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87 Cards in this Set
- Front
- Back
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What are 3 of 5 differences between systemic and mucosal immunity?
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anatomy: immunogen from epithelium
nonspecific factors: for gut only Ab is sIgA major and sIgM minor |
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What are two differences between systemic and mucosal immunity?
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T cells: mucosal specific immunity
Homing system: selective homing to diffuse lymph tissue |
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Where is diffuse lymphoid tissue located?
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mucosal lamina propria
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What are the three main locations of GALT?
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Peyer's patches - t and b cells
Lamina propria - many IgA producing B cells Intraepithelial lymphocytes - lymphocytes between epithelial and under tight junctions |
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What are M cells?
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specialized flattened epithelial cells that pinocytose material from the overlying lumen and transport it to the epithelial cells
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What are nonspecific factors operating with mucosal immunity?
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Mechanical, chemical and mirobiological
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What transmembrane proteins form tight junctions?
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claudin and occludin
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What is the most abundant mucosal Ig?
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IgA - subclass 1 dominates in serum and subclass 2 dominates in secretions
sIgA is resistant to proteolysis |
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How is sIgA antiinflammatory?
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does not activate compliment by either classic or alternate pathways
Binding to neutrophils and phagocytes inhibits phagocytosis NET EFFECT: prevent colonization by pathgens without inducing inflammation |
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How do Tcells regulate IgA synthesis?
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1 Activated Tcells interact with IgM expressing Bcells
2 TGF beta and tcell interactions with bcells induce class switching to IgA |
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what cytokines cause production of sIgA?
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TGF beta causes class switching
Similar to IL-10 as an anti-inflammatory |
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How does sIgA get across epothelium?
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Part of the poly Ig receptor remains bound to sIgA and this part helps it cross as well as stay stuck to the membrane
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What is transcytosis?
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movement of macromolecules from one side of a cell tothe other via receptors
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What is immune exclusion?
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restricts immune responses to mucosal immunogens to the mucosal lyphoid system
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sIgA deficiencies show what?
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increased abs of macromolecules and high levels of immune responses following ingestion of immunogens
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IgM in the mucosal immune system?
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can replace IgA in individuals with Ig deficiency
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IgG in the mucosal immune system?
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not effectively transported across epithelium
Synthesized in large amounts in distal respiratory tract IMPORTANT for pulmonary secretions |
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Describe mucosal homing
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lymphocytes activated in mucosal follicles AFFERENT move to EFFERENT areas like diffuse lymphoid tissues
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Mechanism of mucosal homing for lymphocytes
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integrin alpha4beta7 binds MadCAM-1 on endothelial cells
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Mucosal homing for intraepithelial lymphocytes
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integrin alphaEbeta7 binds epithelial cadherins
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What is oral tolerance?
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it is the suppression of immune cell responses to Ag introduced from the oral route
Failure: crohn's disease or ulcerative colitis |
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what are the mechanisms of oral tolerance?
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regulatory Tcells Treg secrete TGF beta
Induction of tcell anergy and deletion of autoreactive Tcells |
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what Ig is in mother's milk?
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sIgA is a passively transferred immunity
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What are immune factors in mother's milk?
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lysozymes, lactoferrin, Activated leukocytes
Lactadhedrin protects against rotavirus MUCIN-1 protects against ecoli |
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Where is cell mediated immunity most important?
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facultative intracellular infect
obligate intracell infect cellular Ag usually intracellular |
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Where is Ab mediated immunity most important?
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molecular Ag
Extracellular infections usually extracellular |
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What are the major products of Tcells?
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cytokines - not specific
effector t cell is specific for antigen |
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What surface molecules are expressed on all t cells?
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TCRs and CD3
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what enzyme helps construct t cell receptor genes?
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VDJ recombinase
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What are the major locations of t cell development?
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stem cells = bone marrow
thymocytes - thymus peripheral tcells in lymphoid tissue |
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What is positive selection of Tcells?
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promotes survival of tcells that recognize peptides complexed to self-mhc
do not recognize self mhc - do not survive |
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what is negative selection of Tcells?
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deletion of thymocytes whose tcrs recognize peptides derived from self-proteins
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what are double negative thymocytes?
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cells that express neither cd4 or cd8
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what are double positive t cells?
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cells that express both cd4 and cd8
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Describe the first phase of tcell development
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double negative thymocytes undergo stimulation to double positive thymocytes
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2nd phase of tcell development
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double positive thymocytes express cd3 and undergo positive selection
leads to single positive tcells |
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3rd phase of tcell development
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double positive thymocytes undergo negative seletion for self reactivity
then leave thymus and enter blood |
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What are similarities between tcell receptors and antibodies
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amino terminal variable region
variable and constant in each chain |
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Differences between antibodies and t cell receptors
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monovalent vs. divalent
Ag vs. Ag/MHC recognition tcr - 55000mw Ab - 150-190000mw |
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What are gamma delta tcells
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major pop of intraepithelial lymphocytes
Doesn't need MHC! cytotoxic esp to tumor cells |
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Do tcr genes undergo somatic hypermutation?
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no
alpha chain - VJ beta chain - VDJ |
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main role of th1 cells
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Th1 - activate tissue macrophages to eat and kill extracellular pathogens
secrete cytokines |
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main role of Th2 cells
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stimulating b cells to make Ab which bind to extracellular bacteria and virus particles
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What is a super Ag?
