AUTOIMMUNITY- II
Dr. Ashraf Abdelfatah Deyab
Assistant Professor of Pathology
Collage of Medicine, Majmaah University-
Autoimmunity: Part 2
At the end of the session the student should be able to:
• a. List the Genetic factors in autoimmunity
• b. Discuss the Role of infections and tissue
injury.
• Suggested readings: Robbins basic pathology, 8th edition.
Page:138 – 139
Role of Genes Susceptibility-1
Most of Autoimmune diseases due to complex
multigenic disorders predisposed by :
a) Single gene mutation : few number of
autoimmune diseases caused by single gene
defect (Fas, AIRE= Defect in central tolerance).
b) HLA genes “disease-associated alleles”:
have greatest contribution in AD (HLA: B27,
DR2,DR3,DR3\4)- mechanism remain obscure.
III. The mechanism of autoimmunityLoss of
self-tolerance=
breakdown of
c) Non-HLA
gene
mutation
Role of Genes Susceptibility- 2.
b) HLA genes “disease-associated alleles”:
Mechanism: remain obscure but postulated that presence
of MHC alleles defects are lead to
1) Affects the negative selection of T cells in the thymus .
2) Affect the development of regulatory T cells.
C) Non-HLA genes: recent Family & Twins studiesreveals multiple disorders specially gene defect
proved to be among monozygotic greater than > 4
The mechanism
of autoimmunitytimes III.
in dizygotic
twins.
– three
recentof
examples.........................................cont.)
Loss
self-tolerance= breakdown of
Role of Genes Susceptibility.
Recent examples: 1- Polymorphisms in a gene called PTPN-22 (most
frequently implicated with AD, a\w RA & type 1 DM.
Mechanism : defect in encoded phosphatase >
defect in control of tyrosine kinases activity>defect
of lymphocyte responses>> excessive activation
2- Polymorphisms in the gene for NOD-2 (NOD-2 is a
cytoplasmic sensor of microbes) , a\w Crohn disease.
Mechanism : NOD-2 defect>> ineffective at sensing
III. microbes>>
The mechanism
of autoimmunityintestinal
entry of microbes>>
chronic
Loss of
self-tolerance=
breakdown
of
inflammatory
responses
against well-tolerated
commensal
bacteria
Role of Genes Susceptibility
3- The genes encoding the IL-2 receptor
(CD25) and IL-7 receptor α chains are
associated with multiple sclerosis and other
autoimmune diseases
OUTCOME> These cytokines may control the
maintenance of regulatory T cells
The end