Term
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Definition
| The science of self-nonself discrimination |
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Term
| 2nd property of immune system |
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Definition
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Term
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Definition
| Same for repeated infections |
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Term
| Components of innate immunity |
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Definition
| Physical barriers, blood components (complement,etc.), phagocytic cells, cytokines |
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Term
| Timing of innate immunity |
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Definition
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Term
| Timing of adaptive immunity |
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Definition
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Term
| Components of adaptive immunity |
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Definition
| B cells, T helper cells, Cytotoxic T cells |
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Term
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Definition
| Shared structures (PAMPS) |
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Term
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Definition
| Specific portions of peptides |
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Term
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Definition
| Limited, no rearrangement |
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Term
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Definition
| Large, rearrangement of gene segments |
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Term
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Definition
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Term
| Earliest adaptive immunity |
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Definition
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Term
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Definition
| TLR, N-formyl-methionyl receptor, mannose receptor, scavenger receptor |
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Term
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Definition
| Same for one type of cell vs. same for all cells of the class |
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Term
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Definition
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Term
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Definition
| Phagocytosed vs. intracellular |
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Term
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Definition
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Term
| Cell-mediated responding cells |
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Definition
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Term
| Humoral effector and transfer mech |
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Definition
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Term
| Cell-mediated effector and transfer mech |
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Definition
| T cells (Th activate mac's) |
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Term
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Definition
| Neutralization of microbe, phagocytosis, complement activation |
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Term
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Definition
| Activate mac's, inflammation, activate T/B cells |
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Term
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Definition
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Term
| Reg T cell effector function |
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Definition
| Suppression of immune response |
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Term
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Definition
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Term
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Definition
| Allow immune system to respond to new Ag's without "stale" responses interfering |
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Term
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Definition
| Stimulate memory response vs. no memory |
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Term
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Definition
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Term
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Definition
| Give live Ag and allow response to develop |
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Term
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Definition
| Increase 2° adaptive response |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Inability to effectively react to Ag stim |
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Term
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Definition
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Term
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Definition
| WBC's that specifically recognize Ag epitopes |
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Term
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Definition
| Cluster of differentiation |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Separate cells based on markers and give readout based on fluorescent results |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Erythrocyte, Platelet, Basophil, Eosinophil, Neutrophil, Monocyte |
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Term
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Definition
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Term
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Definition
| Toxic proteins,fuse with phagosomes to destroy pathogens, fuse with outer membrane to destroy parasites |
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Term
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Definition
| PMNs, eosinophils, basophils, mast cells |
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Term
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Definition
| Release granules intor surrounding area, innate immunity to parasites, allergic reactions |
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Term
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Definition
| Inflammation and allergic reactions, similar to eosinophils (distinguished by basic staining) |
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Term
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Definition
| In gut, toxins dissipated over time |
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Term
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Definition
| Effector cells of hypersensitivity and allergic reactions, found in all tissues of body |
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Term
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Definition
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Term
| Peripheral lymphoid organs |
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Definition
