Immune Modulators

Question 1

Autoimmunity Def

Answer 1

Immune system fails to recognise self antigens leading to tissue destruction. Inherited, caused by infection or mediated by drugs eg lupus erthromeatous

Question 2

Organ Transplant Outline

Answer 2

Compatible human donor organ transfer after organ failure. 2 types HvGD and GvHD

Question 3

Host vs Graft Disease Outline

Answer 3

Recipient’s immune system targets transplant as host’s T cells recognise it as foreign

Question 4

Graft vs Host Disease Outline

Answer 4

After irradication of host’s immune cells with radiation (in cases of autoimmunity, donor’s stem cells are administered to replace them. Stem cells once differentiated may recognise host cells (eg RBCs) as foreign

Question 5

DMARDs Outline

Answer 5

Disease Modifying Anti-Rheumatic Drugs. Suppressing immune system to reduce inflammation. Slow progression of autoimmune and organ rejection. 2 types: traditional and biologics

Question 6

Traditional DMARDs Outline

Answer 6

Older medications. Broad immune system suppression, targets fast multiplying cells: targeting Purine and Pyrimidine synthesis in dividing cells, include alkylating agents. Also used as an anti-cancer. Side effects; absolute leukopenia, alopecia (hair loss) and nausea

Question 7

Biological DMARDs Outline

Answer 7

Newer medication (molecular biology techniques). Target specific immune system components

Question 8

Methotrexate Outline

Answer 8

Traditional DMARD. Folic acid antagonists (prevents folate in cells), inhibiting transcription, immune cell proliferation (B&T) and pro-inflammatory cytokine release. Most effective: cancer, immune and trophoblastic (ectopic pregnancy) cells

Question 9

Azathioprine Outline

Answer 9

Traditional DMARD. Converts to 6MP which acts as analogue of ionsinc acid (blocking purine synthesis) and guanylic acid (blocking DNA/RNA synthesis). Inhibits phagocytic cells (except NK) and suppresses T cells (antibodies and serum IL-2 inhibition). Risk: monocytopenia

Question 10

Leflunomide Outline

Answer 10

Traditional DMARD. Blocks pyrindene synthesis (theorised: inhibits dihydrooate dehydrogenase). Blocking B and T cell proliferation (and other rapidly dividing cells). Used in RA and psoriac arthiritis. Side effects: mild GI disturbances

Question 11

Cyclophosphamide Outline

Answer 11

Traditional DMARD. Adds an alkyl group onto DNA of cells, damaging DNA, preventing DNA proliferation. Used in: oncology (high dose), rhuematology and bone marrow transplant (low dose)

Question 12

Traditional DMARD Toxicity

Answer 12

Increased infection risk, fatigue, hepatotoxicity,alopecia

Question 13

Calcineurin (Protein Phosphate Kinase) Outline

Answer 13

Intracellular Ca and calmodulin dependent serine/theronine phosphate. An enzyme that dephosphorylates NFAT (transcription factor) allowing T cell activation (promoting IL-2 expression)

Question 14

Calcineurin Inhibitors Outline

Answer 14

Biological DMARDs. Immunosuppressants traditionally used in for organ transplant prophylaxis and autoimmune treatment. Inhibits T and B cell proliferation and thus IL-2 secretion

Question 15

2 Types Of Calcineurin Inhibitors

Answer 15

Cyclosporine and Tacrolimus

Question 16

Calcineurin Inhibitors Side effects

Answer 16

Nephrotoxicity (impaored kidney function), hypertension, neurotoxixty and increased infection risk