Term
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Definition
| It is a reaction to infection or injury that initiates defense and repair. It results in an accumulation of fluid and leukocytes in the extravascular spaces. |
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Term
| What are benefits to inflammation? |
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Definition
-Eradicates the cause of injury
-Promotes healing
-Allows antibodies at site of action |
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Term
| What is the bad side to inflammation? |
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Definition
| It is bad when it becomes a chronic condition that leads to damage of healthy tissues or when it is so acute that it leads to permanent damage or death. |
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Term
| List the five classical signs of inflammation |
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Definition
Redness
Swelling
Heat
Pain
Loss of function |
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Term
| List the three stages of inflammation |
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Definition
1. Initiation
2. Amplification
3. Termination |
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Term
| Describe what happens during inflammation initiation |
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Definition
Increased blood supply to the damaged area.
Increased vascular permeability and exudation of serum proteins.
Migration of leukocytes out of the capillaries into the damaged area. |
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Term
| Describe what happens during inflammation amplification |
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Definition
| Activated immune system cells secrete cytokines and chemokines that amplify the response. |
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Term
| Describe what happens during inflammation termination |
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Definition
| As toxins, microbes, debris are cleared the response wanes. Direct inhibitory mechanisms are also in place to shut down response. |
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Term
| What are the two classifications of inflammation? |
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Definition
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Term
| Describe acute inflammation |
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Definition
Self-limiting response that mostly results in accumulation of neutrophils, eosinophils, basophils, and macrophages at site of injury.
Toxins and microbes are cleared by cellular and soluble mediators and the response is terminated upon clearance of microbe or healing of wound. |
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Term
| Describe chronic inflammation |
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Definition
Long-term response that is mediated by persistence of inflammatory cells, especially T cells and macrophages.
Can cause blood vessel proliferation, tissue damage, and excessive scarring.
Cause of diseases such as RA, psoriasis, and asthma. |
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Term
| List the principle cellular mediators of inflammation. Which are circulating and which are already present in tissue? |
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Definition
Tissue resident: Mast cells, Macrophages
Circulating: Neutrophils, Eosinophils, Basophils, Lymphocytes, Monocytes |
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Term
| Describe the role of neutrophils in inflammation |
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Definition
Usually first leukocytes that leave circulation and infiltrate site of injury or infection.
Important for phagocytosis of microbes (a process that also usually kills the neutrophil). |
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Term
| Describe the role of macrophages in inflammation |
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Definition
Secrete inflammatory factors and cytokines that activate other leukocytes.
Phagocytose microbes.
Present antigen to T cells.
Secrete factors that are important in regulating fibroblasts and endothelial cells.
Important cell in determining whether chronic inflammation will occur. |
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Term
| Describe the role of B cells in inflammation |
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Definition
| Secrete antibodies (IgE antibodies activate mast cells to release histamine) |
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Term
| Describe the role of T cells in inflammation |
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Definition
| Secrete cytokines that amplify the response; can directly kill infected cells. Prolonged T cell involvement is a hallmark of chronic inflammation. |
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Term
| Describe the role of mast cells in inflammation |
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Definition
| IgE crosslinking on surface of the mast cells leads to degranulation (release of histamine from the granules). |
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Term
| Define chemokines, as they relate to inflammation. |
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Definition
| Low molecular weight cytokines that stimulate leukocyte movement. They regulate the migration of leukocytes into and out of sites of inflammation. |
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Term
| Give example of chemokine mediators of inflammation. |
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Definition
| IL-8, GRO, and IP-10 secreted by activated macrophages. |
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Term
| Give example of proinflammatory molecules of inflammation. |
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Definition
| IL-1, IL-12, IFN-γ and TNFα. |
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Term
| How do proinflammatory cytokines promote inflammation? |
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Definition
| A variety of ways which include induction of adhesion molecules on the surface of leukocytes and endothelium, activation of PMNs and other leukocytes, production of other cytokines, and fever. |
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Term
| Define acute phase proteins |
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Definition
C-reactive protein made in liver in response to TNFa, IL-1, and IL-6. Binds to LPS in bacterial cell walls and acts as opsonin.
