Adaptive Immunity Overview

Adaptive Immunity Overview

• Adaptive immunity is a specific defense system against pathogens, developing over time and targeting unique antigens.
• Unlike innate immunity, adaptive immunity is slower, requiring days to weeks for full activation.
• Adaptive immunity is highly specific, targeting unique antigens, and exhibits immunological memory, becoming more efficient upon repeated exposures.

Types of Adaptive Immunity

• Antibody-mediated (Humoral) Immunity: Involves B cells producing antibodies, proteins that neutralize pathogens and toxins, enhance phagocytosis, and provide targeted defense at mucosal surfaces.
• Cell-mediated Immunity: Involves the activation of cytotoxic T cells (CD8+ T cells), which directly kill infected cells or bacteria through lysis.

Cells of Adaptive Immunity

• T Lymphocytes (T Cells): Crucial in cell-mediated immunity.
  • CD4+ Helper T Cells: Orchestrate the immune response, activating other immune cells (B cells, macrophages, CD8+ T cells).
  • CD8+ Cytotoxic T Cells (CTLs): Directly kill infected cells or bacteria.
• B Lymphocytes (B Cells): Responsible for antibody production.
  • Plasma Cells: Activated B cells secreting large amounts of antibodies.
  • Memory B Cells: Long-lived cells providing immunological memory, enabling a faster, stronger response to subsequent exposures.
• Antigen-Presenting Cells (APCs): Bridge innate and adaptive immunity by capturing, processing, and presenting antigens to T cells.
  • Dendritic Cells: Most effective APCs, linking these two systems. They express pathogen-recognition receptors (PRRs) like TLRs to detect various pathogens. Upon activation, they migrate to lymph nodes and present antigens to T cells, initiating the adaptive response.
  • Macrophages: Can also present antigens but are less efficient at migrating to lymph nodes.

Antigens: Targets of the System

• Antigen: Any molecule recognized by the immune system, typically from microbes, transformed cells (e.g., tumors), or self-cells.
• Epitope: The specific region of an antigen recognized by antibodies or T cell receptors.
• Haptens: Small molecules that are not immunogenic on their own; become immunogenic when bound to a larger carrier molecule.
• Immunogen: A subset of antigens that can directly trigger an immune response. All immunogens are antigens, but not all antigens are immunogens.

Antigen Processing and Presentation

• Adaptive immunity relies on antigen presentation by APCs to T cells.
• MHC Class I Pathway: Presents endogenous antigens (produced inside the cell, e.g., viral proteins, intracellular bacteria).
  • Involves most nucleated cells.
  • Intracellular antigens are broken down, transported, and loaded onto MHC class I molecules. The resulting complex travels to the cell surface to be presented to CD8+ T cells, activating them into CTLs.
• MHC Class II Pathway: Presents exogenous antigens (from outside the cell, e.g., bacterial proteins, phagocytosed pathogens).
  • Primarily occurs in professional APCs (dendritic cells, macrophages, B cells)
  • Exogenous antigens are taken up, processed, and bound to MHC class II molecules. The complex is displayed on the cell surface for presentation to CD4+ T cells, activating them.

MHC Polymorphism

• MHC genes are highly polymorphic (many versions or alleles within a population), crucial for immune system diversity.
• Inherited unique combinations of MHC alleles ensure individual variations in antigen recognition.
• While providing broad recognition, individual MHC molecules cannot present all antigens, explaining why some individuals are more susceptible to certain infections.

T Cell Development and Selection

• T cells originate in the bone marrow and mature in the thymus.
• In the thymus, T cells differentiate and mature in thymus lobules.
• T cell receptor (TCR) diversity: Variable region genes of the TCR undergo rearrangement, creating a vast repertoire of antigen-recognizing TCRs.
• T cell selection: T cells interact with MHC molecules on thymic cells.
  • Positive selection: T cells that recognize self-MHC are selected for survival.
  • Negative selection: T cells that strongly bind self-antigens presented on MHC are eliminated to prevent autoimmunity.
• Maturation concludes with T cells expressing either CD4+ or CD8+ and their specific functions.
• Naive T cells: Mature T cells not yet exposed to their specific antigen, circulating in the blood and lymphatic system.

