CH 16 Adaptive Immunity: Mechanisms, Cells, and Molecular Basis

Adaptive Immunity

Overview of Adaptive Immunity

Adaptive immunity is the body's highly specific defense mechanism against distinct pathogens and their products. Unlike innate immunity, adaptive immunity is characterized by its ability to recognize a vast array of antigens and remember previous encounters for a faster response upon re-exposure.

• Specificity: Targets unique antigens, mainly proteins, with high precision.

• Inducibility: Activated only in response to specific antigens.

• Clonality: Generates clones of lymphocytes specific to the antigen.

• Unresponsiveness to self: Normally does not react to self-antigens, preventing autoimmunity.

• Memory: Remembers previous antigens for a more rapid and robust response upon re-exposure.

Adaptive immunity involves two main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). B cells mature in the bone marrow, while T cells mature in the thymus. The two main branches of adaptive immunity are cell-mediated immunity (primarily T cells) and humoral immunity (primarily B cells and antibodies).

Comparison of Innate and Adaptive Immunity

Key Differences

• Distribution: Adaptive immunity is found only in vertebrates; innate immunity is present in almost all multicellular eukaryotes.

• Targets: Adaptive immunity recognizes billions of unique antigens; innate immunity recognizes a limited set of conserved microbial patterns (PAMPs).

• Immune Receptors: Adaptive immunity uses T cell receptors and antibodies; innate immunity uses pattern recognition receptors (e.g., Toll-like receptors).

• Cellular Presence: Adaptive immunity is mediated by lymphocytes; innate immunity involves almost all cells.

• Memory: Adaptive immunity has immunological memory; innate immunity does not.

The Lymphatic System and Immune Function

Tissues and Organs of the Lymphatic System

The lymphatic system is composed of lymphatic vessels, lymphoid cells, tissues, and organs. It screens the body's tissues for foreign molecules and is essential for the initiation of adaptive immune responses.

• Lymphatic vessels: One-way system that returns lymph (fluid similar to plasma) from tissues to the circulatory system.

• Primary lymphoid organs: Red bone marrow and thymus (sites of lymphocyte development).

• Secondary lymphoid organs: Lymph nodes, spleen, tonsils, and mucosa-associated lymphoid tissue (MALT).

Antigens and Epitopes

Properties and Types of Antigens

Antigens are molecules recognized as foreign by the immune system, provoking a specific immune response. The specific regions recognized by immune receptors are called epitopes or antigenic determinants.

• Best antigens are large, complex macromolecules (e.g., proteins of microbes).

• Antigens can be exogenous (from outside the cell), endogenous (produced within infected cells), or autoantigens (from normal cellular processes).

Major Histocompatibility Complex (MHC) and Antigen Presentation

MHC Molecules

The major histocompatibility complex (MHC) consists of glycoproteins on cell membranes that present antigenic peptides to T cells. There are two main classes:

• MHC class I: Present on all nucleated cells (except red blood cells); present endogenous antigens.

• MHC class II: Present only on antigen-presenting cells (APCs) such as macrophages, B cells, and dendritic cells; present exogenous antigens.

Antigen-Presenting Cells (APCs)

APCs, especially dendritic cells, are crucial for processing and presenting antigens to T cells. They internalize pathogens, process them, and display peptide fragments on MHC molecules for T cell recognition.

T Lymphocytes (T Cells)

Development and Function

T cells are produced in the bone marrow and mature in the thymus. They circulate in the blood and lymph and migrate to secondary lymphoid organs. Each T cell expresses a unique T cell receptor (TCR) that recognizes antigenic peptides only when presented by MHC molecules.

• TCRs: Bind only to epitopes associated with MHC proteins.

• Types of T cells:

  • Cytotoxic T cells (Tc): Kill infected or abnormal cells directly.

  • Helper T cells (Th): Regulate immune responses; include Th1 and Th2 subtypes.

  • Regulatory T cells (Treg): Suppress inappropriate immune responses.

Clonal Deletion of T Cells

Self-reactive T cells are eliminated in the thymus through apoptosis, preventing autoimmune responses.

B Lymphocytes (B Cells) and Antibodies

Development and Function

B cells mature in the bone marrow and are primarily found in the spleen, lymph nodes, and MALT. Their main function is the production and secretion of antibodies (immunoglobulins).

• Each B cell expresses a unique B cell receptor (BCR) capable of binding a specific epitope.

• BCR diversity is generated by random recombination of gene segments (V, D, J) by the enzyme RAG.

Antibody Structure and Classes

Antibodies are Y-shaped proteins secreted by plasma cells (activated B cells). They have two antigen-binding sites and are classified into five main classes based on their structure and function:

• IgM: First antibody produced during an immune response.

• IgG: Most common and long-lasting; crosses the placenta.

• IgA: Found in body secretions (e.g., saliva, tears, breast milk).

• IgE: Involved in allergic responses and defense against parasites.

• IgD: Function not fully understood.

Functions of Antibodies

• Activation of complement and inflammation

• Neutralization of toxins and pathogens

• Opsonization (enhancing phagocytosis)

• Agglutination (clumping of antigens)

• Antibody-dependent cellular cytotoxicity (ADCC)

Clonal Deletion of B Cells

Self-reactive B cells are eliminated or inactivated in the bone marrow to prevent autoimmunity.

Immune Response Cytokines

Types and Functions

Cytokines are soluble regulatory proteins that mediate communication between immune cells. Major types include:

• Interleukins (ILs): Signal among leukocytes.

• Interferons (IFNs): Antiviral proteins and immune modulators.

• Growth factors: Stimulate cell division.

• Tumor necrosis factor (TNF): Induces inflammation and apoptosis.

• Chemokines: Attract leukocytes to infection sites.

Cell-Mediated Immune Responses

Mechanisms and Functions

Cell-mediated immunity is primarily directed against intracellular pathogens (e.g., viruses, some bacteria, cancer cells). Cytotoxic T cells kill infected or abnormal cells via two main pathways:

• Perforin-granzyme pathway: Releases proteins that induce apoptosis in target cells.

• CD95 pathway: Involves interaction with death receptors on target cells to trigger apoptosis.

Memory T Cells

Some activated T cells become memory T cells, which persist long-term and respond rapidly upon re-exposure to their specific antigen.

Antibody (Humoral) Immune Responses

Plasma Cells and Memory B Cells

Upon activation, B cells proliferate and differentiate into plasma cells (which secrete antibodies) and memory B cells (which persist for rapid response upon re-exposure).

Primary and Secondary Immune Responses

• Primary response: First exposure to antigen; slower and produces fewer antibodies.

• Secondary response: Subsequent exposures; faster and more robust due to memory cells.

Types of Acquired Immunity

Active vs. Passive Immunity

• Naturally acquired active immunity: Response to antigens encountered in daily life (e.g., infection).

• Naturally acquired passive immunity: Transfer of antibodies from mother to child (e.g., via placenta or breast milk).

• Artificially acquired active immunity: Response to antigens introduced by vaccination.

• Artificially acquired passive immunity: Transfer of antibodies (e.g., antiserum injection).

Additional info: This summary integrates foundational concepts of adaptive immunity, including the molecular and cellular mechanisms, and highlights the importance of antigen recognition, lymphocyte diversity, and immunological memory in host defense. The included images reinforce key structural and functional aspects of the immune response.