Binds to C1q and activates the classical pathway of complement fixation in the absence of specific antibody. |
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Term
| Describe complement components, a soluble inflammatory mediator |
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Definition
| Found in serum. C5a and C3a are called “anaphylatoxins.” They activate mast cells to release histamines. C5a is a chemoattractant. |
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Term
| Define vasoactive amines, a soluble inflammatory mediator |
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Definition
| Histamine released by mast cells is an example. It causes vasodilation, vascular permeability, and release of arachidonic acid. |
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Term
| Define Platelet activating factor (PAF), a soluble inflammatory mediator |
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Definition
| Causes platelets to release serotonin (similar to histamine in effects). PAF is a strong chemoattractant for neutrophils. |
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Term
| How do microbial products activate macrophages? |
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Definition
| By binding to Toll-like Receptors (TLRs) on the macrophage |
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Term
| How does lipopolysacchride (LPS) from gram (-) bacteria activate macrophages? |
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Definition
| LPS binds to a TLR4/CD14 complex on macrophages and activates gene transcription via AP-1 and NF-kB activation. |
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Term
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Definition
AP-1 and NF-kB are important transcription factors for the production of a number of inflammatory mediators.
Activated via TLRs |
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Term
| What drug class inhibits NF-kB, a transcription factor for inflammatory mediators? |
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Definition
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Term
| Other than killing microbes, what do activated macrophages do in inflammation? |
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Definition
| They also secrete factors that are important mediators of tissue remodeling and wound healing. |
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Term
| List three cellular processes a leukocyte takes to get to the site of infection during inflammation |
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Definition
1. Margination
2. Transmigration
3. Chemotaxis |
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Term
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Definition
| Leukocytes adhere to vascular endothelium (via selectin and integrin binding) near sites of infection or injury. |
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Term
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Definition
| Leukocytes migrate through the endothelium. Vasodilation aids this process. |
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Term
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Definition
| Leukocytes follow a gradient of chemical attractants to the site of infection or injury. |
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Term
| List the three steps of margination |
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Definition
1. Rolling on endothelial surface (mediated by selectins::addressins)
2. Integrin activation by chemokines
3. Stable adhesion (by VCAM1, ICAM1) |
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Term
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Definition
| Surface molecules found on leukocytes and endothelium that bind to carbohydrates. These molecules allow for loose binding that slows leukocytes and facilitates the initial rolling of lymphocytes along the cell walls of blood vessels. |
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Term
| What are the three types of selectins and where are they found? |
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Definition
1. P-selectins are found on platelets and endothelium.
2. E-selectins are found on endothelium and activated T cells.
3. L-selectins are found on leukocytes |
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Term
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Definition
| Another word for transmigration |
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Term
| List some chemoattractants that causes chemotaxis |
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Definition
Bacteral peptides such as N-FMLP, chemokines, and lipid mediators.
Chemokine receptor classes CXCR and CRR on leukocytes bind to these |
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Term
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Definition
Integrins are present on the surface of leukocytes and enable firm adhesion of the leukocytes to endothelium via binding to adhesion molecules ICAM-1 and VCAM-1 found on the surface of the endothelial cells.
Activated by cytokines such as IL-1 and cell interactions with chemokines |
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Term
Picture Dr. Teague's drawing of inflammation.
List the four major steps. Picture what happens.
(Drawing on back of card) |
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Definition
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Term
| What β2 integrins facilitate ICAM-1 binding? |
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Definition
LFA-1 on the surface of lymphocytes
MAC-1 on macrophages |
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Term
| Define Leukocyte Adhesion Deficiency I |
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Definition
| Lack of β2 integrins (which facilitate ICAM binding) |
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Term
| Define Leukocyte Adhesion Deficiency II |
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Definition
| A deficiency in Sialyl-Lewis factor which is the receptor for E-selectin and P-selectin |
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Term
What do PAMPs stand for?
What do PRRs stand for? |
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Definition
PAMPs = Pathogen Associated Molecular Patterns
PRRs = PAMP Recognition Receptors |
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Term
| Define PRRs and give two examples |
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Definition
PAMP Recognition Receptors, on activate innate immunity and are necessary for initiation of inflammation but overactivation can lead to endotoxic shock and be potentially fatal.
