Adaptive Immunity

Overview of Adaptive Immunity

Adaptive immunity is the third line of defense in the immune system, characterized by its specificity and memory. It involves specialized lymphocytes—T cells and B cells—and the production of antibodies to target specific pathogens.

• Specialized lymphocytes: T cells (cell-mediated immunity) and B cells (humoral immunity)

• Antibodies: Proteins produced by B cells that bind to antigens

Learning Objectives

• Compare and contrast adaptive and innate immunity

• Differentiation between humoral and cellular immunity

• Define antigen and epitope

• Explain antibody function and describe their structural/chemical characteristics

• Name one function for each of the five classes of antibodies

• Compare and contrast T-dependent and T-independent antigens

• Differentiation of plasma cell from memory cell; describe clonal selection

• Describe four outcomes of an antigen-antibody reaction

• Describe the functions of: T helper cells, CTLs, NK cells; differentiate T helper and T cytotoxic cells

• Define antigen-presenting cell

• Describe the function of natural killer cells

• Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity

• Distinguish a primary from a secondary immune response

• Contrast the four types of adaptive immunity

Adaptive Immune Response

Types of Immunity

Adaptive immunity is divided into two main branches: humoral immunity and cell-mediated immunity. Both are mediated by lymphocytes and are induced by exposure to antigens.

• Humoral Immunity: Involves B cells, which differentiate into plasma cells (secreting antibodies) and memory cells. Most effective against extracellular pathogens.

• Cell-Mediated Immunity: Involves T cells, which differentiate into effector cells (cytotoxic T cells and helper T cells). Most effective against intracellular pathogens.

Antigens and Epitopes

Definition and Interaction

Antigens (Ag) are molecules that activate lymphocytes in the body. B cells interact with antigens via surface immunoglobulins (antibodies), while T cells interact via surface antigen receptors. Antigens contain smaller segments called epitopes or antigenic determinants, which elicit an immune response.

• Epitope: The specific part of an antigen recognized by antibodies or T cell receptors; can be a protein, peptide, or complex polysaccharide.

• Example: Bacterial cell wall components can serve as antigens with multiple epitopes.

Antibody Structure and Diversity

Structure

Antibodies are Y-shaped molecules composed of two heavy chains and two light chains, each with constant and variable regions. The variable regions possess variable amino acid sequences and form the antigen-binding sites. The Fc region (stem) binds to host cell receptors.

• Antibody classes: IgG, IgD, IgE (monomers); IgM and IgA (aggregates of 2 or more monomers)

Functions and Classes of Antibodies

Humoral Immune Response

B Cell Activation and Clonal Selection

The humoral immune response involves B cells binding to specific epitopes via surface immunoglobulins. B cells usually require interaction with T helper cells (TH), especially for T-dependent antigens. The key process is clonal selection, where B cells that recognize a specific antigen proliferate and differentiate into plasma cells (secreting antibodies) and memory cells.

• T-dependent antigens: Require TH cell help for B cell activation (via MHC class II receptors)

• T-independent antigens: Can activate B cells without TH cell help

Antibody Responses

Primary and Secondary Responses

Antibody responses can be classified as primary or secondary, depending on the exposure to antigen.

• Primary response: Occurs after initial infection or vaccination; antibodies appear after several days. B cells differentiate into plasma cells (first IgM, then IgG) and memory B cells.

• Secondary response: Occurs upon re-exposure to the same antigen; due to memory B cells, the response is faster, larger, and mainly involves IgG. This is the basis for immunization.

Outcomes of Antigen-Antibody Reactions

Protective Mechanisms

Binding of antibodies to antigens leads to several protective mechanisms:

• Agglutination: Antibodies cause pathogens to clump together, facilitating removal.

• Opsonization: Antibodies coat pathogens, enhancing phagocytosis.

• Neutralization: Antibodies block attachment of bacteria and viruses to host cells, or neutralize toxins.

• Activation of complement: Antibody binding triggers the complement system, leading to inflammation and cell lysis.

• Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies attached to target cells facilitate destruction by immune cells such as NK cells.

Cell-Mediated Immunity

T Cell Functions

Cell-mediated immunity involves T cells recognizing antigens presented on the surface of infected cells (intracellular pathogens).

• T cytotoxic cells (TC): Differentiate into cytotoxic T lymphocytes (CTLs); target self-cells altered by infection or cancer. Recognize endogenous antigens with MHC class I molecules via CD8+ co-receptor. Kill target cells via perforin proteins and induction of apoptosis by granzymes.

• T helper cells (TH): Recognize antigens presented by antigen-presenting cells (APCs), such as dendritic cells and macrophages, via CD4+ co-receptors and MHC class II molecules. Activation leads to cytokine release.

• TH 1 cells: Cytokines activate macrophages, complement, promote inflammation and opsonization, and differentiation of CTLs.

• TH 2 cells: Cytokines mainly promote antibody production by B cells.

Types of Adaptive Immunity

Classification

Adaptive immunity can be acquired naturally or artificially, and can be active or passive.

Summary and Key Concepts

• Adaptive immunity is divided into humoral (antibody-mediated) and cellular (cell-mediated) branches.

• Antigens elicit antibody responses and may contain multiple epitopes.

• Antibodies are Y-shaped molecules with two heavy and two light chains, each with constant and variable regions.

• The five antibody classes are: IgG, IgM, IgA, IgD, IgE.

• Secondary antibody response is faster, larger, and longer than the primary response due to memory B cells.

• Types of T cells include helper T cells and cytotoxic T cells.

• The classical pathway for complement activation is a key mechanism in immune defense.

Key Equations and Concepts

• Clonal Selection:

• Antibody-Antigen Binding: