Autoimmunity (1/17)

Question 1

What are autoimmune diseases & how are they classified?

Answer 1

A group of common diseases that result from tissue injury and inflammation

Culmination of an adaptive immune response to self-antigens

Systemic (rheumatic/collagen diseases i.e. rheumatoid arthritis) or organ-specific (Celiac, MS, psoriasis, type 1 diabetes)

Question 2

How do autoimmune diseases present?

Answer 2

Self recognition/genetic predisposition phase: autoantibody negative

Loss of tolerance of one or a few T cell clones: autoantibody low positive

Intensification and spread of autoimmune response when it acquires ability to damage tissue: autoantibody high positive

Question 3

Which alleles are most associated with autoimmune disease?

Answer 3

MHC allele

Different HLA alleles encode the ability to bind different self peptides, and when an autoimmune response is triggered, different autoimmune diseases ensue

Question 4

What is the main abnormality of autoimmunity?

Answer 4

T cell clone specifically recognizes & persistently responds to a self peptide presnted by a particular allomorphic MHC molecule

T cell is not tolerant of self MHC

Which MHC allomorph is involved determines which self peptides are the focus of the response/ which autoimmune disease you get

Question 5

Which point(s) of T cell life cycle does autoimmune disease develop?

Answer 5

Can be during: self-tolerizing process (inadequate expression of self-peptides in thymus or failure in neg selection), T cell clonal triggering, or in subsequent regulation of clonal expansion

Question 6

What is the role of AIRE in autoimmune disease?

Answer 6

Involved in tissue specific autoimmune disease (not systemic)

Question 7

Why does DR4 allele associate with RA in some populations but not others?

Answer 7

Because of a slight difference between alleles!!

Lack of susceptibility/ even dominant protection against RA associated with having negatively charged alleles at the bottom

Question 8

What is the role of non-MHC genes in autoimmune diseases?

Answer 8

Same genes seem to be associated with multiple autoimmune diseases

i.e. interleukins, JAK2, T cell receptor

Depending on which variant, can enhance the disease or can inhibit the disease

The combination of total SNPs that you have confers your total risk of developing autoimmune diseases

Question 9

What type of antibodies are involved in autoimmune diseases?

Answer 9

IgG