Year 1 Immunology Stuff

• • Two classes of MHC molecules: 
  • MHC class I molecules present peptide antigens derived from pathogens that replicate inside the cell, such as viruses and some bacteria.  
  • is expressed in all nucleated cells in the body. 
  • CD8 Helper cells involved. 
  • MHC class II molecules present peptides from pathogens and antigens that are present outside the cell taken up by endocytic vesicles of phagocytic cells. 
  • it's only expressed on macrophages, dendritic cells and B cells. 
  • CD4 helper cells involved. 
• • B cells recognize native proteins, whereas T cells recognize degraded proteins bound by major histocompatibility complex (MHC) molecules. 
  • B cells and antibodies can see antigen in its natural/native state. 
  • T cells cannot do this. T Cells need the antigen to be degraded and presented by the MHC. 
• • Biological Activity of Ig’s: 
  • IgG  
  • most abundant (80% of total serum Ig)  
  • expressed on the surface of B cells. 
  • IgM  
  • accounts for 5-10% of total serum Ig  
  • expressed on the surface of B cells. 
  • IgD  
  • co-expressed on the surface of B cells with IgM.  
  • function unknown? 
  • IgA  
  • predominant Ig expressed in external secretions.  
  • to prevent attachment of pathogens to epithelial surfaces 
  • IgE  
  • mediate the immediate hypersensitivity/allergy
  • parasitic infection
• • You always start out as an IgM. But then once you encounter antigen, you now start to change your phenotype/ differentiate to the site of where it's going to be most impactful. E.g., a cell starts as an IgM. Once it gets around to the gut, it'll just make IgA, because IgA is important in terms of protection in the gut whereas in the lung you preferentially have B cells that are making IgE. 
  • IgG is the most abundant, followed by IgA, then IgM and IgE. 
• • Two signals required for B cell activation
  • 1st signal binding of antigen to Ig
  • 2nd signal = helper T cell recognizes degraded fragments of antigen as peptides bound to MHC class II molecules on B cell surface
  • When B cell receptor binds to antigen, it takes some in through endocytosis, degrades into small fragments and presents it to T cells via MHC
  • The Th2 helper cells recognizes it and helps make antibody by producing cytokines
  • B cells proliferate + differentiate into plasma cells which secrete antibody
  • B cell requires T cells to produce cytokines to make antibodies

   
• • Upon primary antibody challenge, you produce and IgM response. So every time you encounter a new antigen for the first time you make IgM.
  • But upon secondary challenge/boost/reinfection there is a class switch to IgG and the response is quicker and greater, showing immunological memory which is a hallmark of an adaptive immune response. The level of IgG remains high. IgG has a high affinity and is the best antibody you make; this is what is passed on through the placenta to newborn offspring. 
• • Two main classes of T cells have different functions: 
  • Two main classes of T cells are classified on the basis of cell surface expression of glycoproteins co-receptors CD8 or CD4:  
  • CD8 T cells or cytotoxic T cells, which recognise antigen in association with MHC class I  
  • CD4 T cells, either T helper 1 or T helper 2 cells, which recognised antigen in association with MHC class II 

   
• • If its an intracellular pathogen, its MHC Class I 
  • If its an extracellular pathogen, its MHC Class II 
• • CD8 Cytotoxic T cells: 
  • CD8 T cells have a cytotoxic function, and they are also known as cytotoxic T cells  
  • Effector T cells kill cells infected with viruses or other intracellular pathogens  
  • A CD8 T cell recognises only 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. 
• • CD4 Helper T Cells: 
  • CD4 TH1 – produces gamma interferon which activates macrophages to continue the process of phagocytosis. Further macrophage activation. 
  • CD4 TH2 – produces Interleukin 4, 5 and 6 which activates B cells to make antibodies. Mainly interacts with B cells. B cell proliferation. 
  • Both use MHC Class II only