Micro U2 L9.

Question 1

How do autoimmune disease occur?

Answer 1

two hit mechanism: 1. defects in immunoregulation and 2. environmental trigger

Question 2

What supports the idea that environmental factors play a role in autoimmune disease?

Answer 2

increase in disease incidence with industrialization

Question 3

Thymus and autoimmunity

Answer 3

self-antigen not expressed in thymus and/or defects in AIRE - allows auto reactive T cells to escape into periphery

Question 4

Defects in anergy?

Answer 4

insufficient levels of CTLA-4 (grave’s disease)

Question 5

Genetic factors causing susceptibility to autoimmune disease

Answer 5

1. genes located in MHC region 2. variants of complement 3. variants of CTLA-4 4. variants of AIRE 5. variants of Fas and Fas ligand

Question 6

Hormonal factors causing susceptibility to autoimmune disease

Answer 6

estrogen (why there is more autoimmune in females) and chemicals PCBs and dioxin (same effects as estrogen)

Question 7

Environmental factors causing susceptibility to autoimmune disease

Answer 7

1. alteration of the structure of self antigens by drugs (penicillin) 2. chemicals (PCBs, dioxins, pesticides), metals in the environment 3. breakdown of tissue integrity due to trauma - release of sequestered self antigens 4. loss of oral tolerance to food proteins 5. infections (molecular mimicry, bystander effect, damage to tissue - releases self antigens)

Question 8

What are other factors causing susceptibility to autoimmune disease

Answer 8

1. sunlight 2. exposure to metals 3. aging 4. atrophy of thymus 5. thymus 6. nutrition 7. stress

Question 9

Organ-specific autoimmune disease

Answer 9

antibody mediated - correspond to type II hypersensitivity

Question 10

Examples of autoimmune diseases that correspond to Type II hypersensitivity reactions

Answer 10

organ-specific - autoimmune hemolytic anemia, autoimmune thrombocytopenia, goodpasture’s syndrome, grave’s disease, myasthenia gravis, insulin-resistant diabetes, hashimoto’s disease

Question 11

Goodpasture’s syndrome

Answer 11

IgG against Type IV collagen - inflammatory response in renal tissue

Question 12

Grave’s disease

Answer 12

hyperthyroidism - antibodies bind to the thyroid-stimulating hormone (TSH) receptor acting as an agonist - thyroid hormones overproduced

Question 13

Myasthenia gravis

Answer 13

antibodies to AChR - induce muscle cell endocytosis of receptors - antibodies also compete with acetylcholine - inprogressive muscle weakening

Question 14

insulin-resistant diabetes

Answer 14

insulin binding to receptor is blocked by antibody - insulin accumulates causing hyperglycemia (resistance to insulin) - glucose is deplete to low levels resulting in hypoglycemia

Question 15

Hasimoto’s disease

Answer 15

hypothyroidism - progressive destruction of normal thyroid tissue by antibodies and effector T cells

Question 16

Temporary symptoms of antibody-mediated disease

Answer 16

antibodies can be passed from affected mothers to newborn babies (grave’s disease)

Question 17

immune-complex-mediated autoimmune disease

Answer 17

systemic autoimmune response - type III hypersensitivity

Question 18

Examples of autoimmune diseases that correspond to Type III hypersensitivity reactions

Answer 18

SLE - immune complexes are deposited in blood vessels, kidneys, and joints which initiate inflammatory reactions

Question 19

T-cell mediated autoimmune disease

Answer 19

antigens in tissue are targets by Th1-type Tcells - corresponds to Type IV hypersensitivities

Question 20

Examples of autoimmune diseases that correspond to Type IV hypersensitivity reactions

Answer 20

Insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, SLE (has a T cell component - can be considered both)

Question 21

Insulin-dependent diabetes mellitus

Answer 21

Type I diabetes - CD8 T cells kill pancreatic beta cells - insulin production is insufficient to control glucose levels in the blood

Question 22

Rheumatoid arthritis

Answer 22

Rheumatoid factors (IgG and IgA antibodies specific for the Fc region of human IgG) and cellular infiltrate contribute to inflammation in the joints

Question 23

Multiple Sclerosis

Answer 23

autoimmune response to antigens in the myelin sheath of nerve cells involving Th1 CD4 T cells and macrophages resulting in the production of sclerotic plaques - progressive paralysis

Question 24

Celiac disease

Answer 24

shares many similarities to autoimmune disease - inflammation of the small intestine is caused by CD4 T cell response which are specific for gluten-derived peptides which are presented by HLA-DQ8 or HLA-DQ2

Question 25

Treatments for autoimmune disease

Answer 25

1. physical removal of antigen, antibody, immune complexes 2. intravenous immunoglobulin 3. anti-inflammatory drugs 4. cytotoxic drugs to kill immune cells 5. drugs that block the interaction of immune cells 6. replace of necessary chemical/hormone (insulin for diabetes) 7. hormonal therapy, diet, exercise