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345 Cards in this Set
- Front
- Back
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what cells constitute innate immune response
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macrophage, NK cell, complement, neutrophils, dendritic cells
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what cells constitute adaptive immune response
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B cells, T cells, antibodies
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what to TLRs recognize
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conserved nonself Ag's on pathogens "PAMPs"
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what pathway do TLRs involve
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NFkB
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what are types of mhc
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1 (a,b,c) on all nucleated cells, 2 (dp, dq, dr) on APCs
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what does mhc 1 bind
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binds tcr, cd8
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what does mhc 2 bind
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tcr, cd4
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where is antigen loaded onto mhc i
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rer
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where is antigen loaded onto mhc2
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acidified endosome after release of invariant chain
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what is function of b2 microglobulin? What is it associated with
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binds w/ mhc1, helps to carry it to cell surface
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what is associated with hla a3
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hemochromatosis
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what is associated with hla b27
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PAIR = psoriasis, ankylosing spondylitis, IBD, reiters
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what is associated with hla b8
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graves, celiac
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what is associated with hla dr2
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Hay Good Slims! = hay fever, goodpasture, SLE, MS
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what is associated with hla dr3
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DM1
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what is associated with hla dr4
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DM1, RA
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what is associated with hla dr5
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pernicious anemia, Hashimoto
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what is associated with hla dr7
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steroid responsive nephrotic syndrome
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how does NK kill stuff
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granzyme, perforin
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what class of cell is NK cell
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lymphoid
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what cytokines can enhance the activity of NK cells
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IL12, IFNalpha&beta
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what can induce an NK cell to kill
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1. nonspecific activation signal 2. absence of MHC 1
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functions of antibodies
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1. opsonize bacteria 2. neutralize virus (IgG) 3. activate complement 4. sensitize mast cells
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what types of antibodies neutralize viruses
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G
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what types of antibodies activate complement
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G,M
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what is the most important mechanism for immune killing of neoplastic cells
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CTLs
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where are T cell precursors located
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bone marrow
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where does positive selection take place? Where does negative selection take place
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cortex of thymus. Medulla
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what induces formation of Th1 cells? Th2 cell?
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IL12. IL4
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what makes up majority of circulating lymphocytes
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T lymphocytes
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what is the ratio of Th cells to Tc cells
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2:1
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describe the 6 steps of acute inflammation
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1. margination 2. rolling 3. adhesion 4. diapedesis 5. chemotaxis 6. phagocytosis
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what occurs in margination
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vasoconstriction permits leukocytes to move to periphery close to blood vessel wall
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what occurs in rolling
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activation of selectin molecules to slow down motion of leukocytes
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what occurs during adhesion
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leukocytes adhere to endothelium using beta integrins, c5a, and ltb4, which bind to icam and vcam on endothelium.
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what factors promote expression of icam and vcam on endothelium
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il1, tnf
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what occurs during diapedesis
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leukocyte travels through blood vessel wall
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what occurs during chemotaxis
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leukocyte localizes to site of inflammation - C5a, LTB4, bacterial products, IL8 set up gradient
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what occurs during phagocytosis
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leukocytes phagocytose opsonized products and kill them with respiratory burst
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describe the difference between these forms of inflammation: puruplent, fibrinous, serous, pseudomembranous
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purulent = pus forming organism (e.g. coagulase + organisms) 2. fibrinous = fibrin rich exudate w/ increased vessel perm 3. serous = watery 4. pseudomembranous = necrotic mucosal lining
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3 types of apcs
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1. macrophage 2. b cells 3. dendritic cells
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describe how Th cells are activated
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1. binding of MHCII to TCR 2. binding of MHC to CD4 3. binding of CD28 and B7 (on APC)
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describe how Tc cells are activated
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1. binding of MHCI to TCR 2. binding of CD8 3. binding of IL2 made from Th1 to IL2r on Tc
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describe how B cells are class switched
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1. binding of Il4,5,6 to receptors on B cell 2. binding of CD40 to CD40L on Th2
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what cytokines do Th1 vs Th2 secrete
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Th1: IFNgamma, IL2. Th2: IL4,5,10
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what type of T cells activate macrophages and CTLs
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Th1
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what type of T cells activate B cells
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Th2
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what inhibits Th1 cells
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IL10
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what inhibits Th2 cells
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IFNgamma
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what is the interaction between macrophage and lymphocyte
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lymphocytes make INFgamma. M0 makes TNF, IL1
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6 mechanisms by which autoimmune dz occurs
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1. release of sequestered Ag's 2. imbalance of Th over Tsupp 3. mimicry 4. alteration of self Ags 5. abnormal immune response on chr 6 (mhc related) 6. polyclonal B cell activation
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are lymph nodes encapsulated