Ex. TLRs and Nuclear Oligomerization Domains (NODs) |
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Term
| Which toll-like receptors recognize gram negative bacteria? |
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Definition
LPS binds to TLR-4,
flagellin binds to TLR-5,
bacterial CpG DNA-binds to TLR-9 |
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Term
| Which toll-like receptors recognize gram positive bacteria? |
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Definition
peptidoglycans bind to TLR-2, NOD1, and NOD2,
bacterial CpG DNA binds to TLR-9,
Lipoproteins bind to TLR1/2 |
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Term
| Which toll-like receptors recognize viruses? |
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Definition
| ds-RNA binds to TLR-3; also TLR-7, TLR-8, TLR-9 |
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Term
| How is arachidonic acid activated to be released? |
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Definition
| Exposure of many cell types to bacterial products (LPS), cytokines, histamine, or bradykinin causes elevation of phospholipase A2 (PLA2) to release the arachidonic acid from membrane phospholipids |
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Term
| What inflammatory mediators can be produced from arachidonic acid? |
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Definition
Leukotrienes, protaglandins, thromboxanes, and prostacylins
There are numerous metabolites of each type with varying functions |
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Term
| What are the effects of leukotrienes and prostaglandins? |
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Definition
| Leukotrienes and prostaglandins cause capillary endothelial leakiness and edema during inflammation. They also are potent chemotactic factors for leukocytes. |
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Term
| What are the effects of thromboxane? |
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Definition
| A vasoconstrictor during inflammation |
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Term
| What are the effects of prostacyclin? |
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Definition
| A vasodilator during inflammation |
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Term
| List characteristics of chronic inflammation |
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Definition
Persistence of T cell and macrophage activity
Presence of high levels of inflammatory cytokines
Pain
Swelling
Unnecessary scarring
High levels of matrix metalloproteinases (MMPs)
Elevated levels of reactive oxygens
Tissue destruction |
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Term
| What enzyme converts arachidonic acid to leukotrienes? |
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Definition
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Term
| What enzyme converts arachidonic acid to postacyclins/prostaglandins/thromboxanes? |
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Definition
| Cyclooxygenases COX-1 and COX-2 |
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Term
| What causes chronic inflammation? |
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Definition
•Genetic traits (complement receptor mutations in lupus for example)
•Autoimmunity due to improper lymphocyte development
•Persistent irritation or injuries (wear on joints for example) |
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Term
| List the three common types of inflammatory diseases |
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Definition
1. Cellular mediated immunity (DTH)
2. Immune Complexes
3. Anaphylaxis |
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Term
Describe inflammatory disease caused by cellular mediated immunity (DTH)
Give two examples |
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Definition
Tissue damage caused by autoreactive T cells and persistent macrophages.
Examples include psoriasis and rheumatoid arthritis. |
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Term
Describe inflammatory disease caused by immune complexes
Give two examples |
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Definition
IgG antibodies produced by plasma cells form complexes with (self or foreign) antigens that damage capillary beds.
Ex. glomerulonephritis and uveoretinitis |
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Term
| Describe inflammatory disease caused by anaphylaxis |
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Definition
Acute inflammatory response that can be lethal.
After primary sensitization, a secondary exposure to antigen (bee stings, peanuts, penicillins, etc) leads to rapid hypersensitivity.
IgE bound to mast cells or basophils is crosslinked with antigen and causes degranulation and high titers of histamine, prostaglandins, leukotrienes, substance P, bradykinins, etc. |
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Term
| What drugs inhibit cyclooxygenases, thereby inhibiting prostaglandins? |
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Definition
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Term
| List NSAIDS and whether they inhibit COX1 or COX2 |
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Definition
Inhibitors of both COX-1 and COX-2: Aspirin, Ibuprofen, Naproxen
Inhibitor of COX-1: Indomethacin
Inhibitors of COX-2: Celecoxib (Celebrex), Rofacoxib (Vioxx) |
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Term
| What drugs are leukotriene receptor antagonists? |
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Definition
| montelukast (Singulair) and zafirlukast (Accolate) – asthma treatment |
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Term
| What drugs are 5-lipoxygenase antagonists, thereby inhibiting leukotrienes? |
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Definition
| zileuton (Zyflo) – asthma treatment |
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Term
| What drug acts as a monoclonal antibody against integrin-α4, thereby inhibiting VCAM-1 binding and leukocyte migration? |
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Definition
| Natalizumab (Tysabri)– used in treatment of MS and Chrohn’s |
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Term
| Give an example of a H2 histamine receptor antagonist |
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Definition
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Term
| Name two drugs which inhibit PLA2 and therefore inhibits AA metabolism, inhibits T cell proliferation, and causes T cell apoptosis? |
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Definition
| Hydrocortisone, dexamethasone |
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Term
| List four cytokne inhibitor drugs |
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Definition
Anakinra (Kineret)
Etanercept (Enbrel)
Adalimumab (Humira)
Infliximab (Remicade) |
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Term
| Name a drug used as a monoclonal antibody that binds to and blocks IgE |
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Definition
| Omalizumab (Xolair)- to treat allergy related asthma |
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Term
| How is methotrexate, the anti-cancer drug, also used as an immunity drug? |
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Definition
| General immunosuppressant; inhibits DNA synthesis and therefore inhibits cell growth. |
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