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.