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yes
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where do b cells mature
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BM, then they migrate to germinal centers in lymph nodes and await activation
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review picture of lymph node
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p200
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1* vs 2* follicles
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1* are dense and dormant, 2* have pale germinal centers and are active
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medullary cords vs medullary sinuses
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medullary cords are packed lymphocytes and plasma cells. Sinuses leads to efferents and contain reticular cells and macrophages
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what part of lymph nodes contain high endothelial venules? What are they responsible for
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paracortex. T and B cells from circulation enter thru here
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what part of lymph node will become severely enlarged in a cellular immune response
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paracortex
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what types of cells are found in paracortex
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t cells
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what drains upper limbs and lateral breast
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axillary
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what drains stomach
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celiac
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what drains duodenum and jejunum
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superior mesenteric
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what drains sigmoid colon
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colic -> inferior mesenteric
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what drains rectum (above pectinate)
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internal iliac
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what drains anal canal below pectinate
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superficial inguinal
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what drains testes
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superfical & deep plexus -> paraarotic
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what drains scrotum
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superficial inguinal
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what drains superficial thigh
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superficial inguinal
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what drains lateral dorsum of foot
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popliteal
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what drains right arm and half of head
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right lymphatic duct
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where is the thoracic duct found
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junction of subclavian and internal jugular
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how are abscesses formed
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release of contents from neutrophils and m0
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review picture of spleen
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p201
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where are follicles located in the spleen
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white pulp
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where is the PALS located in the spleen
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adjacent to the central arteriole in the white pulp
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what is found inside follicles of spleen
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b cells
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what is found inside PALS of spleen
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t cells
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what does red pulp of spleen contain
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rbcs
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what does marginal zone of spleen contain
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APCs
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changes seen post splenectomy
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1. howell jolly 2. target cells 3. thrombocytosis
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what type of antibodies decline after splenic dysfunction
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IgM
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is thymus encapsulated
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yes
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what does thymus originate from
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ventral 3rd branchial pouch
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what does cortex vs medulla of thymus contain
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cortex = immature t cells. Medulla = mature t cells and epithelial reticular cells and Hassall's corpuscules
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positive vs negative selection
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positive = mhc restriction. Negative = nonreactive to self
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at what age is lymphadenopathy suspicious for malignancy
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30
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painful vs painless lymphadenopathy
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painful suggests inflammation. Local = local infection, generalized = systemic dz like mono or sle. Painless = malignancy
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what type of cancer will drain to: submental
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SCC in floor of mouth
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what type of cancer will drain to: cervical
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head and neck tumors, Hodgekin
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what type of cancer will drain to: left supraclavicular
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Virchow = stomach, pancreas
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what type of cancer will drain to: right supraclavicular
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lung, esophagus, hodgekin
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what type of cancer will drain to: axillary
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breast
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what type of cancer will drain to: epitrochlear
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cat scratch, NHL
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what type of cancer will drain to: hilar
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lung, sarcoid
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what type of cancer will drain to: mediastinal
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lung, nodular sclerosing Hodgekin, t cell lymphoma
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what type of cancer will drain to: tonsillar
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SCC in oral cavity
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what type of cancer will drain to: paraaortic
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testicular, Burkitt
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what type of cancer will drain to: inguinal
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vulvar, penis
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what type of pathology could cause follicular hyperplasia of lymph nodes
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b cell antigenic response (eg worms)
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what type of pathology could cause paracortical hyperplasia of lymph nodes
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t cell antigenic response (oft dermatologic, can see melanin)
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what type of pathology could cause mixed b & t cell hyperplasia of lymph nodes
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B henselae, toxo, mono, tularemia
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what type of pathology could cause medullary sinus histiocytosis in lymph nodes
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benign histiocytic response draining tumor (good sx in breast cancer)
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what ctl mechanism is thought to be defective in autoimmune dz and why
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FasL stimulated destruction of autoreactive T cells
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what type of cells does ctl kill
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virus infected, neoplastic, donor graft
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mechanism of ctl killing
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perforin, granzyme, granulysin (the latter 2 induce apoptosis).
