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189 Cards in this Set
- Front
- Back
Who and what year:
recognized that only those who had recovered from the plague could nurse the sick without becoming sick again. |
430 BC- Thucydides
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variolation
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Fifteenth century- Chinese and Turks used dried crusts from smallpox pustules (inhaled or inserted into small cuts in the skin “variolation”) to induce immunity.
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Who and what year:
realized milkmaids who had contracted cowpox (mild disease symptoms compared to smallpox) were not susceptible to smallpox. |
1796 - Jenner
Dude got lucky |
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M. tuberculosis?
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bacteria
mycobacterium tuberculosis |
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C. albicans?
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candida albicans
fungus that causes thrush, systemic candiasis |
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T. Brucei
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Parasitic protozoa that causes sleeping sickness
Trypanosoma Brucei |
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-gram positive bacterium that colonizes human skin, pimples & boils (other strains = food poisoning)
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Staphylococcus aureus
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The four kinds of pathogens that cause disease?
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Bacteria, fungus, virus, protozoa
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The GI tract is exterior or interior?
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exterior
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pH of vagina and skin?
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acidic
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Defensins general mechanism?
Associated with what epithelial cells? |
"Poke holes in the pathogen"
All epithelial cells |
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Lymphocytes?
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B, T, and NK cells
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Granulocytes? In order from darkest staining to lightest
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Basophils
Eosinophils Neutrophils |
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Dendritic cell function?
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Main function is the presentation of antigen to T cells
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Hematopoiesis
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The generation of the cellular elements of blood, including:
Red blood cells (RBC) White blood cells (WBC) or leukocytes Megakaryocyte - Platelets |
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These cells originate from __________ stem cells (HSC) whose progeny differentiate and divide under the influence of various hematopoietic _________
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-pluripotent hematopoietic
-growth factors |
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Most abundant leukocytes are the _________
Followed by _________ |
-neutrophils
-lymphocytes |
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General term for WBC?
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leukocyte
ALL LYMPHOCYTES ARE LEUKOCYTES |
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NK cells?
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Large granular lymphocytes
Natural killer (NK) cells, lymphocytes of innate immunity |
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small lymphocytes are resting cells that have not interacted with antigen
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Naïve lymphocytes
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lymphocytes that have interacted with antigen and proliferate
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Lymphoblasts
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Lymphoblasts eventually differentiate into ________ or ________
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effector cells or into memory cells
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NK cells (large granular lymphocytes) are found throughout the tissues of the body but mainly in the
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circulation
remain in blood until infection |
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NK cells are particularly important for?
secrete? |
important for protection against viruses and some tumors
Secrete cytokines which prevent viral replication and helps to activate T cell-mediated immunity |
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main cause of pus?
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neutrophils
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Neutrophils granules?
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Are phagocytic cells that contain toxic substances in intracellular granules (primary and secondary granules)
Employ oxygen-dependent and oxygen-independent pathways to destroy pathogens |
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_______ circulate in the blood for about _______, then mature and migrate into tissues, they are then referred to as _______.
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-Monocytes
-8 hours -macrophages |
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Function of dendritic cell folds
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folds allow maximum interaction with other cells of the immune system
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What molecules do dendritic cells use to present?
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MHC-1
AND MHC-2 |
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Follicular dendritic cells (FDC) ?
Related to dendritic cells? |
hold intact antigens in specialized areas of lymphoid tissues
not related |
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Mast cells are found ?
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in the skin, connective tissue and mucosal epithelial tissue of the respiratory and digestive tracts
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Basophil = ?
Eosinophil = ? |
Basophil = allergic reactions
Eosinophil = parasitic worms |
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The nucleus of the megakaryocyte is very large and lobulated, which, under a light microscope?
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can give the false impression that there are several nuclei
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Megakaryocyte function is determined by a large number of cytokines, including _____
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thrombopoietin
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Thrombopoietin
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glycoprotein hormone produced mainly by the liver and kidney that regulates the production of platelets by the bone marrow
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Do erythrocytes have a role in immunology?
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erythrocytes have an important immunological role in clearing immune complexes from the circulation in persistent infections and in some autoimmune diseases
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Site if hematopoesis at the following:
embryo? 3-7 months fetus? After 7 months? |
yolk sac ->spleen & liver -> bone marrow
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pH of the phagolysosome?
