Immunosuppresion Flashcards
What are the 9 organs of the immune system?
- Adenoid
- Tonsil
- Thymus
- Lymphatic vessels
- Lymph nodes
- Spleen
- Peyer’s patches in small intestine
- Appendix
- Bone marrow
What is the goal of an immune response?
To recognize and remove invading microorganisms and tumor cells
What is the goal of immunosuppression?
To minimize the impage of exagggerated or inappropriate immune responses
Describe the following characteristics of the innate immune system:
- Onset
- Mechanism of action
- Cell types involved
- Soluble factors
- Onset: immediate
- Mechanism of action: Pattern recognition receptors recognize common molecules on microbes and viruses
- Cell types involved: Macrophages, neutrophils, mast cells, naturall killer cells, NK T cells, innate lymphoid cells
- Soluble factors: Complement, Type I interferon, select cytokines and chemokines
Describe the following characteristics of the acquired immune system:
Onset
Mechanism of action
Cell types involved
Soluble factors
- Onset: days to weeks
- Mechanism: Antigen-specific receptors (T-cell receptor, B-cell receptor)
- Cell types: Dendritic cells, T cells, B cells
- Soluble factors: Select cytokines and chemokines
What are the steps involved in Cell mediated Acquired immunity?
- Antigen presenting cell binds Th1 and pCTL, converting pCTL into an effector CTL (with TH1 Interleuken 2)
- Effector CTL binds tumor cell and causes cell lysis
What are the processes involved in humoral acquired immunity?
- APC binds Th2 cell, turning it into activated T cell
OR
- Memory B cell binds Th2 cell, turning it into activated T cell
- Activated T cell binds B cell, becoming activated B cell
- Activated B cell becomes Memory B cell (For future infections)
- Activated B cell becomes Plasma cell (proliferation of antibodies)
Name four reasons to use immunosuppresive agents
- Autoimmune disease
- Isoimmune disease (eg Rh hemolytic disease of the newborn)
- Organ transplantation
- Prevention off cell proliferation
What is Rhesus hemolytic disease?
Isoimmune disease
- During birth, Rh+ fetal erythrocytes leak into maternal blood after embryonic chorion ruptures.
- Maternal B cells are activated by Rh antigen and produce large amounts of anti-Rh antibodies
- Rh antibody titer is elevated in mother’s blood from first exposure
- Rh antibodies are smol enough to cross embryonic chorion and attack fetal erythrocytes
Mother is fine (physically 😢) and fetus dies
What are 4 types of organ transplant?
- Isograft (identical twins)
- Autograft (within an individual)
- Allograft (non identical individuals) *best HLA match
- Xenograft (between species)
What are HLA antigens and what can they help determine?
Human leukocyte antigens
Major determinant of tissue compatibilty
Ligand/receptor pairings on APCs/Tcells
Name the three targets for immunosuppresive drugs in order of selectivity (lowest to highest)
- Cell proliferation (lowest)
- T cell function
- Antibody approaches: antigen recognition (highest)
Name two types of drugs for Cell proliferation and name an example of each
- Glucocorticoids
- Prednisone
- Cytootoxic drugs
- Cyclophosphamide
- Azathioprine
- mycophenolate mofetil
- methotrexate
What is the effect of prednisone?
Glucocorticoid receptor agognist
How do glucocorticoids function?
- Decrease transcription of inflammatory genes
- Increase expression of anti-inflammatory genes
- Decrease production of prostaglandinsm cytokines and interleukins (IL-1,IL-2)
- Decrease proliferation and migration of lymphocytes and macrophages
What does cyclophosphamide do?
Alkylates DNA, induces DNA crosslinks, and inhibits cell proliferation
What does Azathioprine do?
- Prodrug - metabolized into 6-mercaptopurine*
- inhibits purine synthesis, blocks DNA and RNA synthesis
What does mycophenolate mofetil do?
- Inhibits inosine monophosphate dehydrogenase
- Blocks de novo purine synthesis
- Inhibits T and B cell
What does methotrexate do?
Inhibits Dihydrofolate reductase, starves cells of thymidine
Name 3 immunosuppression drugs that target T cells
- Calcineurin inhibitors
- Cyclosporine
- Tacrolimus
- Sirolimus
What does calcineurin do?
Main substrate in cytokine IL-2 production
What happens whan calcineuin is inhibited?
T cells fail to respond
What does Sirolimus do?
Inhibition of mTOR which blocks cell cycle progression at the G1-S phase transition
What are two examples of polyclonal antibodies? What is the effect of them?
- Anti-lymphocyte globulin (ALG)
- Anti-thymocyte globulin (ATG)
Rapid depletion of peripheral lymphocytes: prevent initial graft rejection
True/False? Monoclonal antibodies from other animals can be humanized to be biocompatible
True
Name a murine monoclonal antibody and its effect on the (human) body
Muromonab (OKT3), anti-CD3
Binds T cell CD3 ligand and induces T-cell receptor internalization
Kill cytotoxic human T cells
(Used to reverse acute allograft rejection)
What is TNF?
Tumor necrosis factor
“able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells”
Name an anti-TNFalpha drug? what does it do?
Infliximab
Prevents TNF from being recognized at target cells
What disease are anti-TNF biologicals used for?
Crohn’s disease and rheumatoid arthritis
What is Daclizumab? What does it do?
Humanized anti-IL2-receptor alpha (CD25)
Targets antigen-activated T cells by binding to alpha chain of IL-2 R (CD25)
Used with calcineurin inhibitors to prevent acute organ rejection
What drugs are used to treat autoimmune disorders?
- Glucocorticoid: Prednisone
- Anti-metabolites: Methotrexate
- TNFalpha receptor antagonists: Infliximab
- B cells/CD20: Rituximab
What is fingolimod and what does it do?
Sphingosine 1-Phosphate receptor modulator
Used for multiple sclerosis
How can you prevent Rhesus hemolytic disease?
Specific antibody administration to mother at 28 weeks / within 72 hours of birth
How can you prevent organ transplant rejection?
- Patient preparation and donor selection (HLA match)
- Immunosuppression (multilayered, intensive induction/lower dose maintenance)
Induction of biological agents:
- poly/monoclonal antibodies (ATG, muromonab, daclizumab etc)
Maintenance:
- Calcineurin inhibitor, glucocorticoid, mycophenolate mofetil
What is a coronary stent?
balloon catheter used to prop up vessel during heart surgery, held up by stents
Stents can be drug-eluting, which release immunosuppressants over time to reduce chances of rejection
What are two unwanted effects of immunosuppressive agents?
Increased risk of infections
Increased risk of lymphomas/secondary malignancies
