Immunomodulators Flashcards
3 classes of immunostimulatory cytokines
Interleukins
Colony stimulating factors
Interferon
4 major classes of immunosuppressants
Corticosteroids
Calcineurin inhibitors
Antiproliferative/antimetablic agents
Biologic (antibodies)
Prednisone
Decreases inflammation
Increases apoptosis of lymphocytes
Used to treat autoimmune diseases
Side effects: fluid retension, weight gain, increased blood sugar, osteopenia, hyperactivity
Dexamethasone
Potent synthetic glucocorticoid class of steroid drugs
Anti inflammatory and immunosuppressant
More potent than prednisone
Transactivation
Permits expression of anti-inflammatory genes
Transrepression
Decreases expression of pro-inflammatory genes
Corticosteroid general mechanism of action
Transactivation and transpression
Cyclosporine mechanism
Blocks the function of calcineurin
Fails to dephosphorylate NF-ATc
T cells do not produce IL 2!
Same as tacrolimus
Anti-TNFa biologicals
Block TNFa
Antibodies that target soluble TNFa, or receptor bound TNFa
What is the fundamental problem that causes autoimmune diseases
Failure of self tolerance
General mechanism of autoimmune diseases
Failure of auto-antibodies and T cells to recognize own cells
Auto-antibodies and T cells launch attack against own cells
What are the 3 classes of autoimmune disease?
Type 2: antibody against cell-surface antigen or matrix antigens
Type 3: immune complex disease
Type 4: T cell mediated disease
Graves disease
Type 2 (antibody mediated)
Antibodies to TSH receptor
Leads to hyperthyroidism (loss of negative feedback)
Systemic lupus erythematosus
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
How does type 4 (T cell mediated disease) work?
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
Rheumatoid arthritis
Type 4 (T cell mediated disease)
Superantigens cause non specific activation of T cells
Results in polyclonal T cell activation and massive cytokine release
Psoriasis
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
What can you use to treat psoriasis?
Corticosteroids Vitamin D analogue creams Topical retinoids Moisturizers Topical immunosuppressants Coal tar
How do vitamin analogues work to treat psoriasis?
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
How does
1. Alefacept
2. Etanercept
work to treat psoriasis?
- Interferes with lymphocyte activation
2. Binds to TNFa and b and blocks binding with receptor