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acidic
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Binding to macrophage C3B = ?
Binding to macrophage TLR = ? |
C3B = phagocytosis
TLR engagement = cytokine secretion |
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Primary lymphoid organs?
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Thymus and bone marrow are primary organs
Where maturation of lymphocytes takes place |
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Secondary lymphoid organs?
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Lymph nodes, spleen and mucosal-associated tissues are secondary organs
Which trap antigen and promote lymphocyte activation |
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Lymphocytes recirculate at a rate of ?
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Lymphocytes recirculate at a rate of 5 X 10^6 cells/min
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Lymphocytes arrive at lymph nodes in __________; then they ________
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Lymphocytes arrive at lymph nodes in arterial blood; extravasate from capillaries
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Expansion of the lymph nodes occurs in ________
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lymphoid follicles
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cells in the spleen that take-up antigen and stimulate T an B-cells
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Spleenic macrophages and dendritic cells
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White pulp of spleen consists of sheath of lymphocytes called the ?
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periarteriolar lymphoid sheath (PALS)
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The gut associated lymphoid tissues, GALT include
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tonsils, adenoids, appendix and Peyer’s patches that line the gut
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BALT?
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Bronchial-associated lymphoid tissues
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Most secondary lymphoid tissue is associated with?
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the gut
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Pathogens arrive through direct delivery across mucosa mediated by specialized cells called
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M cells
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frequency of inherible innate immune disease?
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rare
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What infects the interstitial spaces, blood, and lymph?
Defense mechanism? |
-Everything
-complement, macrophages, neutrophils |
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What infects epithelial surfaces?
Defense? |
-neisseria gonorrhoeae and candida albicans
-Antimicrobial peptides |
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What infects the cytoplasm?
Defense mechanism? |
-viruses, listeria, and protozoa
-NK cells |
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What infects the vesicles?
Defense mechanism? |
-mycobacteria, trypanosomes
-Activated macrophages |
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Intracellular pathogens in nucleus or cytosol attacked by ?
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killing the infected host cell
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____ is by far the most important molecule in the complement cascade
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C3
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The quickest of the 3 complement pathways is the
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alternative pathway
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The Classical pathway is part of both the innate and adaptive immune response and can be activated by _______ or _______
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C-reactive protein (innate) or antibody (adaptive) binding to the pathogen.
Always assume antibodies |
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______ is the product of C3 hydrolysis
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iC3
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alternative pathway soluble C3 convertase?
Bound C3 convertase? |
iC3Bb
C3bBb |
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Pathogen bound C3b fragments (Bb is absent) can perform what function?
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They can bind to Complement Receptor 1, CR1, on macrophages to optimize phagocytosis
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What is the alternative C5 convertase?
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Binding of C3b to existing C3bBb complexes at pathogens surface forms the alternative C5 convertase = (C3b)2+Bb
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Classical C5 Convertase?
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C4b2a3b
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C5 convertase function?
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Cleaves C5 into C5a and C5b
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C5b function?
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C6 and C7 bind and exposes the hydrophobic sites of C7 allowing it to insert into the lipid bilayer.
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What happens when C8 binds C5b?
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hydrophobic sites on C8 are exposed and it is inserted into the membrane with C6+C5b+C7
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C8 function?
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C8's exposed hydrophobic site once in the membrane initiates the polymerization of C9 forming the pores
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C5a function? notable feature?
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recruits neutrophils to infection site
Most potent anaphylatoxin |
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Factor P function? aka?
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Up-regulates C3bBb and prevents inhibition by factor H.
aka properdin |
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Factor H function
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Factor H plasma protein reduces complement reactions by making C3b susceptible to cleavage by factor I creating a iC3b fragment that is incapable of forming a C3 convertase
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Factor I function
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cleaves C3b into iC3b
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DAF function? Aka?
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leans over and binds to C3bBb and displaces Bb fragment
aka decay-accelerating factor |
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MCP function? aka?