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what type of enzyme is granzyme
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serine protease
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review picture of antibody
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p205
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which ig and what part of ab fixes complement
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Fc part of IgM/IgG, the part closest to the variable region
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do light chains contribute to Fc
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no
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what is idiotype
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unique antigen binding pocket. Determined by Fab
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what part of ab is carboxy terminal
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Fc
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what part of ab can have carbohydrate side chains
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Fc
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4 mechanisms of antibody diversity
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1. VDJ recombination 2. Random assortment of heavy chains with light chains 3. Somatic hypermutation after ag stimulation 4. addition of nucleotides to DNA during recombination by TdT
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what is terminal deoxynucleotidyl transferase
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adds random nucleotides to variable region of Ab in order to increase diversity during recombination
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what kinds of breaks occur in VDJ recombination, and what enzyme is responsible for fixing
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DSB, RAG
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what is allotype
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different alleles of the VDJ gene found from person to perosn
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what are types of light chains
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lambda or kappa
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ratio of lambda to kappa light chains
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1:2
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how does composition of antibodies change in MM
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increased light chains, the ratio of lambda to kapppa changes
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what types of ig's are expressed by mature b lymphocytes
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IgM, IgD
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what types of cells secrete IgA, IgE, IgG
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plasma cells
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what is the most abundant antibody
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IgG
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what type of antibody can cross placenta
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IgG
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what is the half life of IgG
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21d
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what type of antibody is found both intra and extravascular
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IgG
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function of IgA
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prevents attachment of bacteria and viruses to mucous membranes
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is IgA a monomer or dimer
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monomer in circulation, dimer when secreted
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how does IgA get across epithelial cells
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transcytosis
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what types of body fluids is IgA found in
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tears, saliva, mucus, breast milk
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is igm found intravascular? Extravascular
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yes, no
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when igm is present on b cell surface, is it monomer?
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yes
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what antibody is important in killing worms
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IgE
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what antibody activates eosinophils
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IgE
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thymus-dependent vs independent antigens
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1. dependent antigens have protein component, and thus can be presented by mhc 2. dependent antigens thus stimulate class switching and immune memory whereas independent does not
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do babies gain immunity from IgGs found in breast milk?
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no, only iga's are found in milk
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what activates alternative vs classic pathway
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igm/igg activates classic pathways. Microbial surface proteins activate alternate pathway
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what are the two opsonins in bacterial defense
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c3b, igg
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what factor helps to clear immune complexes
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c3b
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other names for decay accelerating factor
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cd55, cd59
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what factors help to prevent complement activation on self
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daf, c1 esterase
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what complement factors help to neutralize virus
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c1,2,3,4
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what complement factors are involvemed in anaphylaxis
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c3a, c5a
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deficiency of what factor is implicated in recurrent neisseria infection
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c5-c8
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deficiency of what factor is implicated in hereditary angioedema
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c1 esterase
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deficiency of what factor leads to recurrent severe pyogenic sinus and respiratory infections
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c3
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what complement factor is involved in neutrophil chemotaxis
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c5a
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Ham's test can dx
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PNH (rbc's lyse at lower pH)
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how is DAF anchored to RBC
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GPI anchor (not transmembrane)
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does lectin on microbial surfaces activate classic or alternative pathway
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classic
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complement proteins involved in alternative vs classic
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alternative: C3 starts off right away. Classic: C1, C2, C4
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what can decrease il1 levels
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estrogen, testosterone
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2 functions of IL6
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1. pyrogen 2. induces APP's
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what cytokine functions like GMCSF
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IL3
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what cytokine is critical in TB infection
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IL12
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2 functions of IL12
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1. Th1 formation 2. NK activation
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what cell secretes il1
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macrophage
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what cell secretes il6
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macrophage, Th
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what cell secretes il8
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macrophage
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what cell secretes il12
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macrophage, B cell
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what cell secretes tnfalpha
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macrophage
