103293
Description
Flashcards by tanitia.dooley, updated more than 1 year ago
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Created by tanitia.dooley
about 11 years ago
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| Question | Answer |
| What are the effects of histamine at H1 receptors? Give an example of a drug that is used to treat inflammation? | vasodilation, increased vascular permeability, contraction of smooth muscle in lung. Fexofenadine |
| What is 12-HETE? | a chemokine eicosanoid |
| Which prostaglandins are vasodilators? | PGI2, PGE2, PGD2 (also inhibits platelet aggregation) |
| What prostaglandins are vasoconstrictors? | PGF2A |
| What is the effect of thromboxane A2? | vasoconstriction |
| What is the effects of LTC4, LTD4 and LTE4? | vasoconstrictor and increased vascular permeability. LTC4 and LTD4 are metabolised to LTE4 and eliminated from the body |
| What is the effect of LTB4? | chemotaxin |
| Which prostaglandin predominates? | PGE2 |
| Describe the synthesis of PAF? | Acyl PAF is converted to lyso-glycerl phosphorylchloride by phospholipase A2 which is then converted to PAF by acetyl transferase |
| What is the role of PAF in asthma? | lung chemotaxin in monocytes, neutrophils and eosinophils |
| How are glucocorticoids linked to PAF? | they have anti inflammatory effect by inhibiting PAF formation |
| How is bradykinin formed? | by the cleavage of kininogens by killikrein |
| Describe B1 and B2 bradykinin receptors | B1 expressed at low levels-expression induced with stress/inflammation. B2= constitutively expressed in many normal cells. Causes vasodilation and increased vascular permeability and stimulation of pain nerve endings |
| What is the effect of NO? What happens when present in high levels? | vasodilation, enhances prostaglandin production, increased vascular permeability. It degrades into reactive nitrogen oxide species which damage invading pathogens and potentially host cells |
| What is sulfasalazine? | an antirheumatoid drug which produces remission of the disease by reducing phagocytosis by scavenging ROS and NO |
| What are gold compounds? | antirheumatoid drugs which reduce joiny pain and swelling-mech unknown may be due to inhibiting cytokine release by phagocytes |
| what is anti cytokine therapy? What are the disadvantages? | greatest break conceptual breakthrough in treatment of chronic inflammatory disease. It is biopharmaceutical- recombinantly enginerred Ab specific for human protein- therefore difficult to produce and expensive |
| What is infliximab? | Ab against TNFa- binds to it and prevents its action |
| What is basiliximab? | Monoclonal Ab against IL-2 receptor- binds to the receptor and prevents effective T cell proliferation |
| What is anakinara? | IL-1b receptor antagonist |
| What is azathioprine? | interferes with purine synthesis and is cytotoxic- DNA synthesis required for T cell proliferation therefore inhibits cell-mediated immune reaction. Metabolised to mercaptopurine |
| What is copaxone? | It is a future drug- found to supress experimental models of MS and slows progression of disease in humans- competes with myelin Ag for TCR and binds with high affinity preventing native binding |
| What is peptide based immunotherapy? | aim is to develop a peptide which can form a complex with MHC, can be administered as a drug, can be recognised by TCR but not send signals for activation of the T cell, must prevent native peptide from coordinating with TCR |
| Describe CD80 blocking drugs? | at preliminary stage in clinical trials- experimental models have found that antiCD80abs can decrease disease severity and antiCD86 can increase it- however only successful at treating primary disease before symptoms=not possible |
| What is histamine synthesised from? | histidine using histadine decarboxylase |
| Where is histamine stored? | in high concs in mast cells and basophils in granules which bind acidic proteins and macroheparin to remain inactive |
| How is histamine releaed? | Ag binds to IgE associated Fc receptors, Following reexposure to Ag= cross linking of IgE=increased cytoplasmic Ca2+=mast cell degranulation and release of mediators such as histamine |
| Give an example of a glucocorticoid | hydrocortisone |
| What do COX2 inhibitors reduce? | vasodilation, oedema and pain not accumulation of inflammatory cells |
| What happens in the COX enzyme in the absence of an inhibitor? | arachidonic acid travels down the channel to the catalytic site where it is converted to prostaglandin E2 which binds with lower affinity and is therefore released |
| What is the role of CD80 and CD86 on APCs? | CD80 binds to CD28 on T cells and has positive regulation, CD86 binds CTLA-4 on T cells=negative regulation |
| How do NSAID work? | Bind channel of COX enzyme and prevents arachidonic acid from reaching the catalytic centre so it is not converted to prostaglandin E2 |
