Immunology: Secondary Response and Hypersensitivity

Overview of Immune Responses

Primary and Secondary Immune Responses

  • Equal numbers of T cells and B cells are required to generate a secondary immune response.

  • The presence of a secondary number of B cells and T cells facilitates this response.

  • Altering the carrier, specifically the peptide part of the hapten carrier which interacts with T cells, necessitates that T cells revert to primary mode, initiating a primary immune response despite the same hapten being present.

Key Experiments in Immunology

  • Thymectomy Experiment:

    • An important experiment conducted by Waxman, demonstrating the role of the thymus in immune response.

  • Radiation Experiment by Kleiman:

    • Radiation was used to eliminate specific cells; only fibrous and bone marrow cells were affected.

    • Confirmed B cells reside primarily in the bone marrow.

    • Following bone marrow transplant, cell populations were restored.

Role of Macrophages in Immune Response

  • Separation of T and B cell populations; macrophages are essential for antigen presentation.

  • Presentation of antigen to T cells requires macrophages; T and B cells activated upon interaction with presented antigens.

  • Importance of understanding how to prepare single cell suspensions of T cells, B cells, and macrophages.

    • Procedures must allow efficient separation of these cells.

Immune Cell Interactions

  • All immune cells are necessary for an anti-body response: T cells differentiate into two populations:

    • One helps B cells.

    • One helps cytotoxic cells.

  • Discussed the detailed pathway for T cell differentiation and how they mediate immune responses.

Cytokines and Their Roles

  • Cytokines play a major role in T cell activation and differentiation.

    • IL-2: Essential for T cell proliferation; acts in autocrine manner (T cell produces IL-2 and expresses its receptor).

    • Key cytokines for differentiation into T helper types (Th1 and Th2).

  • Focus on a limited number of key cytokines, understanding their roles in immune responses is more beneficial than memorizing all.

Mechanisms of Cytotoxic T Cells

  • Cytotoxic T cells are responsible for killing infected cells.

  • Introduction of delayed hypersensitivity reaction and its significance.

  • Emphasis on the necessity of a single kill, rather than multiple, in type four reactions.

Types of Hypersensitivity Reactions

  • Hypersensitivity Overview: Explanation of the four types of hypersensitivity reactions:

    • Type I (Immediate Hypersensitivity): Antibody-mediated (IgE, IgG).

    • Type II (Cytotoxic): Antibody-mediated, targets cells directly.

    • Type III (Immune Complex): Involves immune complexes causing tissue damage.

    • Type IV (Delayed-type): Mediated by T cells without antibodies.

Type I Hypersensitivity
  • Mediated by IgE antibody, featuring:

    • Sensitization Phase: Exposure to allergen, leading to IgE synthesis.

    • Activation Phase: Second exposure results in degranulation of mast cells and release of mediators.

    • Elicitation Phase: Effects include bronchoconstriction in lungs, dilation and leakage in blood vessels, leading to fluid build-up and allergic symptoms.

  • Key mediators include histamine, prostaglandins, and leukotrienes.

Type II Hypersensitivity
  • Characterized by cytotoxic reaction, leading to cell lysis through antibody-dependent pathways.

  • Examples include hemolytic anemia and reactions to Rh factor during pregnancy (Rh incompatibility) leading to damage in red blood cells of the fetus.

Type III Hypersensitivity
  • Dependent on immune complexes, leading to inflammation and tissue damage via the complement cascade.

  • Example: Serum sickness, wherein antigens (like horse serum) trigger immune complex formation that deposit in tissues.

Type IV Hypersensitivity
  • Delayed reaction due to T cell sensitization and activation, characterized by pro-inflammatory cytokines.

  • Often involves contact dermatitis and requires careful management by avoiding allergens.

Tolerance and Autoimmunity

  • Discussion of autoimmune diseases, associative traits and genetic predispositions.

  • Contrast between central tolerance (occurs in the thymus and bone marrow) and peripheral tolerance (occurs in the lymph nodes).

    • Central tolerance eliminates autoreactive cells through selective pressure during maturation.

    • Peripheral tolerance involves additional steps requiring T cell cooperation for B cell activation.

Autoimmunity Characteristics

  • More prevalent in females, often linked with having multiple autoimmune conditions.

  • Relevant concepts: Molecular mimicry and polyclonal activation can trigger autoimmunity.

  • Hypersensitivity reactions can also stem from external exposures triggering immune responses in predisposed individuals.

Examples of Autoimmune Diseases

  • Overview of common autoimmune diseases and the necessity to categorize them by type of hypersensitivity reaction (I-IV).

  • Need to understand each disease’s specific autoantibody and target autoantigen for comprehensive knowledge.

Conclusion