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Autoimmunity and Tolerance

The document discusses tolerance and autoimmune disease, explaining that tolerance involves immunological unresponsiveness to self-antigens and occurs through central tolerance in the thymus and peripheral tolerance outside the thymus. It also examines the mechanisms of autoimmunity, noting that loss of self-tolerance can result in autoimmune diseases through antibody- or cell-mediated immune responses targeting various self-components. Factors like genetics, infections, and tissue damage are described as potentially contributing to breaking self-tolerance and the development of autoimmune conditions.

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205 views17 pages

Autoimmunity and Tolerance

The document discusses tolerance and autoimmune disease, explaining that tolerance involves immunological unresponsiveness to self-antigens and occurs through central tolerance in the thymus and peripheral tolerance outside the thymus. It also examines the mechanisms of autoimmunity, noting that loss of self-tolerance can result in autoimmune diseases through antibody- or cell-mediated immune responses targeting various self-components. Factors like genetics, infections, and tissue damage are described as potentially contributing to breaking self-tolerance and the development of autoimmune conditions.

Uploaded by

api-19969058
Copyright
© Attribution Non-Commercial (BY-NC)
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Tolerance and

Autoimmune Disease
Dr. Mejbah Uddin Ahmed
Autoimmunity and Tolerance

Tolerance:
Specific immunologic unresponsiveness to certain
antigen in spite of immune system is functional is
called tolerance.
Both T cells and B cells participate in tolerance.
But T cells play primary role in tolerance.
Tolerance is Two types:
a) Central tolerance.
b) Peripheral tolerance.
T cell
Thymus
precursors Abnormal release of
autoreactive T cells

Selected T cells

Central
Tolerance

Peripheral
Tolerance
anergy /
deletion/
suppression
Bone marrow
Autoimmunity and Tolerance

T cell tolerance:
Central tolerance: Central tolerance of T cell
acquire in the thymus by the process called clonal
deletion.
Clonal deletion: Killing of T cells that react against
self MHC proteins is called clonal deletion/
negative selection.
Autoimmunity and Tolerance

Peripheral tolerance: Peripheral tolerance of T


cells acquire outside the thymus.
Mechanism of peripheral tolerance:
a) Some are killed.
b) Some are inhibited.
c) Some are suppressed by regulatory T
cells.
(Self reactive T cells die by a process of
programmed cell death called apoptosis).
Autoimmunity and Tolerance

Peripheral tolerance:
Clonal anergy: Self reactive T cells are not
activated because proper costimulation
does not occur.
Clonal ignorance: This means self reactive T
cells ignore self antigen. May be due to
physical separation or antigens are very
small amount.
Costimulation: CD28, B7 and CD40L, CD 40

CD28 B7

T cell CD4 or 8 APC


TcR MHC

CD40L CD40
Autoimmunity and Tolerance

B-cell Tolerance:
B cell Tolerance is less complete than T cell,
So most autoimmune disorders are antibody
mediated. B cells tolerance involves:
a) Clonal deletion: Probably in the bone
marrow.
b) Clonal anergy: In the periphery.
Autoimmunity and Tolerance
Induction of Tolerance:
Whether an antigen will induce tolerance or
immune response, depends on:
a) Immunologic maturity of host.
b) Structure and dose of antigen.
c) T cell become tolerant rapidly and remain
longer than B cell.
d) Administration of cross reacting antigen.
e) Administration of immunosuppressive
drugs.
Autoimmune
disease

• Autoimmunity is a
problem of self/ non-
self discrimination.

• Loss of self tolerance


to self antigen may
result in autoimmune
diseases.
Autoimmunity and Tolerance
Factors causes autoimmune disease:
 Genetic:HLA-DR4 =›Rheumatoid Arthritis, HLA-
DR27 =›Ankylosing spondylitis.
 Hormonal factors.
 Bacterial and Viral infection.
Mechanism:
 Molecular mimicry.
 Tissue damage & release of sequestered antigen.
 Alteration of normal protein due binding of drugs.
Autoimmunity and Tolerance

Autoimmune diseases occurs due the


following types of immune response:
a) Antibody to receptors.
b) Antibody to cell components other than
receptors.
c) Cell mediated.
Autoimmunity and Tolerance

1. Antibody to receptors:

Disease Target of immune


response

Myasthenia gravis Acetylcholine receptor


Graves disease TSH receptor
Autoimmunity and Tolerance
Antibody to cell components other than receptors:

Autoimmune diseases Target of immune response

SLE DNA, histones


Rheumatoid Arthritis IgG
Rheumatic fever Heart, Joints
Hemolytic anemia RBC membrane
AGN Glomerular basement
membrane
Guillain-Barre SyndromeMyelin protein
Autoimmunity and Tolerance

 Cell mediated:

Autoimmune diseases Target of immune


system
Allergic Reaction to myelin
encephalomyelitis and protein causes
multiple sclerosis demyelination of brain
Celiac disease Enterocytes
Autoimmunity and Tolerance

 Microbial infection associated with Autoimmune


diseases:
Bacteria:
Streptococcus pyogen=› Rheumatic fever
Campylobacter jejuni =› Guillain-Barre syndrome
Chlamydia trachomatis =› Reiter’s syndrome,
Shigella species =› Reiter’s syndrome
Autoimmunity and Tolerance

Microbial infection associated with Autoimmune


diseases:
Viruses:
Hepatitis B virus =› Multiple sclerosis
Measles virus =› Allergic encephalitis
Cytomegalovirus =› Scleroderma

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