Immunology: Adaptive Immunity and T Cell Activation

MHC Class I and II

• MHC class one:
  • Present in all nucleated cells (e.g., hepatic cells, alveolar cells).
  • Presents intracellular antigens to the immune system.
• MHC class two:
  • Found on white blood cells.
  • White blood cells patrol and identify invaders.

B Cells and Antibody Production

• B cells originate from bone marrow.
• Responsible for producing antibodies.
• Differentiate into plasma cells that manufacture antibodies.
• MHC class two on their surface.
• B cells encounter extracellular antigens, internalize them, and present them on MHC class two.
• Require T helper cells for activation.

T Helper Cells and B Cell Activation

• T helper cell (specifically, T_H2) activates B cells.
• T_H2 releases interleukin-4 (IL-4).
• IL-4 signals the B cell to become a plasma cell and produce antibodies.
• Clonal selection ensures only the correct B cell (matching the antigen) is activated to prevent the production of incorrect antibodies.

Antibody Functions: Clumping, Opsonization and Complement

• Antibodies facilitates the following mechanisms:
  • Clumping (agglutination).
  • Opsonization: C3b coats pathogen to enhance phagocytosis
  • Membrane Attack Complex (MAC).
  • Inflammation: C3a and C5a induce inflammatory response.
    * Opsonization enhances phagocytosis.
  • Complement activation occurs via the classical pathway, initiated by antibodies binding to antigens.
    * Classical pathway starts with C1.

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

• Antibodies attach to large targets (e.g., microbes).
• Triggers destruction by macrophages, eosinophils, and natural killer (NK) cells.
• Effective against microbes with exotoxins on the outside.

T Helper Cell Interaction with B Cells

• T helper cells are essential for activating B cells.
• B cells present extracellular antigens on MHC class two.
• CD4+ T helper cells recognize the antigen presented by B cells.
• These T helper cells differentiate into plasma cells, which produce antibodies.
• T helper cells are CD4+ cells, which can be TH1, TH2, or T_H17.

Cellular Immunity and T Cell Activation

• T cells have T cell receptors (TCRs) that bind to antigens presented on MHC (either class one or class two).
• Activation leads to differentiation into CD4+ or CD8+ T cells.
• CD8+ T cells are cytotoxic, destroying cells with intracellular antigens.
• CD4+ T cells release interleukins like IL-4.
• CD8+ T cells target pathogens inside host cells.

Antigen Presentation and CD4+ T Cell Subsets

• Antigen-presenting cells (APCs) include:
  • B cells.
  • Dendritic cells.
  • Macrophages.
• APCs present antigens on MHC class two to CD4+ T helper cells.
• Dendritic cells engulf antigens and present the most important part on their MHC class two molecules.
• CD4+ T cells differentiate into subsets: TH1, TH2, and T_H17.

Specific Functions of T Helper Cell Subsets

• T_H2 cells:
  • Activate B cells.
  • Produce IL-4, leading to antibody production.
• Antigen-presenting cells (APCs) present antigens to the immune system.
• Dendritic cells engulf antigens, present them on MHC class two, and activate CD4+ T cells.

CD4+ T Cell Differentiation Based on Antigen Type

• CD4+ T cells differentiate into TH1, TH2, or T_H17 depending on the antigen type.
• T_H17 cells:
  • Release IL-17.
  • Promote neutrophil recruitment to the site of infection.
  • Effective against fungal infections.
• T_H2 cells:
  • Trigger mast cell activation, leading to histamine release.
  • Increase eosinophil production, targeting parasites.
  • Activate basophils.
• T_H1 cells:
  • Enhance the effects of CD8+ T cells on intracellular pathogens.
    *Engulf bacteria

Killing of Virus-Infected Cells

• Cells infected by a virus present viral antigens on MHC class one.
• CD8+ cytotoxic T lymphocytes (CTLs) recognize MHC class one- bound viral antigens.
• The CTLs release perforin and granzymes to induce apoptosis in the infected cell, preventing further viral replication.

Secondary (Amnestic) Response

• The secondary response is more rapid, lasts longer (more days), and is of greater magnitude compared to the primary response.
• Characterized by class switching from IgM to IgG, which is more specific to the antigen.
• Antibody titer measures the relative amount of antibody in the serum.
• Vaccines induce a primary immune response, creating memory cells.
• Upon subsequent exposure to the actual pathogen, the body mounts a rapid and strong secondary response.
• Naturally acquired active immunity results from getting sick and going through the primary and secondary immune responses.

Passive Immunity

• Naturally acquired passive immunity involves the transfer of antibodies from mother to baby via the placenta or colostrum.
• Artificially acquired passive immunity involves injecting antibodies (e.g., during the president's COVID treatment) and does not produce memory.
• Important for immunocompromised individuals who cannot be vaccinated. This may include people who are HIV positive.