| LN's, spleen, mucosal/cutaneous lymphoid tissues |
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Term
| Location of new protein synth, proliferation |
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Definition
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Term
| Larger amount of ER and cytoplasm |
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Definition
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Term
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Definition
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Term
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Definition
| ID'd by membranous projections, arise from bone marrow precursors |
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Term
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Definition
| capture microbial protein Ag's and transport to LN's (for Ag presentation) |
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Term
| Phagocytic function of DC's |
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Definition
| Up as immature, down as mature (downreg. of receptors) |
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Term
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Definition
| Change from naive to effector allows increased access to parts of body |
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Term
| Locations of memory cells |
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Definition
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Term
| 2 important properties of stem cells |
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Definition
| Ability to renew and differentiate |
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Term
| What do growth factors such as erythropoietin do to stem cells? |
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Definition
| Drive differentiation and prevent apoptosis (allow survival) |
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Term
| What are some clinical signs of leukemia and why do these happen? |
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Definition
| Low RBC/platelet count, High or low WBC, caused by crowding from leukemia blast cells |
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Term
| What happens in primary lymphoid tissues? |
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Definition
| Hematopoietic stem cells differentiate into lymphoid progenitors and then are educated/mature in their respective tissues |
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Term
| What happens in secondary lymphoid tissues? |
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Definition
| Ag recognition, concentration of APC's |
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Term
| Residence of long-lived plasma cells |
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Definition
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Term
| Morphology of hemato. active BM |
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Definition
| Spongelike reticular network with boney trabeculae, penetrated with many blood sinusoids |
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Term
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Definition
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Term
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Definition
| Surrounded by stromal cells and hemato. precursors |
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Term
| Dumping point of sinusoids |
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Definition
| Central vein (deliver cells to periphery) |
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Term
| Determination of release from BM |
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Definition
| Deformability, receptors (respond to cytokines to allow release), membrane charge and blood flow |
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Term
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Definition
| Increase throughout youth, decrease with age afterwards |
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Term
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Definition
| 2 (separated incompletely by parenchyma) |
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Term
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Definition
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Term
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Definition
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Term
| why does the cortex stain darker? |
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Definition
| Dense population of T cells (small amount of cytoplasm) |
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Term
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Definition
| Thymic epithelia and T cells |
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Term
| Functions of Thymic epithelial cells |
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Definition
| Produce IL-7 and thymosin, assist in T cell differentiation |
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Term
| Why does medulla stain lighter? |
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Definition
| Fewer lymphocytes, numerous macrophages/DC's |
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Term
| What do Hassall's corpuscles confirm? |
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Definition
| Presence of thymus in sample |
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Term
| Morphology of Hassall's corpuscles |
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Definition
| Flattened epithelial reticular cells wrapped in concentric layers |
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Term
| Function of Hassall's corpuscles |
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Definition
| Produce lymphopoietin (prod. of reg. T cells) |
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Term
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Definition
| Blood vessels in/out, Efferent lymphatics out |
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Term
| Markers on T cells as enter thymic cortex |
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Definition
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Term
| Markers during T cell proliferative phase |
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Definition
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Term
| Function of lymphatic vessels |
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Definition
| Drain interstitial fluid (lymph) from tissues, transport mac's/DC's to facilitate humoral/cell-mediated immunity |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Smaller --> larger lymphatics --> Thoracic duct --> Superior vena cava |
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Term
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Definition
| Thin connective tissue capsule and a subcapsular sinus |
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Term
| Supportive structure of LN's |
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Definition
| Reticulum from reticular cells |
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Term
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Definition
| Lymphoma in dogs, reactive lymphatics in cats |
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Term
| Sequence of lymph movement |
