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Chapter 17: Specific Immunity (Adaptive Immunity)

Key terms and definitions

  • Antigen: a substance foreign to the body that elicits an immune response.
  • Antibody (immunoglobulin): a protein produced by select immune cells to target antigens.
  • Immunoglobulin: another term for antibody.
  • Titer: the level of antibodies in a person’s system at a given time.
  • Apoptosis: programmed cell death.

Acquired immunity: natural vs artificial; passive vs active

  • Acquired (adaptive) immunity has two main sources: natural and artificial.
  • Passive acquisition means the recipient is not producing antibodies; preformed antibodies are received from another source.
  • Active acquisition means the host actively produces antibodies.

Natural acquired immunity

  • Passive natural: antibodies transferred from mother to infant (colostrum/breast milk and placenta transfer).
  • Passive natural duration: not long-lasting; the infant will need to mount its own immune response later.
  • Active natural: infection by a pathogen elicits an immune response with antibody production.

Artificial acquired immunity

  • Passive artificial: receiving preformed antibodies via immunoglobulin shots (e.g., for hepatitis treatment).
  • Active artificial: immunizations or vaccinations.

Vaccines: killed vs attenuated

  • Killed vaccine: inactivated pathogen; presents antigen without risk of infection.
  • Attenuated vaccine: weakened live strain (e.g., polio vaccine in some forms); can cause a low-grade infection that stimulates immunity.
  • Caution: attenuated vaccines are not ideal for immunocompromised individuals due to insufficient immune response and risk from even a low-grade infection.

Humoral immunity vs cell-mediated immunity

  • Humoral immunity: B cells are the major players; best at combating extracellular pathogens.
  • Cell-mediated immunity: T cells (especially cytotoxic T cells) are the major players; best at intracellular pathogens.
  • These two arms can work together and influence one another (integration toward end of Chapter 17).

B cells and antibodies (humoral immunity)

  • B cells originate in the bone marrow (in humans); in birds, B cells were first discovered in the Bursa of Fabricius.
  • B cells differentiate into plasma cells upon stimulation by antigens; plasma cells release antibodies.
  • Immature B cells have not yet been stimulated by an antigen; mature B cells have and can differentiate into plasma cells.

Antibody classes (five major classes)

  • IgG: monomer; most abundant in humans; can cross the placenta; major component of memory; primary antibody in secondary infections; t_{1/2} ext{ (half-life)} \approx 20 ext{ days}
  • IgM: first responder during primary infection; t_{1/2} ext{ (half-life)} \approx 10 ext{ days}
  • IgE: involved in allergic reactions; can range from mild to anaphylaxis; t_{1/2} ext{ (half-life)} \approx 2 ext{ days}
  • IgA: mainly a mucosal antibody; is a dimer; important for mucosal immunity; t_{1/2} ext{ (half-life)} \approx 6 ext{ days}
  • IgD: monomer; mostly associated with B cells as a receptor; t_{1/2} ext{ (half-life)} \approx 2 ext{ days}
  • Note: IgG can cross the placenta and contribute to fetal/metal immunity; memory B cells produce IgG upon re-exposure.

Antibody structure: Fab and Fc regions

  • An antibody monomer consists of four polypeptides: two light chains and two heavy chains.
  • Fc (Fragment Constant) region: the constant portion; determines antibody class (e.g., IgG, IgE); remains constant across same class.
  • Fab (Fragment antigen-binding) region: the variable portion that binds antigen; highly variable and determines specificity.
  • Variable region length: about 110 \text{ to } 130 \text{ amino acids} per variable domain; recombination creates diversity.
  • The variable region is what is programmed during B cell maturation to target the antigen that initiated activation.

Clonal selection and B cell activation

  • B cell activation begins when the variable region of IgD (the B cell receptor) binds to the antigenic determinant (epitope) of the antigen.
  • Antigenic determinant (epitope): the specific part of the antigen recognized by the antibody.
  • Activated B cells differentiate into plasma cells and memory cells.
  • Plasma cells secrete antibody; antibodies have variable regions that bind the antigen’s epitopes.
  • Antibody-antigen complexes can lead to several immune outcomes.

