Adaptive Immunity and Vaccines

Chapter 16

Adaptive Immunity and Vaccines

Module 12: Adaptive Immunity & Immunization

Upon completion of this module, you will be able to:

  • MLO12.1 Differentiate between humoral and cell-mediated immunity.

  • MLO12.2 Recognize the role of antigens, antibodies, B cells, and T helper cells in humoral immunity.

  • MLO12.3 Identify the role of Major Histocompatibility Complexes (MHC), antigens, cytokines, and T cells in cell-mediated immunity.

  • MLO12.4 Differentiate between active and passive immunization.

  • MLO12.5 Identify types, benefits, and adverse reactions of vaccines.

The Impact of Vaccines and Adaptive Immunity

Historic Threat of Infectious Diseases

  • Smallpox and Polio:

    • Once caused widespread death and disability.

    • "Iron lung" wards were used for polio patients in the 1950s.

Vaccination Successes

  • Smallpox Eradication:

    • Eradicated globally; last case reported in 1977.

  • Polio Control:

    • Near eradication achieved.

  • Reductions in Other Diseases:

    • Significant reductions in chickenpox, measles, mumps, whooping cough, and German measles.

Why Vaccines Work

  • Target the Adaptive Immune System:

    • Highly specific to pathogens, providing long-term protection.

  • Mechanism:

    • Provides protection through either active infection or vaccination.

    • Vaccination has eliminated polio in most countries, showcasing the success of vaccines.

Key Features of Adaptive Immunity

Definition of Adaptive Immunity

  • Specificity: Targets specific pathogens.

  • Memory: Immunity is established after exposure, leading to a quicker response.

  • Example:

    • Recovery from chickenpox allows the body to respond faster to a subsequent exposure to the varicella-zoster virus.

Mechanism of Response

  • Primary Response:

    • This occurs upon first exposure to a pathogen or vaccine, "programming" immune cells for future encounters.

  • Secondary Response:

    • Upon re-exposure, the response is faster and stronger, specific to the pathogen.

  • Important Note:

    • Immunity to one pathogen does not offer protection against another (e.g., chickenpox does not protect against measles).

  • Graph Information:

    • Illustrates primary and secondary immune responses, highlighting the faster and higher concentration of antibodies in secondary responses.

Cells of Adaptive Immunity

Two Main Types of Lymphocytes

  • B Cells (B Lymphocytes):

    • Maturation: Occurs in the bone marrow.

    • Function: Produce antibodies (immunoglobulins) to defend against extracellular pathogens and toxins.

    • Role: Humoral immunity.

  • T Cells (T Lymphocytes):

    • Maturation: Occurs in the thymus.

    • Function: Orchestrates innate and adaptive responses; destroys infected cells.

    • Role: Cell-mediated (cellular) immunity.

Antigens and Activation of Adaptive Immunity

Definition of Antigens

  • Antigens:

    • Pathogen-specific molecules that trigger adaptive immune responses, also called immunogens.

    • Unique to specific pathogens (unlike general Patterns Associated with Molecular Patterns (PAMPs)).

Functions of Antigens

  • Stimulate both humoral immunity (antibody production) and cell-mediated immunity.

Sources and Types of Antigens

  • Bacteria:

    • Capsules, cell walls, fimbriae, flagella, pili, toxins/enzyme secretions.

  • Viruses:

    • Capsids, envelopes, spike proteins for cell attachment.

Acquired vs Innate Immunity

Feature

Innate Immunity

Acquired Immunity

Speed

Immediate (minutes to hours)

Slow (days to weeks)

Specificity

Non-specific; recognizes broad patterns (PAMPs)

Highly specific; recognizes unique antigens

Memory

No immunological memory

Develops immunological memory

Components

Anatomical barriers, phagocytes (e.g., macrophages)

B and T lymphocytes

Response to Re-exposure

Identical response every time

Faster and stronger response upon subsequent exposures

Epitopes and Haptens

Definitions

  • Epitopes:

    • Small, exposed regions on an antigen recognized by antibodies and T cells.

    • A single antigen can present multiple epitopes, allowing for binding by different antibodies.

    • Example: Bacterial flagella can present hundreds/thousands of unique epitopes.

  • Haptens:

    • Small molecules that cannot trigger an immune response unless attached to a larger carrier molecule (conjugate antigen).

    • Examples of Hapten-induced Responses:

      • Urushiol from poison ivy leads to contact dermatitis.

      • Penicillin can cause drug allergies.

Antibodies

Structure and Function of Antibodies

  • Antibodies (Immunoglobulins):

    • Glycoproteins found in blood and tissue fluids.

    • Basic Structure: Y-shaped monomer composed of 2 heavy chains and 2 light chains connected by disulfide bonds.

Key Regions of Antibodies

  • Fab Region:

    • Contains two "arms" of the Y, with a variable region that binds to specific epitopes.

    • Functions:

      • Neutralization of pathogens.

      • Agglutination/aggregation of pathogens.

      • Antibody-dependent cell-mediated cytotoxicity.

  • Fc Region:

    • The trunk of the Y, responsible for binding complement factors and phagocytic cells to mediate opsonization.

Antibody Classes

Overview of Antibody Classes (Isotypes)

  • Defined by the constant region of heavy chains; consists of five main classes:

    • IgG (γ):

    • Most abundant (~80% of serum antibodies); crosses placenta providing passive immunity.

    • Versatile in pathogen defense.

    • IgM (μ):

    • First antibody produced during immune response; effective in binding pathogens due to its pentameric structure.

    • IgA (α):

    • Predominantly found in mucus secretions, breast milk, tears, and saliva; functions in trapping pathogens.

