In-depth Notes on Lymphocytes and Immunology

Lymphocytes

  • Introduction to Medical Sciences: Immunology
    Dr. Cédric Duval, University of Leeds

Key Objectives

  • Differentiate between types of B and T cells and their roles.
  • Mechanisms of B cell activation and the germinal center response:
    • Naïve B cells
    • Clonal expansion
    • Somatic hypermutation
    • Class switching
    • Plasma cells
  • Types of antibodies and their structures:
    • IgG, IgA, IgM, IgE, IgD (monoclonal, polyclonal)
    • Structure: constant/variable regions, light chain/heavy chain
    • Differences between primary and secondary antibody responses.
  • Role of antigen presentation through MHC Class I and II in T cell activation.
  • Definitions:
    • Tolerance
    • Anergy

Overview of the Immune System

  • Innate Immunity:

    • Rapid, non-specific response to infections, includes physical and chemical barriers (skin, gastric acids).
    • Uses interferons, defensins, lysozymes for immune defense.
    • Involves acute and chronic inflammation involving various immune cells.

  • Adaptive Immunity:

    • Slower, specific response relying on antigen recognition.
    • Develops long-term immunity via memory B and T cells.

Immune Cells Involved

  • Progenitor Cells:
    • Common myeloid and lymphoid progenitors originating from multipotential hematopoietic stem cells (Hemocytoblast).
  • Major Immune Cell Types:
    • Dendritic cells
    • T lymphocytes (Helper T and Cytotoxic T cells)
    • B lymphocytes (Memory B and Plasma cells)
    • Natural Killer cells
    • Granulocytes (Neutrophils, Eosinophils, Basophils)
    • Macrophages
    • CD4 and CD8 T cells

B Cell Development and Activation

  • Types of B Cells:
    • Plasma Cells: Terminally differentiated, produce antibodies.
    • Memory B Cells: Dormant, initiate rapid response on re-exposure.
    • Naïve B Cells: Circulate until activated.
  • Activation Process:
    • Binding antigens to B cell receptors triggers activation.
    • B cells present antigens to Th2 cells (via MHC II).
    • Proliferation and differentiation into plasma and memory B cells occur in germinal centers.

The Germinal Center Response

  • Processes:
    • Clonal Expansion: B cells proliferate to form centroblasts in the dark zone of the germinal center.
    • Somatic Hypermutation: Introduced mutations in centroblasts allowing for improved antibodies (AID enzyme).
    • Class Switching: Changes in antibody types (e.g., from IgM to IgG).

Antibodies Overview

  • Types:
    • IgM: First response, activates complement, can function as a BCR.
    • IgG: Most abundant, opsonin properties, crosses the placenta.
    • IgA: Found in mucosal sites, binds pathogens; does not activate complement.
    • IgD: Signals mature B cells ready for circulation.
    • IgE: Associated with allergic responses, binds mast cells and basophils.
  • Antibody Structure:
    • Composed of heavy and light chains with variable and constant regions, Fab and Fc regions.

Antibody Responses

  • Primary Response:
    • Initial IgM followed by IgG production from activated naive B cells; short-lived plasma cells produce low-level antibodies.
  • Secondary Response:
    • Memory B cells rapidly produce IgG from long-lived plasma cells in response to repeat infection.

Major Histocompatibility Complex (MHC)

  • MHC Class I:
    • Present on all nucleated cells; recognized by CD8 T cells.
    • Displays intracellular antigens (e.g., from viral proteins).
  • MHC Class II:
    • Present on professional antigen-presenting cells (B cells, macrophages).
    • Recognized by CD4 T cells and displays extracellular antigens.

T Cell Activation

  • Process:
    • T cell receptors recognize antigens presented by MHC.
    • CD4 helper T cells promote activation of CD8 T cells via IL-2.
  • Clonal expansion of helper T cells occurs following activation.

Tolerance and Anergy

  • Tolerance:
    • Immune system non-reactivity to self-antigens; involves clonally deleting self-reactive B and T cells.
  • Anergy:
    • Reduced activation capability of immune cells, leading to non-responsiveness to specific antigens.

Summary

  • Understanding of lymphocyte roles, activation mechanisms, and the immune response helps in grasping immunological functions and therapeutic approaches.