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129 Cards in this Set
- Front
- Back
4 Types of Pathogens
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Bacteria, Viruses, Fungi and Parasites
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Granulocytes (Polymorphonuclear Leukocytes)
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Neutrophils, Eosinphils and Basophils
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Monocytes
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Macrophage, Dendritic Cell and Mast Cell
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Neutrophils
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most abundant WBC
Phagocyte & effector cell of innate immunity |
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Eosinophils
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Defense against worms and parasites
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4 Types of Pathogen
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Bacteria, Fungi, Viruses, Parasites
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Granulocytes (Polymorphonuclear Leukocytes)
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Neutrophils, Eosinophils, Basophils
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Monocytes
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Macrophages, Dendritic Cells, Mast Cells
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Neutrophils
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Most abundant WBC
Phagocytic- the Effector of innate immunity |
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Eosinophil
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Defense against worms and parasites
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Basophil
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Stores histamine and is involved in inflammatory responses (liken to Mast Cell)
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Macrophage
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First Phagocyte to sense pathogen
Cytokines secrete neutrophils Does not travel |
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Dendritic Cells
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Sample pathogen to take to lymphoid organ to recruit adaptive response
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Mast Cells
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Inflammation
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Antigen of B Cell
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Whole protein, carbohydrate
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Antigen of T Cell
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Peptide fragment on MHC
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MHC I
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Presents products made by cells own protein synthesis machinery
Present on all cells but rbcs |
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MHC II
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Present peptides derived from phagocytosis of extracellular material
Present only on Antigen-Presenting cells |
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Positive Selection of T Cell
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T cells that correctly "fit" the antigen presenting molecules are selected for further growth (Called MHC restriction)
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Negative Selection of T Cell
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Deletes the T Cells that recognize either the MHC molecule itself or self antigens
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What is the C3 convertase of the alternative pathway?
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C3bBb
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Properdin
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Stabilizes the C3bBb so that it is effective longer
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Factor H
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Binds C3b on pathogen surface so that Factor B can't but Factor I can
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Factor I
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Binds the Factor H/ C3b complex and cleaves C3b leaving iC3b on human and pathogen surfaces
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iC3b
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Tag on self or pathogenic cells recognized by phagocytic cells
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DAF
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Complement regulatory molecule that causes dissociation of C3bBb on human cells
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MCP
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Complement regulatory molecule that causes dissociation of C3bBb on human cells and also allows Factor I to attack to generate iC3b
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Properdin Deficiency
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Increased neisseria infection susceptibility
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DAF and MCP Deficiency
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Paroxysmal Nocturnal Hemoglobinuria (complement attacks RBCs)
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CR1
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Recognizes C3b
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CR3 and CR4
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recognize iC3b
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What binds C5?
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C3b2Bb
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What complement complex inserts into the pathogen membrane?
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C5b67
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What proteins prevent the soluble C5b67 complex from entering the membrane?
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S protein, clusterin, and factor J
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What proteins prevent recruitment of C9 into the membrane?
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HRF (Homologous Restriction Factor), and protectin (CD59)
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What is caused by defective synthesis of a lipid tail shared by HRF, DAF and protectin?
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Paroxysmal nocturnal hemoglobinuria
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What are the anaphalatoxins?
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C5a, C3a, C4a
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Name a bacterial protease inhibitor
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Alpha2Macroglobulin: has a thioester group that resembles complement
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Defensins
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Antimicrobial peptides expressed on some cells that protect various tissues
Two classes: alpha and beta |
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What are PAMPS and what binds them?
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Pathogen-associated molecular patterns, bound by Toll-like Receptors on macrophages
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The ligand for TLR4
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LPS
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Ligand for TLR3
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dsRNA (viral infections)
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Ligand for TLR9
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Unmethylated CpG (Cytosine-phosphate-guanine on bacterial and viral genomes)
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First step of TLR4 signaling pathway
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LPS is bound to CD14; MD2 and TLR4 assemble making complex
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Deficiency of the TLR4 signaling pathway gives trouble with what bacteria?
