Ags_Ag_Receptors_Lecture_A_BMS2045_2025

Antigens and Antigen Receptors

Lecture Overview

Lecture A: Antigens & Antigen Receptors by Dr. Natalie RiddellContact: n.riddell@surrey.ac.ukDiscussion Board: Theme 3

Theme 3 Introduction

Aims:

  • Understanding the composition, properties, and complex interactions of antigens in the immune response.

  • Comprehensive knowledge of the structure and function of the following components:

    • B cell receptors (BCR): Essential for antigen recognition and initiating B cell activation.

    • T cell receptors (TCR): Critical for recognizing processed antigens presented by MHC molecules.

    • Major Histocompatibility Complexes (MHC): Presented on cell surfaces and play a vital role in immune recognition.

Lecture Content Breakdown

Lecture A (Today):

  • Part 1: General Principles, Antigens, and Immunogens

  • Part 2: The B Cell Receptor and Antibodies

Lecture B (Wednesday, 10 am):

  • Part 1: Epitopes, Affinity, and Avidity

  • Part 2: The T Cell Receptor, Polyclonal Responses

Lecture C (Thursday, 2 pm):

  • Part 1: MHC Class I & II, Antigen Processing and Presentation

  • Part 2: Genetics of Antigen Recognition

Lecture A, Part 1

Definitions
  • Antigen: A molecule or molecular structure that can provoke an adaptive immune response. These can originate from various sources, including pathogens and abnormal cells in the body.

  • Immunogen: A specific type of antigen capable of eliciting a full immune response, often requiring certain characteristics such as molecular size and complexity.

Factors Influencing Immunogenicity
  • The uniqueness, size, structural complexity, and stability of antigens are critical in determining their immunogenic potential.

  • Important distinctions exist between T cell and B cell antigens, with B cells recognizing native antigens and T cells requiring processed antigens bound to MHC molecules.

Immune System Overview

The human immune system has evolved to recognize and effectively defend against a wide range of pathogens. This system possesses a sophisticated memory mechanism allowing it to remember previously encountered antigens, enhancing the speed and efficacy of subsequent responses.

  • Antigens (Ag): Substances that trigger an immune response, recognized by specific immune receptors.

  • Key Immune Cells: Include antigen-presenting cells (APCs), B lymphocytes which produce antibodies, and T lymphocytes that carry out cell-mediated immunity.

  • Vaccines: Utilize attenuated or inactivated pathogens or their components to stimulate an immune response and establish immunological memory without causing disease.

Phases of Adaptive Immune Response

  1. Recognition Phase: Antigens are detected by specific receptors on B and T cells.

  2. Activation Phase: Lymphocytes undergo proliferation and differentiation into effector and memory cells.

  3. Effector Phase: Target antigens are eliminated through various mechanisms, including cell-mediated cytotoxicity or antibody-mediated opsonization.

  4. Homeostasis: Recovery of immune cells to a non-reactive state, while memory cells persist to facilitate faster responses upon re-exposure to the same antigen.

Antigen Presentation

  • Antigen presentation occurs in various tissues based on the origin of the antigen:

    • Free antigens: Found within tissues.

    • Dendritic cells: Capture and present antigens in lymph nodes, activating T cells.

    • Blood-borne antigens: Captured by antigen-presenting cells such as macrophages in the spleen.

Types of Antigens and Immunogens

Characteristics
  • Antigens can be proteins, lipids, carbohydrates, or combinations, and they can either be foreign or self-derived.

  • Antigenic determinants (epitopes): The specific parts of the antigen recognized by the immune receptors.

Foreign versus Self
  • Foreign Antigens: Typically derived from microbes such as bacteria, viruses, and fungi.

  • Altered Self Antigens: Produced from damaged or senescent own cells, which may trigger an immune response in autoimmunity.

Influencing Factors of Immunogenicity

  • Size: Larger antigens are generally more immunogenic than smaller ones.

  • Route of Entry: Different administration routes can significantly affect immunogenicity, e.g., subcutaneous infections tend to elicit more robust immune responses than intravenous ones.

  • Complexity: Structural complexity and modifications play a significant role in eliciting responses.

Role of Adjuvants

Adjuvants are substances that enhance the body’s immune response to an antigen. They improve effectiveness by:

  • Increasing the persistence of antigens in the body

  • Promoting effective cellular interactionsCommon adjuvants include Complete Freund’s (a water-in-oil emulsion) and Alum (aluminum salts).

Antigen Receptors

Types
  1. Innate (Non-Specific): Utilize Pattern Recognition Receptors (PRRs).

  2. Adaptive (Specific): Comprised of B cell Receptors (BCR) and T cell Receptors (TCR), essential for pathogen-specific immune responses.

Functionality
  • B cells interact directly with native antigens, while T cells recognize processed antigens bound to MHC molecules for effective immune function.

Immunoglobulins (Antibodies)

Structure
  • The basic structure of antibodies: Monomer featuring two heavy chains and two light chains, with variable regions conferring specificity for distinct antigens.

Class Differences
  • Five Classes of Immunoglobulins: IgM, IgA, IgG, IgD, IgE, each serving unique roles in different types of immune responses (e.g., IgG is predominant in secondary responses).

B Cell Receptor (BCR)
  • Comprising a membrane-bound immunoglobulin along with signaling components (Igα and Igβ), the BCR is critical for antigen binding and internal signaling, leading to B cell activation and differentiation into memory and plasma cells.

Conclusion

Next topics will include discussions on epitopes, affinity, avidity, and the structure of T cell receptors.

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