Autoimmune diseases
Learning objectives: At the end of lecture, the students should be able to:
1-Mention the mechanisms of autoimmune diseases.
2-Write short notes on genetic theory of autoimmune disease.
3- Explain the role of infections in autoimmune diseases.
Mechanisms of autoimmune diseases
Mechanisms:
1-Genetic theory.
2-Microbial theory.
Genetic theory
-Role of susceptibility genes.
*HLA.
*Non-MHC genetic loci-associated with autoimmunity(e.g. Systemic lupus erythromatosis {SLE} and type I Diabetic mellitus).
1- In mice (mutations)
A-Fas and Fas ligand-----interfer with activation- induced cell death.
B- Autoimmune regulator(AIRE).
C- CTLA-4.
D-IL-2(promotes Fas-mediated apoptosis).
2-In human(mutations)-----Autoimmune diseases.
A- Fas.
B- Autoimmune regulator(AIRE).
C- CTLA-4.
D- Foxp3.
Microbial theory
Role of infections.
1-expression of costimulators on antigen-presenting cells(APC)-----breakdowen of clonal anergy-----autoimmune diseases(e.g. multiple sclerosis).
2-Molecular mimicry(e.g. rheumatic heart disease) or infection induce production of cytokines that recruit lymphocytes including autoreactive lymphocytes to site of self-antigens.
Epitope spreading:
Infection-----immune response-----release and damage self antigens and exposure of epitope of antigens(normally concealed from immune system, or cryptic)-----continuing activation of new lymphocytes-----that recognize these previously cryptic epitopes(not expressed normally).
Questions
Q1)Discuss the pathogenesis of autoimmunity.
Q2) Explain the mechanism of type I Diabetes mellitus.
Q3) Discuss the mechanism of multiple sclerosis.
Q4) Explain the mechanism of systemic Lupus erythromatosis(SLE).
Q5) Explain the mechanism of Goodpastture syndrome.
References:
1-MacSween R.N.;and Whaly K.(Murs Textbook of pathology); 13th edition,Arlond.1997.
2-Kumar V.;Abbas A.; and Fausto N.(Robbin and Cortan, Pathologic basis of disease).7th edition. Elsevier Sounder. 2004.
3-Rosal J. (Ackerman s surgical pathology); 9th edition.Mosby.2003.
4-Walts J.B.,Talbot L.c.(general pathology ); 7th edition ,Churchill Livingstone; 1996 .
5-Krishna V.(Text book of pathology );Orient Longman Private limited. 2004 .