Chapter 16: Adaptive Immunity

Adaptive Immunity: An Overview

Comparison of Innate and Adaptive Immunity

Adaptive immunity is a specialized branch of the immune system that provides specific, inducible, and long-lasting defense against pathogens. It is distinct from innate immunity in several key aspects:

	Innate	Adaptive
Distribution	Almost all multicellular eukaryotes	Only in vertebrates
Targets	Limited number of key structures (PAMPs)	Antigens, mostly proteins; highly diverse
Immune Receptors	Pattern recognition receptors (e.g., TLRs)	T cell receptors and antibodies
Cellular Presence	Almost all cells	Lymphocytes only
Discrimination	Host cells lack PAMPs	Tolerance for self-antigens (can break down in autoimmunity)
Immunological Memory	Absent	Present

Key Attributes of Adaptive Immunity

• Specificity: Targets unique antigens.

• Inducibility: Activated in response to specific pathogens.

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

• Unresponsiveness to Self: Normally does not attack the body's own cells.

• Memory: Remembers previous encounters for faster future responses.

Cells and Organs of Adaptive Immunity

Lymphocytes

Lymphocytes are the central cells of adaptive immunity, including B lymphocytes (B cells) and T lymphocytes (T cells). B cells mature in the bone marrow, while T cells mature in the thymus. Both circulate in the blood and reside in lymphoid organs.

Lymphatic System

The lymphatic system is composed of lymphatic vessels, lymphoid cells, tissues, and organs. It screens the body for foreign molecules and returns lymph to the circulatory system. Primary lymphoid organs include the red bone marrow and thymus; secondary organs include lymph nodes, spleen, tonsils, and MALT (mucosa-associated lymphoid tissue).

Antigens and Epitopes

Definition and Properties

Antigens are molecules recognized as foreign and capable of provoking an immune response. The specific regions recognized by immune receptors are called epitopes or antigenic determinants. Large, complex molecules such as proteins make the best antigens.

Types of Antigens

• Exogenous antigens: Toxins and components of microbial cell walls, membranes, flagella, and pili.

• Endogenous antigens: Produced by microbes that reproduce inside body cells (e.g., viruses).

• Autoantigens: Derived from normal cellular processes; can be involved in autoimmune diseases.

Major Histocompatibility Complex (MHC) and Antigen Presentation

MHC Molecules

MHC molecules are glycoproteins found on cell membranes that present antigenic peptides to T cells. There are two main classes:

• MHC Class I: Present on all nucleated cells; present endogenous antigens.

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

Antigen-Presenting Cells (APCs)

Dendritic cells are the most common APCs, capturing antigens and presenting them to T cells to initiate adaptive responses.

T Lymphocytes (T Cells)

T Cell Receptors (TCRs)

T cells possess T cell receptors (TCRs) that recognize antigenic peptides only when presented by MHC molecules. TCRs do not bind free antigens directly.

Types of T Lymphocytes

• Cytotoxic T lymphocytes (Tc): Directly kill infected or abnormal cells.

• Helper T lymphocytes (Th): Regulate B cells and Tc cells; include Th1 and Th2 subtypes.

• Regulatory T lymphocytes (Treg): Suppress immune responses to prevent autoimmunity.

Lymphocyte	Site of Maturation	Representative Cell-Surface Glycoproteins	Notable Secretions
Helper T cell type 1 (Th1)	Thymus	CD4 and distinctive TCR	Interleukin 2, IFN-γ
Helper T cell type 2 (Th2)	Thymus	CD4 and distinctive TCR	Interleukin 4 and 5
Cytotoxic T cell (Tc)	Thymus	CD8, CD95L, and distinctive TCR	Perforin, granzyme
Regulatory T cell (Tr)	Thymus	CD4, CD25, and distinctive TCR	Interleukin 10

Clonal Deletion of T Cells

Self-reactive T cells are eliminated in the thymus through apoptosis to prevent autoimmune responses.

B Lymphocytes (B Cells) and Antibodies

B Cell Receptors (BCRs)

B cells possess B cell receptors (BCRs) that bind specific epitopes directly. Each B cell expresses a unique BCR, allowing the immune system to recognize a vast array of antigens.

Generation of BCR Diversity

The enzyme RAG recombines variable (V), diversity (D), and joining (J) gene segments to generate diverse BCRs, enabling recognition of millions of different epitopes.

Antibody Structure and Classes

Antibodies (immunoglobulins) are secreted by plasma cells and have antigen-binding sites identical to the BCR of the activated B cell. There are five main classes of antibodies, each with distinct functions and structures:

Class	Structure	Main Functions	Location
IgM	Pentamer	First produced, agglutination, complement activation	Serum
IgG	Monomer	Most abundant, opsonization, neutralization, crosses placenta	Serum
IgA	Dimer (secretory)	Secretions, mucosal immunity	Secretions, serum
IgE	Monomer	Allergy, antiparasitic responses	Serum, bound to mast cells
IgD	Monomer	Unclear function, B cell receptor	B cell surface

Antibody Functions

• Neutralization: Blocks pathogen attachment or toxin activity.

• Opsonization: Enhances phagocytosis by marking pathogens.

• Agglutination: Clumps pathogens for easier clearance.

• Complement Activation: Triggers lysis and inflammation.

• Antibody-Dependent Cellular Cytotoxicity (ADCC): Directs killing by immune cells.

Clonal Deletion of B Cells

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

Cytokines in Immune Regulation

Definition and Types

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

• Interleukins (ILs): Signal among leukocytes.

• Interferons (IFNs): Antiviral and immune-modulating proteins.

• Growth Factors: Stimulate cell division.

• Tumor Necrosis Factor (TNF): Inflammation and apoptosis.

• Chemokines: Attract immune cells to sites of infection.

Cytokine	Source	Target	Action
IL-2	Th1, Tc cells	Tc cell	Cloning of Tc cell
IL-4	Th2 cell	B cell	B cell differentiation
IL-12	Dendritic cell	Th1 cell	Th1 differentiation
IFN-γ	Th1 cell	Macrophage	Increases phagocytosis
TNF	Macrophages, T cells	Body tissues	Triggers inflammation/apoptosis

Cell-Mediated Immune Responses

Activation and Function of Cytotoxic T Cells

Cytotoxic T cells (Tc) recognize and kill infected or abnormal cells via two main pathways:

• Perforin-Granzyme Pathway: Tc cells release perforin (forms pores) and granzymes (induce apoptosis).

• CD95 Pathway: Tc cells engage CD95 on target cells, triggering apoptosis.

Memory T Cells

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

Antibody (Humoral) Immune Responses

Plasma Cells and Antibody Production

Plasma cells are differentiated B cells that secrete large amounts of antibodies specific to the encountered antigen. These cells are short-lived, but the antibodies and memory B cells they produce provide lasting immunity.

Immunological Memory

Memory B cells persist in lymphoid tissues and enable a rapid, robust secondary immune response upon re-exposure to the same antigen. The primary response is slower and produces fewer antibodies, while the secondary response is faster and stronger.

Types of Acquired Immunity

Active vs. Passive, Natural vs. Artificial

• Naturally Acquired Active Immunity: Immune 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: Immune response to antigens introduced by vaccination.

• Artificially Acquired Passive Immunity: Transfer of antibodies (e.g., antitoxins) by injection.