tolerance and autoimmunity

Question 1

describe general process of autoimmune disease

Answer 1

normal autoimmunity (healthy with self tolerance) -> genetic predisposition and environmental factors causing a breakdown of self tolerance -> autoimmune disease (adaptive immune response with specificity for autoantigens)

Question 2

4 criterion for a disease to be autoimmune

Answer 2

evidence of disease-specific adaptive immune response in affected target tissue, organ or blood; passive transfer of autoreactive cells or antibodies replicates disease; elimination of autoimmune response modifies disease; history of autoimmune disease (personal or family), and/or MHC associations

Question 3

sources of data for genetic factors of autoimmune disease (polygenic)

Answer 3

twin and family studies, GWAS

Question 4

5 autoimmune risk factors

Answer 4

usually female (except T1DM), infections (inflammatory environment), poor diet (obese, high fat, affect gut microbiome), stress, microbiome (perturbation)

Question 5

locations of microbiome

Answer 5

respiratory system, skin, GI tract, urogenital tract

Question 6

mechanism of autoimmunity

Answer 6

adaptive immune reactions against self use same mechanisms as immune reactions against pathogens and environmental antigens, with autoimmune diseases involve breaking T-cell tolerance to produce IgG auto-antibodies (class switching)

Question 7

duration of autoimmune disease and why

Answer 7

because self tissue is always present, autoimmune diseases are chronic conditions (often relapsing)

Question 8

what do effector mechanisms of autoimmunity resemble

Answer 8

those of hypersensitivity reactions, types II, III, and IV

Question 9

impact of autoimmune disease, and impact of pregnancy

Answer 9

incidence increasing (hygeine hypothesis), approx 100 chronic disorders related to autoimmunity; if Th2 antibody mediated response, becomes worse during pregnancy, but if cellular mediated response, becomes better during pregnancy (flare-up occurs post-partum)

Question 10

3 features which classify autoimmune reactions

Answer 10

spectrum of organ-specific to multi-systemic diseases; involvement of specific autoantigens; type of immune response (usually hypersensitivity II, III and IV)

Question 11

3 examples of organ-specific autoimmune diseases

Answer 11

Grave’s, Hashimoto’s thyroiditis, T1DM

Question 12

3 examples of multi-systemic autoimmune diseases

Answer 12

systemic lupus erythematosus, rheumatoid arthritis, vasculitis

Question 13

what play a direct role in immunopathogenesis of various autoimmune diseases

Answer 13

autoantigens (direct link between auto-antibodies and disease)

Question 14

3 immune reactions which play a direct role in immunopathogenesis of various autoimmune diseases (not type I IgE as this is atopy)

Answer 14

antibody response to cellular or EC matrix (insoluble) antigen (type II), immune complex formed by antibody against soluble antigen (type III), T-cell mediated disease (delayed type hypersensitivity reaction type IV)

Question 15

type II vs type III antibody deposition and tissue injury

Answer 15

type II: injury caused by antitissue antibody (tissue injury); type III: immune complex-mediated tissue injury (vasculitis so more widespread)

Question 16

type II and type III mechanism of antibody deposition and tissue injury

Answer 16

complement and Fc receptor-mediated recruitment and activation of inflammatory cells (enzymes, reactive oxygen species)

Question 17

normal T-cell response to antigens

Answer 17

antigen presented to T-cells by MHC expressed on surface of APCs, causing proliferation and function; involves CTL and Th cells

Question 18

what is the dominant genetic factor affecting susceptibility to specific autoimmune disease and significance

Answer 18

MHC class II, hence strong implication for role of T cells (CD4+ T cells) in initiating different autoimmune disease (varying susceptibilities due to varying alleles in MHC class II)