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certain bacterial toxins that bind MHC class II and TCR without Ag processing
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Where do super ag's bind
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outside the peptide binding region of class 2 and to the variable beta side of TCR
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process of super ag destruction
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profound immune stimulation without costimulation
profound immune suppression from anergy or apoptosis |
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mechanism of toxic shock
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massive t cell activation and the resulting cytokine release contributes to the pathology of TSS
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what is the result of stimulation of the tcell without costimulation
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anergy - absent or decreased response to an immunogen
can be persistent mechanism of peripheral tolerance to self |
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Which cytokine is responsible for clonal expansion of tcell in 1' response and who produces it?
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IL-2 is produced by T helper cells
IL-2R are not on resting tcells They appear on activation of tcell |
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name cytokines produced by Th0 cells
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secrete interferon gamma and IL-4
depending on other cytokines, they will change into Th1 or Th2 |
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cytokines produced by Th1 cells
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stimulated by IL-12
make IL-2, interferon gamma, and TNFbeta |
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How do Th1 cells benefit macrophage response?
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enhances intracell killing
induces isotype switch in b cells to IgG1 for which macrophages have a receptor (Fc gamma) |
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cytokines produced by Th2 cells
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stimulated by IL-4
make IL-4, 5, 6, 10, 13 |
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What do Th2 cells promote?
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growth and differentiation of various inflammatory cells (mast cells, basophils, and eosinophils)
Class switch to IgE |
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what 2 cells mutually inhibit each other and the balance between 2 is specific
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Th1 and Th2
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What are Treg cells?
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inhibitory for inflam response
secrete IL-10 and TGF beta allergy - good for tolerance cancer - bad because they turn off anti-tumor response |
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describe Th17 cells
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promote inflam
make IL-17 hallmark of chronic inflammation IL-23 promotes their development |
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How do CTL kill target cells?
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lysis -- perforins released by CTL
apoptosis -- Fas-ligand on CTL activates FAS-receptor on Target cell |
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What cells are targeted by CTL?
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virus infected cells, cells infected with other intracell pathogens, allografts
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What accounts for most of the 2' characteristics of the Tcell response?
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the increased number of antigen reactive cells that accounts for most of the characteristics of the 2' immune response
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What is the most important NK cell receptor? describe the activation
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Fcgamma receptors
ADCC - Antibody Dependent Cell mediated Cytotoxicity 2 receptors needed for crosslink activation activation = lytic granule release |
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Describe NK cells
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not immunogen specific and not MHC restricted
Generally inhibited by MHC class I First line of defense |
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Define cytokines
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cytokines are intercellular regulatory proteins produced by many different cells that ultimately control every aspect of the body's defenses
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cytokine properties
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low mw proteins
extremely potent autocrine or paracrine, minor endocrine functions pleitropic - different effects on different target cells |
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3 ways of coping with pleiotropy
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1 only activated cell expresses receptor
2 limited ratius of effectiveness 3 short half life |
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Describe costimulation using CD28 and B7
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CD28 is on tcell and binds to B7 on APC cell to cause costimulation
without costim, the T cell becomes anergic |
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describe IL-1 production and function
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produced by APC's
stimulates T helper cells similar to TNF alpha Induces ICAM expression chemotactic |
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IL-2 production and function
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produced by Th1 cells
stimulates tcell proliferation and activation enhances cytoxicity of NK cells and CTL |
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IL-3 production and function
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produced by T cells and NK cells
stimulates growth factor for hematopoetic cells |
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IL-4 production and function
IL-5 |
produced by Th2 cells and mast cells
stimulates proliferation and differentiation of B cells Induces IgG to IgE promotes Th2 proliferation and mast cell growth |
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IL-6
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produced by Th2 cells
aids in Bcell development Proinflammatory Wound healing aids Th2 mediated events |
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IL-8
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produced by macrophages
also known as CXCL8 chemoattractant for neutrophils and tcells |
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IL-10
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Produced by Th2 and Treg cells
Anti-inflammatory similar to TGF beta |
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IL-17
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produced by Th17 cells
proinflammatory |
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Interferon alpha and beta
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produced by all cells
antiviral properties well known for induction of MHC class I on all somatic cells |
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Interferon Gamma
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produced by Th1 cells, CTL, and NK cells
enhances macrophage activity and pushes production to IgG |
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TNF alpha
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produced by macrophages, Th1, and mast cells as well as almost all other cells
stimulates acute phase of inflam causes cytokine secretion by inflammatory cells |
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TNF alpha is similar to what interleukin and which cells have receptor for TNF alpha
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Similar to IL-1
all nucleated cells have receptors for TNF alpha |
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TGF beta
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produced by Treg cells
stimulates antiinflam response similar to IL-10 |
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CSF
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colony stimulating factors
promote formation of colonies of myeloid lineage in bone marrow |
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how are chemokines different from cytokines
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different from other cytokines due to
1 bind to vascular bed like adhesion molecules 2 may bind to one or several chemokine receptors |
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IL-12
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produced by macrophage
stimulates T cells into Th1 cells activates NK cells |
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CXC vs. CC
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CXC have 2' structural motif
ELR+ -- acute inflam ELR- -- chronic inflam CC aka beta chemokines |
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Major families of cytokine receptors
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Ig superRF
Hematopoietin RF INF RF TNF RF Chemokine RF |
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IL-2 receptor
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NK cells express beta-gamma - mid affinity
Tcells have gamma only the alpha subunit is inducible |
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Th1 cells make what cytokines?
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IL-2 INF gamma and TNFbeta
promote macrophage mediated response |
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Th2 cells make what cytokines
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IL-4 IL-5 IL-6 IL-10
promote some allergic reactions and responses to some extracellular pathogens |
