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107 Cards in this Set
- Front
- Back
What are the functions of the immune system?
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1. Primary function is to recognize and eliminate invading pathogens (must distinguish between self and non-self)
2. Mechanisms of an immune response include recognition, activation, deployment, discrimination, and regulation |
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What are the two arms of the immune system?
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1. Innate immunity (non-specific)
2. Adaptive immune system (specific) |
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Innate immunity is comprised of what exterior defenses?
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skin, mucus, cilia, normal flora, saliva, low pH of the stomach, skin, genitourinary tract
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Adaptive immunity is compromised of what exterior defenses?
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none
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What is the specificity of innate immunity?
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it is limited and fixed
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What is the specificity of adaptive immunity?
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it is extensive
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What memory does the innate immune system have?
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none
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What memory does the adaptive immune system have?
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extensive memory
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How long does it take for the innate immune system to respond?
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hours
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How long does it take for the adaptive immune system to respond?
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days
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What soluble factors make up the innate immune system?
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lysozymes
complement C-reactive protein interferons mannose-binding lectin antimicrobial peptides |
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What soluble factors make up the adaptive immune system?
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antibodies
cytokines |
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What cells make up the innate immune system?
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neutrophils
monocytes macrophages natural killer cells eosinophils |
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What cells make up the adaptive immune system?
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B lymphocytes
T lymphocytes |
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What is self-tolerance?
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Self-tolerance is the ability to distinguish between self and nonself. Failure of self-tolerance may lead to the development of autoimmune diseases.
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What are the primary organs of the immune system?
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1. Bone marrow - primary effector cells of the immune system are derived from the pluripotent hematopoietic stem cells
2. Thymus - primary site of T cell maturation and differentiation |
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What are the secondary organs of the immune system?
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1. Spleen - red pulp is the site of removal of old or damaged red cells; white pulp contains mostly B and T lymphocytes and macrophages
2. Lymph nodes - filter antigens from the lymphatics |
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What makes up the physical defenses of the innate immune system?
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1. Skin
2. GI tract (stomach acid) 3. Respiratory tract (cilia, mucous) 4. Mechanical defenses (normal urine flow, tears, saliva) |
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What are the 2 mechanisms by which phagocytosis occurs?
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1. Opsonin-dependent - coating of the infectious pathogen by antibody, complement or lectin must occur to phagocytosis to be initiated
2. Opsonin-independent phagocytosis - innate leukocytes use pattern recognition receptors like lipoproteins or terminal mannoses that are expressed by a large number of microorganisms; leads to immediate phagocytosis of the pathogen |
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What are the first cells to respond to an area of damage or inflammation?
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neutrophils
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Maturity of neutrophils
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1. Segmented (Segs) are the most mature neutrophils and usually make up the majority of circulating neutrophils
2. Banded (Bands) are less mature and adhere to vessels of peripheral blood, lungs, spleen, and liver |
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What is "left shift"?
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Left shift is a shift from more segs to more bands in circulating blood. This is a sign of infection, usually bacterial.
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What is the primary defense against non-phagocytable multicellular pathogens (like parasites)?
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eosinophils
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Where are eosinophils usually found in high numbers?
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1. Around antibody-antigen complexes
2. In tissues infected with parasites 3. Sites of allergic reactions |
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What activates eosinophils?
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IgE
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What is primary role of macrophages and monocytes?
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They are phagocytes. Macrophages exist in tissue and monocytes in the blood stream. Macrophages are more active and have more Fc and complement receptors.
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What is the role of mast cells?
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They release inflammatory mediators (histamine, heparin, serotonin) and areassociated with IgE-mediated inflammation. They can phagocytize, destroy, or present bacterial antigens to T lymphocytes.
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What is the role of basophils?
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They release inflammatory mediators (histamine). They are bloodstream cells associated with IgE mediated inflammation.
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What are granulocytes?
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Cells that contain cytoplasmic granules filled with inflammatory mediators or digestive enzymes which can be released from the cell.
1. Neutrophils 2. Eosinophils 3. Basophils |
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What are the major functions of the complement system?
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1. To lyse certain microorganisms and cells
2. To stimulate the chemotaxis of phagocytic cells 3. To coat (opsonize) foreign pathogens 4. Clear immune complexes |
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What is the classic pathway to stimulate the complement cascade?
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Antibody binds to its target antigen and activates the frist component of complement (C1), which initiates the complement cascade. Both IgG and IgM are capable of activating complement.