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Streptococcus pneumoniae and staphylococcus aureus
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IKK
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essential modulator of NF-kappa-B, the transcription factor for macrophage inflammatory cytokines
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IKK (NEMO) mutations cause
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Incontinentia pigmenti, Hypohydrotic ectodermal dysplasia, and impaired antibody class switching
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Cytokines involved in fever
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IL-6, TNF-alpha, IL-1beta
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CXCL8
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Chemoattractant cytokine that recruits neutrophils and basophils
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First step of neutrophil extravasation
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Sialyl-Lewis-x on the neutrophil weakly binds a selectin expressed on the vascular endothelium
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What molecules interact to produce tight binding between the neutrophil and the endothelium
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LFA-1 and CD3 on the neutrophil interact with ICAM-1 of the endothelium
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Chediak-Higashi Syndrome
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Large cytoplasmic granules in neutrophils interfere with diapedesis
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What cytokine is involved in neutrophil extravasation?
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CXCL8
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What enzyme is involved with making superoxide in neutrophils and how many subunits does it have?
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Superoxide Dismutase- 4 subunits
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Chronic Granulomatous Disease
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Deficiency of any one of the 4 subunits of NADPH Oxidase causes this
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Mannose Binding Lectin
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Plasma protein that binds mannose-containing carb on surface of pathogen and acts like C1 to cleave C4 and C2
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What is the Classical C3 Convertase
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C4b2a
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C1
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Binds to C-reactive protein on pathogen surface and acts to cleave C4 an C2 to form C4b2a convertase
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C1INH Deficiency
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Results in excessive C4 and C2 consumption
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Hereditary Angioneurotic Edema
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Associated with C1INH deficiency because of excessive C2 kinin production
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What develops the killer functions of NK cells?
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Ifn- alpha and Ifn-beta
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How does Papain cleave Ab?
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2 Fab
1 Fc |
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How does Pepsin cleave Ab?
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1 Fab2 and lots of little pieces
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Which Antibodies have 4 domains in the heavy chain C region?
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IgM and IgE
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How many different genes code for IgG?
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4- that's why there are 4 subclasses of IgG
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How many different genes code for IgA?
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2
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Epitope
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Site on an antigen that is recognized by the antibody
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Early Pro-B Cell
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DJ recombination has occurred
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Late Pro-B Cells
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DJ has recombined with V
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What info in contained in the primary RNA transcript of a naive B Cell?
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VDJ, C-mu and C-delta
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Large Pre-B Cell
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mu chain is expressed on B cell surface
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Small Pre-B Cell
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mu and delta heavy chains wait to be combined with a light chain
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Immature B Cell
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IgM is expressed on cell surface
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Mature Naive B Cell
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IgM and IgD are expressed on cell surface
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What must be expressed with the B cell receptor in order to have signal transduction?
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Ig-alpha and Ig-beta dimer
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What directs Ab class switching?
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Cytokines
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What is the half life of IgG3 compared to the other IgGs
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7 days as opposed to about 3 weeks
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Antibodies involved in neutralization
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IgGs and IgA
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Antibodies involved in opsonization
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IgG1 and IgG3
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Antibodies that sensitize for killing by NK cells
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IgG1 and IgG3
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Antibodies involved with mast cell sensitization
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IgE
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Abs that activate complement system
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IgM and IgG3
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Abs transported across epithelium
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IgA
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Abs transported across placenta
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IgGs (esp IgG1)
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Abs that diffuse into extravascular sites
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IgGs
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What Ab is present in greatest amt in the serum?
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IgG1
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Omenn Syndrome
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RAG1 or RAG2 deficiency leads to problem with B cells and T Cells (SCID)
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T Cell signal transduction depends on the presence of what molecules as coreceptor?
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CD3 complex and zeta chain
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What is the structure of an MHC I molecule?
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1 alpha chain with 3 domains and a beta-2-m
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What is the structure of an MHC II molecule?
