Immunology - 5 - Ag Capture

Question 1

structure and cellular distribution of MHC molecules.

Answer 1

MHC I

• 2 alpha chains
• ALL nucleated cells
  
  • CD8+ CTLs can kill any virus-infected cell

MHC II

• 1 alpha, 1 beta
• Dendritic cells, macrophages, B cells
  
  • CD4+ helper T lymphocytes interact w. presenting cells

General Properities:

• co-dominant expression
  
  • both parental alleles of each MHC gene = expressed
    
    • increases # of diff MHC molecules that can present peptides to T cells
• polymorphic genes
  
  • many diff alleles are present in population
    
    • ensures that different individuals are able to present & respond to different microbial peptides

APC:

• Dendritic cells
  
  • increased by INF-y
  • inducible by TLR ligands, IFN-y, T cells
    
    • Fxn = initiation of T cell response to protein Ags
• Macrophages
  
  • inducible by INF-y
  • inducible by TLR ligands, IFN-y, T cells
    
    • Fxn = effector phase of cell mediated immune response
• B lymphocytes
  
  • increased by IL-4
  • inducible by T cells, Ag receptor, cross-linking
    
    • Fxn = Ag presentation to CD4+ helper T cells in humoral immune response;
    • cognate T-cell-B-cell interactions

Question 2

Compare and contrast antigen presentation via the Class I and Class II pathways.

Answer 2

MCH I pathway (CD8) - INTRACELLULAR

• Production of proteins in cytosol
• Proteolytic degradation of proteins
  
  • Ub tagging
• Transport of peptides from cytocsol –> ER
• Assembly of peptide-class I complex in ER
• Surface expression of peptide-class I complexes
  
  • –> CD8 cytotoxic T lymphocyte

MCH II pathway (CD4) - EXTRACELLULAR

• Uptake of extracellular proteins into vesicular compartments of APC
• Processing of internalized proteins in endosomal/lysosomal vesicles
• Biosynthesis & transport of MHC II molecules to endosomes
  
  • from Er –> golgi –> vesicle
• Associaion of processed peptides w/ MHC II molecules in vesicles
• Expression of peptide-MHC complexs on cell surface
  
  • –> CD4+ helper T cell

Question 3

Outline the process of antigen presentation via the Class I and Class II pathways.

Answer 3

MHC I - presentation of cytosolic Ag to cytotoxic T lymphocytes

• cytosolic antigen
• CD8+ cytotoxic T lymphocyte
  
  • —> killing of Ag-expressing target cell

MHC II - presentation of extracellular Ag to helper T cells

• Macrophage + extracellular Ag –> CD4+ helper T cells
  
  • cytokine release
    
    • –> Macrophage activation; destruction of phagocytosed Ag
• Ag specific B cells + extracellular Ag –> CD4+ helper T cells
  
  • cytokines release
    
    • B cell Ab secretion –> Ab::Ag

Question 4

Describe the T cell receptor and its accessory molecules.

Answer 4

T cell receptor (TCR)

• MHC :: Ag :: TCR
  
  • CD3 interaction –> signal transduction
• cant have signal transduction on its own…more complex]
  
  • variable region + constant region

B cell receptor (Ab & Ig)

• Ag :: membrane Ig
  
  • IgA & IgB ==> signal tranduction
• Secretes Ab
  
  • Effector fuctions:
    
    • complement fixation; phagocyte binding

Question 5

Explain Ag capture & Presentation by DCs

Answer 5

• Ag capture by dendritic cells
  
  • TLR ligands, cytokines
  • DC in epidermis phenotypically immature
• Activation of dendritic cells
  
  • Afferent lymph vessel migreation
  • enters lymph node
    
    • mature dendritic cell presenting Ag to naive T cell