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3 functions of tnfalpha
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1. activates endothelium like il1 2. recruits leukocytes 3. vascular leak
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what cell secretes il3
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t cells
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function of il3
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stimulates bone marrow
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3 functions of il1
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1. pyrogen 2. activates endothelium 3. induces chemokine secretion to attract lymphocyte
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what cell secretes il2
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th1
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what cell secretes ifngamma
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th1
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function of ifngamma
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1. activates m0 and th1 2. suppresses th2 3. m0 needs ifngamma to activate respiratory burst
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function of il4
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1. th2 diffentaiton 2. b cell growth 3. class switching to igg/e
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function of il5
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1. stim b cell 2. class switch to iga 3. activate eosinophil
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what 2 cytokines help to resolve inflammatory response
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il10, tgfbeta
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function of il10
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1. stops th1 2. activates th2
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what cells secrete il10
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th2, treg
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mechanism of interferon
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induce production of ribonuclease that inhibits viral mRNA
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what is ifnalpha used to treat
|
hep B&C, Kaposi, MM, leukemia
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what is ifnbeta used to treat
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ms
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what is ifngamma used to treat
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cgd
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function of alpha and beta ifn
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inhibit viral protein synthesis, activate nk
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function of ifn gamma
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increase mhc expression and antigen presentation
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what are important neutrophil chemotactic factors
|
CILK = c5a, il8, ltb4, kallikrein
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why is fever a useful inflammatory response
|
1. increased temp right shifts hc curve and more o2 for burst 2. increased temp slows growth of organisms
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what is CD3 expressed on
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t cells
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what cell expresses: CD28
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T cell
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what cell expresses: CD4
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Th
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what cell expresses: CD19
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B
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what cell expresses: CD8
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Tc, Tsupp
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what cell expresses: cd20
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B
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what cell expresses: cd40
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B, M0
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what cell expresses: cd21
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B
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what cell expresses: b7
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B, M0
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what cell expresses: cd14
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M0
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what cell expresses: C3b-receptor
|
M0
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what cell expresses: MHCI receptor
|
NK
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what cell expresses: CD16
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NK
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what cell expresses: cd56
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NK
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what cell expresses: CD1
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histiocyte
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what cell expresses: CD45
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all leukocyte
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what is anergy
|
self reactive T cells become nonreactive without costim
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anergy in b cell vs t cell
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b cells can be anergic but tolerance is less complete
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mechanism of superantigen
|
cross linking of beta unit of tcr to mhc2 -> leads to ifngamma from T cell -> Il1, il6, tnf from m0
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what is the endotoxin receptor
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cd14
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are th cells involved in endotoxin response? How?
|
no, because lps stimulates cd14 directly
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name 3 bacteria that have antigen variation
|
salmonella, borrelia, neisseria
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name a parasite that has antigen variation
|
trypanosoma
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give some examples where passive immunity is administered
|
tetanus, botulinum, hbv, rabies, rsv inbabies
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|
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3 immunologic markers of infection
|
1. absolute neutrophilic leukocytosis 2. toxic granulation in neutrophils (more myeloperoxidase) 3. left shift (more band cells)
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what type of hypersensitivity triggers vasoactive amines
|
1
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how to dx hs1
|
scrach test, radioimmunosorbent assay
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how to dx hs2
|
direct and indirect coombs
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what causes dmg in hs2
|
complement activation, phagocytosis of self
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what causes dmg in hs3
|
deposition of ic attracts neutrophils, which blow up
|
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what is serum sickness
|
foreign ag triggers ab response, which forms ic and results in deposition
|
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what is arthus rxn
|
intradermal injection of ag induces abs which form Ics IN THE SKIN
|
|
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timeline of serum sickness vs arthus
|
arthus = 5-12h. Serum sickness = 5d
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mcc of serum sickness
|
drugs
|
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dx for hs3
|
IF
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which cytokines are involved in granuloma formation in hs4
|
ifngamma (activates macrophage to kill), macrophage inhibitory factor (helps macrophage to form giant cell)
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what type of hs: hemolytic anemia
|
2
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what type of hs: sle
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3
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what type of hs: pernicious anemia
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2
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what type of hs: dm1
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4
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what type of hs: ms
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4
|
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what type of hs: ITP
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2
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what type of hs: RA
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3
|
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what type of hs: polyarteritis nodosum
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3
|
|
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what type of hs: erythroblastosis fetalis
|
2
|
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what type of hs: acute hemolytic transfusion rxn
|
2
|
|