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Definition
| Into LN, across capsule and into subcapsular sinus, then through cortex into medulla |
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Term
| Hilar region is where what happens? |
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Definition
| Arteries enter and efferent lymphatics exit |
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Term
| How do lymphocytes exit the blood |
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Definition
| Through use of CD markers in High Endothelial Venules |
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Term
| What receptor is important in homing lymphocytes to specific LN's? |
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Definition
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Term
| Why do primary follicles stain darker? |
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Definition
| More nuclei in resting cells |
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Term
| Why do secondary follicles stain lighter? |
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Definition
| More cytoplasm in active cells |
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Term
| What kind of cells do lymphoid follicles contain? |
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Definition
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Term
| What is a germinal center? |
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Definition
| Site of B cell proliferation in the secondary follicle |
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Term
| Location and resident cells of paracortical region |
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Definition
| Surrounding the follicles, contains T cells, DC's, Mac's and reticular fibers |
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Term
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Definition
| Lymphos, plasma cells, mac's |
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Term
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Definition
| Segregation of T/B cells through cytokines/chemokines; ensure contact with correct APC's |
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Term
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Definition
| Increased size of LN's, inflammation |
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Term
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Definition
| Erythocyte/platelet reservoir, filtration of blood by mac's, remove old RBC's, extramedullary hematopoiesis |
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Term
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Definition
| Single artery in hilar region to trabec. arteries to central arteries to sheathed capillaries through red pulp to venous sinuses to trabec. veins to splenic vein in hilar region |
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Term
| What type of framework supports the spleen? |
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Definition
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Term
| White pulp is similar to what of LN? |
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Definition
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Term
| What cells compose the periarterial lymphatic sheaths (PALS)? |
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Definition
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Term
| Lymphatic nodules in the spleen are made up of? |
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Definition
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Term
| What is the marginal zone? |
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Definition
| A region near the marginal sinus that forms the outer boundary of white pulp; marginal zone B cells are functionally distinct from follicular B cells |
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Term
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Definition
| Erythrocyte storage/destruction and filtration, main clean-up functions of spleen |
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Term
| Function/location of keratinocytes |
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Definition
| Epidermis/produce cytokines for immune response/inflammation |
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Term
| Function/location of Langerhans cells |
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Definition
| Suprabasal epidermis/Function as DC's |
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Term
| Function/location of Lymphocytes in cutaneous immune system |
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Definition
| Mainly CD8 gamma/delta T cells in intraepidermis, CD4/CD8 alpha/beta T cells |
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Term
| Intraepithelial lymphocytes |
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Definition
| CD8+ T cells with restricted specificity |
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Term
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Definition
| Contains activated CD4+ T cells, activated B cells, plasma cells, mac's, DC's, mast cells and eosinophils |
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Term
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Definition
| Organized nodules of B cells and some CD4+ T cells (mostly in the ileum of the intestines) |
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Term
| Why is the innate immune system perfect? |
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Definition
| Phylogenetically old and very refined with few mutations |
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Term
| Kind of molecules the innate system recognizes |
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Definition
| Non-peptide, usually carbo and lipid |
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Term
| Soluble components of innate immune system |
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Definition
| Complement, collectins, ficolins, LPS Binding Protein, Mannose Binding Protein, natural Ab, induced acute phase proteins, C-reactive protein, pentraxins, Defensins/cathelicidins, hepcidin |
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Term
| Membrane-bound components of innate |
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Definition
| Pattern recognition receptors |
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Term
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Definition
| Pathogen-associated molecular patterns |
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Term
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Definition
| Mannose, CD14, TLR's, Scavenger, FMLP, Dectin-1 |
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Term
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Definition
| LPS, LAM (mycobacteria), peptidoglycan, CpG DNA (unmethylated form), FMLP\ |
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Term
| Primary site of complement synthesis |
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Definition
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Term
| Types of proteins activated by complement |
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Definition
| Serine proteases, membrane-binding proteins |
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Term
