Cell Mediated Immunity I Flashcards Preview

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Flashcards in Cell Mediated Immunity I Deck (20)
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1

describe the cells and the functions involved in cell-mediated immunity

  • cell involved:
    • antigen specific: T helper CD4 and T cytotoxic CD8
    • antigen non-specific: NK cells, macrophages, neutrophils and eosinophils
  • functions:
    • response to intracellular pathogens
    • activation of M1 macrophages
    • induce B cells (INF-γ) to class switch (IgG) to opsonize
    • direct killing (Tc)

2

describe the function of TH1, TH2 and TH17 cells

3

describe the phases of T cell response

  • Naive T lymphocytes recognize antigen presented by dendritic cells in peripheral lymphoid organs
  • production of cytokines (e.g. IL-2) and its receptors
  • autocrine pathway of cell proliferatoin and differentiation
    • memory cells
    • effector cells
  • some activated CD4 T cells remain in the lymph node, migrate into follicles and help B cells 
  • migration of effector T cells to sites of antigen 
  • T cell effectors
    • CD4 T cells recruit and activate phagocytes
    • CD8 cytotoxic T cells (CTLs) kill infected cells
  • elimination of infection results in elimination of stimuli and death of clones, only memory cells remain

4

describe the selected receptors/ligands part of T-cell activation

5

summarize the selected receptors/ligands involved in T-cell activation

6

describe signal 1 (recognition of MHC-associated peptides)

  • digested protein antigens by phagocytes: Class II MHC
    • recognized by CD4 T cells
  • protein antigens in cytosol: Class I MHC
    • recognized by CD8 T cells
  • coreceptor need to be engaged simulataneously
  • TCR recognizes antigen but can not signal on its own
  • TCR noncovalently associated with CD3

7

describe polyclonal activators and superantigens

  • antibodies for the TCR or CD3
  • carbohydrate-binding proteins (e.g. phytohemagglutinin)
  • superantigens:
    • cause pathology through massive load of cytokines (toxic shock syndrome)
    • crosslinks VBTCR domain with non-polymorphic region MHCII on APC
    • T cell mitogens: induce cell proliferation
    • examples: staphylococcal entertoxins, staphylococcal toxic shock toxin, staphylococcal exfoliating toxin, streptococcal pyrogenic exotoxins

8

describe the adhesion molecules (CAMs)

  • CAMs: selectins, mucins, integrins and immunoglobulin superfamily
  • function: stabilization of binding between ligand on APCs and T-cells
    • overcome moderate affinity between TCR and peptide/MHC
    • most important of adhesion molecules are the integrins:
      • leukocyte function-associated antigen (LFA-1)
        • affinity increases when T cell is activated
        • ligand on APCs: intercellular adhesion molecule I (ICAM-1)

9

describe signal 2, specifically, B7 (co-stimulator)

  • important co-stimulators: B7 molecules (CD80 and CD86)
    • expression increases in APCs when antigen is encountered
    • guarantees response to a foreign antigen
  • recognized by receptor CD28 on T cells
  • CD28/B7 signaling is essential for the response of naive T cells

10

describe signal 2, specifically, CD40 (co-stimulator)

  • CD40 ligand (CD40L or CD154) on T cells and CD40 on APCs
    • instead of activating T cells, they activate APCs to express more B7 co-stimulators and to secrete cyotkines (e.g. IL-12) to enhance T cell differentiation
  • proteins homologous to CD28: CTLA-4 or PD-1 are involved in terminating the immune response

11

describe clinical correlates with the co-stimulators

  • protein antigens used in vaccines fail to elicit T-cell dependent immune response
    • need to activate APCs: adjuvant (one of its uses)
      • bind to PRR on the innate, and activate APCs
  • agents that block B7:CD128 (aka 28) are used in treatment of rheumatoid arthritis, graft rejection, etc.
  • antibodies to CD40: CD40L interaction have been tested for graft rejection
  • antibodies that block CTLA-4 or PD-1 have been used to enhance immune response in cancer patients

12

the first cyotkine to be produced by CD4 T cells is ____ (1-2 hours after activation)

the first cyotkine to be produced by CD4 T cells is IL-2 (1-2 hours after activation)

  • autocrine signal
  • suvival, proliferation and differentiation

13

describe the generation of effector CTLs

  • licensing of dendritic cell by TH1
  • co-stimulatory signal
  • IL-2 production by TH1
  • CTL-P becomes CTL
    • proliferation and cytotoxic function

14

describe the CTL mechanisms of killing

15

describe conjugate formation (step 1 of CTL-mediated death)

  • cell adhesion (LFA-1 on CTL binds ICAM on target cell)
  • recognition of MHC 1: Ag on target cell

16

describe membrane attack (step 2 of CTL-mediated death)

  • granules in CTLs
    • perforin
    • granzymes
  • exocytosis of granule contents
    • Perforin action similar to C9
    • granzymes act as nucleases 

17

describe dissociation and target cell death (step 3 of CTL-mediated death)

  • CTL interacts for about 5 minutes
  • dissociates and can conjugate with other target cells
  • target dies after several hours

18

describe naturak killer cells (NK)

  • innate immunity
  • lymphoid cells
    • 5% of lymphocytes
    • share early lineage to T cells
    • NK cells don't develop exclusively in thymus
  • defend against viruses, other intracellular pathogens and tumors
    • nonspecific cytotoxicity
    • no TCR/CD3
    • not MHC restricted
    • no memory
  • recognizes non-peptide
    • glycolipid and CD1d
  • killing of target cell is similar to that of CTL

19

describe activation vs inhibition of NK cells

  • activation is determined by a balance between activating and inhibitory receptors
  • NK cells do not have capability of recognizing MHC
  • recognize altered cell surface molecules (lowered class I MHC)

20

describe the function of NK cells

  • recognize tumor or virus-infected cells
    • A) cytotoxic granule mediated cell apoptosis (perforin, granzymes, alpha- defensins)
    • B) induce infected macrophages ot kill: respond to IL-12 with IFN-γ production
    • C) antibody-dependent cell mediated toxicity