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leans over and binds to C3bBb and allows factor I to inactivate it
membrane co-factor protein |
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CR2
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B-cell co-receptor and recognizes C3d
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CR3 & CR4
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recognize iC3b
iC3b can be recognized by phagocytic cells |
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C3a and C5a contribute to _________
Also referred to as ________ ____ is more stable and potent than____ |
C3a and C5a contribute to acute inflammation
Also referred to as anaphylatoxins C5a is more stable and potent than C3a |
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alpha-2-macroglobulins
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inhibit potentially damaging proteases
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alpha-2-macroglobulins mechanism
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first trap the protease with a “bait” region -> protease cleaves the bait -> alpha-2-macroglobulin binds covalently through activation of thioester group -> surrounds the protease (still active) but cannot access other protein substrates
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_______ and alpha-2-macroglobulin inhibit potentially damaging proteases
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Serpins
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Amphipathic
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both hydrophobic and hydorphilic
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alpha-defensins produced by?
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Produced mainly by neutrophils and Paneth cells
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Paneth cells ?
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specialized epithelial cells of the small intestine
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beta-defensins
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Expressed mainly by epithelial cells of the respiratory tract the urogenital tract and the skin.
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Macrophage receptor for C3b?
receptor for iC3b? |
-CR1
-CR3, CR4 |
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CR3 and CR4 recognize iC3b and other ligands such as:
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LPS, lipopolysaccharide (Gram negative bacteria)
Lipophosphoglycan Filamentous hemagglutinin Cell-surface structures on yeast |
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Carbohydrate-binding proteins = ?
examples? |
-lectins
-mannose and glucan |
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Scavenger receptors = ?
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Scavenger receptors = preference for molecules that are negatively charged.
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Examples of things scavenger receptors bind?
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Nucleic acids and phosphate-containing lipoteichoic acids (Gram positive bacteria)
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TLR-3
Ligands? Microorganisms recognized? Cells carrying receptor? Cellular Location? |
Ligands = double stranded RNA
Microorganisms recognized = viruses Cells carrying receptor = NK cells Cellular Location = Endosomes |
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TLR-4
Ligands? Microorganisms recognized? Cells carrying receptor? Cellular Location? |
Ligands = LPS
Microorganisms recognized = Gram negative Cells carrying receptor = macrophages, dendritic cells, mast cells, eosinophils Cellular Location = plasma membrane |
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TLR-5
Ligands? Microorganisms recognized? Cells carrying receptor? Cellular Location? |
Ligands = Flagellin
Microorganisms recognized = bacteria with flagella Cells carrying receptor = intestinal epithelium Cellular Location = cell membrane |
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TLR-7:
Ligands? Microorganisms recognized? Cells carrying receptor? Cellular Location? |
Ligands = single stranded viral RNA
Microorganisms recognized = viruses Cells carrying receptor = NK cells, eosinophils, B-cells Cellular Location = |
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Translocation of NFkB to macrophage nucleus initiates
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transcription of proinflammatory cytokines -> IL-1, IL-6, CXCL8, IL-12 and TNF-alpha
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IL-1 local effects? systemic effects?
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activates endothelium and lymphocytes
fever/production of IL6 |
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IL-6?
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systemic effects of fever and acute phase protein production by hepatocytes
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CXCL-8 aka? Local effects?
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aka IL8
chemokine - recruits neutrophils and basophils |
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IL-12
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activates NK cells
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TNF-alpha local? system?
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local = activates endothelium and increases permeability leading to increased entry and drainage
systemic = shock |
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Polymorphonuclear leukocytes
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granulocytes = BEN
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Are neutrophils in healthy tissue?
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nope
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The four structural classes of adhesion molecule present on white blood cells and the cells with which they interact are:
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Selectins
Vascular addressins Integrins Immunoglobulin superfamily |
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Selectins ?
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are carbohydrate-binding lectins
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Vascular addressins
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contain carbohydrate groups to which selectins bind
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Integrins
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typically bind to Ig superfamily proteins
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Macrophage secretes TNF-alpha, CXCL8, IL6 -> causes
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neutrophil release
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In healthy tissue endothelial cells contain granules known as ________ which contain _________
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-weibel-palade bodies
-p-selectin |
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Upon exposure to the inflammatory mediators ____, _____, and _____ the p-selectin in the weibel-palade bodies is transported to the cell surface
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-Leukotriene LTB4
-C5a -histamine |
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______ is also expressed on endothelial surfaces after exposure to TNFalpha or LPS
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E-selectin
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Diapedisis?
