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125 Cards in this Set
- Front
- Back
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The portion of the TCR which is invariant; the same from cell to cell
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CD3 and zeta chains
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The TCR cannot be expressed on the cell surface without
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CD3
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the form of the Ab which recognizes the antigen
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membrane-bound Ig
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the form of the Ab which eliminates the Ag in the effector phase
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secreted Ig
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required for structural integrity and effector functions
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constant domains which are conserved among clones
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has one V and 3-4 C regions depending on the Ab
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the heavy chain
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the Fc is involved in
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effector functions
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the FAB is involved in
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Ag recognition
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the two types of Ab light chains do not differ in their
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function
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isotypes differ in their
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physical and biological properties and effector functions
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Ag-Ab interactions require
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noncovalent interactions
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allows the two Ag binding FAB regions to move allowing them to bind epitopes further away
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hinge region
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ability of an Ab site to react with only one Ag epitope
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specificity
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when an Ab binds to a structurally similar Ag
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cross-reactivity
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coreceptors of the TCR
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CD4 or CD8
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T-cell activation requires coreceptors binding to
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nonpolymorphic regions on MHC molecules
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bind the greatest variety of Ag with highest affinity (low concentrations required for neutralization)
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Ab
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the reason accessory molecules are required for T-cell activation
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the affinity of TCR's is low
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3 processes involved in lymphocyte maturation, common for both B and T cells
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proliferation
expression selection |
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proliferation of immature lymphocytes is stimulated by __, made in the stromal cells
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IL-7
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B/T cell with no portion of receptor
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pro-B/T cell
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B/T cell which expresses one chain of Ag receptor (1/2 of the receptor)
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Pre-B/T cell
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B/T cell which delivers signals for proliferation
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Pre-B/T cell
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B/T cell which expresses the complete Ag receptor
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Immature B/T cell
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Mature B/T cells which do NOT recognize self Ag are said to undergo
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failure of position selection
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the diversity of the expression of B/T Ag receptors is generated during
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somatic recombination of gene segments which code for V regions
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only the Ig heavy chain and the TCR-beta loci contain; whereas ALL Ag receptors contain V, C, and J genes
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diversity (D) gene segments
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limited by the no. of V, D, and J genes in the genome
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combinatorial diversity
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diversity of Ag receptors is maximized by
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unlimited junctional diversity
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process of adding or removing nucleotides from V, D, J segments of genes
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junctional diversity
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hallmark of pre-B cells
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expression of cytoplasmic mu heavy chain
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each B cell only expresses Ig from one of the two inherited parental alleles
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allelic exclusion
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assures that B cell expresses receptors of a single specificity
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allelic exclusion
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immature B cells must express __ to survive
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functional IgM (complete heavy and light chains)
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designates a mature B cell capable of responding to Ag in the peripheral lymphoid tissue
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coexpression of IgM and IgD
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if a B cell binds to self Ag with high affinity and DOES NOT undergo apoptosis; this can occur
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reactivation of recombinase for a second (different)light chain; receptor editing
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progenators of T cells which do not express CD4 or 8
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pro-T cells or double-negative T cells
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double-negative T cells must express _ to survive
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TCR beta chain
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after the beta chain of the T cell is expressed; allelic exclusion occurs and subsequently
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the alpha chain is formed
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the T cell which expresses the beta chain only
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the pre-T cell
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double-positive immature T cells express
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CD4 and 8 and complete alpha and beta chains
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weak recognition of class II MCH and peptide by a double-positive immature T cell yields
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mature CD4+ (single-positive T cell)
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role is to combat infections by INTRACELLULAR microbes
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cell-mediated immunity, mediated by T lymphoctyes
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two ways microbes can enter cells
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phagocytosis
viruses bind and replicate in cytoplasm |
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where naive T lymphocytes first encounter processed protein Ags
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peripheral lymphoid organs
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once a T cell recognizes an Ag it responds by
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producing cytokines which bind on the T cell's own cytokine receptors; this leads to proliferation
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IL-2 is a
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cytokine
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IL-2 binding to the IL-2 receptor on the T cell leads to (along with 1st and 2nd signals)
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rapid clonal expansion
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when naive T cells become effector cells
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differentiation
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the immune system returns to basal resting state once
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Ag is eliminated and effector T cells die
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coreceptors recognize
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MHC molecules (rather than peptides)
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recognize ligands B7-1/B7-2 on APCs
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CD28 on the Helper T cell
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LFA-1 receptor on the T cell binds __ to strengthen the binding to APC
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ICAM-1
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TCR is clonally distributed while __ are exactly the same from cell to cell (invariant)
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accessory molecules
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provides the first or initiating signal for T cell activation
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CD4/8 binding to MHC molecule
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CD4 coreceptor only recognize __ and will only bind
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extracellular Ag, MHC class II
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ensure that the correct T cells respond to the correct types of microbes
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CD4/8 specificities for different MHC molecules
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2nd signals required for T cell activation
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costimulators (CD28:B7)
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on T cells, can increase cytokines (IL-12) and increase B7 expression, leading to increased chance of costimulation (CD28:B7)
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CD40 binding to its receptor
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why would blocking CD28:B7 or CD40:CD40L be useful in grafting and transplantation?
