4 Antigen presentation

Antigen Presentation

  • Definition of Antigen Presentation: The process by which antigen-presenting cells (APCs) display antigens on their surface using molecules of the Major Histocompatibility Complex (MHC) to allow T cells to recognize and respond to these antigens.

  • Professional Antigen Presenting Cells (pAPCs):

    • Include macrophages and dendritic cells, which are specialized to perform antigen presentation.

    • Function by capturing, processing, and presenting antigens using MHC molecules.

  • T Cell Recognition:

    • T cells utilize T-cell receptors (TCRs) to recognize the presented antigen on the MHC. This recognition initiates the activation of the adaptive immune response.

Adaptive Immunity

  • Overview of Adaptive Immunity:

    • A specific immune response that is developed and refined upon exposure to foreign substances known as nonself antigens (e.g., spike protein of SARS-CoV-2).

    • Carried out primarily by lymphocytes, which include T cells and B cells.

Three Lines of Defense against Foreign Invaders

  1. Natural Barriers: Physical and chemical barriers (e.g., skin, mucous membranes).

  2. Innate Immunity: Immediate, non-specific immune responses (e.g., inflammation, phagocytes).

  3. Adaptive Immunity: Delayed, specific immune responses that develop after exposure to antigens.

Lymphocyte Development

  • Lymphocyte Origins:

    • Lymphocyte development occurs primarily in:

    • Bone Marrow: The site of mature naïve B cells and T cell precursors.

    • Thymus: The site where immature T cells mature.

    • Lymph Nodes: Where naïve lymphocytes await exposure to antigens.

  • Maturation of Lymphocytes:

    • Mature Naïve B Cell: Organizes with a B cell receptor (BCR).

    • Mature Naïve T Cell: Organizes with a T cell receptor (TCR).

Clonal Diversity in Lymphocytes

  • Definition of Clonal Diversity:

    • Each mature lymphocyte clone has a receptor specific for a single antigen, contributing to the vast diversity of the immune response.

  • Gene Rearrangement:

    • Lymphocytes possess over 500 gene segments that undergo rearrangement or "shuffling" to produce approximately 101310^{13} possible combinations of receptors.

    • Different somatic recombinations lead to diverse amino acid sequences in finished proteins, allowing for recognition of various antigens.

Clonal Deletion and Self-Tolerance

  • Definition of Clonal Deletion:

    • A process that establishes self-tolerance by eliminating lymphocyte clones that recognize self antigens.

    • Clones with BCR or TCR that bind to self antigens undergo apoptosis (programmed cell death).

  • Importance of Self-Tolerance:

    • Prevents autoimmune responses and allows the immune system to focus on nonself antigens.

Clonal Selection and Expansion

  • Definition of Clonal Selection:

    • A process where a single naïve lymphocyte clone is activated by recognition of a foreign antigen, leading to its proliferation and differentiation into effector cells that combat the pathogen.

  • Clonal Expansion:

    • Following selection, there is rapid division of the selected lymphocyte to increase the population that can respond to the specific antigen.

Major Histocompatibility Complex (MHC)

  • Definition of MHC:

    • A group of proteins present on cell surfaces that plays a critical role in the immune system, facilitating antigen presentation to T cells.

  • Classes of MHC:

    • MHC Class I:

    • Expressed by all nucleated cells.

    • Presents endogenous antigens (e.g., from intracellular microbes) to CD8/cytotoxic T cells.

    • MHC Class II:

    • Expressed by professional APCs, including dendritic cells, macrophages, and B cells.

    • Presents exogenous antigens (e.g., from extracellular microbes) to CD4/helper T cells.

T Cell Receptors (TCR)

  • Structure of TCR:

    • Each TCR consists of two chains (α and β chains) that combine with the CD3 complex for intracellular signaling.

    • Has a specific binding site that recognizes peptide antigens presented by MHC molecules.

    • Co-receptors:

    • TCR requires the CD4 co-receptor to bind to MHC Class II and the CD8 co-receptor to bind to MHC Class I.

B Cell Receptors (BCR)

  • Structure of BCR:

    • Composed of four chains (two heavy chains and two light chains) associated with Igα and Igβ for signaling.

    • BCR can recognize native antigens (no MHC required) through their epitopes.

  • Activation of B Cells:

    • Naïve B cells can act as APCs by presenting exogenous antigens with MHC Class II to CD4 helper T cells.

    • When activated, T cells secrete cytokines that further activate B cells, leading to a robust antibody response.

Summary of Key Terms

  • Antigen: A substance that triggers an immune response, often recognized by receptors on immune cells.

  • Lymphocytes: Immune cells (T cells and B cells) responsible for adaptive immunity.

  • Clonal Diversity: The variety of lymphocyte clones capable of recognizing different antigens.

  • Clonal Deletion: The process of eliminating self-reactive lymphocytes to prevent autoimmunity.

  • Clonal Selection and Expansion: The activation and replication of specific lymphocyte clones upon encountering their respective antigens.

  • MHC: Major Histocompatibility Complex, essential for presenting antigens to T cells.