Chapter Summary

24.1

  • An antigen can elicit an antibody response. An antigen is usually made of many different epitopes (antigenic determinants), each of which binds to a different, specific antibody.
  • Humoral immunity against infection is the result of antibody production originated by B cells.
  • Cell-mediated (cellular) immunity involves a type of lymphocyte called T cells, which control antibody production and can directly kill host cells.

24.2

  • Proteins are better immunogens than nucleic acids and lipids because proteins have more diverse chemical forms.
  • Antigen-presenting cells such as phagocytes, degrade microbial pathogens and present distinct pieces on their cell surface MHC proteins.
  • Immunological specificity means that antibody made to one epitope will not bind to different epitopes (although some weak cross-binding to similar epitopes can happen; for example, antibody to cowpox virus will bind to a similar epitope on smallpox virus).
  • A hapten is a small compound that must be conjugated to a larger carrier antigen to elicit production of an antibody.

24.3

  • Antibodies, or immunoglobulins, are members of the immunoglobulin superfamily.
  • Antibodies are Y-shaped molecules that contain two heavy chains and two light chains.
  • There are five classes (isotypes) of heavy chains. Each antibody isotype is defined by the structure of the heavy chain.
  • Each antibody molecule contains two antigenbinding sites. Each binding site is formed by the hypervariable ends of a heavy- and light-chain pair.
  • The Fc portion of an antibody can bind to specific receptors on host cells. This binding is antigen independent.

24.4

  • The primary antibody response to an antigen begins when B cells differentiate into antibodyproducing plasma cells and memory B cells. IgM antibodies are generally the first class of antibodies made during the primary response.
  • Isotype switching occurs during the primary response when a subpopulation of B cells switches during differentiation from making IgM to making other antibody isotypes.
  • The secondary antibody response occurs during subsequent exposures to an antigen and arises because memory B cells are activated. IgG is the predominant antibody made.
  • Clonal selection is the rapid proliferation of a subset of B cells during the primary or secondary antibody response.
  • A B-cell receptor consists of a membrane-embedded antibody in association with the Igα and Igβ proteins. Binding of antigen to the B-cell receptor triggers B-cell proliferation and differentiation.

24.5

  • Progenitor B cells can make any antibody isotype but are programmed to bind only one epitope.
  • Mature (naive) B cells have undergone VDJ rearrangement and make IgM and IgD surface antibodies (part of B-cell receptors).
  • Experienced B cells have completed isotype switching, which occurs after naive B cells bind their target.
  • Progenitor B cells can make any antibody isotype but are programmed to bind only one epitope.
  • Mature (naive) B cells have undergone VDJ rearrangement and make IgM and IgD surface antibodies (part of B-cell receptors).
  • Experienced B cells have completed isotype switching, which occurs after naive B cells bind their target

24.6

  • The major histocompatibility complex (MHC) consists of membrane proteins with variable regions that can bind antigens. Class I MHC molecules are on all nucleated cells, while antigen-presenting cells contain both class I and class II MHC molecules.
  • Antigen-presenting cells (APCs) such as dendritic cells present antigens synthesized during an intracellular infection on their surface class I MHC molecules, but place antigens from engulfed microbes or allergens on their class II MHC molecules.
  • Activation of a TH0 cell requires two signals: TCR/ CD4 binding to an MHC II–antigen complex on an antigen-presenting cell, and CD20-B7 interaction.
  • TH0 cell differentiation to TH1 or TH2 cells is influenced by different cytokine “cocktails” secreted by macrophages and NK cells during an infection.
  • Activation of a B cell into an antibody-producing plasma cell usually requires two signals: antigen binding to a B-cell receptor and binding to a TH2 cell activated by the same antigen
  • Activation of cytotoxic T cells requires two signals: TCR/CD8 molecules that recognize MHC I–antigen complexes and cytokines such as IL-2 made from activated TH1 cells. The activated cytotoxic T cells in turn destroy infected host cells.
  • Superantigens stimulate T cells by directly linking TCR on a T cell with MHC on an APC without undergoing APC processing and surface presentation.

24.7

  • The classical pathway for complement activation begins with an interaction between the Fc portion of an antibody bound to an antigen and C1 factor in blood. (The alternative pathway does not need antibody but begins when C3b binds to LPS on a bacterium.)
  • The Fc-C1 complex reacts with C2 and C4, leading to production of C3b and a novel C5 convertase specific to the classical pathway.
  • After C5 convertase cleaves C5, the classical pathway is the same as the alternative pathway, resulting in the formation of a membrane attack complex (MAC).
  • CD59 and/or factor H prevent inappropriate MAC formation in host cells.

24.8

  • Allergens cause the host immune system to overrespond or react against self.
  • Type I hypersensitivity involves IgE antibodies bound to mast cells by the antibody Fc region. Binding of antigen to the bound IgE causes mast cell degranulation. Can occur within minutes of exposure.
  • Type IV hypersensitivity (delayed-type hypersensitivity, or DTH) involves antigen-specific T cells. TH1 cells release cytokines that activate macrophages and NK cells. TC cells can directly kill cells that present the antigen. Reaction seen within a few days of exposure.
  • Autoimmune disease is caused by the presence of lymphocytes that can react to self.
  • Autoreactive B cells (B cells that make antibody directed against self epitopes) are activated when they present a nonself epitope on their surface MHC. T cells that recognize the nonself epitope activate the B cell, which then secretes antibody against the self epitope.
  • Cytotoxic T cells can produce autoimmune disease by killing host cells that make a self protein that closely resembles a foreign antigen.