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without this second signal, T cells are not activated
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induce expression of costimulators on APCs to secrete cytokines that help activate T cells
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adjuvants (ex: CD40)
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most adjuvants are products of
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microbes or subs that mimic microbes
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regarding the TCR complex, the TCR recognizes the Ag while the CD3 and zeta chain
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transduce signals
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aside from the normal peptide-MHC complex; T cells can also be polyclonally activated by
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superAgs
Abs specific for TCR or CD3 CHO-binding proteins |
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purpose of adhesion molecules
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to increase binding (normally low) of TCR to peptide-MHC complex for a sufficient amount of time to initiate a signal
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adhesion molecules are aka
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integrins
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most important factor in the binding of T cells to APC
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integrins
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in resting (naive) T cells, integrins like LFA-1 are in this state
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low-affinity
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switches integrins from low affinity to high avidity (conformationally different) binding state
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release of chemokines by the APC and binding to receptor on the T cell
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integrin LFA-1 binds
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ICAM-1 on APC
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first cytokine to be produced by CD4 T cells within 1-2 hours of activation
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IL-2
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IL-2 binding to the three-chained IL-2R induces
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T cell proliferation
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aka T cell growth factor
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IL-2
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the reason CD4 cells may help activate CD8 cells be releasing cytokines
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CD8 cells do not appear to secrete a lot of IL-2
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effector function of the CD4 cell
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activation of B cells to produce Ab or activation of macrophages
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the reason CD8 cells clonally expand at 10,000x rather than CD4's at 1,000X
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CD8 cells actually kill infected cells, not just activate others by secretion of cytokines
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the most important cell surface protein involved in the effector function of the CD4 cell is
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CD40 ligand (CD40L)
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CD40L binds to CD40 on __ for activation
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B cells and macrophages (or dendritic cells)
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CD40L:CD40 on dendritic cells leads to
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increased expression of costimulatory molecules and production of T cell activating cytokines
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the most important cytokine produced by TH1 cells is
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interferon(INF)-gamma
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a potent activator of macrophages
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INF-gamma
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INF-gamma stimulates production of antibody isotypes which promote
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phagocytosis (Ab binds to Fc receptors on the phagocyte)
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increases expression of MHC II and B7, making better APCs to amplify T cell response
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INF-gamma
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produce IL-4 and IL-5
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TH2
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principal action is switching a B cell to IgE
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IL-4
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principal action is activation of eosinophils
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IL-5
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especially effective against parasites
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eosinophil mediated immunity
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TH2 cytokines inhibit
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TH1 cell mediated immunity
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promotes the differentiation of the T cells into TH1 subset
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IL-12
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IL-12 from APC in response to a microbe is this type of response
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innate
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if a microbe does not induce IL-12 this is induced
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differentiation toward TH2
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effector CTLs kill by
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secreting proteins which create pores in cell membranes and induce DNA fragmentation and apoptosis
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do not secrete cytokines or kill infected cells, but can be stimulated to upon subsequent recognition of Ag
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memory T cells
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time when proliferated cells die after eradication of infection
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1-2 weeks, only memory cells then remain
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ensures T cells do not respond to harmless proteins
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requirement of costimulatory molecules expressed on APC in response to a microbe
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IL-12 is secreted from __ to stimulate differentiation to __ which secrete __
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macrophages, TH1, INF-gamma
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IL-12 ultimately leads to
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increased (better) Ag presentation to T cells
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seen when differentiation toward one CD4 subset inhibits development of the reciprocal population
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cross-regulation
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play no role in eradication of infections by microbes that are living INSIDE host cells
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Ab
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Ag is first recognized and T cell expansion and differentiation occur
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induction phase of T cell mediated immunity
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T cells encounter Ag again (2nd time) at the site of infection, resulting in activation of effector functions
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effector phase
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migrating effector T lymphocytes express high levels of
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adhesion molecules
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naive T lymphocytes home in the lymph node b/c
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L-selectin binds to its ligand on HEVs which are found only in the LN
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as part of the innate immune response, macrophages secrete __ and __ which cause increased E and P selectin and ligands for integrins
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TNF and IL-1
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reason activated T cells stay out of the LN
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cells do not express L-selectin required for migration to LN
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a cell-mediated response test used to determine previous exposure to an Ag
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DTH
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all nucleated cells in the body express MHC class
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I
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a death inducing receptor
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FAS
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express Fas ligand on their cell surfaces which bind to CD95 on target cells
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CTL
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cleave and activate caspases inducing DNA fragmentation and apoptosis
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granzymes
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many viruses inhibit MHC class I, reducing loading of peptide into the MHC molecule, this results in
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reduced surface expression of MHC class I molecules
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HIV works by
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direct killing of T lymphocytes
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neutralizes and eliminates extracellular microbes and toxins
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humoral immunity
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naive B lymphocytes express these two Abs
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IgM and IgD
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when B cells differentiate from IgM to other isotypes with the same Ag specificity
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heavy chain class switching
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repeated exposure to a protein Ag results in the production of Ab with increasing affinity for Ag
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affinity maturation
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effector T cells are generated in peripheral lymphoid organs by
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activation of naive T lymphocytes
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the migration of T cells to the site of infection is independant of
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Ag
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produce ROI and NO that kill microbes
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activated macrophages (by INF-gamma)
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in the primary response to infection, the major Ab made is
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IgM, (and then some IgG)
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in the secondary humoral response to Ag, affinity is higher and this Ab is made
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IgG
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memory cells do not secrete
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Ab
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examples of T-independant Ag
(do not require Helper T participation) |
polysaccharides, lipids, and other nonprotein Ag
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cannot bind to MHC and therefore cannot be seen by T cells
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nonprotein Ags
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T-ind responses differ in that
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little or no isotype switching, affinity maturation and memory cell induction occur
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