    • IgD (δ):

    • Primarily membrane-bound on B cells; functions as an antigen receptor on immature B cells.

    • IgE (ε):

    • Least abundant; involved in anti-parasitic defense and allergic reactions.

Comparison of Antibody Classes

  • IgG:

    • Structure: Monomer.

    • Function: Neutralization, agglutination, opsonization.

  • IgM:

    • Structure: Pentamer.

    • Function: Effective pathogen binding and diagnostic marker for recent infections.

  • IgA:

    • Structure: Dimer.

    • Function: Traps pathogens in mucus, prevents them from reaching epithelial cells.

  • IgD:

    • Structure: Monomer.

    • Function: Serves as B-cell receptor; not secreted.

  • IgE:

    • Structure: Monomer.

    • Function: Triggers release of inflammatory mediators from mast cells and basophils during allergic reactions.

Antigen-Antibody Interactions

Mechanisms

  1. Neutralization:

    • Antibodies bind to pathogens or toxins, preventing their attachment to host cells.

    • Key classes involved: IgG, IgM, IgA.

    • Examples:

      • Secretory IgA in mucosal surfaces.

      • Antibodies preventing viral infections.

  2. Opsonization:

    • Pathogens are coated with opsonins (e.g., complement factors, IgG antibodies) facilitating phagocytosis by immune cells like macrophages and neutrophils.

    • Enhances efficiency of innate immune responses.

  3. Agglutination:

    • Antibodies cross-link multiple pathogens, forming large aggregates.

    • Key classes: IgG, IgM.

    • Benefits include easier filtering from blood and enhanced phagocytosis.

  4. Complement Activation:

    • Antibodies trigger the classical complement pathway upon binding to pathogens.

    • Effects include inflammation, phagocyte recruitment, and direct pathogen killing.

  5. Antibody-dependent cell-mediated cytotoxicity (ADCC):

    • Binding of IgG to a large pathogen activates immune effector cells (e.g., NK cells) leading to target cell destruction.

Major Histocompatibility Complex Molecules

Overview of MHC

  • Definition: A group of genes encoding proteins on the surface of almost all nucleated cells; known as Human Leukocyte Antigen (HLA) genes in humans.

  • Function:

    • Identify "self" to immune cells.

    • Present antigens to T cells for immune system activation.

Two Classes of MHC Molecules

  • MHC Class I:

    • Found on all nucleated cells.

    • Presents intracellular pathogen antigens to CD8+ T cells (cytotoxic).

  • MHC Class II:

    • Present on antigen-presenting cells (APCs) like macrophages and dendritic cells.

    • Presents self and non-self peptides to CD4+ T cells (helper).

Antigen Processing and Presentation

Mechanisms in APCs

  1. APCs and MHC Presentation:

    • MHC I Molecules: Present antigens from all nucleated cells to cytotoxic T cells, signalling cell health status.

    • MHC II Molecules: Only specialized APCs can present antigens, activating helper T cells.

  2. Process Overview:

    • Macrophages and Dendritic Cells: Recognize and engulf pathogens, process antigens, and present them on MHC molecules.

    • Internalization and Presentation: The complex of MHC and antigen is displayed on the cell surface for T cell recognition.

Thymic Selection and Peripheral Tolerance

T Cell Production and Maturation

  • T cells develop in the thymus, an essential organ for maturation and selection.

  • Thymic Selection: Three critical steps ensuring T cells are functional and not self-reactive.

    • Functional TCR Selection: Development of a functional T-cell receptor (TCR) for activation by APCs.

    • Positive Selection: Examines MHC interaction, ensuring adequate immune response.

    • Negative Selection: Eliminates self-reactive thymocytes to prevent autoimmunity.

Peripheral Tolerance

  • Acts as a second line of defense against self-reactive T cells that escape thymic selection.

    • Mechanisms include:

      • Anergy (nonresponsiveness) without co-stimulation.

      • Regulatory T cells (Tregs) inhibit self-reactive T cell functionality through anti-inflammatory cytokines.

T-Cell Receptor (TCR)

Structure and Diversity

  • Composition of TCR: Two peptide chains (alpha and beta) span the T cell's cytoplasmic membrane, differing from antibodies.

  • Genetic Rearrangement: Achieves diversity necessary for the immune response via V(D)J recombination during thymic selection.

    • Process Details: Involved selection and combination of variable region gene segments to generate diverse TCRs.

Activation and Function of T Cells

  • Helper T Cells (CD4+):

    • Recognize antigens presented via MHC II; orchestrate immune responses.

  • Cytotoxic T Cells (CD8+):

    • Engage antigens via MHC I to destroy infected cells and elicit memory responses.

B Cell Activation and Function

B Cell Maturation

  • Arise from hematopoietic stem cells in the bone marrow.

    • Positive Selection: Ensures functional antigen receptors are present.

    • Negative Selection: Removes autoreactive B cells.

  • Mature B cells migrate to peripheral lymphoid tissues for activation.

B Cell Activation Pathways

  • T Cell-Dependent Activation: Requires help from T-helper cells for full activation while presenting antigens via MHC II.

  • T Cell-Independent Activation: Direct activation via T-independent antigens without T cell aid, typically involves repetitive epitopes.

Immune Responses

Primary vs Secondary Responses

  • Primary Response: Slow reaction (~10 days lag); involves clonal expansion and antibody production.

  • Secondary Response: Rapid and robust (~2-3 days lag); leads to higher concentrations of specific antibodies.

    • Memory cells formed during the primary response ensure quick action upon re-exposure.