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.
• $F(ab')_2$, 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.