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squeezing through endothelial cells
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extravasation?
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the process by which neutrophils migrate out of blood capalaries and into tissues
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Neutrophil receptors for phagocytosis?
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Fc
scavenger CR3 N-formyl-met (not human) mannose CD14 (LPS receptor) CR4 glycan |
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Fc receptor?
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binds to Fc region on antibodies
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respiratory burst?
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Respiratory burst = Transient increase in oxygen consumption = purpose is to raise the pH of the phagosome so the granule contents can become active to kill pathogen
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C-reactive protein Binds to ________ component of LPS of bacterial and fungal cell walls but not in human cells
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phosphorylcholine
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C-reactive protein can bind _____ to initiate classical pathway of complement fixation in absence of antibodies
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C1q
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mannose binding lectin binds
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Binds mannose-containing carbohydrates of bacteria and yeast
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Mannose containing carbohydrates on human cells do not bind MBL because ?
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their geometry does not permit multipoint attachment to MBL
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Do monocytes express macrophage mannose receptor?
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no
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Monocytes do not express the macrophage mannose receptor but have receptors that can bind to ________ coating a bacterial surface
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MBL molecules
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Type I interferon function?
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Interfere with viral replication by infected cells
Alert immune system cells that infection is present Make virus-infected cells more vulnerable to killer lymphocyte attack |
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Interferon type 1 mechanism
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viral material enters cell -> transctiption factor IRF3 + NFkb + AP-1 turn on IFN-beta gene -> IFN-b is secreted -> IFN-b binds in autocrine to cell -> IFN-b causes IRF7 to cause expression of IFN-alpha
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Does IFN-alpha expression depend on NFkB?
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no
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Type _______ interferon induce proliferation of NK. In addition, NK cells are also activated by ____ and _____
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-type 1
-IL-12 (macrophages) and TNF-a (macrophages) |
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Stimulation of NK cells with IFN-a and IFN-b favors?
Stimulation of NK cells IL-12, IF-gamma release favors ? |
-favors the development of cytotoxic effector function
-the production of cytokines |
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NK cells provide an early response to virus infection and ___________ take over to finish the job
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effector T cells
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Effector T cells enter the site of infection -> become major source of _____ and cell-mediated cytotoxicity -> secrete inhibitory cytokine _____.
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-IFN-gamma
-IL-10 |
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Function of IL-10?
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turns off NK cells
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NK cells are analagous to what adaptive immune cell?
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CD8 T-cells
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two terms for the part of the antigen bound by Ig or TCR
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Epitope or antigenic determinant
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(MHC) is a cluster of genes on the short arm of human chromosome __
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chromosome 6
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The genes for immunoglobulin heavy chain and T-cell receptor B-chain have arrays of _______ segments
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V, D, and J segments
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Genes for the immunoglobulin light chain and the T-cell receptor alpha chain have ______ segments
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D and J
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Cytotoxic t-cells are know as ______ and are presented antigens by ______.
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-CD8 t-cells
-MHC class 1 |
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What is CD8?
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The coreceptor that ensures cytotoxic t-cells only bind MHC1.
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How many subunits of MHC1 are membrane bound?
MHC 2? |
MHC1 = 1 anchor
MHC2 = 2 anchors |
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Helper T-cells are called _____ and have antigens presented to them via _________
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-CD4 T-cells
-MHC-2 |
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Coreceptor for MHC2 molecules?
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CD4
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MHC class 2 molecules are found on
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macrophages, dendridic cells, and b-cells
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MHC class I presents antigens derived from the _______
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cytosol
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The TCR recognizes both the _______ and ________
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antigen and MHC molecule
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Why type of pathogens do CD8 T-cells mainly kill?
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viruses
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TH1 cells mainly activate ?
TH2 cells ? |
TH1 cells mainly activate macrophages
TH2 cells chiefly help B cells |
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antibody isotypes are named according to their?
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heavy chain
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IgE?
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binds to mast cells -> allergic reactions
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First antibody produced in primary adaptive immune response?
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IgM
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IgM structural component?
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pentameric -> 10 bind sites
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Highest quantity antibody in the body?