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What is alternative pathway to stimulate the complement cascade?
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Relies on the inability of some bacteria to clear spontaneously produces C3b from their cell surface. Excessive buildup of this complement protein can activate the cascade.
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How does complement produce cell lysis?
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Through the formation of the cylinder shaped protein structure, the Membrane Attack Complex (MAC)
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What things differentiate the adaptive immune system from the innate immune system?
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-specificity
-memory -ability to amplify the immune response via cytokines -evolves with each subsequent infection |
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What are the 2 different forms of T-cell receptor?
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1. Receptor found on T helper cell in association with CD4+
2. Receptor on T cytotoxic cells in association with CD8+ |
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What are the 4 major subgroups of T cells?
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1. T helper cells - recruit B lymphocytes to produce antibodies
2. T cytotoxic cells - kill target cells 3. T suppressor cells - inhibit certain immune responses 4. T delatyed-type hypersensitivity cells (memory cells ) - induce inflammation |
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What are CD4+ cells?
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They are primarily T helper cells
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What are CD8+ cells?
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They are primarily T suppressor and T Cytotoxic cells (killers)
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What are the 2 types of CD4+ cells and what do they do?
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1. T helper type I which contribute to cellular immunity by interacting with CD8+ cells
2. T helper type II which contribute to humoral immunity by recruiting B cells |
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What do T suppressor cells (CD8+) do?
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They inhibit proliferation of T and B cells. Increase production of IgA.
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What do cytotoxic T cells (CD8+) cells do?
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Attach to target cells and release cytotoxic substances (perforins), which produce cell lysis.
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What is the primary function of B lymphocytes?
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The primary function of B cells is antigen recognition and production of antibodies (humoral immunity). They can differentiate into plasma cells and memory B cells.
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General Info on Major Histocompatibility Complex.
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Made up of Human Leukocyte Antigens (HLA). There are 2 classes of HLA (Class I and II). Class I genes (HLA-A, B, and C) can be found on all nucleated cells. Class II genes (HLA-DP, DQ, and DR) are found primarily on immune cells and vascular endothelium.
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What are the antigen presenting cells?
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1. Macrophages
2. Dendritic cells 3. B cells |
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What is required for T lymphocyte activation?
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1. Presentation of processed antigen with MHC
2. Co-stimulation on the antigen presenting cell (APC) |
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What important roles do CD8+ T lymphocytes play?
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1. clear the body of virus infected cells
2. eradication of tumor cells 3. rejection of transplanted organs |
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What are the 2 mechanisms by which cytotoxic (CD8+) T cells destroy target cells?
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1. Perforin system in which they insert a pore into the target cell leading to apoptosis
2. Fas ligand pathway in which ligand binds to the Fas receptor on the target cell and the CD8+ cell destroys the target cell |
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How do B lymphocytes recognize antigens?
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1. Via its antibody
2. Via immunoglobulin located on its cell surface. |
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Once activated, what happens to B lymphocytes?
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1. They become plasma cells that produce antibody
2. They become memory B cells |
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General characteristics of Antibody
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It is a glycoprotein composed of heavy and light chains. The stem or heavy chain contains the Fc portion. The Fc portion activates complement and is recognized by Fc receptors on phagocytes.
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General facts about IgG
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It is the most prevalent antibody (80% of serum antibodies). It exists as a monomer. It is the only antibody that can cross the placenta.
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What is the only antibody that can cross the placenta?
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IgG
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What is the most prevalent antibody?
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IgG
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General facts about IgM
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IgM is found on the surface of B lymphocytes. It exists as a pentamer, which means it can bind 5 antigens. It lacks the Fc portion, but can still fix complement.
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Which antibody exists as a pentamer?
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IgM
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General facts about IgA
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It is found in fluid secretions (tears, saliva, nasal fluids) and in the GI tract, GU tract, and respiratory tract. It prevents pathogen colonization. It is the primary antibody secreted in nursing mothers' breast milk. It exists as a dimer.
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General facts about IgE
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IgE is the least common antibody. It is bound to Fc receptors on mast cells. It causes release of inflammatory mediators (histamine).
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General characteristics of Cytokines
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Cytokines provide communication between the divisions of the immune system. They are produced by APCs mostly promote chemotaxis for other cells and induce a state of inflammation. They are classified as regulatory or hematopoietic growth factors.
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What are the different types of cytokines?
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1. interferon
2. tumor necrosis factor 3. interleukin |
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What are the 3 types of interferon and where are they produced?
