Page 120 - Concise Pathology for Exam Preparation ( PDFDrive )

5 Diseases of Immunity 105

Q. Write briefly on lepromin reaction.

Ans. Lepromin (emulsified, lepromatous tissue rich in lepra bacilli and standardized
according to lepra bacilli contents) is injected intradermally and the response is noted.

Two Phases
• �Early reaction of Fernandez develops in 24–48 h and subsides in 3–5 days. It mani-

fests with erythema and induration. Poorly defined, this reaction has little significance.
It is analogous to tuberculin reaction.
• �Late reaction of Mitsuda starts in 1–2 weeks, reaches its peak in the 4th week and

gradually subsides over the next few weeks. It manifests with an indurated skin nodule,
which may later ulcerate. Histological sections show infiltration by lymphocytes and
formation of epithelioid and giant cells.
Note: This test is used to check CMI status of the individual against lepra bacilli. It is not
helpful as a diagnostic test.

Q. Define immunologic tolerance. What are its different types?

Ans. An individual is incapable of developing an immune response to a specific self-antigen

and, hence, is capable of living in harmony with one’s own cells and tissues. This is called

immunologic tolerance. Tolerance is of two types—central tolerance and peripheral toler-

ance. Central tolerance develops very early in the life of an immune cell. It encounters the

i

self-molecules n the body during development and this initiates a self-destruction pathway,

which leads to the death of the cell before it attains maturity. This process, called clonal

deletion, helps ensure that ‘self-reactive’ T cells and B cells, that could develop the ability

to destroy the body’s own cells, do not mature and attack healthy tissues.

In peripheral tolerance, the body’s immune cells might recognize a self-molecule but do not

build up an immune response to it (switch off) because some of the chemical signals required to

activate the T or B cell are absent. This is labelled clonal anergy. A special class of regulatory T cells

that inhibits helper or cytotoxic T cell is involved in the development of peripheral tolerance.

Mechanisms of development of central tolerance (clonal elimination or deletion):
1.
(a)
Central tolerance develops during lymphocyte development and operates in the
thymus and bone marrow.
Here, T and B lymphocytes that recognize self-antigens are deleted before they
(b)
mature into fully immunocompetent cells, preventing autoimmunity.

(

c

) Self-antigens are present in both organs due to endogenous expression within the

organ and importation of antigen due to circulation from peripheral sites. In the case

of T cell central tolerance, additional sources of antigen are made available in the

b

thymus y the action of the transcription factor AIRE (autoimmune regulator).

(d)
�Positive selection occurs first when näive T cells are exposed to antigens in the

thymus. T cells, which have receptors with sufficient affinity for self-MHC mole-
cules are selected. Other cells that do not show sufficient affinity to self-antigens
will undergo a deletion process known as death by neglect, which involves apop-
tosis of the cells. This does not occur in B cells.
�Negative selection of T cells with a very high affinity of self-MHC molecules is
(e)

induced to anergy or lineage divergence to form T-regulatory cells.
Mechanisms of development of peripheral tolerance
2.
(a)
�Clonal anergy
• �Prolonged or irreversible inactivation of lymphocytes is labelled anergy.
• �Activation of antigen-specific T cells requires two signals:
- Recognition of peptide antigen in association with MHC molecule on the
surface of antigen-presenting cell
- Second set of costimulatory signals provided by antigen-presenting cells
• �Certain T cell-associated molecules such as CD28 must bind to their ligands
B7-1 and B7-2.
• �If the antigen-presenting cell does not bear a CD28 ligand, a negative signal is
generated to induce anergy.
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