Outcomes after antibody-antigen complex formation

  • Agglutination/neutralization: antibodies bind multiple antigenic determinants on the same or different antigens, causing clumping and neutralization; this aids phagocytosis by non-specific cells like macrophages.
  • Opsonization: antibodies coat the antigen, enhancing phagocytosis.
  • Complement activation: activation of the complement system promotes lysis or phagocytosis.
  • Overall result: clearance of the pathogen and resolution of illness when agglutination occurs.

Cell-mediated immunity (T cells)

  • T cells originate from stem cells in the red bone marrow; differentiate in the thymus.
  • Two major T cell types: helper T cells (CD4) and cytotoxic T cells (CD8).
  • CD4 and CD8 classification comes from their surface receptors (CD4, CD8).
  • Communication among immune cells is largely via cytokines, especially interleukins.

Antigen-presenting cells and MHC

  • Antigen-presenting cells (APCs) present antigenic fragments via MHC (Major Histocompatibility Complex) on their surface.
  • A change in MHC signaling the presence of an infection alerts other immune cells.
  • APCs release interleukin-1 (IL-1) to activate helper T cells.
  • Helper T cells, upon receiving IL-1, migrate to the APC, bind, and release interleukin-2 (IL-2).

Activation and cytotoxic response

  • IL-2 activates other T cells, including cytotoxic T cells.
  • Cytotoxic T cells release perforin, an exoenzyme that perforates the target cell membrane.
  • Perforin enables entry of proteases into the infected cell, leading to apoptosis and lysis of the infected cell.

Interplay with humoral immunity

  • Cytotoxic T cells and helper T cells influence B cells as well:
    • IL-2 can stimulate B cells to form plasma cells, linking cellular and humoral immunity.
    • Helper T cell activity can support antibody production by B cells.
  • The immune system operates as an integrated network rather than two isolated arms.

Real-world relevance and safety considerations

  • Attenuated vaccines provide a live but weakened pathogen; they can cause a low-grade infection in a healthy person but may be risky for immunocompromised individuals.
  • Natural immunity involves actual exposure to pathogens, which may carry illness risk but can generate strong memory.
  • Placental transfer of IgG provides fetal immunity; memory IgG supports faster protection upon re-exposure.
  • Understanding the timing differences between primary and secondary responses is key for evaluating vaccine schedules and herd immunity concepts.

Connections to foundational principles

  • Specificity and diversity: many different antibodies arise from recombination in the variable region to target a vast array of antigens (over > 10^8 possible antibody specificities).
  • Clonal selection: only B cells with receptors matching the antigen proliferate and differentiate into plasma and memory cells.
  • Memory: secondary responses rely on memory B cells and rapid production of high-affinity IgG.
  • Cooperation between arms: Helper T cells help both cytotoxic T cells and B cells; innate and adaptive immune components communicate via cytokines (e.g., IL-1, IL-2).

Quick numerical reference

  • Antibody half-lives: t{1/2} ext{(IgG)} \approx 20 \text{ days}, \; t{1/2} \text{(IgM)} \approx 10 \text{ days}, \; t{1/2} \text{(IgE)} \approx 2 \text{ days}, \; t{1/2} \text{(IgA)} \approx 6 \text{ days}, \; t_{1/2} \text{(IgD)} \approx 2 \text{ days}.
  • Antibody structure: two light chains and two heavy chains per monomer.
  • Variable region length: 110 \leq \text{length} \leq 130 \text{ amino acids}.
  • Diversity: more than about 10^8 possible antibody molecules due to variable region recombination.
  • IgG characteristics: crosses placenta; major memory antibody; long-lived response contributor.
  • Primary vs secondary response pattern (general): IgM first in primary response; IgG rises and dominates; in secondary response, IgG rises quickly and to a higher titer with variable IgM presence.