Animal Defence Part 2

Humoral Immune Response

• Humoral immune response primarily involves B cells.
• B cells have specific receptors on their surface, similar to antibodies, that recognize antigens.
• Antigens are information received from potential pathogens.
• When a B cell receptor encounters an antigen, it interacts with T helper cells.
• This interaction leads to the B cell making more copies of itself and releasing antibodies into the bloodstream.
• Antibodies recognize the antigen on the pathogen's surface.

Antibodies (Immunoglobulins)

• Antibodies, also known as immunoglobulins, are Y-shaped molecules with two flexible arms.
• These arms recognize antigens and adjust to their shape.
• Antibody production requires more than one gene.
• Antibodies have two regions:
  • Constant Region: Defines the antibody type, function, and destination.
  • Variable Region: Specific to each immunoglobulin; provides the site for antigen binding.
• Each antibody has two antigen-binding sites.

Types of Immunoglobulins

• There are five types of immunoglobulins (IgM, IgG, IgA, IgE, IgD).
• IgM is pentameric and the first immunoglobulin released during adaptive immunity.
  • Has high avidity (overall binding strength) but low affinity (strength of a single binding interaction) for antigens.
• IgG binds antigens presented by macrophages.

Monoclonal vs. Polyclonal Antibodies

• Monoclonal Antibodies: Produced by B cells (plasma cells) instructed to produce a specific immunoglobulin repeatedly.
• Polyclonal Antibodies: Produced by different B cells, each with specificity for different antigens.

Use of Monoclonal Antibodies

• Monoclonal antibodies can be produced in large amounts for scientific and medical purposes.
• B cells producing a specific antibody are merged with a myeloma cell line to create a hybridoma.
• Hybridomas can massively produce specific antibodies.

Applications

• Immunoassays: Utilize antibodies' ability to recognize specific chemical structures.
• Immunotherapy: Production of specific antibodies for pathology-related purposes.
• Tracers: Antibodies coupled with radioactive tracers for detection, recognizing specific proteins.

T Lymphocytes and Cellular Immune Response

T Lymphocyte Receptors

• T lymphocytes (T helper and T cytotoxic cells) also have receptors.
• These receptors differ in structure from B cell receptors (antibodies).
• T lymphocyte receptors also have variable and constant regions.
• The variable region interacts with the antigen.

Antigen Presentation and MHC

• Cellular immune response involves T lymphocytes and their interaction with antigens presented by the major histocompatibility complex (MHC).
• Infected cells digest pathogen information and present it on their surface via MHC molecules.
• T lymphocytes recognize the antigen presented by the MHC.

Cytotoxic T Cells

• Recognize and destroy virus-infected or mutated cells.

T Helper Cells

• Coordinate both cytotoxic T cells (cellular response) and B cells (humoral response).

Major Histocompatibility Complex (MHC)

• MHC proteins present antigens to lymphocytes.
• Two classes of MHC:
  • Class I:
    • Expressed on all nucleated cells (except red blood cells).
    • Presents antigens to cytotoxic T cells (CD8+ cells).
    • CD8 on cytotoxic T cells binds to MHC class I during antigen presentation.
    • This interaction activates the cytotoxic T cell, leading to enzyme release that creates pores in the infected cell, causing cell death.
    • CD8^+ cells
  • Class II:
    • Expressed on antigen-presenting cells (APCs, e.g., B cells and macrophages).
    • Macrophages digest pathogens, extract information, and present it on the surface via MHC class II.
    • Antigen presented by MHC class II is recognized by T helper cells (CD4+ cells).
    • CD4^+ cells

Summary of MHC Interactions

• MHC Class I presents antigens to cytotoxic T cells.
• MHC Class II presents antigens to T helper cells.
• Macrophages and B lymphocytes express MHC Class II.

CD4 and CD8 Markers

• T helper cells express CD4, while cytotoxic T cells express CD8.
• CD4 and CD8 are clusters of differentiation that help distinguish between T cell types.

Importance of MHC

• Key molecules in antigen presentation and lymphocyte screening.
• T lymphocytes are selected based on their ability to recognize MHC.
• If MHC presents a self-antigen, the T cell is destroyed.

