Autoimmune Disease

Question 1

What is the 2 hit mechanism contributing to autoimmune disease?

Answer 1

Immunoregulation and an environmental trigger in a genetically susceptible individual

Question 2

What should happen to a self-reactive B cell?

Answer 2

It should be eliminated in clonal deletion

Question 3

How can lack of T cell help control B cell activation?

Answer 3

Autoreactive B cells activated by antigen migrate to secondary lymph nodes. If there is no T cell help, B cell dies via apoptosis

Question 4

How can B cell anergy occur?

Answer 4

B cell encounter with soluble self-antigen without costimulation

Question 5

What two defects would allow an autoreactive T cell to escape into periphery?

Answer 5

Self-antigen not expressed in the thymus, or defects in (Autoimmune regulator [AIRE])

Question 6

Describe the process in which clonal anergy is ineffective or overcome by T cell co-stim

Answer 6

Defects - insufficient levels of soluble CTLA-4 so it cannot compete with CD28 for binding to B7; Inappropriate co-stim: Cells express costim molecules and activate T cells

Question 7

What markers and cytokines are expressed by regulatory T cells?

Answer 7

CD4, CD25, FoxP3, CTLA-4 secrete IL-4, 10 and TGF-Beta

Question 8

What are several gene defects that can make one susceptible to autoimmune disease?

Answer 8

MHC region genes resulting in different allotypes, Complement, CTLA-4, AIRE, Fas and Fas Ligand

Question 9

Why are autoimmune diseases found more frequently in women?

Answer 9

Changes in estrogen levels, or chemicals that have same effects as estrogen (PCBs, dioxin)

Question 10

What are examples of environmental factors that can predispose a person to autoimmune disease?

Answer 10

Alteration of self antigen with drugs, chemicals/metals (PCBs, dioxins, pesticides, metals), breakdown of tissue integrity can result in release of antigen not normally presented to T cells, loss of oral tolerance to food proteins, infections

Question 11

How can infections contribute to AI disease?

Answer 11

Molecular mimicry (pathogen peptide is presented on to T cell and looks like self antigen), production of high levels of interferon gamma (IF-gamma causes production of MHCII which can result in AA disease), damage to tissue to release self antigen

Question 12

Characteristics of Antibody-mediated diseases

Answer 12

Single type of cell (organ) targeted by AutoAbs (organ specific); Type II hypersensitivity rxn

Question 13

What is Autoimmune hemolytic anemia? What type of AI diease?

Answer 13

Loss of RBCs after fixation of complement by IgG and IgM Abs resulting in lysis or clearance via binding to Fc and complement receptors on phagocytes in spleen and liver; Type II hypersensitivity rxn

Question 14

What is AI thrombocytopenia? Type of AI disease?

Answer 14

Platelet antigens are targets of autoAbs; Type II hypersensitivity rxn

Question 15

What is Goodpasture’s syndrome? Type of AI disease?

Answer 15

IgG against Type IV colagen elicits inflamm response in renal tissue; Type II hypersensitivity response

Question 16

What is Myasthenia Gravis? Type of AI disease?

Answer 16

Abs to AChR on muscle cells induce their endocytosis; Type II hypersensitivity rxn

Question 17

What is Insulin-resistant diabetes? Hypoglycemia Syndrome?

Answer 17

Ab blocks insulin receptor binding so that insulin accumulates and hyperglycemia occurs (antagonist Abs); Agonist Abs deplete glucose to abnormally low levels resulting in hypoglycemia; Type II HR

Question 18

What is Graves’ disease?

Answer 18

AutoAbs bind to TSH receptor of thyroid cells mimicking the action of TSH so more thyroid hormones are released (agonist Ab); Type II hypersensitivity rxn

Question 19

What are some diseases that a fetus can acquire from a mother producing autoAbs? What autoimmune diseases can a fetus not get?

Answer 19

Graves’, Hemolytic disease, Myasthenia gravis, Trombocytopenic purpura, Neonatal Lupus; T cells cannot cross the placenta therefore child cannot acquire T cell mediated disease

Question 20

What kind of AI diseases are Immune-complex mediated AI diseases? Mechanism? Examples?

Answer 20

Type III hypersensitivity rxn; ICs deposit in tissues, fix complement, leading to inflammatory cells and tissue damage; Subacute bac endocarditis resulting in glomerulonephritis; Mixed essential cryoglobulinemia - Rheumatoid factor leading to Systemic vasculitis, SLE - Glomerulonephritis, vasculitis, arthritis

Question 21

What is the relationship between Type III hypersensitivity rxns and T cells?

Answer 21

T cells are important requirement for Ig production!

Question 22

What type of HR is a T cell-mediated autoimmune disease? Mechanism? Examples?

Answer 22

Type IV hypersensitivity; Antigen-specific T cells activated by antigen lead to inflamm response and direct cytotoxic effects; Type 1 diabetes, Rheumatoid arthritis, Multiple sclerosis

Question 23

Describe mechanism leading to juvenille diabetes

Answer 23

CD8 T cells attack Beta-cells in pancreas - target antigen is glutamic acid decarboxylase

Question 24

Describe mechanism of rheumatoid arthritis

Answer 24

Production of Abs (Rheumatoid factor) that reacts with Fc region of other Abs and infiltration of joints with CD4 and CD8 T cells

Question 25

Describe pathogenesis leading to Multiple sclerosis

Answer 25

Myelin sheath is destroyed due to TH1 CD4 T cells which secrete IFN gamma and activate macros

Question 26

Tx for autoimmune disease

Answer 26

Remove antigen (plasmapheresis), Intravenous IgG, Anti-inflamms (NSAIDs, steroids), Immune cell depletion, Block cell signaling (block cytokines), Replacement Tx (insulin for diabetes), Hormones, diet, exercise