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Updated: Aug 27 2023

Humoral-Mediated Immunity

  • Overview
  • Introduction
    • Humoral immunity is based upon the production and activity of antibodies that
      • defend against extracellular threats such as bacteria via
        • opsonization of the surface of the pathogen leading to
          • phagocytosis by innate immune cells like macrophages
          • cytotoxicity by triggering release of toxic compounds by innate immune cells
        • neutralization of pathogens and viruses by
          • blocking interaction of pathogenic proteins with host receptors
          • inactivating virulence factors expressed by pathogens
        • activation of the complement cascade through the classical pathway
    • The main effector cell of humoral immunity B-cell that
      • is activated by displaying peptides to helper T-cells
      • undergoes affinity maturation to make higher affinity antibodies
      • undergoes class switching to develop new classes of antibodies
      • differentiates into plasma cells that are specialized to produce antibodies
    • Humoral immunity occurs in multiple phases including
      • the primary response that occurs immediately after B-cell activation
      • the secondary response after further differentiation of B-cells
  • Activation of Humoral-Mediated Immunity
    • Humoral immunity can be activated by two classes of antigens including
      • thymus independent antigens that do not require T-cell help
      • thymus dependent antigens that require T-cell help
      • Activation of Humoral Mediated Immunity
      • Feature
      • Thymus Independent
      • Thymus Dependent
      • Function
      • Detect conserved non-peptide antigens
      • Identify pathogens that are missed by T-cells
      • Detect peptide antigens
      • Cooperate with T-cells to clear pathogens
      • Activation steps
      • Crosslinking of B-cell receptors by polymeric antigens
      • Examples include bacterial cell wall or lipopolysaccharide
      • Activation by mitogens to promote general B-cell activity
      • Endocytosis of protein antigens that are detected by the B-cell receptor
      • Processing of these antigens in endosomes and presentation on MHC class 2
      • Recognition of MHC complexes by activated helper T-cells
      • Interaction of costimulatory CD40 on B-cells with CD40 ligand
      • Differentiation after cytokine stimulation
      • Limitations
      • Does not lead to class switching or affinity maturation
      • Does not produce immunological memory (require adjuvent)
      • Requires peptide antigen
      • Must have functional helper T-cells
  • Affinity Maturation and Isotype Switching
    • After B-cells are activated they can undergo two main processes including
      • affinity maturation to increase receptor affinity
      • isotype switching to produce different antibody isotypes
    • Affinity maturation is a coordinated process with distinct stages including
      • migration of B-cells to secondary lymphoid organs where
        • B-cells proliferate in germinal centers to form a colony
        • the B-cell receptor is randomly mutated in different cells
      • selection of the cells with the highest affinity receptors within the colony by
        • providing a limited number of survival signals
        • allowing mutated B-cells to compete for these signals
        • pruning less effective B-cells through apoptosis
    • Isotype switching is stimulated after activation and
      • occurs in germinal centers of secondary lymphoid organs
      • is the process of irreversibly switching constant regions by DNA rearrangement with
        • removal of μ (IgM) and δ (IgD) type constant regions
        • addition of other constant regions making IgG, IgE, and IgA
      • is controlled by stimulation with specific cytokines
        • no specific IL required for IgG production
        • IL-5 produces IgA
  • Primary and Secondary Responses
    • Upon activation distinct populations of B-cells will develop including
      • effector B-cells that mediate the primary response by
        • secreting antibodies
        • secreting cytokines
      • proliferating B-cells that mediate the secondary response after
        • undergoing affinity maturation and class switching
        • differentiating into plasma cells
    • These responses differ in a variety of key aspects
      • Primary versus Secondary Responses
      • Feature
      • Primary Response
      • Secondary Response
      • Function
      • Immediately secrete antibodies
      • Contain infection while secondary response develops
      • Develop into a more effective response with higher affinity
      • Clear infection after development
      • Antibody type
      • Low affinity IgM
      • High affinity IgG
      • IgA in mucosal infections
      • IgE in parasitic infections
      • Timing
      • Early in infection
      • Late in infection
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