Autoimmune Diseases

Question 1

Autoimmune diseases are thought to occur via what “2-hit” mechanism?

Answer 1

Defective immunoregulation + environmental trigger (in a genetically susceptible person)

Question 2

Failure to delete self-reactive B-cells in the bone marrow describes what kind of autoimmune-promoting problem?

Answer 2

Breakdown in central B-cell tolerance

Question 3

Inappropriate T-cell activation of autoreactive B cells and defective B cell anergy are examples of what kind of autoimmune-promoting problem?

Answer 3

Breakdown in peripheral B-cell tolerance

Question 4

Incomplete T cell deletion in the thymus is an example of what kind of autoimmune-promoting problem?

Answer 4

Breakdown in central T cell tolerance

Question 5

A defect in what gene can cause incomplete presentation of self-antigens to T cells in the thymus, allowing autoreactive T cells to escape into the periphery?

Answer 5

AIRE

Question 6

Inappropriate T cell co-stimulation and defects in clonal anergy due to low levels of CTLA-4 (which binds to B7 to inhibit the immune response) is an example of what kind of autoimmune-promoting problem?

Answer 6

Breakdown in peripheral T cell tolerance

Question 7

What is the term for the way that some antigens in the body are sequestered in areas where they will not usually encounter lymphocytes? A breakdown in this protective mechanism due to trauma can cause effector T cells to be sensitized to self antigens.

Answer 7

Clonal ignorance

Question 8

Inflammatory Th-17 cells refer to what kind of cells that secrete IL-17 in diseases like Crohn’s, RA, psoriasis, and allergic asthma?

Answer 8

CD4 T cells

Question 9

What is the most important genetic factor in accounting for autoimmune susceptibility?

Answer 9

The HLA gene

Question 10

What hormone seems to exacerbate autoimmune diseases, making them more common in women than in men?

Answer 10

Estrogen

Question 11

What autoimmune condition is associated with HLA-B27 and infections?

Answer 11

Reiter’s syndrome or reactive arthritis (associated with infections such as Chlamydia, Shigella, Salmonella, Yersinia, Campylobacter, etc.)

Question 12

Autoantibody-mediated autoimmunity corresponds to what type of hypersensitivity reaction? Does it tend to be organ-specific or systemic?

Answer 12

Type II hypersensitivity; organ-specific (the antibodies target a specific cell)

Question 13

In autoimmune hemolytic anemia, what autoantigen does the antibody target?

Answer 13

Rh blood group antigens

Question 14

In autoimmune thrombocytopenia purpura, what autoantigen does the antibody target?

Answer 14

Platelet integrin GpIIb/IIIa

Question 15

In Grave’s disease, what autoantigen does the antibody target? Is the antibody an agonist or antagonist?

Answer 15

TSH (thyroid stimulating hormone) receptor; agonist (so it causes hyperthyroidism)

Question 16

In myasthenia gravis, what autoantigen does the antibody target? Is the antibody an agonist or antagonist?

Answer 16

ACh receptor; antagonist (so it causes progresive muscle weakening)

Question 17

Why is it that Grave’s disease, systemic lupus erythematosus, myasthenia gravis, hemolytic disease of the newborn, and thrombocytopenia purpura can all be transferred in utero?

Answer 17

Tthey all involve IgG which can cross the placenta

Question 18

Systemic lupus erythematosus (SLE), subacute bacterial endocarditis, and mixed essential cryoglobulinemia are all examples of what kind of autoimmunity?

Answer 18

Type III/immune-complex-mediated

Question 19

Immune-complex-mediated autoimmunity corresponds to what type of hypersensitivity reaction? Does it tend to be organ-specific or systemic?

Answer 19

Type III; systemic

Question 20

What kind of antibodies are diagnostic for SLE?

Answer 20

Anti-dsDNA

Question 21

Type I diabetes, rheumatoid arthritis, and multiple sclerosis are all examples of what kind of autoimmunity? Does it tend to be organ-specific or systemic?

Answer 21

Type IV/T-cell-mediated; mostly organ specific (because the T cells target specific tissue antigens)

Question 22

Insulin-dependent diabetes mellitus or type I diabetes is associated with what kind of T cells directed against what antigen?

Answer 22

CD8 T cells; against GAD (glutamic acid decarboxylase) on pancreatic β-cells

Question 23

Rheumatoid arthritis is associated with what kind of T cells directed against what antigen?

Answer 23

CD4 and CD8 T cells; targets the Fc region of IgG (the antibody is RF)

Question 24

Multiple sclerosis is associated with what kind of T cells directed against what antigen?

Answer 24

TH1 CD4 cells; against antigens on the neuronal myelin sheaths

Question 25

Autoimmune classifications can get fuzzy. Which 2 common diseases are variably classified as either type 3 or type 4 reactions?

Answer 25

SLE and rheumatoid arthritis.

Question 26

In real life, T cells, B cells, and antibodies all play a role in every autoimmune disease pathogenesis. That being said, what is the primary mechanism of each of the following diseases: type 1 diabetes, SLE, myasthenia gravis, and multiple sclerosis?

Answer 26

Type 1 diabetes and multiple sclerosis are primarily T cells;
SLE is both T cells and antibodies;
Myasthenia gravis is primarily antibodies

Question 27

Compare the mechanisms of autoimmune action for insulin-dependent and insulin-resistant diabetes.

Answer 27

Insulin-dependent diabetes is type 4/T-cell mediated against the pancreatic β-cell; insulin-resistant diabetes is type 2/antibody-mediated against the insulin receptor on tissue cells

Question 28

Compare the mechanisms of insulin-resistant diabetes and antibody-mediated hypoglycemia.

Answer 28

Both involve antibodies for the insulin receptor, but the diabetes antibody is an antagonist while the hypoglycemia antibody is an agonist.

Question 29

Compare the mechanisms of Grave’s disease hyperthyroidism with Hashimoto’s disease hypothyroidism.

Answer 29

Grave’s disease involves antibody agonists to the TSH receptor, while Hashimoto’s disease involves antibodies against the thyroid tissue itself (which leads to T-cell destruction of the thyroid)