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what type of hs: rheumatic fever
|
2
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what type of hs: guillain barre
|
4
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what type of hs: hashimoto
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4
|
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what type of hs: goodpasture
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2
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what type of hs: bullous pemphigoid
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2
|
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what type of hs: pemphigus vulgaris
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2
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what type of hs: poststreptococcal glomerulonephritis
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3
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what type of hs: serum sickness
|
3
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what type of hs: arthus rxn
|
3
|
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what type of hs: graft vs host
|
4
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what type of hs: graves
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2
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what type of hs: myasthenia
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2
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what type of hs: hypersensitivity pneumonitis
|
3
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what autoimmune dz is associated with this: Smith
|
sle
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what autoimmune dz is associated with this: antihistone
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drug induced lupus
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what autoimmune dz is associated with this: anti-IgG
|
ra
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what autoimmune dz is associated with this: centromere
|
crest scleroderma
|
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what autoimmune dz is associated with this: scl70
|
systemic sclerosis
|
|
|
what autoimmune dz is associated with this: antimitochondrial
|
1* biliary cirrhosis
|
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what autoimmune dz is associated with this: gliadin
|
celiac
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what autoimmune dz is associated with this: antiendomysial
|
celiac
|
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what autoimmune dz is associated with this: BM
|
goodpasture
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what autoimmune dz is associated with this: desmoglein
|
pemphigus vulgaris
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what autoimmune dz is associated with this: microsome
|
hashimoto
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what autoimmune dz is associated with this: thyroglobulin
|
hashimoto
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what autoimmune dz is associated with this: jo1
|
polymyositis, dermatomyositis
|
|
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what autoimmune dz is associated with this: ro
|
sjrogren
|
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what autoimmune dz is associated with this: la
|
sjogren
|
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what autoimmune dz is associated with this: ssa/ssb
|
sjogren
|
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what autoimmune dz is associated with this: u1 rnp
|
mixed connective tissue dz
|
|
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what autoimmune dz is associated with this: smooth muscle
|
autoimmume hepatitis
|
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what autoimmune dz is associated with this: glutamate decarboxylase
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dm1
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what autoimmune dz is associated with this: antiproteinase 3
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wegeners
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what autoimmune dz is associated with this: antimyeloperoxidase
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other vasculitis (churg strauss, microscopic polyangiitis)
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what autoimmune dz is associated with this: canca
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wegeners
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what autoimmune dz is associated with this: panca
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other vasculitis (churg strauss, microscopic polyangiitis)
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what autoimmune dz is associated with this: AchR
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myasthenia
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what autoimmune dz is associated with this: TSHr
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graves
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what is defect in bruton's agammaglobulinemia
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btk (needed for b cell differentation)
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inheritance of brutons
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xr
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recurrent bacterial infections after 6 mo postpartum
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brutons
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severe pyogenic infections early in life
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hyper igm syndrome
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number of pro B cells in brutons
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normal
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number of mature b cells in brutons
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decreased
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number of ig's in brutons
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decreased
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defect in hyper igm syndrome
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no cd40L (no class switch)
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what types of igs in hyperigm syndrome
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lots of igm, but decreased igg, iga, ige
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what is defect in selective ig defidiency
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can't isotype switch to some classes (iga most common)
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most common selective ig deficiency
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iga
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what type of infection in selective ig deficiency
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sinus & lung infection, milk allergy, diarrhea
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anaphylaxis on exposure to blood product w/ iga
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selective iga deficiency
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when does common variable immunodeficiency present
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20's - 30's
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number of mature b cells in common variable immunodeficiency
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normal
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number of plasma cells in common variable immunodeficinecy
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decreased
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defect in thymic aplasia
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no pharyngeal pouch 3/4 (22q11) means no T cells
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absent thymic shadow on cxr
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thymic aplasia
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types of infections seen in t cell deficiency
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viral/fungal/opportunistic
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defect in hyper ige syndrome
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can't make ifn gamma
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sx of hyper ige syndrome
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FATED: course faces, cold staph abscess, retained primary teeth (two rows), increased IgE, dermatologic problems (eczema)
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what is chronic mucocutaneous candidiasis
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t cell dysfunction with repeated c albicans infections
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3 common types of scid
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1. no il2r (xr) 2. ada deficiency (ad) 3. can't make mhc2 antigens
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why is bm transplant easy to do in scid
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no allograft rejection
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defect in ataxia-telangiectasia
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defect in DNA repair enzymes (risk of malig)
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triad of ataxia telangiectasia
