T and B Cells

Agranulocytes vs. Granulocytes

  • Agranulocytes:
    • Monocytes: Differentiate into macrophages.
    • Lymphocytes: Include B cells, T cells, and Natural Killer cells.
  • Granulocytes: Neutrophils, Eosinophils, Basophils.

The Immune System

  • Third line of defense: Specific defense mechanisms (immune system).
    • Involves lymphocytes and antibodies.

Lymphocytes

  • Type of white blood cell (leukocyte).
  • Three main types:
    • Large granular lymphocytes: Natural killer cells (NKCs) - Innate immune system.
    • Small lymphocytes: Main agents of the acquired immune system - T cells and B cells.

Lymphocyte Development and Distribution

  • Develop from hematopoietic stem cells in bone marrow.
  • Found mainly in lymphoid organs, blood, and mucosal surfaces.
  • Distributed in lymphoid tissues: central (bone marrow, thymus) and secondary (lymph nodes, spleen).

B-Cells

  • Mature in bone marrow from hematopoietic stem cells.
  • Found in bone marrow, lymph nodes, spleen, intestine, and bloodstream.
  • Encounter antigens and mature into plasma cells, which produce antibodies, and memory cells for rapid response to future infections.
  • Antibodies fit specific antigens like a lock and key.
  • Five major classes of antibodies: IgG, IgA, IgM, IgD, and IgE. IgG and IgA have subclasses.
  • Antibody Structure: Heavy and light chains, variable and constant regions, antigen-binding sites.
  • F(ab′)2F(ab')_2, Fab, Fc, pFc: Fragments after proteolytic cleavage by papain and pepsin.

T-Cells

  • Develop from hematopoietic stem cells in bone marrow, mature in the thymus.
  • Attack virus-infected cells and regulate the immune system.
  • Found in spleen, lymph nodes, bone marrow, and blood.
  • Each T-cell reacts with a specific antigen via molecules similar to antibodies (TCR & BCR).
  • Types of T Cells:
    • Helper T cells (Th or CD4 T-cells): Assist B-cells and killer T-cells.
    • Killer/cytotoxic T-cells (Tc or CD8 T-cells): Destroy infected cells.
    • Suppressor/regulatory T-cells (Treg): Suppress other T-lymphocytes.

Natural Killer Cells (NK Cells)

  • Kill virus-infected cells without prior thymic education.
  • Derived from bone marrow, present in low numbers in blood and tissues.
  • Defend against viruses and potentially prevent cancer.

Lymphocyte Mitogens

  • Mitogen: Chemical substance that triggers cell division (mitosis).
  • Lectins: Proteins that bind to cell surface glycoproteins, triggering cell division.

Types of Adaptive Immunity

  • Humoral Immunity: B lymphocytes, secreted antibodies, eliminate extracellular microbes.
  • Cell-Mediated Immunity: T lymphocytes, cytotoxic T lymphocytes, kill infected cells and eliminate reservoirs of infection.

Antigen Presentation to T Lymphocytes

  • T cells recognize antigens displayed on cell surfaces via MHC (Major Histocompatibility Complex) molecules.
  • Antigen-presenting cells (APCs): Dendritic cells (DCs), macrophages, and activated B cells.
  • APCs migrate to lymph nodes and secondary lymphoid organs to present antigens to T and B cells.

Immunity Response Stages

  • First Stage: Antigen processing discloses the epitope.
    • Antigens are broken down into peptide fragments with the epitope peptide binding to an MHC molecule.
    • The T-cell receptor binds to the MHC molecule and epitope peptide complex.
  • Second Stage: Presenting of antigen by MHC to T-cells.
    • T-cell receptor recognizes short peptide fragments of pathogen proteins bound to MHC molecules.

Types of MHC

  • Human (HLA), Cow (BOLA), Horse (ELA), Sheep (OLA), Mice (H-2 Complex).
    • MHC class I and MHC class II, both important for T cell activation.

MHC Proteins

  • Class I MHC:
    • Recognized by CD8 T cells.
    • Display peptides from endogenous antigens degraded by proteases.
    • Transported via TAP (transporter associated with antigen processing).
    • Displayed on the cell surface.
  • Class II MHC:
    • Found on mature B cells, some T cells, and antigen-presenting cells.
    • Recognized by CD4 T cells.
    • Antigens from pathogens merge with a lysosome
    • CLIP removed by HLA-DM

Pathways of Antigen Processing

  • Class I MHC pathway: Cytosolic microbe, peptides in cytosol, CD8+ CTL.
  • Class II MHC pathway: Endocytosis of extracellular microbe, invariant chain (li), CD4+ T cell.

Co-receptors of MHC

  • Helper T-cells (Th) contain CD4.
  • Cytotoxic T-cells (Tc) & Regulatory T-cells (Treg) contain CD8.

T Cell Activation

  • Two independent signals required for T Cell Activation
    • Binding of the peptide:MHC complex by the T-cell receptor and, the CD4 co-receptor, transmits a signal to the T cell that antigen has been encountered
    • Activation of naive T cells requires a second signal, the co-stimulatory signal, to be delivered by the same antigen-presenting cell.
      • Signals that play a role in differentiation of T-cells.

B-Cell Activation

  • First stage:
    • Antigen binds to BCR, signals B cells.
    • Signals from the bound antigen and from the helper T cell induce the B cell to proliferate and differentiate into a plasma cell secreting specific antibody.
  • Second stage:
    • Antibodies protect the host from infection by neutralization, opsonization, and complement activation.

Helper T Cells (TH)

  • Regulatory cells that play a central role in the adaptive immune response.
    • Stimulate proliferation of other T cells and B cells.
    • Without Th, there is no immune response.