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Definitions |
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Antiendomysial
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Celiac
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Anti-dsDNA
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SLE
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Antihistone
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drug-induced lupus
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Anti-basement membrane
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Goodpastures
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Anti-glutamate decarboxylase
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Type-1 DM
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Howell-Jolly bodies
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splenectomy/asplenic pt
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Antimitochondrial
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primary biliary cirrhosis
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strongest immunogen
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protein (>polysaccharides>lipid>nucleic acids)
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LFA-1
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(binds ICAM-1 on endothelium)
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PAF action
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basoconstriction, vasoconstriction, platelet stimulation
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antibody function
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adaptor proteinsfacilitate phagocytosisfacilitate complement activation
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c5 convertase
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C4b2a3b, cleaves C5
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DAF
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Decay-accelerating Factor. Membrane protein expressed on all cells, esp. RBC's. Prevents formation of C3 convertase!-Alt Pathway - prevents binding of Factor B-Classical Pathway - prevents binding of C4b
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MS immune mechanisms
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o Type IV Hypersensitivity—delayed-type hypersensitivity; depends on T cellso Immune reaction to myelin antigens.
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Antibody that crosses the placenta
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IgG
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Chediak-Higashi syndrome
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Pathophys: Autosomal recessive, microtubular dysfunction --> decreased phagocytosisPresentation: recurrent pyogenic infections by staph and strep, partial albinism, peripheral neuropathy
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factor H
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cofactor for factor I
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How are isotypes determined?
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Fc region
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CD59
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Membrane-bound protein on host cells that prevent binding of C9 - no MAC can kill it!
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Hashimoto's Thyroiditis
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-Type 2 Hypersensitivity-Ab's against thyroglobulin and TPO prevent production of T3/T4-Hypothyroidism! Thyroiditis AND tissue destruction
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Pemphigus Vulgaris
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-Type 2 Hypersensitivity-Ab's against demosglein-3 (desmosomes)-Ab-mediated activation of proteases, disruption of intercellular adhesions-Skin bullae, blisters, erosion of skin-Ashkenazi Jews, HLA D4/DQ3
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polymyositis dx
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• anti-Jo 1 (anti-histidyl transfer RNA synthetase)o auto-antibody seen in **• anti-SRP (anti-signal recognition particle)o auto-antibody seen in **
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multiple sclerosis dx
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immunodiagnosis: CerebroSpinal Fluid (CSF) elevated IgG (high IgG/albumin ratio)
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IFN-gamma
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CD4+ TH1 produce ***, activates macrophages.Macrophages produce TNF-alpha
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Azathioprine: Mechanism
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used early following transplantation Inhibits synth of inosinic acid, blocking DNA synth
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IgA
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dimer in secretion, protects agst enzymatic breakdown of gut
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IL-27
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induces Tbet and STAT6inhibits GATA3 activation
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What do B cells do?
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Secrete antibodies
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CTLA-4
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T cell accessory molecule that binds to B7 and causes T cell to respond LESS well to APC.-Gives T cell activation system balance-Important for inducing anergy to self-ag's
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Graves' Disease
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-Type 2 Hypersensitivity-Ab binds to TSH receptor and STIMULATES it-Hyperthyroidism! Thyroiditis but no tissue destruction
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• Guillain-Barre syndrome (GBS) dx
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Anti-GM1 & anti-GD1 auto-antibodies In CSF: Elevated protein (due to inflammation), Oligoclonal bands may be present
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IL-12 receptor deficiency
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Pathophys: decreased Th1 response Labs: less IFN gamma Presentation: disseminated mycobacterial infections
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Selective Ig Deficiency
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Pathophys: Defective isotope switching (specific Ig missing, most often IgA)Labs: Less of Ig (IgA most likely)Presentation: sinus and lung infections, milk allergies and diarrhea, anaphylaxis on exposure to blood with IgA
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Negative nitroblue tetrazolium dye reduction test
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Chronic granulomatous disease
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hapten
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to small to envoke immune response unless attached to larger antigen
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cross priming
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dendritic cell uptake of apoptic blebs, eventually displayed as class I
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calnexin/calrecticulin
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stabalize newly formed MHC I molecule until B2 invariant binds
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TGF-beta
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-Secreted by CD4 T cells and many cancer cells. -Inhibitory cytokine-generally inhibits T cell proliferation.
-Differentiation and activation of Tregs.
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IFN-alpha and IFN-beta
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Alpha - DC's, macs.Beta - Fibroblasts.-Puts all cells in anti-viral state, upregulates MHC Class I-Activate NK cells
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IL-12
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-Secreted by macs and DC's to activate NK cells and TH1 to secrete IFN-gamma.
-Secreted by APC ("signal 3") to stimulate differentiation into TH1 cell. Release triggered by binding of CD40L to CD40.
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What is the first antibody produced in a B cell?
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IgM
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regulatory T cells
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• IL-2 is especially important for the development and maintenance of ***
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See decreased IFN-gamma in?
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IL-12 deficiency and Job's syndrome
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Path of hyperacute kidney rejection
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vascular fibrinoid necrosis, neutrophil infiltrates within arterioles, glomeruli, peritubular capillaries
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Hyper IgM
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Pathophys: Defective CD40L on Th cells - no B cell class switchingLabs: High IgM, very low IgG, IgA, IgEPresentation:severe pyogenic infections early in life
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double negative thymocyte
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no CD4 or CD8 markersgermline configuration
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Needed for T cell activation
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adhesion molecules (homing)b7/CD28 (2nd signal for activation)CD3 complex (intracellular signaling)CD4/8 (essential for effective T cell stim)
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VLA-4
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binds to VCAM-1, directs T cells to infected tissues
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What type of response is innate immunity (speed)?