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ataxia (cerebellar defect), telangiectasia (spider angioma), iga deficiency
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inheritance of wiskott aldrich
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xr
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triad of wiskott aldrich
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TIE: thrombocytopenia, infeciton, eczema
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what is jobs syndrome
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hyper ige syndrome
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what kinds of labs in wiskott aldrich
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DECREASED IGM, more ige and iga
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what is special about eczema in wiskott aldrich
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non flexor surface
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what is cd18
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LFA-1 integrin found on phagocytes
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sx of lad1
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recurrent bacterial infection, no pus formation, delayed umbilicus seperation
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neutrophil count with lad
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increased (demarginated)
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defect and inheritance of chediak higashi
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ar - defective microtubules
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sx of chediak higashi
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1. recurrent pyogenic infection (staph strep) 2. pt albinism 3. peripheral neuropathy
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defect in chronic granulomatous dz
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lack of nadph oxidase (can't make ROS)
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how to dz cgd
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negative nitroblue tetrazolium dye reduciton
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inheritance of cgd
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xr
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inheritance of myeloperoxidase deficiency
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ar
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what is a syngeneic graft
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graft from identical twin or clone
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what type of hs is hyperacute rejection
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2
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what type of hs is acute rejection
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2,4
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what type of hs is chronic rejection
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2,4
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timeline of rejection
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hyperacute = minutes. Acute = weeks. Chronic = months - years
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vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
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acute rejection
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is acute or chronic rejection reversible
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acute is, chronic isnt
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obliterative vascular fibrosis in graft
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acute rejection
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fibrosis of vessels AND graft tissue
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chronic rejection
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sx of graft vs host
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maculopapular rash, jaundice, hsm, diarrhea
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what transplants is graft vs host more common in and why
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bm, liver cuz richer in lymphocytes
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acute vs chronic rejection in patterns of dmg
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acute has more vascular dmg, chronic has more tissue dmg
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mechanism of cyclosporine
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binds to cyclophilins which blocks calcineurin, which decreases il2 and its receptor
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use of cyclosporine
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transplant rejection, autoimmune dz
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how can you prevent nephrotoxicity from cyclosporine
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mannitol
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risk of what is increased with cyclosporine
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viral infection, lymphoma
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mechanism of tacrolimus
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binds to FK protien which inhibits mTOR, which decreases il2
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toxicity of tacrolimus
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nephro, peripheral neuropathy, htn, pleural effusion, hyperglycemia
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mechanism of sirolimus
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just like tacrolimus, binds to FK, inhibits mTOR, decreases IL2
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mechanism of daclizumab
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monoclonal ab vs il2r
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mechanism of azathioprine
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precursor of 6mp
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tox of azathiprine
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bm suppression, don't use with allopurinol
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what is okt3
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muromonab
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what is muromonab
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monoclonal ab vs cd3
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what does cd3 do
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signal transduction on t cells
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what immunosuppression drugs are used mainly for kidney transplant
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sirolimus , muromonab
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what is filgrastim
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gcsf analog
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what is sargramostim
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gmcsf analog
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what is aldesleukin? Use?
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il2 analog, for rcc and mm
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what is oprelvekin? Use?
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il11 analog, for thrombocytopenia
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what is thrombopoeitin? Use
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used for thrombocytopenia
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what is mycophenylate mofetil? Use?
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blocks imp dehydrogenase. Used in lupus and transplant
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what is adalimumab
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tnf-alpha antibody
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what is abciximab
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antibody vs glycoprotein 2b/3a
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what drug previously used for motion sickness can be used for immunosuppresion? Mechanism
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thalidomide, tnf inhibition
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will interferon activate virus specific cellular immunity
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no, only innate immunity
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what step of differentiation is blocked in brutons
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proB -> preB
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deficiency of cd14 would affect what cell? what type of infections?
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cd14 = endotox receptor on m0. see more gnrs
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people with selective ig deficiency tend to have what coexisting dz
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atopic allergy
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what immunodeficiency is associated with risk of autoimmune dz, lymphoma, and sinopulmonary infection
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cvid
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what immunodeficiency is associated with milk allergy and diarrhea
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selective ig deficiency
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