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1. Alpha interferon is produced by leukocytes
2. Beta interferon is produced by fibroblasts 3. Gamma interferon is produced by T cells |
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What are the functions of interferon?
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Cells that are infected by viruses produce interferon, thus preventing the viruses from infecting other cells. Interferon prevents the uptake and replication of several types of viruses. It also increases the expression of MHC molecules. It also increases the activity of NK cells.
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What is the MOA of interferon?
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As an antiviral, it interferes with viral protein production and budding.
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Interferon has antitumor effects. What tumor types is it used to treat?
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1. Hairy cell leukemia
2. Chronic myelogenous leukemia 3. Kaposi's sarcoma 4. Renal cell carcinoma 5. Multiple myeloma |
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What are the major toxicities associated with interferon?
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1. Flu-like syndrome (may develop tolerance)
2. Fatigue (will not develop tolerance) 3. Cardiovascular - tachycardia and hypotension 4. Anorexia and weight loss with long term use 5. CNS toxicity with high doses 6. Myelosuppression with long term use |
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What is the advantage of pegylated-IFN-alpha over plain interferon?
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It has a longer half-like and once weekly dosing.
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Where is TNF-alpha produced?
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TNF-alpha is primarily produced by monocytes.
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Where is lymphotoxin (TNF-beta) produced?
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Lymphotoxin is primarily produced by T cells.
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What are the functions of TNF
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1. Augment phagocyte activity
2. Enhance neutrophil degranulation 3. Produce fever 4. Increase the expression of adhesion molecules |
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What are the 2 types of interleukins?
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1. Lymphocyte-activating factor or IL-1
2. T cell growth factor or IL-2 |
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What are the functions of the different interleukins?
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1. IL-1 (lymphocyte-activating factor) promotes T and B cell proliferation
2. IL-2 (T cell growth factor) stimulates T cell proliferation |
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What are the different hematopoietic growth factors?
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1. Granulocyte-monocyte colony-stimulating factor (GM-CSF)
2. Granulocyte colony-stimulating factor (G-CSF) 3. Macrophage colony-stimulating factor (M-CSF) |
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What is the effect of G-CSF?
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It has a narrower effect than GM-CSF or IL-3. It effects primarily late development of Neutrophils (segs). It increases migration, phagocytosis, and antibody-dependent cytotoxicity. It is the hematopoietic growth factor that is most commonly used.
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When is M-CSF used?
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M-CSF is used to increase candida and Mycobacterium-avium intracellular killing. It is rarely used.
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What are the clinical uses of hematopoietic growth factors (GM-CSF, G-CSF, M-CSF)?
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-to reduce duration of neutropenia associated with chemotherapy
-graft failure in bone marrow transplant -for neutropenia associated with AIDS -for stem cell harvest in BMT |
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What are the adverse reactions to GM-CSF?
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1. Low-grade fever, myalgias, pain at injection site
2. Bone pain is almost always present 3. Capillary leak syndrome (pleural and pericardial effusions) |
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What are the adverse reactions to G-CSF?
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1. bone pain (25% of patients)
2. myalgias 3. skin rash |
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What are the sources and prinicipal effects of IL-2?
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Sources: CD4+ T lymphocytes
Effects: activation of T lymphocyes, B lymphocytes, NK cells |
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What are the sources and principal effects of IL-6?
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Sources: CD4+ T lymphocytes, macrophages, mast cells, fibroblasts
Effects: T and B lymphocyte growth factor, hematopoietic growth factor, augments inflammation |
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What are the sources and principal effects of TNF-alpha?
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Sources: macrophages, NK cells, T and B lymphocytes, mast cells
Effects: activation of neutrophils, endothelial cells, lymphocytes, liver cells to produce acute phase proteins |
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What are the sources and principal effects of INF-alpha?
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Sources: monocytes, other cells
Effects: antiviral, activation of NK cells and macrophages, upregulation of MHC class I |
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What are the sources and principal effects of INF-gamma?
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Sources: T lymphocytes NK cells
Effects: activation of macrophages, NK cells, upregulation of MHC class I and II |
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What are the sources and principal effects of IL-3?
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Sources: T lymphocytes, macrophages
Effects: maturation and differentiation of hematopoietic and mast cells |
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What are the sources and principal effects of G-CSF?
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Sources: macrophages, endothelial cells, fibroblasts
Effects: maturation and activation of neutrophils |
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What are the sources and principal effects of GM-CSF?
