T cell mediated immunity I+II

• What does the CD8 co-receptor bind to?

  Alpha 3 domain of the MHC class heavy chain

  • so MHC class I molecules present peptides only to CD8 T cells
• What does the CD4 co-receptor bind to?

  Beta 2 domain of MHC class II.

  • ensures that peptides bound to MHC class II only stimulate CD4 T cells
• What is the role of dendritic cells in the immune response?


  They initiate the adaptive immune response
• Why are dendritic cells considered important in immunity?


  • Most potent initiators of adaptive immune response
• MHC class I or II? CD8 or CD4

  
• MHC class I or II? CD4 or CD8

  
• MHC restriction


  • T cells need both MHC and peptide to recognise antigen.
• how is the TCR formed - biosynthesis 


  • mainly from genetic recombination of DNA encoded segments in individual T cells by somatic V(D)J recombination
• How are T cells classified


  Basis of cel surface expression of glycoprotein co-receptors CD8 or CD4
• CD8 T cells recognise


  • also known as cytotoxic t cellls
  • recognise antigen in association with MHC class I
• CD4 T cells recognise


  • helper t cells - either helper subset 1 or 2 cells.
  • recognise antigen in association with MHC class II
• CD3 complex 


  • When the T cell receptor is associated with other molecules - collectively known as CD3 complex
  • expression of the T cells receptor at the T cell surface requires association with proteins of CD3 complex
  • These proteins transmit signals into the T cell when the TCR binds antigen.
• The T and B cell are similar because 


  • receptor contains variable and constant region
• dendritic cell information

  • location in lymph node- throughout
  • uses phagocytosis to uptake antigens
  • Found throughout the body
  • antigens it take up -peptides, viral antigens and allergens
  • express. MHC

  
• Macrophage information


  • Location in lymph node- throughout
  • Phagocytosis - uses to uptake antigens
  • Express MHC
  • Antigens uptaken - particular antigens, intra and extra cellular pathogens
  • Found in lymphoid tissue, connectve tissue and body cavities.

  
• B cell information


  • location in lymph node- in follicles
  • Antigen specific receptor - Ig
  • Express MHC
  • antigens it takes up - soluble antigens, toxins, viruses
  • Location- lymphoid tissue, peripheral blood

  
• T cells require two signals for activation 


  CD28 molecule on T cell delivers a co-stimulatory signal upon engaging either of its ligands B7.1( CD80) or B7.2(CD86)
• how is IL-2 an important cytokine in T cells proliferation


  • resting T cells express moderate affinity IL-2 receptors
  • activated T cells express high affinity IL-2 receptors
  • The binding of IL-2 to its receptor signals the T cells express high to enter the cell cycle.
  • IL-2 induce T cell Proliferation

  
• what happens when T cells are activated?

  they change properties- including increased o decreased cytokine secretion.
• Effector T cells

  • response to infection do not depend on co-stimulators signal
• effector T cell steps

  • stimulation of naive T cells receptor by IL-2,
  • T cell proliferates
  • active effector T cells recognise and kill virus infected target cells
• MHC class I molecules deliver peptides to cell surface using intracellular compartment- cytosol

  transporting- cytosolic pathogen


  • cytosolic pathogens are
  • Degraded in cytosol
  • Peptides of this bind to MHC class I
  • Presented to Effector CD8 T cells Leading to cell death
• MHC class I molecules deliver peptides to cell surface using intracellular compartment- cytosol

  transporting an - exogenous antigen


  • exogenous antigens degraded in- cytosol by retrotranslocation
  • Peptides of these bind to MHC class I
  • Presented to naive CD8 T cells
  • Leads to the presenting cell - usually a dendritic cell activating CD8 T cell.
• MHC class II molecules deliver peptides to cell surface using intracellular compartment - macrophage 


  • used for intravesicular pathogens these are-
  • degraded in endocytosis vesicles - low pH
  • peptides of these bind to MHC class II
  • presented to effector CD4 T cells
  • leads to activation to kill intravesicular bacteria and parasites
• MHC class II molecules deliver peptides to cell surface using intracellular compartment - B cell 


  • used for extracellular pathogens and toxins
  • degraded in endocytosis vesicles - low pH
  • peptides of these bound to MHC class II
  • presented to effector CD4 T cells
  • leads to activation of B cells to secrete Ig to eliminate extracellular toxins/bacteria.
• Function of CD8 T cell


  • comes into contact with virus infected celL
  • Cell contact between the two
  • Leads to dead virus infected cell
• function of TH1


  • TH1 (CD4) T cell comes into contact with macrophage
  • TH1 produces cytokines
  • Leads to macrophage activation
  • Macrophages become more phagocytic and will secrete cytokines to recruit other immune cells
• function of TH2 


  • binds with B cells which activates TH2 leading to cytokine release
  • thus activating the B cells to differentiate into
  • plasma cells that will produce antibodies
• CD8 T cells recognise Ag in association with MHC class I steps


  • virus infects cell
  • Vital proteins synthesised in cytoplasm
  • Peptide fragments of viral proteins bound by MHC class I in ER.
  • Bound peptides transported by MHC class I to the cell surface.
  • Cytotoxic T cell recognise complex of viral peptide with MHC class I and kill infected cell
• cytotoxic T cells?


  • also known as CD8 cells
  • effector T cells kill cells infected with viruses or other intracellular pathogens
  • a CD8 T cell only recognises cells bearing its corresponding peptide antigen presented by an MHC class I molecule.
  • CD8 molecule has a binding site for MHC class I molecules to determine strict specificity
  • contain potent granules that kill the cell
• CD4 T cells recognise antigen in association with MHC class II - TH1 steps


  • macrophage engulfs and degrades bacterium producing peptides
  • Bacterial peptides bound by MHC class II in vesicles.
  • Bound peptides transported by MHC class II to cell surface
  • Helper T cells (TH1) recognises complex of peptide antigen associated with MHC class II and activates macrophage
• what cytokines do TH1 produce

  • IFN-y and CD40Ligand
  • IL-2
  • IL-3 and GM-CSF
  • TNF-a and LT-b
• function of IFN-y 


  • key cytokine that activates macrophages to destroy engulfed bacteria
  • associated with TH1
• IL-3 function 


  • stimulates haematopoietic stem cells to accelerate haematopoiesis.
• GM-CSF function 


  Induces stem cells to migrate to differentiate down a macrophage pathway
• what can go wrong- an exaggerated response.

  • tuberculosis
  • macrophages activate T cells
  • T cells activating macrophages
  • form. a granuloma - formed by the fusion of macrophages
  • T cells then surround this as they try to remove the microbe.
• Important TH1 cytokines 


  IFN-y

  IL-2
• important TH2 cytokines


  IL-4
• IL-2 function


  involved in T cell proliferation
• IL-4 function

  Associated with TH2

  Involved in helping B cell differentiation

  mediates class switching