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IgA
the body includes mucosal surfaces |
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Highest quantity in the blood?
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IgG
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________ are the antibody isotypes found mainly in the blood, lymph and extracellular spaces
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IgM, IgG and IgA
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_____ region of IgE binds to mast cells.
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constant region
|
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Tissue rejection caused by
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extensive polymorphism of MHC class I and II genes
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Memory b-cells are activated and what antibodies are used?
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IgG
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Positive selection?
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T-cells that bind too poorly to MHC are eliminated. Those that bind tight move on to the next step
|
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Negative Selection?
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T-cells that survive positive selection are tested again. If they bind TOO strongly to MHC they will be eliminated
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1st immune system components to be activated = ?
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complement
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1st Step in the alternative pathway involves
|
spontaneous hydrolysis and activation of complement component C3
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_____ is the product of C3 hydrolysis
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iC3
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iC3 binds to _____ in the blood or ECF making it susceptible to cleavage by ______
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factor B
factor D |
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What activates C5 in the alternative pathway? What is it called?
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Alternative C5 convertase = C3b2Bb
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What activates C5 in the classical pathway? What is it called?
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Classical C5 convertase = C4b2a3b
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Difference between DAF and MAP mechanism
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DAF -> DAF binds and Bb is released
MAP -> MAP binds, Bb is released, and then Factor I cleaves C3b to iC3b |
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What do C3a and C5a do?
|
bind mast cells, phagocytes and endothelial cells -> release of histamine -> Histamine increases blood vessel permeability and blood flow
Activate endothelial cells -> direct phagocytes to site of infection |
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C5a Increases the adherence of monocytes and neutrophils to blood vessel walls and acts as a powerful __________ factor
|
chemotactic
|
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what is alpha-2-macroglobulin?
|
a protease inhibitor
|
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Rolling Adhesion:
What binds to selectin? |
sialyl-Lewis X
|
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Rolling Adhesion:
Where is LFA-1? What does it bind to |
LFA-1 is on the neutrophil and binds to ICAM-1
|
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Rolling Adhesion:
Where is ICAM-1? What does it bind to? |
ICAM-1 is on the epithelial cells and binds to LFA-1
|
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Rolling Adhesion:
What is CXCL8 and where does it bind? |
A chemokine that will bind to CXCL8 receptor and help the macrophage enter thru the basement membrane
|
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Rolling Adhesion:
What is CD31? |
Protein between epithlial cells that macrophage slips through
|
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azurophilic granules?
|
proteins and peptides that can distrupt and digest microbes
|
|
specific granules?
|
competes with the microbe from metals (iron and copper)
|
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______ cleaves C4 and C2
|
MASP-2
|
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C3 convertases:
Alternative? Classical? |
C3 convertases:
Alternative – C3bBb Classical – C4bC2a (C4b2a) |
|
C5 Convertases:
Alternative? Classical? |
C5 Convertases:
Alternative = C3b2Bb Classical = C4b2a3b |
|
Alternative C5 Convertase
|
Alternative = C3b2Bb
|
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Classical C5 Convertase
|
Classical = C4b2a3b
|
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When any human cell becomes infected it responds by making cytokines called type 1___
|
interferons
|
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Type two interferons are made by
|
NK cells, CD8 T cells and CD4 TH1 cells
|
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Which type 1 interferon is multiform? single form?
|
single form = type beta
multi = type alpha |
|
Which lymphocytes have a well developed cytoplasm? which dont?
|
B and T dont -> all nucleus
NKs have well developed cytoplasm |
|
Two effector functions of NK cells
|
Cell killing
Secretion of cytokines |
|
MIC ligand is expressed by/on?
receptor for ? |
-virus infected cells
-receptor for NKG2D on NKs |
|
Will a B-cell have somatic recombination of TCR genes?
|
no - false
|
|
IgE ________ region binds to ______ cells
|
IgE constant region binds to mast cells
|
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If IgE variable region catches an antigen what happens?
|
Causes the mast cell to degranulate
|
|
Tissue rejection caused by extensive polymorphism of
|
MHC class I and II genes
|
|
What can Work in the anaerobic conditions found in damaged tissue
|
Neutrophils
|
|
Responsible for puss?
|
neutrophils
|