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78 Cards in this Set
- Front
- Back
what is special about splenic marginal zone B cells?
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they have a repertoire of BCR that is heavily biased toward bacterial cell wall components
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what B cells are particularly important for T independent responses?
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marginal zone b cells (for encapsulated bacteria)
B-1 B cells (create no memory cells, located at peritoneum and |
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what is the B cell response to low and high concentrations of type 1 T-independent antigen (i.e. LPS)
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at low concnetrations a small amount of MONOCLONAL Ab is produced.
at high concentrations, your innate TLR4 induces secretion of polyclonal B cell antibodies to various Ag of the bacteria |
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how do B cells get a robust response to type 2 T-independent antigens?
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repeated polysaccharides structures are able to cross link multiple BCRs
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why are young kids susceptible to infection by encapsulated bacteria?
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for whatever reason, they can't mount effects T independent responses to type 2 antigens
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what cells secrete the majority of interleukins?
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CD4 helper T cells
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CD4 T cells only respond to antigen bound to...
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MHC class II
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what are the MHC gene loci like?
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they are polygenic and polymorphic
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what cells express MHC I and what cells express MHC II?
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MHC I expressed by all cells (any cell is a potential target of a CD8)
MHC II is only expressed by professional Ag-presenting cells (dendritic cells, B cells, macrophages) |
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which MHC class is important in Tissue transplantation?
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MHC class I
(MHC II also helps) |
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what 2 signals are ABSOLUTELY required for T-cell activation?
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1. TCR and peptide:MHC II interaction
2. CD 28 (on T) and CD80/86 (on APC) |
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what is the concept of linked recognition
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the BCR and the TCR must be able to recognize different parts of the same antigen
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how does linked recognition happen?
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clonally expanded B-cell presents antigen to CD4 T cells on MHC II
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what is the germinal center?
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a region in 2nd lymphoid organs where B cells are undergoing somatic hypermutation (most die, but a couple are extra sensitive. Those have undergone "affinity maturation")
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what are centrocytes?
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B cells that have received T cell help and are in the germinal center undergoing somatic hypermutation
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what Ab isotype is produced by B cells that have undergone affinity maturation?
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IgG
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what is the cause of immunodeficiency in nu/nu "nude" mice?
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no "whn" gene results in no epithelial differentiation => no thymus develops
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what is the cause of immunodeficiency in scid/scid mice?
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defect in Ag receptor gene rearrangement. No T or B cells develop in bone marrow
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how can you combine nu and scid mice to get normal immune system?
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bone marrow from nude mice to scid mice
or give thymus of scid mice to nude mice |
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what is teh path of T cells through teh thymus as they mature?
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they go from the cortex (immature) and some die as they move inward toward the medulla, where they exit to peripheral lymphoid organs
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what are the two regions of the TCR?
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2 chains, each with a V-region and a c-region
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what is the mature TCR complex?
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the TCR associates with CD3 (the signaller)
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What formula is good for distention and pain in the epigastrium, due to excess with tidal fever?
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Da Chai Hu Tang
Shao Yang and Tai Yang |
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how does positive selection work/
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MHC I and MHC II positive cells in the cortex express all self proteins and present them, those with some affinity mature further
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what is the caused of APECED autoimmune disease?
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loss of "aire" gene which allows thymic cells to express all self proteins
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why is the negative selection pattern reversed in the periphery?
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because now you want very high affinity binding to lead to lots of cell signalling, not apoptosis
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what happens in the event of low affinity binding of the TCR in the periphery?
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it is ignored because you can't count on the T-cell getting exposed to all self antigen in the thymus
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what is the main determining factor of the TCR repertoire?
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the MHC (because only those TCR that can bind MHC are selected)
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what is unique about professional APCs that makes them able to present well to T-cells?
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they express MHC I, MHC II, AND costimulatory molecules (CD80,86)
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what are the most potent APCs?
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dendritic cells
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what is the difference between mature dendritic cells and immature dendritic cells?
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immature: high phagocytic, low MHC and low co-stim (low CD80 and CD86)
mature: low phagocytic, high MHC and high co-stim (CD80 and CD86 |
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how are endogenous and exogenous antigen different? and how are they presented differently?
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endogenous proteins are viral, made by self machinery, expressed on MHC I (to CD8 killler)
exogenous proteins are from phagocytosed microbes, expressed on MHC II (to CD4 helper) |
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what is the functional difference between Th1 and Th2 CD4 cells?
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Th1 promote cellular immunity
Th2 promote humoral immunity |
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what is the most likely result if your T cells get "signal 1" without "signal 2"
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anergy
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what are the possibilities for "signal 2" for T cell activation?
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B7, CD80 or CD86 can be expressed on teh APC
CD28 is constituitively expressed on T cell CTLA-4 is very high affinity for B7, is only expressed AFTER activation leading to inactivation |
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what is the functional difference between B7 (on APC) binding to CD28 (on T cell) versus B7 binding to CTLA-4?
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B7:CD28 leads to T cell activation
B7: CTLA-4 inactivates the T cells after the job is done (by reducing IL-2 production) |
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what cytokine is most important for clonal expansion of activated T-cells?
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IL-2 (induces mitosis, and is produced by activated T cells leading to more mitosis)
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how is the activation of memory T cells different than naive T cells?
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for CD8 memory T cells, signal 2 is NOT required
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what cytokines do Th1 CD4 T cells release?
