gene,

6. B. B-CELL TOLERANCE
The problem of B-cell tolerance is not so acute because B cells cannot respond to most
antigens unless they receive help from T helper cells.
Nevertheless, B cells become tolerized to self components and, like T cells, this occurs both
in the bone marrow (central tolerance) and elsewhere in the body (peripheral tolerance).
1. Central Tolerance
B cells are formed and mature in the bone marrow. In humans, over half of the developing B
cells produce a BCR able to bind self components.
Any cells that produce a receptor for antigen (BCR) that would bind self components too
tightly undergo a process of receptor editing. They dip again into their pool of gene segments
that encode the light and heavy chains of their BCR and try to make a new BCR that is not a
threat. If they fail, they commit suicide (apoptosis).
Despite these mechanisms, some of the B cells that migrate out of the bone marrow continue
to express self-reactive BCRs and may still be able to produce anti-self antibodies. So a
mechanism is needed to tolerize them out in the tissues ("peripheral tolerance").

7. 2.T-CELL PERIPHERAL TOLERANCE:
The T cells that leave the thymus are relatively — but not completely — safe. Some will have
receptors (TCRs) that can respond to self antigens
That are present in such high concentration that they can bind to "weak" receptors;
That they may not have encountered in the thymus.
Nonetheless, it is clear that there are mechanisms for maintaining T-cell tolerance throughout
the body.
• Negative selection in peripheral immune system .
• Lack of costimulation
• Control by regulatory T-CELLS

8. 2.B-CELL Peripheral Tolerance
B cells with a potential for attacking self can be kept in check by the absence of the T-helper
cells they need; that is, T-cell tolerance is probably the most important (but not the only)
mechanism for maintaining B-cell tolerance.

9. CONCLUSION
◦ If immunological self tolerance is lost the body developes an auto immunity against its own
tissues and cells which becomes the source of autoimmune diseases
◦ Self tolerance plays a key role in the prevention and treatment of immune disorder diseases
especially auto immune diseases.

10. REFERENCES
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11. Thank you