Adaptive Immune Response Activation Notes

Adaptive Immune Response Activation

Humoral vs. Cell-Mediated Immunity

  • Adaptive immune response has two arms:
    • Humoral Immunity: B cells and antibodies
      • Targets extracellular microbes but has a role across all microbe types.
    • Cell-Mediated Immunity: Helper T cells and Cytotoxic T cells
      • Important for intracellular, cytosolic, and extracellular pathogens.

Life Stages of B and T Cells

  • Naive Cells: B and T cells that have never seen an antigen.
    • Circulate the body looking for their specific antigen.
    • No effector function.
    • Need to be activated upon antigen recognition.
  • Effector Cells: Activated cells that can eliminate microbes.
    • Arise from proliferation and differentiation of naive cells after antigen recognition.
    • Undergo apoptosis after the pathogen is dealt with.
  • Memory Cells: T and B cells that remain after the infection is cleared.
    • Do not have effector function but are ready to quickly become effector cells upon re-encountering the same pathogen.

Clonal Selection

  • Underpins the adaptive immune response.
  • Ensures that lymphocytes with the correct specificity are expanded:
    • A small number of lymphocytes with unique specificities exist for each antigen.
    • Upon infection, the antigen selects the clone of lymphocytes that recognizes it.
    • The selected clone activates, proliferates, and differentiates to provide an effective immune response.

Initiation of Adaptive Immune Responses in Secondary Lymphoid Organs

  • Occurs in secondary lymphoid organs like:
    • Lymph nodes
    • Spleen (for blood-borne antigens)
    • Mucosal lymphoid tissues (for mucosal antigens)
  • Lymph nodes are highly structured to maximize the chance of antigen encounter and cell interactions.
  • T and B cells activate in distinct regions:
    • T cell zone for T cells
    • Follicles for B cells

Dendritic Cells: The Link Between Innate and Adaptive Immunity

  • Critical link between the innate and adaptive immune systems.
  • Professional antigen-presenting cells (APCs) that express MHC molecules to activate naive T cells.
  • Can also carry danger signals to activate naive T cells.
  • B cells can be activated with or without T cell help; T cell help requires dendritic cells to first activate the naive T cell.
  • Dendritic cells in the periphery:
    • Survey the environment and engulf pathogens.
    • Become activated and migrate to the T cell zone of the lymph node.
    • Mature along the way and become very efficient at presenting antigen to T cells.
  • Dendritic cells activate T cells and initiate cell-mediated immunity.

Antigen Presentation and T Cell Activation

  • T cell receptors (TCRs) can only recognize peptide antigens presented on MHC molecules.
  • Two types of T cells and MHC molecules:
    • Endogenous antigens (e.g., viral antigens in the cytosol) are processed and presented on MHC class I molecules to activate CD8+ T cells.
    • Exogenous antigens (e.g., extracellular bacteria) are processed and presented on MHC class II molecules to activate CD4+ helper T cells.

Three Signals for T Cell Activation by Dendritic Cells

  • Signal 1: Antigen Recognition
    • TCR recognizes the MHC-peptide complex on the dendritic cell.
  • Signal 2: Co-stimulation
    • Co-stimulatory molecules on the dendritic cell are expressed as a result of pattern recognition receptor signaling.
    • Confirms a real emergency to the T cell.
  • Signal 3: Cytokine Signal
    • Cytokines secreted by the dendritic cell direct the type of immune response that the T cell should mount.
  • Activated T cells differentiate into effector cells and migrate to the site of infection to perform their functions.

B Cell Activation

  • B cells can be activated with or without T cell help.
  • B cells recognize intact antigens (not just peptides in MHC).
  • Non-protein antigens (e.g., carbohydrates) can activate B cells without T cell help.
    • Polysaccharide antigens (repetitive) can activate B cells to produce a short-lived response.
  • Protein antigens require T cell help for better B cell responses.
    • Dendritic cells activate CD4+ T cells.
    • Helper T cells then activate B cells.
  • Activated B cells differentiate into antibody-secreting cells (plasma cells).
    • Plasma cells produce soluble antibodies that circulate and mediate effector functions.

Memory

  • An effective response requires clonal expansion of naive cells after activation.
  • After the microbe is eliminated, the response is contracted, leaving memory cells (T and B cells).
  • Memory cells allow for a rapid and strong response upon re-encounter with the same pathogen.
  • Memory responses are:
    • Stronger
    • Longer-lasting
    • Quicker
  • Primary vs. Secondary Responses:
    • Primary response (first exposure) takes time to develop, is not very strong, and does not last long; memory cells are produced.
    • Secondary response (repeat exposure) activates memory cells quickly, leading to a quick, strong, and long-lasting response.