effector mechanisms

• thymus dependant antibody production:

  1.        Dendritic cells present antigen to CD4T, resulting in T cell activation and differentiation (Tfh)

  2.        BCR recognises surface antigen, which is processes and associates with MHC 2

  3.        B cell presents antigen to Tfh via MHC class 2, and provides co-stimulation (to produce antibodies) and IL-21

  4.        B cells differentiate, proliferate, and secrete plasma cells
• CD4T cells differentiate to help B cells to produce antibodies or migrate into germinal centres
• somatic hypermutation

  BCR undergoes mutations in genes that encode variable regions, so antibodies are of higher affinity
• IgM

  complement activation
• IgG (IgG1 and IGG3)

  opsonisation, phagocytosis, complement, neonatal immunity
• IgE and IgG4

  immunity against helminths and mast cell degraulation
• IgA

  mucosal immunity
• IFN-y stimulates IgG1 and IgG3
• IL-4 stimulates IgG4 and IgE
• TGF-b stimulates IgA
• IFN-y with IL-6 stimulates IgG2
• Antibodies produced by B cells neutralise bacteria and fungi
• Antibody bound to antigens on the surface of cells via Fab and interaction of Fc with FcR on NK cell causes ADCC
• complement coated bacteria 


  augments phagocytosis by phagocytic cells
• Bacteria is directly lysed by complement + antibody complex
• Th1


  targets intracellular pathogens
• Th2

  targets helminths and parasites, activated eosinophils, mast cells, and basophils
• Th17 activates neutrophils, targets extracellular bacteria and fungi
• Tfh

  enables isotope switching and affinity maturation
• Activated Th2 secrete IL-4, IL-4 inhibits differentiation of Th1
• Treg supress differentiation of Th1 and Th2 by secreting TGF-b
• Activated Th1 secrete IFN-y, IFN-y inhibits proliferation of Th2
• IFN-y and IL-4 inhibit development of Th17
• IFN-y and TNF enable macrophage activation and cell mediated immunity, but IL-10, IL-4, and IL-13 can inhibit this
• Granule exocytosis pathway: perforin and granzymes
• Perforins form a pore and deliver granules into the cytoplasm of target cells
• Granzymes activate apoptosis
• Non secretory pathway: Fas/FasL (death inducing signalling complex and apoptosis)

   
• CD8T cells:

  -              Express unique TCR

  -              Recognise target cells via MHC1 + peptide

  -              Pre-activation and differentiation are necessary

  -              DC must present antigen to CD8
• Receptors on NK cells can detect changes or dysregulation in the expression of various cell surface molecules
• Inhibitory receptors recognise molecules that are constitutively expressed by all cells (e.g., MHC 1)
• Activating receptors recognise surface proteins (induced by metabolic stress)
• Inhibitory receptors ensure that activating receptor signalling is not turned on when not needed
• Loss of inhibitory receptors is known as missing self
• Expression of ligands on target cells for NK cell activating receptors triggers activation