| Lectin portion of complement |
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Definition
| recognize microbial components |
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Term
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Definition
| Enhance localization of Ag complexes for Ag processing/presentation (reduce the threshold of T cell response, etc.) |
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Term
| Another important complement property |
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Definition
| Keep the immune complex soluble and not clogging arteries |
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Term
| Disturbance of complement pathway with Ag |
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Definition
| Vasculitis (problems with vessels) |
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Term
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Definition
| Soluble lectins (carbo-binding proteins) |
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Term
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Definition
| Collagen and lectin domains |
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Term
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Definition
| MBP/MBL, CL-43, pulmonary surfactant proteins (SP-A/SP-D) |
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Term
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Definition
| Several stalks with binding portions at ends |
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Term
| Family which collectins belong to |
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Definition
| C-type/Ca-dependent animal lectin |
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Term
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Definition
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Term
| Biological functions of collectins |
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Definition
| Complement regulation, changing microbe/host interactions |
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Term
|
Definition
| Plasma/leukocyte membrane |
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Term
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Definition
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Term
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Definition
| Transcriptional activation via NFkB and AP-1 |
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Term
| Mannose receptor recognizes... |
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Definition
| Carbohydrates via Carbo-recognition-domains |
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Term
| Major cells with mannose receptors |
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Definition
| Mac's (fully developed), DC's, retinal epithelia |
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Term
| Function of mannose receptor |
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Definition
| Pinocytosis, phago, enhancement of MHC-Ag presentation by DC's |
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Term
| Soluble mannose receptor... |
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Definition
| Deliver Ag to spleen for B cell response |
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Term
| Nucleotide-oligomerization domain proteins (NOD's) recognize... |
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Definition
| Microbial motifs from intracellular organisms |
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Term
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Definition
| Prepare microbe for ingestion |
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Term
| Various subversion methods of microbes |
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Definition
| Prevention of complement activation and phago, mimicry of regulatory proteins, sabotage of receptors, regulation of cell death |
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Term
| Methods of innate enhancement |
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Definition
| Cationic peptides, TLR stimulators, CpG oligonucleotides |
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Term
| How many PMN's per minute released? |
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Definition
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Term
|
Definition
| 10 hours max, 7 hours average |
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Term
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Definition
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Term
| Factors to increase PMN's |
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Definition
| Stress, injury, infection, cytokine increase |
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Term
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Definition
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Term
| Differentiation period of PMN's |
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Definition
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Term
| After circulation, where do PMN's go? |
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Definition
| Capillary beds for margination |
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Term
| Why are PMN's most active in gut? |
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Definition
| Large microbial population one cell layer away from aseptic tissue |
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Term
| What inhibits synthesis of PMN's? |
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Definition
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Term
| General steps of PMN killing |
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Definition
| Move to site of infection, attach to microbes, ingest M's/maturation of phagosomes, kill M's |
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Term
| Margination of PMN's caused by? |
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Definition
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Term
| Important adhesion molecules |
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Definition
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Term
| What receptors are present on PMN membrane? |
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Definition
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Term
| After binding, what happens to receptors? |
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Definition
| Internalized and replaced with new ones |
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Term
|
Definition
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Term
|
Definition
| Rearrange cytoplasmic microfilaments and microtubules |
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Term
|
Definition
| Main portion of PMN, upstream from chemotaxins |
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Term
|
Definition
| Knoblike structure downstream of chemotaxins |
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Term
| Two main receptors of PMN's |
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Definition
| Fc (binds Ig coated M's) and beta-2 integrin (binds complement coated M's) |
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Term
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Definition
