Page 121 - Concise Pathology for Exam Preparation ( PDFDrive )

106 SECTION I General Pathology

(b)
Peripheral suppression by T cells
• �A population of T cells is called ‘regulatory T cells’. These cells have the ability
to down regulate function of autoreactive T cells. This is mediated by secretion
of cytokines.

• �CD41 T cells of T H 2 type are the best known ‘regulatory cells’ and are thought
to mediate their action via cytokines like IL4, IL10 and TGF b.
Clonal deletion by activation-induced cell death
(c)
• �CD41 T cells that recognize self-antigens may receive signals that promote their

death by apoptosis.
• �Lymphocytes express Fas (CD95), a member of TNF receptor family.
• �Fas ligand (Fas L) is a member protein that is structurally homologous to the
cytokine TNF, and is expressed mainly on activated T lymphocytes.
• �Engagement of Fas by Fas L induces apoptosis of activated T cells and may cause
peripheral deletion of autoreactive T cells.
• �Self-reactive B cells are also deleted by Fas L on T cells due to engaging of Fas
on B cells.
Antigen sequestration
(d)
Some antigens are hidden from the immune system because the tissues in which these
antigens are located do not communicate with the blood and lymph, eg, testis, eye and
brain.

Q. Differentiate between central and peripheral tolerance.

Ans. Differences between central and peripheral tolerance are enlisted in Table 5.7.

TABLE 5.7. Differences between central and peripheral tolerance
Features Central tolerance � Peripheral tolerance
Origin Thymus/bone marrow Peripheral tissue
Mechanism Clonal deletion of self-T/B cells Clonal deletion, clonal anergy, peripheral
suppression by T cells
Role in autoimmune diseases Failure may not result in autoimmune Failure usually results in autoimmune
diseases diseases

Q. Write in detail on mechanism of development of autoimmunity.
Ans. Development of autoimmunity is related to:

• �Susceptibility genes which influence the maintenance of self-tolerance

• �Environmental triggers, particularly infections, which promote the activation of self-reactive
lymphocytes
Mechanisms of Development of Autoimmunity
�Breakdown of T cell anergy
1.
(a)
Autoreactive T cells that escape clonal deletion are rendered anergic when they
encounter self-antigens expressed on costimulator deficient antigen-presenting
cells (APCs).
(b)
Anergy is broken if APCs are induced to express costimulatory molecules (induc-
tion may occur consequent to infections, tissue necrosis, inflammation, etc.).
2 .
�Failure of activation-induced cell death: Defects (congenital or acquired) in the Fas–Fas

ligand system (responsible for apoptosis) may lead to persistence and proliferation of au-

toreactive T cells in the peripheral tissues.

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