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Sources: T lymphocytes, macrophages, endothelial cells, fibroblasts
Effects: maturation and activation of granulocytes, monocytes/macrophages, and eosinophils |
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What are the sources and principal effects of erythropoietin?
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Sources: kidney, liver
Effects: maturation of red blood cells |
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What are some examples of alterations in mechanical immunodefenses?
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-reduced gastric pH (PPI's)
-break in skin barrier -burns -impaired mucociliary function of the lungs (smoking) -altered urine flow (catheter) |
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What is Cluster of Differentiation (CD)?
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A test for proper amount of T and B cells.
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What is the predominant cellular distribution of CD3 antigens?
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all T lymphocytes
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What is the predominant cellular distribution of CD4 antigens?
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helper T lymphocytes, either TH1 or TH2
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What is the predominant cellular distribution of CD8 antigens?
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cytotoxic/suppressor T lymphocytes
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What is the predominant cellular distribution of CD20 antigens?
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B lymphocytes
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What is the predominant cellular distribution of CD25 antigens?
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activated T lymphocytes, B lymphocytes, interleukin-2 receptor alpha-chain (Tac)
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What is the predominant cellular distribution of CD34 antigens?
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hematopoietic progenitor cells that include the stem cell
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Which tests evaluate immune function?
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1. Delayed hypersensitivity test - tests cell mediated immunity (TB skin test)
2. Tissue biopsy 3. B lymphocyte function assessment - vaccinate then measure response 4. Cylex "ImmuKnow" Assay - determines CD4+ cell suppression |
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What values do you need to know when reading the results of a Cylex "ImmuKnow" Assay?
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1. ~100 ng/ml means the person is immunocompromised and at risk for infection
2. ~250 ng/ml means the person if properly immunosuppressed in the organ transplant setting 3. >500 ng/ml means the person is immunocompetent or at risk of rejection in the transplant setting (this would not prove rejection, would still need biopsy) |
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What is ATG?
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ATG is a polyclonal antibody made from rabbit (thymoglobulin-rabbit). It's action tends to be directed toward all lymphocytes. It is called flu in a bottle because it depletes lymphocytes. Premedicate with APAP, antihistamines, and steroids.
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What is Crotalidae Polyvalent Immune Fab Ovine?
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It is a polyclonal antibody. It has its own Fab region, which means it doesn't activate complement, so it can do its job with less immune response.
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What are recommendations for use of VZIg (varicella-zoster immunoglobulin)?
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-use with persons susceptible to varicella-zoster (never had chicken pox)
-use in persons with significant exposure within 96 hours -use in persons younger than 15 |
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What are some uses of IVIg (IV immunoglobulin)?
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-primary immun deficiencies (agammaglobulinemia)
-viral infections (CMV treatment, HSV) -thrombocytopenias - idiopathic thrombocytopenia pupura -bacterial infections |
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What are some common immunology related MAB drugs?
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infliximab (Remicade)
omalizumab (Xolair) daclizumab (Zenapax) Zevalin Bexxar certolizumab (Cimzia) natalizumab (Tysabri) benamustine (Treanda) abatacept (Orencia) |
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What is a type I allergic reaction?
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Type I reactions are considered anaphylactic. Onset is within 30 minutes and can include shock, pruritis, urticaria, angioedema, respiratory distress, laryngeal edema, and vascular collapse. It often mediated by IgE on mast cells (also histamines, leukotrienes, etc.).
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What are examples of type I allergic reactions?
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1. drug reactions
2. hay fever |
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Treatment for type I allergic reactions?
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1. antihistamines
2. sympathomimetic agents (blood pressure agents) 3. corticosteroids |
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What is a type II allergic reaction?
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Type II reactions are considered cytotoxic reactions. Onset is 5-12 hours. It is both IgG and IgM mediated.
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Treatment for type II allergic reactions?
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1. immunosuppressive agents (reaction is T cell activated, so we must pus back T cells)
2. corticosteroids 3. splenectomy |
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What is a type III allergic reaction?
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Type III reactions are considered immune complex related reactions. Onset is 3-8 hours. They are usually associated with IgG and IgM circulating immune complexes. It is often termed "innocent bystander reaction". Treatment is anti-inflammatory agents.
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What is type IV allergic reaction?
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Type IV reactions are cell mediated, delayed hypersensitivity reactions. The onset is 24-48 hours. T lymphocytes must recognize the antigen. TB skin testing is the classic example. Treated with immunosuppressive drugs.
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