| Pouch-like structure invaginates, displaces nucleus/organelles, forms "phagolysosome," kills microbe |
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Term
|
Definition
| Phagosome fused with granules |
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Term
| Binding to receptors on microbe stimulates... |
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Definition
| mechanisms of killing of M's |
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Term
| Timeframe difference of Mac's vs. PMN's |
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Definition
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Term
| What kind of granules do PMN's have? |
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Definition
| Azurophils, gelatinases and specific granules |
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Term
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Definition
| Myeloperoxidase, lysozyme, serine proteases, anti-bact. cationic proteins |
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Term
| Specific granules contain... |
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Definition
| Lactoferin, Iron-competing proteins, B12 competing protein, NADPH oxidase components |
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Term
| Function of Gelatinase granules |
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Definition
| Digest host membranes (epithelium/endothelium) in order for PMN's to move |
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Term
| Oxygen-dependent killing is caused by what? |
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Definition
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|
Term
| Components of NADPH oxidase complex |
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Definition
| NADPH oxidase enzyme, cytochrome b (from the granule membrane) and a quinone |
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Term
| Function of NADPH oxi. complex |
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Definition
| Reduce O2 to O2- (which is then reduced to OH-/H2O2 by superoxide dismutase from microbes) |
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Term
| Lack of cytochrome b causes |
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Definition
| Chronic granulomatous disease (failure to synthesize O2-, etc.) |
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Term
| Average age of CGD patients |
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Definition
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|
Term
| Function of myeloperoxidase |
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Definition
| Create hypochlorous ions (similar to bleach) |
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Term
| What amino acid is oxidized to produce nitrogen oxide? |
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Definition
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|
Term
| Nitrogen precursors (amines) and NO react to form what? |
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Definition
| Peroxynitrates and chloramines |
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Term
| What triggers oxygen-independent killing? |
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Definition
| Binding of opsonized bacteria to plasma membrane of PMN's |
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Term
| Which granules fuse first in O-independent killing? |
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Definition
| Specific, delivering bactericidal proteins |
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Term
| 50% of azurophil contents are... |
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Definition
| antimicrobial cationic proteins |
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Term
| Cationic proteins cause... |
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Definition
| Disruption of outer membrane of G- mainly (poking holes in membrane) |
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Term
| Chediak-Higashi syndrome is characterized by... |
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Definition
| Premature fusion of PMN granules while still in BM (none left for microbes) |
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Term
|
Definition
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|
Term
| How do microbes evade oxygen-dependent killing? |
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Definition
| Production of superoxide dismutase/catalase, inhibition of respiratory burst/phago, blocking of NADPH recruitment, granule targeting to plasma membrane |
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Term
| Where are cationic microbial peptides? |
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Definition
| Granules of professional phagos (PMNs, Mac's, Monocytes, etc.) |
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Term
|
Definition
| Beta-sheet, 6 strands with S-S bridges |
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Term
|
Definition
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|
Term
| Where do cationic BP's meet with Microbes? |
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Definition
| Cationic (+) charges attracted to (-) on microbial membranes |
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Term
| Mechanisms of cationic peptide resistance |
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Definition
| Efflux pumps, Change membrane charges (-) to (+), production of proteases |
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Term
| Historical definition of inflammation |
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Definition
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|
Term
| Cardinal features of inflammation |
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Definition
| Redness, Swelling, Heat, Pain and Loss of function |
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Term
| Current definition of inflammation |
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Definition
| Well-coordinated/controlled physiological response that brings leukos and plasma molecules to the site of infection/tissue damage |
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Term
| 3 general components of inflammatory reaction |
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Definition
| Increase in blood supply, increase in vascular permeability, enhanced migration of leukos from circulation to tissues |
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Term
| Priorities of inflammatory response |
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Definition
| Stop bleeding (clotting cascade), Prevent use of limb, Immobilize pathogen, Eradicate pathogen (innate and acquired functions) |
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|
Term
| What happens to shear force at the site of inflammation? |
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Definition
| It decreases in order to allow adhesion molecules to interact |
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Term
| Inflammatory portions of IL-1, IL-6 and TNF |
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Definition
| Fever, increased vasc. perm., increased adhesion molecule expression, platelets produced, chemokines induced, T/B cells activated |
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Term
|
Definition
| Complement and leftover Ab |