| How does MHC interact with the T cell receptor? | MHC pockets which AA side chains fit in binding through hydrophobic bonds. certain AA side chains are exposed from the MHC cleft and recognised by the T cell receptor. The peptide provides signals controlling fine specificity of interaction. T cell also interacts with MHC itself and binding of CD4/CD8 to MHC stabilises the structure |
| What two signals are required for the initiating of T cell activation? | 1. peptide antigen cross linking MHC & TCR 2. additional receptor signals from APCs (CD80 & CD86) |
| What is the difference between the COX 1 and COX2 enzyme? | COX 2 has larger channel and additional binding site |
| Describe delayed type hypersensitivity? | CD4 secretes IFN-y which activates macrophages and neutrophils causing the release of NO, ROS and cytokines which causes tissue injury |
| How are COX 2 selective drugs different to non selective ones? | They have increased molecular weight but retained interaction with binding site so too big to pass down COX1. Increase potency by identifying the additional binding site |
| Describe how insulin-dependent diabetes mellitus is caused? | IFN-y secreting T cells around islet of langerhans cause tissue injury of beta cells causing decreased insulin production. |
| What is the susceptibility factor for diabetetes mellitus? | HLA DR3 and DR4-95% susceptible individuals express it compared to 40% healthy individuals. Viral infection |
| What is the symptoms of diabetes mellitus? | ketoacidosis, hyperglycemia |
| What are the common side effects of NSAIDs? | gastric irritation, effects on renal blood flow, tendency to prolong bleeding by inhibiting platelet function, increased liklihood of thrombotic events eg myocardial infarction (exspecially COX2 selective by inhibiting PGI2) |
| What is cyclosporin and what is its effect? | immunosupressant drug, decreases proliferation of T cells by inhibiting IL-2 release= decreased function of effector T cells that secrete cytokines and mediate autoimmune reactions |
| How does cyclosporin inhibit IL-2 release? | binds to the cytosolic protein cyclophilin in T cells which inhibits transcription factor activation and synthesis of IL-2 |
| Describe the disease mechanism of multiple sclerosis? | T cells are activated by myelin/myelin related proteins and migrate into the CNS where they secrete IFN-y. They then cause tissue damage to CNS cells causing myelin destruction which released more myelin related proteins causing the release of more cytokines |
| What are the symptoms of multiple sclerosis? | weakness, paralysis, ocular symptoms |
| What are the susceptibility factors for MS? | HLA-DR2 & viral infection |
| what are the effects of glucocorticoids? | decreased production of NO, histamine and prostaglandin, decreased action of helper T cells by decreasing T cell proliferation, decreased cytokine productiong involved in inflammation and reduced activity of macrophages by decreasing gene txn of IL-2, IFNy and TNFa |
| What is the mechanism of action for glucocorticoids? | Bind intracellular receptors which dimerise, conformation change exposing DNA binding domain- move to the nucleus and interact with glucocorticoid response elemment and/or NFkB, Fos/ Jun to modify gene expression |
| What causes rheumatoid arthritis? | Antigen unknown but activates T cells which secrete IFNy which phagocyte activation and secrete TNFa and IL-1B which acts on synovial cells to produce proteolytic enzymes which cause tissue damage of synovial tissue causing inflammation |
| what are the susceptibility factors in rheumatoid arthritis? | HLA DR1 and 4, viral infection |
| How do infections contribute towards autoimmunity? | by up regulating expression of co-stimulatory molecules on antigen presenting cells thus enhancing antigen presentation |
| describe the Genetic susceptibility of autoimmune diseases? | MHC class II gene HLA DR- corresponds with observation that CD4+ cells involved in disease progression |
| Describe what happens in T cell mediated cytolysis? | viral infected cells cause clonal expansion and then cell killing by perforin/fas |
| Why do T-cells kill all infected cells? | they cant discriminate between latent and destructive viruses |
| Give an example of virally infected cytolysis? | hepatitis, myocarditis |
| what are the effects of prostaglandin? | vasodilation, decreased blood flow |
| What is the difference between the expression of COX1 and COX2? | COX1 is expressed in most tissues and has a housekeeping role in homeostasis. COX2 expression is induced by activated inflammatory cells. When immune cells are activated= increased IL-1 and TNFa which leads to the expression of COX2 |
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