anitbodies humoral antigen

Queen's University Belfast - Wellcome-Wolfson Institute for Experimental Medicine

Overview of Immunology Concepts

Course Information

  • Course Title: Antigen receptors, antibodies, and the humoral response

  • Course Code: BMS2106

  • Instructor: Dessi Malinova

  • Date: 9th October 2025

Learning Outcomes

  • Describe the structural organization of B-cell and T-cell antigen receptors.

  • Explain how receptor diversity is generated at the genetic level.

  • Define antigen receptors and understand their expression.

  • Distinguish the different classes of antibodies along with their structure and function.

  • Understand how B cells become activated and produce antibodies.

  • Describe antibody effector functions and their importance.

  • Explain B cell development and the emergence of the extensive antibody repertoire.

Pathogen Sizes and Types

Different Pathogens and Their Sizes (in mm)

  • Worms: 10^3 (e.g., Filaria, Guineaworm)

  • Protozoa: 10^-1 (e.g., Amoeba, Leishmania)

  • Fungi: 10^-2 (e.g., Aspergillus, Candida)

  • Bacteria: 10^-3 (e.g., Mycobacterium, Staphylococcus)

  • Viruses: 10^4 (e.g., Influenza, Polio)

Immunity

Definition

  • Immunity: The ability of an organism to resist infection.

  • Innate Immune Activation:

    • Immediate/Continuous Response

    • Components:
      (1) Physical barriers to pathogens
      (2) Chemical defenses
      (3) Innate immunity responses (minutes to hours)
      (4) Adaptive immunity responses (days)

Phases of Immune Responses

  1. Recognition of Pathogen

  2. Reaction Against It (Elimination)

  3. Resolution of Immune Response

  • Adaptive immunity is specific and memory-based.

Antigen Receptors

Types and Structures

  • B-cell Receptor (BCR):

    • Comprised of:

    • Light Chain

    • Heavy Chain

    • Fab and Fc regions

    • Igα and Igβ for signaling

  • T-cell Receptor (TCR):

    • Comprised of:

    • α chain

    • β chain

    • ITAM (Immunoreceptor Tyrosine-based Activation Motif)

Function in Humoral Response Activation

  1. Antigen Targeting to APC (Antigen-Presenting Cell)

  2. Antigen Processing and Presentation

  3. T Cell Activation: Antigen-bound MHC (Major Histocompatibility Complex) markers.

    • CD4+ T cells and CD8+ T cells involved.

Antibodies

Definition and Structure

  • Antibodies are immunoglobulins, glycoprotein molecules recognizing diverse antigens including proteins, carbohydrates, nucleic acids, and small molecules.

  • Structure:

    • Comprised of heavy chains and light chains, linked by disulfide bonds.

Classes of Antibodies

  • IgM: First antibody type produced during primary response.

  • IgD: Present mostly on B-cell membranes; constitutes 0.25% of serum Ig.

  • IgG: Most prevalent in secondary responses; crosses the placenta for neonatal protection.

  • IgA: Found in secretory form on mucosal surfaces.

  • IgE: Major role in allergic reactions and responses to parasites.

Antibody Function and Distribution

  1. Neutralization: Prevents toxins and viruses from affecting host cells.

  2. Opsonization: Enhances phagocytosis of pathogens.

  3. Induction of inflammation: Antibody binding can trigger inflammatory responses.

  4. Complement Activation: Triggers the complement cascade for pathogen destruction.

  5. Transport across epithelial barriers and placenta: Ensures effective immune responses.

  • Mean serum levels (in mg/ml): IgM (1.5), IgD (0.04), IgG1 (9), IgG2 (3), IgG3 (1), IgG4 (0.5), IgA (2.1), IgE (30).

B Cell Development

Stages of Development in the Bone Marrow and Periphery

  1. Pro-B Cell: Precursor stage.

  2. Pre-B Cell: Assembles components of the B-cell receptor (BCR).

  3. Immature B Cell: IgM present on the surface.

  4. Mature B Cell: Fully developed BCR recognized.

  5. Activation and Differentiation: Leads to memory B cells and plasma cells producing antibodies.

Antibody Diversity Mechanisms

  • VDJ Recombination: Heavy chain segments V (variable), D (diversity), and J (joining) lead to diverse antibody products.

  • Light Chain Gene: Undergoes VJ recombination.

Mechanism of Rearrangement

  • RAG1-RAG2 complex facilitates the recombination resulting in diverse antibody forms.

  • Mutations in this process can lead to severe combined immunodeficiency (SCID) due to lack of both B and T cells.

T-dependent and T-independent Responses

T-dependent Response

  1. Interaction of dendritic cells with naive T cells.

  2. Activated T cells assist B cell interaction.

  3. Clonal expansion and differentiation occur in the germinal center.

T-independent Response

  • B cells can be activated directly by antigens without T cell help, generally quicker response times.

Immunological Memory

Responses

  • Primary Response: Upon first encounter with an antigen.

  • Secondary Response: Rapid, robust response upon subsequent encounters due to memory cells.

  • Provides basis for vaccination efficacy.

Applications of Immunology

Research and Therapeutic Applications

  • Antibodies as tools for research and diagnostics.

  • Development of immunotherapy approaches and understanding immunological tolerance.

Classroom Questions

  1. What is an antibody?

  2. How does an antibody bind to an antigen?

  3. How does antibody diversity arise?

  4. What is class-switch recombination?

  5. Outline the molecular details of VDJ recombination.

  6. Provide five examples of antibody-mediated host defenses.

Further Reading

  • Janeway's Immunobiology

  • Adaptive Immunity by Kavathas, Krause, and Ruddle in Immunoepidemiology.

  • Pearls on antibody engineering and immunological principles from Drs. Reihill, Small, Kissenpfennig and Fitzgerald.