immuno test 2

• Two types of adaptive immune response:

  • Humoral response mediated by antibodies (from B cells) to target extracellular pathogens
  • Cell-mediated response by cytotoxic T cells to target virus-infected cells
• Complex repertoire of adaptive immune responses that enable the immune system to deal more effectively with different situations
• Innate and adaptive immune responses interact in diverse ways that further expand the capabilities of the immune system overall
• Different classes (isotypes) of antibodies:

  • IgM (and IgD)
  • IgG
  • IgA
  • IgE
• Different subsets of CD4+ helper T cells:

  • TH1
  • TH2
  • TH17 (sometimes called TH3)
  • Treg (regulatory T cell)
• Domain structure of antibody:

  • Ig domains shown as blue boxes
  • Heavy chains (green) contrasted with light chains (yellow)
  • Constant (C) regions (blue) contrasted with variable (V) regions that form antigen binding site (red)
  • Fc region binds to an Ig receptor on cells (an Fc receptor)
• Increases binding strength:

  • Affinity: The binding strength of one antigen binding site
  • Avidity: The combined strength of two or more antigen binding sites
  • Crosslinking: The bivalent structure of antibodies enables crosslinking of foreign molecules or pathogens to create immune complexes
• Antibodies are bivalent with two identical antigen binding sites
• Secondary diversification of the antibody repertoire stimulated by interaction of helper T cell with B cell
• Antibody receptors:

  • IgG: FcgRI - Neutrophils, macrophages
  • IgE: FceRI - Mast cells, eosinophils
  • IgA: FcaRI - Epithelial cells
• IgM is the first antibody to be secreted in an immune response, forming a pentamer that increases the overall strength of antigen binding
• Interaction of B cells with helper T cell subsets activates appropriate antibody class-switching
• Naïve CD4+ T cell matures into effector CD4 T+ cell with multiple subsets (TH1, TH2, TH17, Treg)
• T cell-mediated immune responses:

  • TH1: IgG, complement, bacterial infection
  • TH2: IgE, parasitic infection, allergy
  • TH17 and Treg: IgA, mucosal immunity
• Immune response to parasitic infection involves TH2 cells stimulating immunoglobulin class switching in B cells to produce IgE
• Allergies are exaggerated responses involving IgE, mast cells, and eosinophils, similar to immune response to parasitic infections
• Susceptibility to allergies is likely a combination of genes and the environment
• eosinophils cover the parasite and attack it with a variety of toxic molecules. This helps to kill or dislodge the parasite.
• TH2 cells stimulate immunoglobulin class switching in B cells to produce IgE, and recruit mast cells and eosinophils
• Mast cells are concentrated in the mucosa and areas under the skin, in locations where parasites normally get access to the body
• IgE binds to its receptor (FceR1) on mast cells
• Crosslinking of IgE by antigen then activates the mast cells which produce inflammatory mediators
• Parasitic helminths (worms) are multicellular eukaryotic organisms They are larger and more difficult for the immune system to attack because they cannot be removed by phagocytosis.
• Allergies are exaggerated (hypersensitive) responses to certain antigens called allergens
• Allergies are inappropriate TH2 responses: they involve antibodies of the IgE class, mast cells and eosinophils
• Anti-specific antibodies can neutralize bacterial toxins or viruses by binding to them, preventing them from attacking cells by blocking their binding sites
• Opsonization involves coating bacteria or pathogens with proteins like antibodies to facilitate their removal by phagocytic cells such as neutrophils and macrophages
• Complement proteins assist in opsonization and complement the function of antibodies
• IgG is the main antibody isotype used in opsonization
• IgG receptors on neutrophils and macrophages bind to IgG antibodies, tethering pathogens to the cell surface and stimulating phagocytosis and cell activation
• Antibodies with a bigger hinge region, like IgG3, are more efficient at binding to pathogens but are more susceptible to proteolytic attack, limiting their lifetime
• The four subclasses of IgG help balance the trade-off between efficiency and susceptibility to proteolytic attack
• Complement proteins are activated by a proteolytic cascade following antibody binding to antigens on pathogens
• Complement C3b adds another layer of opsonization and complements the action of antibodies
• Complement proteins are normally present in the blood in an inactive form and are activated following an infection
• IgG and IgM antibodies can activate complement and phagocytes
• The classical complement pathway is initiated by binding of complement C1 to antibodies, depending on an adaptive immune response
• C3b opsonizes pathogens and activates the membrane-attack complex, leading to pathogen cell lysis
• Complement C5b-C9 form the membrane-attack complex that kills bacteria by creating a lytic pore in the membrane
• Complement fragments C3a, C4a, and C5a act as mediators of inflammation and assist in immune cell recruitment