Adaptive Immunity: Specific Defenses of the Host

Introduction to Adaptive Immunity

Adaptive immunity refers to the host's ability to mount a specific defense against pathogens following exposure. This system distinguishes "self" from "nonself" and is activated when innate immunity fails to eliminate a microbe. Adaptive immunity is acquired through infection or vaccination and is characterized by a primary response (first exposure) and a secondary response (subsequent exposures, which are faster and more effective due to immunological memory).

• Adaptive immunity: Specific, acquired defense against pathogens.

• Primary response: Initial immune reaction to a new antigen.

• Secondary response: Enhanced response upon re-exposure to the same antigen.

Dual Nature of the Adaptive Immune System

Humoral Immunity

Humoral immunity is mediated by antibodies produced by B lymphocytes. These antibodies target antigens, which are foreign molecules, for destruction. B cells are generated and mature in the red bone marrow and, once mature, reside in blood and lymphoid organs.

• B cells: Lymphocytes that recognize antigens and produce antibodies.

• Antibodies: Proteins that bind specifically to antigens.

• Antigens: Substances that elicit antibody production; may be microbial (capsules, cell walls, flagella, toxins, viral capsids/spikes) or nonmicrobial (egg white, pollen).

Cellular Immunity (Cell-Mediated Immunity)

Cellular immunity involves T lymphocytes, which recognize antigenic peptides processed by phagocytic cells. T cells mature in the thymus and reside in blood and lymphoid organs. Their surface T cell receptors (TCRs) interact with antigens, leading to cytokine secretion rather than antibody production. Cellular immunity is most effective against virus-infected cells and intracellular bacteria.

• T cells: Lymphocytes that mediate cellular immunity.

• T cell receptors (TCRs): Surface molecules that recognize antigens.

• Best targets: Virus-infected cells, intracellular bacteria (e.g., M. leprae, L. monocytogenes).

Cytokines: Chemical Messengers of Immune Cells

Types and Functions of Cytokines

Cytokines are protein messengers produced in response to stimuli and regulate immune responses. Overproduction can lead to a cytokine storm, which is harmful.

• Interleukins (ILs): Mediate communication between leukocytes.

• Chemokines: Induce migration (chemotaxis) of leukocytes.

• Interferons (IFNs): Interfere with viral infections.

• Tumor necrosis factor alpha (TNF-α): Involved in inflammation and autoimmune diseases.

• Hematopoietic cytokines: Control development of blood cells.

Antigens and Epitopes

Antigen Structure and Recognition

Antigens are substances that provoke an immune response, typically by stimulating antibody production. Antibodies recognize specific regions on antigens called epitopes (antigenic determinants). Haptens are small molecules that become antigenic only when attached to carrier molecules.

• Epitopes: Specific regions on antigens recognized by antibodies.

• Haptens: Small molecules that require a carrier to elicit an immune response.

Humoral Immunity: Antibodies

Structure and Classes of Immunoglobulins

Antibodies (immunoglobulins, Ig) are compact, soluble proteins that bind antigens. Each antibody has a valence, indicating the number of antigen-binding sites. The basic structure consists of two identical light chains and two identical heavy chains, forming a Y shape. The variable (V) regions bind epitopes, while the constant (Fc) region determines the class.

• Five classes of Ig: IgG, IgM, IgA, IgD, IgE

Humoral Immunity Response Process

Clonal Selection and Expansion

B cells interact with antigens in lymphoid organs. Each B cell has numerous surface immunoglobulins serving as antigen receptors. Upon binding its specific antigen, a B cell is activated (clonal selection) and proliferates (clonal expansion), differentiating into antibody-secreting plasma cells and memory B cells.

• Clonal selection: Activation of B cell by antigen binding.

• Clonal expansion: Proliferation and differentiation into plasma and memory cells.

Activation of B Cells

• T-dependent antigens: Require T helper cell (TH) assistance; involve protein antigens.

• T-independent antigens: Do not require TH cell; often polysaccharides.

Antigen-presenting cells (APCs) display antigens with major histocompatibility complex (MHC) molecules. Class I MHC is on all nucleated cells; Class II MHC is on APCs (B cells, macrophages, dendritic cells).

Diversity and Results of Antigen-Antibody Interaction

Antibody Diversity

Humans can produce up to (100 billion) different antibodies due to gene segment rearrangement. Clonal deletion removes self-reactive B cells.

Antigen-Antibody Complex Effects

• Agglutination: Clumping of antigens.

• Opsonization: Coating antigen to enhance phagocytosis.

• Antibody-dependent cell-mediated cytotoxicity: Destruction of large pathogens.

• Neutralization: Blocking toxins or viruses.

• Complement activation: Triggering the complement system for pathogen lysis.

Cellular Immunity Response Process

T Cell Development and Function

T cells mature in the thymus, where thymic selection eliminates self-reactive cells. They migrate to lymphoid tissues and attach to antigens via TCRs. Pathogens in the gastrointestinal tract are transferred to lymphocytes and APCs via microfold cells (M cells) over Peyer's patches.

• Antigen-presenting cells (APCs): Dendritic cells, macrophages, B cells.

• Dendritic cells: Engulf and degrade microbes, present antigens to T cells.

• Macrophages: Activated by cytokines or antigen ingestion, present antigens to T cells.

Classes of T Cells

• CD4+ T helper cells (TH): Activate B cells and other immune cells; bind MHC class II.

• CD8+ Cytotoxic T lymphocytes (CTL): Destroy infected or abnormal cells; bind MHC class I.

Summary Table: Key Features of Immunoglobulin Classes

Additional info:

• Immunological memory is crucial for long-term protection and is the basis for vaccination.

• Major histocompatibility complex (MHC) molecules are essential for antigen presentation and immune recognition.

• Natural killer (NK) cells are part of the adaptive immune system and destroy virus-infected and tumor cells without antigen stimulation.