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|
Term
| Leukocyte adhesion cascade |
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Definition
| Selectin mediated rolling, Chemokine triggered activation, integrin dependent arrest, intravascular crawling, para/transcellular migration |
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Term
|
Definition
| Binding=C-type lectin and EGF-like domain, Flexibility = repeat sequence |
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Term
|
Definition
| P and E = tethering/rolling on endothelium, L = recruit lymphos to LN's |
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Term
|
Definition
| Constitutive on platelets, endo. cells, timing = within minutes |
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Term
|
Definition
| Inducible in endo. cells, peak expression within 4 hours |
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Term
|
Definition
| Constitutive in leukocytes, shed from surface during activation |
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Term
|
Definition
| Activate integrins at site of inflammation and direct migration of leukos to sites of inflammation |
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|
Term
| How do chemokines form gradient? |
|
Definition
| Binding to activated endothelium |
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|
Term
| In what molecule do chemokines induce a change? |
|
Definition
| Integrins (unwind for clearer binding to ICAM) |
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Term
|
Definition
| Signaling into cell, change in adhesion to outside |
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Term
|
Definition
| alpha and beta chains (heterodimers), families based on beta chains |
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|
Term
| Control for clotting/activated endothelium |
|
Definition
| Transient production of inflammatory mediators |
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Term
|
Definition
| Rapid internalization of p-selectin, transient prod. of mediators, rapid degradation of e-selectin |
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|
Term
| Control for integrin activation |
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Definition
| Expression of specific chemokine receptors, transient chemokine production |
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Term
|
Definition
| Transient expression of adhesion molecules and transient production of chemokines |
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|
Term
| Docking structures used in crawling |
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Definition
|
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Term
|
Definition
| PECAM zipper and use of JAMs allow travel BETWEEN endothelial cells |
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Term
|
Definition
| ICAM-1 ligation allows formation of channel THROUGH endothelial cell |
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|
Term
| Migration through pericyte sheath |
|
Definition
| Leukos can digest portions of the basement membrane where less cells are present to reach site of inflammation; can also use integrins to slide through BM |
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|
Term
| Selectin binds what on leukos? |
|
Definition
|
|
Term
| ICAM-1 binds what on leukos? |
|
Definition
|
|
Term
| Where does hematopoiesis occur in a fetus? |
|
Definition
|
|
Term
| How about hematopoiesis in an embryo? |
|
Definition
|
|
Term
| What cells are resident macrophages derived from? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| DC's derived from monocytes |
|
Definition
|
|
Term
| Experimental mouse macrophages |
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Definition
| Peritoneal (resident/elicited) and bone-marrow derived (differentiate after stim with GF) |
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|
Term
| Experimental human macrophages |
|
Definition
| Monocyte-derived mac's (differentiate on their own) |
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|
Term
|
Definition
| Need to reproduce in vivo before publication |
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|
Term
| Classical activation pathway of mac's |
|
Definition
|
|
Term
| What does IFN-gamma cause in classical mac pathway? |
|
Definition
| Increased upreg of gene expression (APC genes), decreased expression of mannose receptor and transferrin receptor (lower amount of iron available to pathogen), increased production of RO/RN intermediates and pro-inflammatory cytokines (IL-12/6)/chemokines (MIP-alpha and MCP1) |
|
|
Term
| Functions of Classical Mac's |
|
Definition
| APC, killing intracellular pathogens, pro-inflammatory cytokines |
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|
Term
| Alternative activation pathway of mac's |
|
Definition
|
|
Term
| What do IL-4/13 cause in alternative mac pathway? |
|
Definition
| Increased upreg of mannose receptor, Dectin-1 (bind beta glucan sugars), and CD23 (IgE binding), production of IL-10 for inhibitory functions |
|
|
Term
| Functions of alternative mac's |
|
Definition
| Collagen formation, tissue repair, increased humoral/allergic immunity, increased parasite killing |
|
|
Term
| Innate activation by mac's |
|
Definition
| Recognized by TLR's (PRR-like), Production of proinflammatory cytokines/viral immunity cytokines, synergenesis with IFN-gamma for antimicrobial gene production |
|
|
Term
| Which complement component is important in opsonization? |
|
Definition
|
|
Term
|
Definition
| Activation of many signaling pathways (upon binding M), Rearrangement of cytoskeleton, Extension of membrane/engulfment, Maturation of phagosome, Killing of M |
|
|
Term
| Endoplasmic reticulum is thought to do what in phagocytosis? |
|
Definition
| Contribute membrane to the vesicle |
|
|
Term
| What cytosolic factor is phosphorylated to activate NADPH oxidase? |
|
Definition
|
|
Term
|
Definition
| Natural Resistance Associated Macrophage Protein |
|
|
Term
| What is the function of NRAMP1? |
|
Definition
| Endosomal protein that transports iron into phagosome after fusion |
|
|
Term
| Why is iron important in phagosomes? |
|
Definition
| Catalyze production of OH radicals from O2- and H2O2 by Fenton reaction |
|
|
Term
| What if NRAMP1 is hung up in the ER? |
|
Definition
| No iron = microbes can grow faster |
|
|
Term
| How is nitric oxide synthesized? |
|
Definition
| iNOS (inducible NO synthase) oxidizes Arg to Citrulline + NO, NO then reacts with O2- to form more toxic peroxynitrate |
|
|
Term
| Which TLRs are on the plasma membrane? |
|
Definition
|
|
Term
|
Definition
| Bacterial triacylated lipopeptides |
|
|
Term
|
Definition
| Bacterial peptidoglycan, lipoprotein, etc., viral hemagglutin |
|
|
Term
|
Definition
| G- LPS, Mannose, phospholipids, viral envelopes |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Viral/bacterial DS/SS DNA |
|
|
Term
|
Definition
| Leucine rich repeat motif (binding), Cysteine rich flanking motif, TIR domain |
|
|
Term
| 2 options of TLR4 signaling |
|
Definition
| MyD88-dependent (use early phase of NFkB, produce inflammatory cytokines), MyD88-independent (use IRF3 and late-phase NFkB, produce IFN-beta/IFN-inducible genes) |
|
|
Term
| Inflammatory cytokines from mac's |
|
Definition
|
|
Term
| Anti-inflammatory cytokine from mac's |
|
