Antigen Capture and Presentation to Lymphocytes Flashcards Preview

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Flashcards in Antigen Capture and Presentation to Lymphocytes Deck (19)
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1

describe how B and T lymphocytes differ in the type of antigen they recognize

  • B-cells:
    • protein, polysaccharides, lipids, nucleic acid
    • soluble form or cell surface-associated antigens
  • T-cells
    • peptide fragments of protein antigens
    • only when presented on specialized molecules

2

describe T-cell antigen presentation by dendritic cells

  • dendritic cell in epithelium: capture microbial antigen
  • activation of dendritic cells
  • migration to draining lymph node (chemokines)
  • maturation: due to cytokines and TLR-signaling
  • expression of MHCII and co-stimulators for stimulation of T cells

3

contrast the MHC I pathway vs the MHC II pathway

4

describe class I MHC

MHC I are expressed on the majority of nucleated cells

  • heterodimeric protein (Ig superfamily)
    • alpha chain
      • transmembrane
      • encoded by A, B and C regions in human MHC complex
    • beta chain: B2-microglobulin
      • encoded by highly conserved gene on different chromosome

5

describe MHC I peptide binding

  • α1/α2 highly polymorphic peptide-binding region
  • α3 binds to CD8 on cytotoxic T cells
  • bind short peptides, usually between 8-10 amino acids
  • presents an endogenously processed antigens

6

describe the class II MHC protein

MHC II expessed on antigen presenting cells (APC)

  • heterodimeric protein (Ig superfamily)
    • α1 and α2 chain
      • transmembrane
    • β1 and β2 chain
      • transmembrane

7

describe MHC II peptide binding

  • α1/β1, highlypolymorphic peptide-binding region
  • β2, highly conserved, binds to CD4 on helper T cells
  • α2, highly conserved
  • bind long peptides, usually between 13-25 amino acids
  • present Ag of extracellular origin

8

describe MHC restriction

  • CD8+ Tc cells are MHC class I restricted
    • can only recognize antigen presented by MHC class I molecules
    • therefore, cells with MHC class I are called "target cells" killed by cytotoxic T cells
  • CD4+ Th cells are MHC class II restricted
    • cells with MHC class II are called antigen-presenting cells (APCs)

9

explain the mechanism of action of CD4+ T cells and CD8+ T cells

10

describe how the site of pathogen replication or mechanism of antigen uptake determines the antigen processing pathway used

11

describe how antigens generated by endogenous vs exogenous antigen processing activate different effector functions

12

contrast the cytosolic pathway vs. the endocytic pathway

  • cytosolic pathway (endogenous, non-lysosomal)
    • endogenous antigens--produced in cell, in infected cell
    • antigens presented to Tc cells by MHC class I
  • endocytic pathway (exogenous, lysosomal)
    • exogenous antigen--taken in by endocytosis by antigen-presenting cells
    • antigens presented to Th cells by MHC class II

13

describe the endogenous processing of Ag

  • proteins targeted for lysis are tagged with ubiquitin
  • the protein is then degraded by the proteasome
    • the components of the proteasome include MECL-1, LMP2, LMP7
    • these components are induced by IFN-gamma
  • peptides need access to the ER in order to be loaded onto MHC class I molecules
    • transporters associated with antigen processing (TAP1 & 2)
  • cytoplsamic peptides are loaded onto the MHC molecule and the structure becomes compact and exported to the cell surface 

14

describe the evasion of immunity by interference with endogenous antigen processing

  • many viruses produce immunoevasins that interfere with antigen presentation by MHC class I molecules
    • viruses block MHC class I from properly presenting them to CD8 T cells
      • inhibit peptide transport
      • inhibit peptide loading
      • cause MHC class I degradation

15

describe the cytosolic pathway

16

describe non-lysosomal antigen processing from inactive vs active viruses

  • inactive viruses raise a weak CTL response
  • the processing of antigens from inactive viruses is sensitive to lysosomotrophic drugs (increase pH on endosome)
  • antigens from inactive viruses are processed via the exogenous pathway (MHC class II presentation)

 

  • infectious virus raises a strong CTL resposne
  • the processing of antigens from infectious viruses is NOT sensitive to lysosomotrophic drugs
  • protein synthesis is required for non-lysosomal antigen processing
  • antigens from infectious viruses are processed via the endogenous pathway (MHC class I presentation)

17

summarize the endocytic/exogenous pathway

18

describe bacteria evasion of MHC II antigen presentation

  • escape endosomes
  • neutralize endosome acidification
  • block fusion with lysosome
  • sequesters MHC class II molecules after vesicle fusion, preventing from going to the surface

19

describe cross-presentation, cross-priming and an example

  • cross presentation
    • exogenous antigens normally processed by phagolysosomes (MHC-II) are presented by MHC-I (exception to the MHC class I rule)
  • cross-priming
    • then presented to and activate CD8+ T-cell
  • example:
    • Rickettsia rickettsia
    • endocytosed but rapidly lyse endosomal membrane and escape prior to phagolysosome formation
    • degraded by proteasome and presented on MHC I