Hematopoiesis and T Lymphocyte Development

Hematopoiesis and T Lymphocytes

• Hematopoiesis occurs in three stages: Yolk sac (initiates lymphocyte production) → Liver → Bone marrow.
• T lymphocytes are key players in the immune response and are involved in antibody regulation.
• T lymphocyte maturation starts in the bone marrow, where undifferentiated thymocytes are generated.
• Thymocytes express both CD4 and CD8 markers but are classified only after undergoing selection processes.

T Lymphocyte Selection

• Positive selection: Allows T cells with functional T cell receptors (TCRs) that recognize self-MHC antigens to survive.
• Negative selection: Eliminates T cells that react with self-antigens to prevent autoimmune responses, resulting in apoptosis.
• MHC restriction: Only T cells reacting with host MHC molecules survive.

Subtypes of T Lymphocytes

• T-Helper Cells: 70%, CD4(+) - predominant, assist in antibody production.
• T-Suppressor Cells: 30%, CD8(+) - second most numerous.
• T-Cytotoxic Cells: CD8(+) - directly kill infected intracellular organisms.

Immunoglobulin Structure and Types

• Immunoglobulins consist of heavy and light chains with variable and constant regions.
• IgG is the most abundant immunoglobulin, playing a major role in neutralizing toxins and viruses, found primarily in serum.

Major Functions of Immunoglobulin G (IgG)

• Fixes complement: Activates the complement system.
• Opsonization: Coats antigen to enhance phagocytosis.
• Neutralizes toxins and viruses: Prevents their harmful effects.
• Smallest immunoglobulin type, allowing better diffusion for immunological responses.

Immunoglobulin M (IgM)

• Known as macroglobulin; a pentameric structure aiding in agglutination.
• Accounts for 5% to 10% of serum immunoglobulins, having a half-life of 6 days.
• Primarily seen as a monomer on B cell surfaces and as a pentamer in secretions.
• Functions in complement activation and opsonization.

Immunoglobulin A (IgA)

• Represents 10% to 15% of serum immunoglobulins; exists as a monomer or a dimer.
• Secretory IgA found in mucosal areas acts as a first line of defense, neutralizing toxins and preventing bacterial adherence.
• High valency and protective features against enzymatic digestion in mucosal defense.

Immunoglobulin D (IgD)

• Found on the surface of B cells and in very low serum concentrations (less than 0.001%).
• Plays a key role in B-cell activation and regulates B-cell maturation and differentiation.

Immunoglobulin E (IgE)

• Represents only 0.0005% of serum immunoglobulins; involved in allergic reactions.
• Bind to mast cells and eosinophils, triggering inflammatory responses upon antigen recognition.
• Significant in responses to parasitic infections.

Gene Organization and Antibody Production

• Immunoglobulin gene clusters on chromosomes: H chain genes on 14, kappa on 2, lambda on 22.
• Rearrangement of genes is required for the synthesis of functional antibodies.
• The primary immune response (IgM) occurs within 5 to 7 days, with subsequent responses (IgG) being faster and more robust.

Monoclonal Antibodies

• Created by fusing an activated B-cell with a myeloma cell, resulting in hybridoma capable of producing specific antibodies.
• Widely used in diagnostics and therapy due to their specificity and ability to deliver therapeutic agents.

Explore the three stages of hematopoiesis, highlighting the critical sequence from the yolk sac to the liver and ultimately to the bone marrow. This quiz also delves into the characteristics of thymocytes, particularly their expression of CD4 and CD8, and the implications for classifying double positive cells.