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IFN-gamma
TNF |
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what cytokines do TH2 CD4 T cells release?
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IL-4, IL-5, IL-10
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what cytokines drive CD4 cells toward Th1 and Th2, respectively
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IL-12, IFN-gamma toward Th1
IL-4, IL-10 toward Th2 |
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do CD8 (CTLs) need 2 signals in order to mediate effector function?
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no, they only need their antigen on MHC I
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what cytosolic proteins are released by CTLs to induce apoptosis?
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perforin, granzymes, and Fas ligand
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what are SMACs (Supramolecular Adhesion Complex)
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the organelles of CTLs line up in the CTL cytoplasm right next to the target cell in order to release and kill it
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how do Th1 cells mediate their function?
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they express CD40L and bind CD40 on the macrophage to induce killing of phagocytosed microbes
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what is the main antinflammatory cytokine?
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IL-10
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how are Th2 cells partly responsible for some allergic reactions
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Th2 cells induce expression of IgE and promote produciton of eosinophils
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how are Th1 cells responsible for delayed type hypersensitivity reactions?
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they overactivate in response to antigen, not just to macrophages
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what are the 4 steps of CTL effector function?
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adhesion (via integrins)
granule release (perforin, granzymes) apoptosis CTL leaves and roams for other cells to kill |
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what is the key issue for recognition of tumor cells by CD8 T cells?
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if they recognize the altered self proteins and
if they receive signal 2 (B7-CD28) |
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what is Activation Induced Cell Death (ACID)?
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Fas and Fas ligand are upregulated with activation, but the T cell only has a 4-5 day window during which it is resistant to apoptosis
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what allows T cells to be resistant to their own Fas and Fas ligand during activation?
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the expression of FLIP (fas ligand signal blocker)
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what are the cell markers on Regulatory T cells
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CD4, CD25, FOXP3
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what are the key marker's on NK cells?
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CD16 (an Fc receptor), CD56
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how do NK cells decide whether or not to kill a cell?
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if it doesn't have MHC class I, it kills the cell
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what cells have low levels of MHC class I?
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virally infected cells, tumor cells
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what are the effector mechanisms of NK cells?
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perforin and granzymes (just like CD8 T cells)
induction of apoptosis Antibody dependent cellular cytotoxicity (CD16, an Fc receptor, recognizes IgG Ab) |
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what are lymphokine activated killer cells?
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a type of NK cell that kills with or without MHC class I
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what is diapedesis?
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movement of leukocytes across blood vessel wall into tissue through an endothelial monolayer
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what are the structural similarities of chemokines?
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a 4-cysteine motiff, 60-140 motif
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what is the main function of induced chemokines vs. constituitive chemokines?
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induced: mediating local inflammatory response
constituitive: development, maturation, adaptive immune responses |
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what type of receptors are chemokine receptors?
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they are GPCRs
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what are the major classes of chemokines?
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CC and CXC (C: cysteine, X: some AA)
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what is the function of CCR7 and when is it expressed?
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it guides T and B cells to the secondary lymphoid tissue, it is expressed on naive T/B, downregulates after activation
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what is the function of CXCR3 and when is it expressed?
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guides Th1 cells to sites of inflammation and is expressed after T cell activation
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what Selectin:Addressin binding leads to rolling of WBCs on endothelium?
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L-selectin on neutrophils binds CD34 on endothelium
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what selectin:ligand binding leads to diapedesis in secondary lymphoid tissue of naive lymphocytes
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L-selectin binds GlyCAM-1 on HEV
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what integrin interaction allows leukocytes to integrate at endothelium
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LFA-1 on leukocytes binds ICAMs on endothelium
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what interactions result in leukocyte rolling and arrest?
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rolling: selectin:addressin
arrest: LFA:ICAM |
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what is the role of IL-8 in neutrophil diapedesis?
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IL-8 secreted by inflamed tissue binds the IL-8R on neutrophils.
binding of IL-8R changes conformation of LFA-1 so it binds ICAM-1 better |
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what interaction mediates rolling at the HEV?
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L-Selectin (lymphocyte)
binds GlyCAM-1 on HEV |
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what interactions medate arreset at the HEV?
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CCL21 (constituitively expressed chemokine at HEV) is bound by CCR7 on lymphocyte
that induces change in LFA-1 increased affinity for ICAM-1 |
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how is the spleen unique as a lymphoid organ
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it is the only lymphoid organ (it is 2ndary) which has no lymphatic ducts. lymphocytes enter and leave directly from blood stream
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what triggers an immature dendritic cell to mature?
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a danger signal (TLR4) so that the antigen it has taken up is broken down and loaded onto MHC I and II
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what changes in mature dendritic cells favor activation of naive CD4 T cells?
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increased MHC
increased co-stim secrete CCL18 (attracts naive T cells) |
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how do TCR:Ag and BCR:Ag interactions facilitate linked recognition between B and T cells?
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binding of each downregulates CCR7 and upregulates CXCR5 which move them toward each other, at the intersection between the B cell follicle and the T cell area
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what cells express CD40L and when do they express it?
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CD40L is expressed only on CD4 T cells. It is only expressed when activated, otherwise you would have hyperactive macrophages causing lots of tissue damage with their ROS and such
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what does IL-8 do?
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it acts on NEUTROPHILS increases the affinity of LFA-1 for ICAM
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