Cellular Immune Response Activation

• Occurs in lymphoid tissue.
• Macrophage encounters a pathogen, digests it, and presents the antigen via MHC Class II.
• T helper cells recognize the antigen and release chemokines and proliferate, cloning themselves to recognize the specific antigen.

Effector Phase

• T Helper Cell Activation of B Cells
  • T helper cell activated by a B cell presenting an antigen via MHC Class II.
  • T helper cell recognizes the antigen and signals the B cell to:
    • Make more of itself.
    • Become a plasma cell.
    • Produce antibodies.

Cytotoxic T Cell Activation

• Infected cells present an antigen via MHC Class I.
• Cytotoxic T cells recognize the antigen and are instructed to replicate.
• Cloned cytotoxic T cells recognize and destroy cells expressing the same antigen.

Safeguard Mechanisms

• B7 protein: Activates cytotoxic T cells upon recognition of an antigen presented by MHC Class I.
• T Regulatory cells: Recognize self-antigens and regulate cytotoxic T cell activity to prevent autoimmunity.

Tolerance to Self-Antigen

• Tolerance is the process where potentially harmful T lymphocytes are selected against and destroyed.
• Prevents recognition of self-antigens and subsequent autoimmune reactions.
• Failure of tolerance leads to autoimmunity, where lymphocytes attack self-antigens.

Antibody and T Cell Receptor Production

Gene Rearrangement

• One gene does not code for one entire antibody protein.
• Different regions of antibodies and T cell receptors are produced by selectively picking segments of a specific gene (e.g., variable and constant regions).
• This mechanism allows for a vast number of possible combinations, essential for recognizing diverse antigens.
• The process is random, and combinations are selected based on their ability to avoid recognizing self-antigens.

Class Switching

• Mechanism to determine which immunoglobulin a B cell should express (IgM, IgG, IgA, IgE, IgD) or what specific T cell receptor to produce.
• T helper cells interact with B cells and use cytokines to instruct the B cell on which immunoglobulin to produce.
• The selection of the right immunoglobulin is called class switching.
• The previous mechanism, where segments of genes are combined, is called somatic hypermutation.

Immunodeficiency and Immune System Disorders

Immunodeficiency

• Occurs when the immune system fails to function properly.
• Can result in allergic reactions, immediate hypersensitivity, and autoimmunity.

Allergic Reactions

• Immune system overreacts to generally harmless antigens.
• Example: Hay fever, where IgE overreacts to pollen, causing mast cells to produce histamine.

Hypersensitivity

• Immediate hypersensitivity (e.g., sneezing from pollen).
• Delayed hypersensitivity (e.g., poison ivy rash).

Autoimmunity

• The immune system recognizes self-antigens and attacks its own tissues/cells.
• Caused by B and T cells that were not properly selected during tolerance.
• Examples:
  • Systemic Lupus Erythematosus
  • Rheumatoid Arthritis
  • Hashimoto's Thyroiditis
  • Diabetes Type 1: Immune cells destroy insulin-producing cells in the pancreas.

Immunodeficiency Disorders

• Examples:
  • HIV (Human Immunodeficiency Virus): Affects T helper cells, impairing B cell activation and antibody production.

HIV and AIDS

• HIV infects and reduces the number of T helper cells.
• This leads to decreased B cell activation and antibody production.
• Opportunistic infections that are normally harmless can become lethal due to the weakened immune system.
• AIDS (Acquired Immunodeficiency Syndrome) is the final stage of HIV infection.
• HIV is treated with reverse transcriptase inhibitors.

Summary of Key Concepts

Innate Immunity

• First line of defense.
• Non-selective and rapid.
• Key cells: Leukocytes, especially macrophages.

Macrophages

• Bridge between innate and adaptive immunity.
• Antigen-presenting cells.
• Express MHC Class II, presenting antigens to T helper cells.

Adaptive Immunity

• Involves lymphocytes (T helper cells and cytotoxic T cells).
• T helper cells activate B cells to produce antibodies.
• B cells also express MHC and interact with T helper cells.

Cytotoxic T Cells

• Part of the cellular response.
• Recognize antigens presented by any cell with a nucleus via MHC Class I.
• Kill cells presenting antigens via MHC Class I.