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Rapid response
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What do naive B cells express?
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IgD and IgM
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From where do naive lymphocytes enter lymph nodes?
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From blood
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CD62-L (L-selectin)LFA-1
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Homes T cells to HEV in lymph node.
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bystander activation
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activation of T cells specific for an antigen X during an immune response against antigen Y
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negative selection
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eliminates cells that bind with a high affinity to self peptides
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pepsin digestion
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yields single frag with 2 Ag binding sites (F(ab)2), Fc portion is degraded
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What are other isotypes besides IgD and IgM
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IgG, IgE, IgA
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What do C5b - C9 do?
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Cellular damage and lysis
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Characteristics of IgA?
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1. mediates direct killing of bacteria and tumor cells
2. secretory IgA protects against microbes on mucosal surfaces (gut, resp. tract, etc)
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Characteristics of IgE?
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1. binding to IgE receptors can mediate allergic response
2. effective against parasites
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CD64 (FcgammaR1)
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FcR on macs and neutrophils. Binds Fc region of IgG to phagocytose opsonized ag's.
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CCR7
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Homes DC's and T cells to the T cell zone of lymph nodes and spleen.
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What 3 processes generate antibody diversity?
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1. somatic recombination
2. somatic hypermutation
3. isotype switching or class switch recombination
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Mechanism: Muromonab-CD3 (OKT3)
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binds to CD3 on T cells, blocks interaction with CD3, and blocks T cell signal transduction
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DAF (decay accelerating factor)
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diass Bb from C3bsame function as CR1
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signal 2 for activation of T cell
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CD28:B7costimulationleads to clonal expansionbacteria induces expression on macrophages and B cells
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What is the major effector function of IgG1?
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Opsonization
Transport across placenta
Diffusion into extravascular sites
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What do MACs do?
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Make holes in pathogen cell membranes and destroy pathogen
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What are the 5 types of granulocytes?
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1. neutrophils
2. eosinophils
3. basophils
4. mast cells
5. monocytes
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What are C5a, C3a and C4a responsible for? What is the order of their strength?
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Anaphylatoxin
Activating vascular endothelium
Chemoattractant
Actavating phagocytes
C5a > C3a >> C4a
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What are basophils? What percent of granulocytes do they make up?
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involved in histamine reaction
<1%
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What is negative selection?
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Removal of lymphocytes that bind HLA too strongly
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If T cells only undergo negative selection in the thymus, why are they not self reactive to cells in other tissues?
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Autoimmune regulator (aire) is expressed in the thymus which is a transcription factor that promotes the expression of many different genes in the thymus at low levels. What condition results from a mutation in the aire gene?
Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy
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What makes up the B cell receptor?
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immunoglobulin and two other transmembrane proteins Igα and Igβ
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signals produced by dendritic cells
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CCL18- attracts naive T cellsDEC 205: phagocytosisICAM-3: T cells
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How many signals are required by naive T-cells to induce immunity?
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1st and 2nd signal
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How do specific antibodies act on bacteria in extracellular space?
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Opsonization and ingestion by macrophages
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Paroxysmal Nocturnal Hemoglobinuria
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Defect in DAF and MCP on RBC's. No regulation of complement cascade --> hemolysis. -No DAF - C3b buildup on RBC's-No MCP - no Factor I to inactivate C3b to iC3b
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What are the professional antigen presenting cells and what do they express on their surface?
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Cells that express MHC Class II molecules are professional antigen presenting cells. They alert T-cells to the presence of extracellular infections.
B cells
Macrophages
dendritic cells
epithelial cells of thymus
What cells types don't express any MHC?
rbcs and neurons
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What kinds of nucleotides are randomly added into the coding joint between gene segments during somatic recombination? How are they added in?
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P-nucleotides: cleavage of the DNA hairpin left by V(D)J recombinase by hairpin endonuclease at a random site yields nucleotides that were originally complementary in the double stranded DNA
N-nucleotides: enzyme terminal deoxynucleotidyl transferase adds nucleotides at random ends to the ssDNA ends.
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What are other attributes of adaptive immunity?
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1. specific for given antigen
2. establishes memory
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In the alternate pathway:
What does C3b do?
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Splits factor B into Ba and Bb
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What are mast cells? Where are they found?
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Active against bacteria & parasites; associated w/ allergy
- in tissues
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Where does negative selection occur in self reactive T cells?
What cells mediate the negative selection?
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In the corticomedullary region of the thymus.
dendritic cells and macrophages.
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What syndrome is seen in patients with at a mutation in CD40L ?
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Hyper IgM syndrome because CD40:CD40L interactions are necessary for isotype switching
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Of the 3 possible paths of double positive T cells, which is positive selection?
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Binding neither class I/II and subsequent death
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What are the 2 types of acquired immunity?
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1. active (own Abs)
2. passive (ready-made Abs)
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In what circumstances is adaptive immunity activated?
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If threat is high enough for long enough time
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What are the 2 types of stem cells that stem cells divide into?
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1. lymphoid stem cell
2. myeloid progenitor
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What are the 2 fates of CD4+ and CD8+?
Which is negative selection?
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1. bind strongly and die
2. bind weakly and live
Bind strongly and die
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