Immunopharmacology Flashcards
What are the three main applications of immunosuppressants?
- Suppression of rejection to transplanted organs and tissue.
- Suppression of GVHD which arises from donor lymphocytes.
- Combat autoimmune diseases.
What are the tissues targeted by immunocompetent cells in donor grafts?
Liver, skin, mucosa, gut.
What is rheumatoid arthritis?
Autoimmune disease primarily affecting the joints.
What is lupus?
Multi-organ auto-immune disease characterized by rash on cheeks.
What is ulcerative colitis?
T-cell infiltration and ulceration in the colon.
What is psoriasis?
Auto-immune disease leading to scaly patches of skin
What are the two main stages of the immune response?
- Induction phase.
2. Effector phase.
What are the two stages of of the induction phase?
- Antigen presentation.
2. Clonal expansion and maturation.
Explain what happens in the antigen presentation stage:
Antigen presenting cell presents antigen to CD4 (Helper T-cell). This activates autocrine response in CD4 cells by releasing IL-2.
The helper T-cells then begin to divide.
Explain what happens in the clonal expansion stage:
Helper T-cells differentiate into Th1 and Th2 cells.
What do Th1 cells become?
Killer/helper T-cells that initiate cell-mediated responses against foreign/infected cells.
What do Th2 cells become?
They activate B-cells.
What do B-cells produce?
Antibodies.
What do Th1 cells produce?
Cytokines.
What are the five sites of immunosuppressant regulation?
- Inhibition of IL-2.
- Inhibition of cytokine gene expression.
- Cytotoxicity to kill immune cells.
- Inhibition of nucleic acid synthesis.
- Blockage of T-cell surface receptors to prevent antigen presentation.
What is the calcineurin-NFAT pathway?
Pathway required by T-cell expansion; activate expression of IL-2 leading to activation and proliferation of T-cells.
How is calcineurin activated?
Activation of T-cell receptors, causes dephosphorization of NFAT.
What is the key detail of the cyclosporine mechanism?
Inhibition of calcineurin by the cyclophilin:cyclosporine complex to prevent NFAT-mediated gene transcription.
What is the key detail of the tacromilus mechanism?
Inhibition of calcineurin by the FKBP:tacromilus complex to prevent NFAT-mediated gene transcription.
What are proliferation signal inhibitors?
Drugs that interfere with downstream signals of IL-2 receptor activation.
How is rapamycin different from tacromilus?
Rapamycin-FKBP complex does not inhibit calcineurin, it inhibits mTOR.
What is mTOR?
mammalian target of rapamycine; responsible for promoting cell growth and proliferation.
What are cytotoxic agents?
Drugs that lead to cross-linking of neighboring bases (interferes with DNA replication)
What is the structure of antibodies?
2 Heavy chains
2 Light chains
Fab/Fc region
What is the Fab region?
Determines antigen specificity
What is the Fc region?
Determines antibody ‘class’ (recognized by different immune cells, leads to different responses)
What is humanization/chimerization of antibodies?
Replacement of conserved regions of the mouse monoclonal antibody with corresponding sequences of human antibodies.
How are therapeutic monoclonal antibodies named?
- umab or -zumab for humanized.
- imab or -ximab for chimeric
What is the mechanism of Alemtuzumab?
Recognizes domain on immune cells and signals for cell death by lysis or phagocytosis.