T Cell Activation

• Naive T cells become activated when their TCR recognizes a specific antigen presented by MHC molecules on APCs.
• CD8+ T cell activation: Activated by MHC class I presenting intracellular antigens.
• CD4+ T cell activation: Activated by MHC class II presenting extracellular antigens.
  • CD40-CD40 ligand interaction enhances the response to antigen presentation.

Role of IL-2

• Activated T cells (CD4+ and CD8+) produce IL-2 (cytokine promoting T cell proliferation)
• IL-2 receptors are upregulated on activated T cells.
• IL-2 acts autocrine and paracrine to stimulate T cell division and differentiation, leading to clonal expansion and a more robust immune response.

CD4+ Helper T Cell Functions

• B cell activation: CD4+ helper T cells provide crucial signals for B cell activation, proliferation, and differentiation into antibody-producing plasma cells.
• Macrophage activation: CD4+ T cells secrete cytokines activating macrophages, enhancing their pathogen-killing ability and inflammatory response.
• CD8+ T cell activation: Direct activation help to CD8+ T cells.

B Cell Activation and the Antibody Response

• B cell receptor (BCR): B cells express BCRs specific for particular antigens.
• Two Activation Pathways:
  • T cell-dependent: Requires CD4+ helper T cells, producing highly specific IgG antibodies and memory B cells.
  • T cell-independent: Doesn't require T cells; triggered by certain antigens (e.g., LPS), producing mainly IgM antibodies with limited specificity, without memory B cells.

Immunoglobulins (Antibodies)

• Antibodies (Ig) are crucial components of the adaptive immune system. They perform various functions: neutralizing pathogens, opsonizing microbes for phagocytosis, activating complement, and preventing microbial attachment to mucosal surfaces.
• Their structure consists of light and heavy chains, variable (antigen-binding) regions, and constant (complement binding) regions.
• Antibody diversity is achieved through gene rearrangement and somatic hypermutation.

Antibody Diversity Generation

• Gene rearrangement: Reshuffling of variable gene regions of light chains.
• Somatic hypermutation: Point mutations in variable regions leading to greater diversity and enhanced antigen affinity.

Consequences of T Cell Help for B Cell Activation

• Clonal expansion: Cytokines (IL-4, IL-5) drive B cell proliferation into clones.
• Isotype switching: Generates different antibody classes (from IgM to IgG, IgA, or IgE) switching based on T helper cell help.
• Somatic hypermutation: Introducing point mutations in variable regions for further diversity and affinity maturation.

B Cell Memory and Long-Term Immunity

• Memory B cells: Long-lived cells generated during T cell-dependent B cell activation.
• Secondary response: Upon re-exposure to the same antigen, memory B cells induce a rapid, stronger response producing primarily high-affinity IgG antibodies.

Phases of B Cell Differentiation

• Phase 1: Initial activation and migration of naive B cells.
• Phase 2: Germinal center formation and differentiation of activated B cells into long-lived plasma cells or memory B cells.

Secondary Immune Response

• Faster and stronger response upon second antigen exposure due to memory B and T cells.
• Peak antibody response occurs faster, producing predominantly high-affinity IgG antibodies.

Vaccination and Immunological Memory

• Vaccines mimic natural infection, inducing a primary immune response leading to memory B and T cell formation.
• Subsequent encounters with the pathogen lead to a robust secondary response.

Summary: Timeline of Immune Response

• Primary response (first exposure): Peak antibody levels around 7 days, predominantly IgM, some IgG.
• Secondary response (second exposure): Peak antibody response within 3 days, significantly higher IgG production

Herd Immunity

• Widespread vaccination generates herd immunity, limiting pathogen transmission and protecting even unvaccinated individuals.

Explore the intricate mechanisms of adaptive immunity, a critical defense system against pathogens. This quiz covers the distinctions between antibody-mediated and cell-mediated immunity, as well as the role of various immune cells. Test your knowledge of how adaptive immunity develops and its implications in the immune response.