Definition
|
|
Term
| Activating cytokines from mac's (for NK/Th1 cells) |
|
Definition
|
|
Term
| What is the complement system? |
|
Definition
| Group of serum/plasma and membrane proteins |
|
|
Term
| What do these complement proteins do? |
|
Definition
| Form cascades of enzymatic reaction, are interrelated and very important effectors in innate/adaptive |
|
|
Term
|
Definition
|
|
Term
| How many complement proteins? |
|
Definition
|
|
Term
| Consequences of complement activation |
|
Definition
| Lysis of target cells by osmotic disruption, Opsonization to facilitate clearance by erythrocytes/phagos, cellular activation by ligand binding with PMN's and mac's |
|
|
Term
| Which Ig is more efficient with complement? |
|
Definition
|
|
Term
| What type of binding is prevalent between immune complex and C1q? |
|
Definition
| Covalent (strong, no breaking) |
|
|
Term
| How is the C1 complex formed? |
|
Definition
| C1q binds immune complex and causes conformational change in itself, Induces binding and activation of C1r and C1s (2x C1r auto-activate each other and then activate 2x C1s) |
|
|
Term
| What is the structure of intact C1q? |
|
Definition
| Tulip-like, with globular heads for binding 2+ arms of Ig |
|
|
Term
| How is the classical C3 convertase formed? |
|
Definition
| C1 complex (mainly C1s2) cleaves C4 into C4a/b, and C4b binds covalently to many nearby surfaces through carbonyl group of thioester bond; C2 binds C4b and C1s cleaves C2 to form C2a/b; C2a binds C4b to form the C3 convertase |
|
|
Term
| What is the classical C3 convertase? |
|
Definition
|
|
Term
| What is the catalytic subunit of the classical C3 convertase? |
|
Definition
|
|
Term
|
Definition
| Cleaved to reveal thioester group |
|
|
Term
| With what does the thioester group of C3b react? |
|
Definition
| Water (in non-inflammatory situations) and bacterial surface proteins (inflammatory situation) |
|
|
Term
| What is the difference between plasma and serum? |
|
Definition
| Serum contains clotting factors and plasma doesn't |
|
|
Term
| What are the two most important domains of C3? |
|
Definition
| Anaphylatoxin (pull out = C4a gone, conformational change) and Thioester domain (binding site to microbes) |
|
|
Term
| Greatest complement component (concentration) |
|
Definition
|
|
Term
| What types of bonds replace the thioester bond when interacting with antigens (complement)? |
|
Definition
| Covalent ester (C4b)/amide (C4a) |
|
|
Term
| After cleavage of C3, C3b interacts with what to form the classical C5 convertase? |
|
Definition
|
|
Term
| What is the classical C5 convertase? |
|
Definition
|
|
Term
| How is the alternative complement pathway activated? |
|
Definition
| With a tick-over mechanism based on hydrolysis |
|
|
Term
| What is the sequence of alternative complement activation? |
|
Definition
| C3 hydrolyzed to form C3i, Factor B binds C3i and is then cleaved (by Factor D) to C3iBb and Ba, C3iBb is a weak convertase, splits C3 to get C3bBb (alternative convertase) |
|
|
Term
| Who discovered alternative pathway? |
|
Definition
|
|
Term
| What part of the alternative pathway binds the microbe? |
|
Definition
|
|
Term
| Alternative C5 convertase? |
|
Definition
|
|
Term
|
Definition
| MBL binds two serine proteases (MASP1/MASP2) and this complex activates C4 and C2 without the immune complex needed for classical activation |
|
|
Term
| Where is the MBL/Lectin pathway important? |
|
Definition
| In neonates and immuno-suppressed patients |
|
|
Term
| Where do all complement pathways intersect? |
|
Definition
|
|
Term
| Why is positive feedback important in the complement pathway? |
|
Definition
| More products lead to more enzymes which lead again to more products, etc. |
|
|
Term
| How is the membrane attack complex formed? |
|
Definition
| C5 convertase cleaves C5 into C5a/b, C5b binds C6 and C7 and this complex inserts into membrane, C8 binds complex and inserts further into membrane, C8 induces polymerization of C9 monomers and formation of lytic tunnels (causes osmotic shock) |
|
|
Term
|
Definition
|
|
Term
| Who discovered complement? |
|
Definition
|
|
Term
| Which is heat labile, Ab or complement? |
|
Definition
|
|
Term
| All Cxb's are larger except which one? |
|
Definition
|
|
Term
| All Cxa's are smaller except which one? |
|
Definition
|
|
Term
| Uncontrollable complement activation can lead to what? |
|
Definition
|
|
Term
| Schemes of complement regulation (3) |
|
Definition
| Block binding site for next protein, promote dissociation of multi-unit enzymes, destroy foundation (through degradation of C3b/C4b) |
|
|
Term
| C1 INH prevents activation of what? |
|
Definition
|
|
Term
| Malfunction of C1 inhibitor causes... |
|
Definition
| blockage of airways and circulation with C2 |
|
|
Term
| Classical C3 convertase (C4b) dissoc caused by... |
|
Definition
|
|
Term
| Alternative C3 convertase (C3b) dissoc caused by... |
|
Definition
|
|
Term
| Where are the C3 convertase dissoc components? |
|
Definition
|
|
Term
| Mutation in Factor H causes... |
|
Definition
| Age-related macular degeneration |
|
|
Term
| Proteolysis of C3b is caused by... |
|
Definition
| Factor I with MCP/CR1 as cofactors |
|
|
Term
| Destruction of C3/C4 prevents what? |
|
Definition
|
|
Term
| Why is cobra venom harmful to complement system? |
|
Definition
| Contains C3 homolog not able to be regulated by Factor I = exhaustive depletion of C3 |
|
|
Term
|
Definition
| Polymerization of C9, formation of the MAC |
|
|
Term
| What does S-protein prevent? |
|
Definition
| Insertion of C5b-6-7 into the lipid bilayer |
|
|
Term
| Where are CD59 and the S-protein found? |
|
Definition
|
|
Term
| Biological activities of C5a |
|
Definition
| Strongly activate PMN's, mac's, monocytes, baso's, mast cells, cause chemotaxis |
|
|
Term
| Biological activities of C3a |
|
Definition
| Weakly activate PMN's, cause weak respiratory burst, no chemotaxis |
|
|
Term
| What inactivates C5a/C3a? |
|
Definition
| Carboxypeptidase N (removal of carboxy terminal Arg) |
|
|
Term
| 4 Effects of C3b/C4b + immune complex binding |
|
Definition
| Adherence of immune complex to RBC/ transference to liver/spleen for disposal, facilitate phagocytosis, reduce size of immune aggregates/prevent precipitation, promote trapping of IC's by DC's in germinal centers = activation of B cells |
|
|
Term
| What receptor on RBC's picks up immune complexes? |
|
Definition
|
|
Term
|
Definition
| B cells, RBC's, Professional phagos |
|
|
Term
| How do M's interact with complement proteins? |
|
Definition
| Use as receptors for cell entry |
|
|
Term
| How are genes for most of complement proteins formed? |
|
Definition
| Gene duplication and exon shuffling |
|
|
Term
| What do gene duplications produce in complement? |
|
Definition
| alpha2 macroglobulin family (all with thioester bond), perforin family (all assoc. with MAC), collectin family, serine protease family (C1r/s, C2, Factor B/D/I) |
|
|
Term
| What do exon shufflings produce in complement? |
|
Definition
| Proteins with short consensus repeats/complement controlling protein repeats (sushi domains) |
|
|
Term
| Where are genes for C3 convertase components located? |
|
Definition
| Class III region of MHC complex gene (HLA) |
|
|
Term
| Where are genes for regulatory proteins (such as C2, Factor H, CR1, etc.) located? |
|
Definition
| Regulator for complement activation locus |
|
|
Term
