Adaptive Immunity: Mechanisms and Components

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 to remember previous encounters for a more rapid response upon re-exposure.

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

• Inducibility: Activated only in response to specific pathogens.

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

• Unresponsiveness to self: Normally does not react to the body's own molecules.

• Memory: Remembers previous encounters, enabling a faster and stronger 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 major branches of adaptive immunity are cell-mediated immune responses (primarily T cells) and antibody (humoral) immune responses (primarily B cells).

Comparison of Innate and Adaptive Immunity

	Innate Immunity	Adaptive Immunity
Distribution	Almost all multicellular eukaryotes	Only in vertebrates
Targets	Limited number of key structures (PAMPs)	Billions of different antigens
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 (autoimmunity)
Immunological Memory	Absent	Present

Elements of Adaptive Immunity

The Lymphatic System

The lymphatic system is a network of vessels, cells, tissues, and organs that screens the body for foreign molecules and is essential for immune function. Lymphatic vessels form a one-way system that returns lymph (a fluid similar to plasma) from tissues to the circulatory system.

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

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

Antigens

Antigens are molecules recognized as foreign by the immune system and capable of provoking an immune response. The specific regions recognized by immune receptors are called epitopes or antigenic determinants.

• Large, complex macromolecules (proteins, polysaccharides) are the most effective antigens.

• Antigens can be derived from microbes, viruses, fungi, protozoa, food, or dust.

Types of Antigens

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

• Endogenous antigens: Produced by microbes that reproduce inside host cells.

• Autoantigens: Derived from normal cellular processes (self-antigens).

Major Histocompatibility Complex (MHC) and Antigen Presentation

The major histocompatibility complex (MHC) consists of glycoproteins found on the membranes of most vertebrate cells. MHC molecules hold and present antigenic epitopes to T cells, playing a critical role in immune recognition and tissue compatibility.

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

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

Antigen Processing

Antigens must be processed before they can be presented by MHC molecules. The processing pathway differs for endogenous and exogenous antigens:

• Endogenous antigens: Processed within infected cells and presented on MHC I molecules.

• Exogenous antigens: Processed by APCs and presented on MHC II molecules.

T Lymphocytes (T Cells)

Development and Types of T Cells

T cells are produced in the red 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 specific antigen-MHC complexes.

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

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

• Regulatory T cells (Tr): Suppress immune responses to prevent autoimmunity.

Clonal Deletion of T Cells

To prevent autoimmunity, T cells that react to self-antigens are eliminated through clonal deletion in the thymus. Only T cells that recognize foreign antigens in the context of self-MHC survive.

B Lymphocytes (B Cells) and Antibodies

B Cell Receptors (BCRs) and Antibody Diversity

B cells are primarily found in the spleen, lymph nodes, and MALT. Their main function is the production of antibodies. Each B cell expresses a unique B cell receptor (BCR) capable of binding a specific epitope. The diversity of BCRs is generated by the recombination of gene segments (V, D, J) during B cell development.

Antibody Structure and Function

Antibodies (immunoglobulins) are secreted by activated B cells (plasma cells) and have antigen-binding sites identical to the BCR of the parent B cell. Antibodies function in:

• Activation of complement and inflammation

• Neutralization of toxins and pathogens

• Opsonization (enhancing phagocytosis)

• Agglutination (clumping of antigens)

• Antibody-dependent cellular cytotoxicity (ADCC)

Classes of Antibodies

There are five main classes of antibodies, each with distinct functions and properties:

• IgM: First antibody produced; effective in agglutination and complement activation.

• IgG: Most abundant and long-lasting; crosses placenta; important in secondary responses.

• IgA: Found in secretions (e.g., saliva, tears, breast milk); protects mucosal surfaces.

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

• IgD: Function not fully understood; acts as a BCR in some cases.

Clonal Deletion of B Cells

Self-reactive B cells are eliminated or inactivated in the bone marrow to prevent autoimmunity. Some may change their BCR specificity rather than undergo apoptosis.

Immune Response Cytokines

Types and Functions of Cytokines

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

• Interleukins (ILs): Signal among leukocytes.

• Interferons (IFNs): Antiviral proteins that also act as cytokines.

• Growth factors: Stimulate stem cell division.

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

• Chemokines: Attract leukocytes to sites of infection.

Cytokine	Source	Target	Action
Interleukin 2 (IL-2)	Th1 cell, Tc cell	Tc cell	Cloning of Tc cell
Interleukin 4 (IL-4)	Th2 cell	B cell	B cell differentiates into plasma cell
Interleukin 12 (IL-12)	Dendritic cell	Th cell	Th cell differentiates into Th1 cell
Gamma interferon (IFN-γ)	Th1 cell	Macrophage	Increases phagocytosis
Tumor necrosis factor (TNF)	Macrophages, T cells	Body tissues	Triggers inflammation or apoptosis

Cell-Mediated Immune Responses

Activation and Function of Cytotoxic T Cells

Cell-mediated immunity targets intracellular pathogens (e.g., viruses, cancer cells, intracellular bacteria and protozoa). The activation of cytotoxic T cells involves:

1. Antigen presentation

2. Helper T cell differentiation

3. Clonal expansion

4. Self-stimulation

Cytotoxic T cells kill target cells via two main pathways:

• Perforin-granzyme pathway: Release of perforin (forms pores) and granzymes (induce apoptosis).

• CD95 pathway: Activation of apoptosis through CD95 ligand interaction.

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-MHC complex. This secondary response is more effective than the primary response.

Regulation of T Cell Responses

Regulation is essential to prevent autoimmunity. T cells require additional signals from antigen-presenting cells for activation, and regulatory T cells help moderate immune responses.

Antibody (Humoral) Immune Responses

T-Dependent Antibody Immunity and Clonal Selection

Antibody responses are mounted against exogenous pathogens and toxins. T-dependent antibody immunity requires helper T cells and involves:

1. Antigen presentation for Th activation and proliferation

2. Differentiation of helper T cells into Th2 cells

3. Activation of B cells

4. Proliferation and differentiation of B cells into plasma cells and memory cells

Plasma Cells and Memory B Cells

• Plasma cells: Short-lived cells that secrete large amounts of antibodies specific to the antigen.

• Memory B cells: Long-lived cells that do not secrete antibodies but can rapidly respond to future exposures to the same antigen.

Primary and Secondary Immune Responses

The primary immune response produces small amounts of antibody and takes several days to reach peak levels. The secondary response, mediated by memory cells, is faster and produces higher antibody levels, primarily IgG.

Types of Acquired Immunity

Active vs. Passive Immunity

Acquired immunity can be classified based on how it is obtained:

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

• Artificially acquired: Response to antigens introduced via vaccination.

• Active immunity: The body produces its own antibodies or T cells in response to antigen exposure.

• Passive immunity: Antibodies are transferred from another individual (e.g., maternal antibodies, antiserum).