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an alpha chain and a beta chain, each with 2 domains
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CD8 stabilizes binding of T Cell to MHC by associating with what portion?
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alpha 3 domain
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CD4 stabilizes binding of T Cell to MHC by binding what portion?
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Beta-2 domain
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What kind of peptides are bound by MHC 1 and 2?
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MHC 1 binds short peptides (9aa)
MHC 2 binds longer peptides (13-25aa) |
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What molecule is MHCI complexed with in the ER?
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Calnexin
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How is peptide delivered to the ER where it binds MHCI?
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TAP
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What protects MHCII in the ER?
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Invariant chain
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What is responsible for cleaving the invariant chain away from MHCII and what is left?
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Proteases in the vesicle- CLIP is left
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What removes CLIP from MHCII?
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HLA-DM in the vesicular membrane
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What is a superantigen?
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Binds MHCII and the TCR with very high affinity such that they are forced to interact
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What chromosome houses MHC?
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6
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What are the MHCI isotypes?
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A, B, C, E,F, and G but only A, B and C are polymorphic and thus diverse among inividuals
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What are the MHCII isotypes?
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DM, DO, DP, DQ, DR but only DP, DQ and DR are polymorphic
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How many MHC1 genes do you have on each chromosome?
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3
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How many DR-B genes does each person have?
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2 on each chromosome. 1 DRB-1 and either a pseudogene or one more of DRB-3,4,5
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Autograft (Autologous) transplant
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Patient is his own source of transplant material
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Isograft (Syngeneic) transplant
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Identical twin is source of transplant material
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Allograft (Allogeneic)
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Transplant material obtained from someone else who is a good "match"
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Alloantibodies
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Maternal anti-HLA antibodies against fetus that expresses some of dad's haplotype
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What T Cells mediate transplant rejection?
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CD8 T Cells
**Match for MHC1 |
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Isohemaggutinins
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Antibodies against blood antigen you do not express (non self antigen)
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Hyperacute Rejection
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Antibody-mediated
Antibody already made against donor's antigen |
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Is hyperacute rejection affected by routine (T cell) immunosuppressive therapy?
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No bc its Ab mediated
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Acute Rejection
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T Cell mediated, takes days
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Graft-versus-Host
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Donor is immunocompetent but recipient is immunocompromised so the donor cells attack recipient tissue
(Issue in BM transplant) |
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Bruton's X-linked Agammaglobulinemia
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Failure of VDJ recombination due to BTK deficiency
Decreased Ig levels |
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Where in the maturational process of B Cells does Bruton's XLA occur?
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No V-DJ recomb so problem with Late Pro B Stage
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What does the PreB Cell Receptor consist of?
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A Mu heavy chain and a surrogate light chain of VPreB and Lambda5
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Burkitt's Lymphoma is characterized by translocation of what gene?
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MYC
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What does a B-1 cell have that a B-2 cell doesn't?
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CD5 cell surface protein
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Malignant transformation of B-1 cells?
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Chronic Lymphocytic Leukemia
Occurs because of the capacity of B1 for self renewal |
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Expression of surface IgD with little or no IgM is characteristic of what?
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Anergic B Cells
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What is the path of a B Cell in the lymph node?
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Enter T Cell Cortex via HEV, migrate through primary follicle and back through T Cell area before leaving via efferent lymphatics
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How do B Cells encounter antigen?
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CD4 T Cells (Th2) present antigen in the T Cell area
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Where do plasma cells mainly live?
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Medulla of lymph node and bone marrow
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When baby thymocytes first begin to encounter thymic epithelial cells, what is the first surface marker they express?
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CD2
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Name of the surrogate pre T receptor alpha chain?
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ptalpha
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Two surface proteins of Treg
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CD25 and Fox P3
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FoxP3 deficiency
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IPEX Syndrome, an overwhelming systemic autoimmunity
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DiGeorge Syndrome
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a midline deformity and no thymus development...no T Cell education
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