| Complement deficiencies cause what? |
|
Definition
| Recurrent infections, Autoimmune diseases (such as Lupus = form IC against self cells) and Vascular diseases |
|
|
Term
| What are two possible outcomes of tissue/organ transplantation? |
|
Definition
|
|
Term
| What are isogeneic grafts? |
|
Definition
| From one animal to itself (not rejected) |
|
|
Term
| What are syngeneic grafts? |
|
Definition
| Between two genetically identical inbred animals |
|
|
Term
| What are allogeneic grafts? |
|
Definition
| Between two genetically differenty inbred animals |
|
|
Term
| What are xenogeneic grafts? |
|
Definition
| Between two different animal species |
|
|
Term
| What is the human MHC loci and where is it located? |
|
Definition
|
|
Term
| What is the mouse MHC loci and where is it located? |
|
Definition
|
|
Term
| what response do major histo. Ag's cause? |
|
Definition
| Rapid rejection (within 14 days), production of Ab and cytotoxic response |
|
|
Term
| What response do minor histo. Ag's cause? |
|
Definition
| Slow rejection (within 300 days), cytotoxic response only |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| With what molecule are MHC I proteins expressed? |
|
Definition
| beta2 microglobulin (non-covalent binding) |
|
|
Term
| In what cells are CI molecules expressed? |
|
Definition
| All nucleated cells (constitutive) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| I-A, I-E (no equiv to HLA-DQ) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| 32-34kD alpha chain, 29-32kD beta chain |
|
|
Term
| On what cells are CII molecules expressed? |
|
Definition
| DC's, B cells and Mac's (Pro-APC's) |
|
|
Term
| By how many amino acids does each allele differ on the polymorphic residues of the MHC loci? |
|
Definition
|
|
Term
| To what family do the MHC molecules belong? |
|
Definition
|
|
Term
| What is the structure of MHC I molecules? |
|
Definition
| 3 alpha chains with a B2-microglobulin associated |
|
|
Term
| What is the structure of the MHC binding cleft? |
|
Definition
| alpha-helices as walls, beta-sheets as floor |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| How does the presence of pockets affect the MHC binding cleft? |
|
Definition
| It allows peptide side chains to fit in for tighter binding |
|
|
Term
| With what T cells do MHC I/II molecules interact? |
|
Definition
|
|
Term
| In what regions are the polymorphic residues located in MHC I molecules? |
|
Definition
|
|
Term
| In what regions are the polymorphic residues located in MHC II molecules? |
|
Definition
|
|
Term
|
Definition
| TLR's dimerize, adapter proteins bind to TIR domain of TLR (MyD88 and MAL = adapters), MyD88 interacts with IRAK protein which interacts with TRAF-6 which activates TAK1 which activates MAP kinase and inhibitor of NFkB (IkB) kinase cascades, leads to expression of AP-1 and NFkB transcription factors |
|
|
Term
|
Definition
| After TLR dimerization, TRAM/Trif bind TIR domain and then interact with TBK1 which activates IRF-3 |
|
|
Term
| MyD88 with intracellular TLR's |
|
Definition
|
|
Term
|
Definition
| Expression of many genes for innate immunity and inflammation |
|
|
Term
|
Definition
| Both enhance expression of IFN-alpha/beta genes |
|
|
Term
|
Definition
| Breed rapidly, large numbers of progeny, large numbers of genetically characterized strains |
|
|
Term
|
Definition
| genetically identical at all loci |
|
|
Term
|
Definition
| genetically identical except for short segment of DNA (change in one haplotype) (XXX.YY = x's determine similar grouping) |
|
|
Term
| What is the distance between k and d in the mouse H-2 complex? |
|
Definition
| 1 because of 1% (low percentage = close because can't recombine easily) |
|
|
Term
| What is a transgenic mouse strain? |
|
Definition
| Strain produced by introduction of foreign genes (transgenes) into germline or by knockout/disruption of a gene |
|
|
Term
| How are knockouts generated? |
|
Definition
| Homologous regions "match up" and the intervening DNA is inserted from one section to another, disrupting the region where it has inserted (lack of homologous recombination = lack of knockout = no good for research) |
|
|
Term
| How are conditional knockout mice generated? |
|
Definition
| Use of Cre recombinase and lox P sites |
|
|
Term
| How does Cre recombinase work? |
|
Definition
| It deletes gene segments flanked by lox P sites (which are added through homologous recombination, and therefore if the gene hasn't been disrupted, the only time the mouse will be a knockout is when the Cre recombinase is activated) |
|
|
Term
| What are 2 examples of Cre recombinase mice? |
|
Definition
| LysMcre (cre under control of lysozyme promoter, deletions in mac's and PMN's) and Alb-Cre (cre under control of albumin promoter, deletions in liver cells) |
|
|
Term
| Where are the Tapasin and TAP1/2 genes located? |
|
Definition
|
|
Term
| What type of expression is CI? |
|
Definition
|
|
Term
| How are MHC II hybrids created? |
|
Definition
| Different combinations of parental alpha/beta chains |
|
|
Term
| Which HLA genes express only one of each chain? |
|
Definition
| DPA1/B1(No equiv), DQA1/B1(Aalpha,Abeta), DRalpha(Ealpha) |
|
|
Term
| How many DRbeta genes are there? |
|
Definition
| Nine(Mouse equiv = Ebeta) |
|
|
Term
| What components of the proteasome and peptide loading are located in CII region of MHC genes? |
|
Definition
|
|
Term
| What is a major nonclassical gene present in CI region? |
|
Definition
|
|
Term
| For what cells do HLA-E/G provide receptors? |
|
Definition
| NK cells, effector T cells |
|
|
Term
|
Definition
| Regulation of iron absorption by binding transferrin (Mutation causes iron deposition in organs) |
|
|
Term
| Why is HLA typing essential in BM transplants? |
|
Definition
| Prevention of graft vs. host disease |
|
|
Term
| Routine HLA typing focuses on which genes? |
|
Definition
|
|
Term
| What is a complement-dependent cytotoxicity assay? |
|
Definition
| An assay that uses complement to check for lysis by Ab against cells of a particular HLA type (important in transfusions, etc.), lysis = Ab present for that HLA molecule (trypan blue is taken up by dead cells) |
|
|
Term
| In what cells are MHC II molecules inducible? |
|
Definition
| Vascular endothelium, dermal fibroblasts, placental cells and melanocytes |
|
|
Term
| Besides pro. APC's, on what molecules are CII molecules present? |
|
Definition
| Thymic epithelium and activated T cells |
|
|
Term
| What cytokines upreg CI gene expression? |
|
Definition
| IFNalpha/beta/gamma, TNFalpha |
|
|
Term
| What cytokine upregs/induces CII expression? |
|
Definition
| IL-4 in B cells, IFNgamma in mac's (inducible) |
|
|
Term
| What molecule reg's CI expression? |
|
Definition
|
|
Term
| What molecule reg's CII expression? |
|
Definition
| CIITA (class II transcriptional activator) constitutive in B cells and induced in mac's |
|
|
Term
| Why are MHC genes highly polymorphic? |
|
Definition
| Positive selection by infection with pathogens |
|
|
Term
| Which is higher in MHC regions, non-altering aa substitions or altering aa substitions? |
|
Definition
|
|
Term
| Do MHC genes mutate at higher rate than other genes? |
|
Definition
| No, just have an ability to express multiple alleles |
|
|
Term
| How is polymorphism maintained? |
|
Definition
| Balanced selection from coevolution of host/pathogen and MHC dependent mating preferences |
|
|
