Immunomodulators

Question 1

3 classes of immunostimulatory cytokines

Answer 1

Interleukins
Colony stimulating factors
Interferon

Question 2

4 major classes of immunosuppressants

Answer 2

Corticosteroids
Calcineurin inhibitors
Antiproliferative/antimetablic agents
Biologic (antibodies)

Question 3

Prednisone

Answer 3

Decreases inflammation
Increases apoptosis of lymphocytes
Used to treat autoimmune diseases
Side effects: fluid retension, weight gain, increased blood sugar, osteopenia, hyperactivity

Question 4

Dexamethasone

Answer 4

Potent synthetic glucocorticoid class of steroid drugs
Anti inflammatory and immunosuppressant
More potent than prednisone

Question 5

Transactivation

Answer 5

Permits expression of anti-inflammatory genes

Question 6

Transrepression

Answer 6

Decreases expression of pro-inflammatory genes

Question 7

Corticosteroid general mechanism of action

Answer 7

Transactivation and transpression

Question 8

Cyclosporine mechanism

Answer 8

Blocks the function of calcineurin
Fails to dephosphorylate NF-ATc
T cells do not produce IL 2!
Same as tacrolimus

Question 9

Anti-TNFa biologicals

Answer 9

Block TNFa

Antibodies that target soluble TNFa, or receptor bound TNFa

Question 10

What is the fundamental problem that causes autoimmune diseases

Answer 10

Failure of self tolerance

Question 11

General mechanism of autoimmune diseases

Answer 11

Failure of auto-antibodies and T cells to recognize own cells
Auto-antibodies and T cells launch attack against own cells

Question 12

What are the 3 classes of autoimmune disease?

Answer 12

Type 2: antibody against cell-surface antigen or matrix antigens
Type 3: immune complex disease
Type 4: T cell mediated disease

Question 13

Graves disease

Answer 13

Type 2 (antibody mediated)
Antibodies to TSH receptor
Leads to hyperthyroidism (loss of negative feedback)

Question 14

Systemic lupus erythematosus

Answer 14

Type 3 (immune complexes)
Wide variety of autoantibodies to cytoplasmic and nuclear antigens (anti-DNA, anti-histone, anti-soluble ribonucleoprotein. IgG anti-ds DNA is characteristic)
Symptoms include rash, arthritis, glomerulonephritis, and vasculitis

Question 15

How does type 4 (T cell mediated disease) work?

Answer 15

Direct T cell cytotoxicity via CD8+ cytotoxic T lymphocytes
Self destruction of tissue cells induced by cytokines
Recruitment and activation of macrophages leading to bystander tissue destruction
Induction of target tissue apoptosis by the T cell membrane protein FasL

Question 16

Rheumatoid arthritis

Answer 16

Type 4 (T cell mediated disease)
Superantigens cause non specific activation of T cells
Results in polyclonal T cell activation and massive cytokine release

Question 17

Psoriasis

Answer 17

Autoimmune disease that occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells
Activated T cells end up in skin cells
Can cause severe itching, pain, skin cracks, and bleeds

Question 18

What can you use to treat psoriasis?

Answer 18

Corticosteroids
Vitamin D analogue creams
Topical retinoids
Moisturizers
Topical immunosuppressants
Coal tar

Question 19

How do vitamin analogues work to treat psoriasis?

Answer 19

Synthetic vitamin D3 derivatives
Vitamin D3 acts on the vitamin D receptor to regulate cell growth, differentiation, and immune function (also Ca and P metabolism)
D3 also inhibits the production of IL2 and IL6, blocks the transcription of IFNy and GM-CSF and inhibits cytotoxic T cells and NK cells

Question 20

How does
1. Alefacept
2. Etanercept
work to treat psoriasis?

Answer 20

1. Interferes with lymphocyte activation

2. Binds to TNFa and b and blocks binding with receptor