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 specific antigens, remember previous encounters, and mount stronger responses upon re-exposure.

• Specificity: Targets unique antigens.

• Inducibility: Activated in response to specific pathogens.

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

• Unresponsiveness to self: Does not attack the body's own cells.

• Memory: Remembers antigens for faster future responses.

Adaptive immunity involves two main types of lymphocytes:

• B lymphocytes (B cells): Mature in the bone marrow and are responsible for antibody-mediated responses.

• T lymphocytes (T cells): Mature in the thymus and are responsible for cell-mediated responses.

There are two main types of adaptive immune responses:

• Cell-mediated immune responses

• Antibody immune responses

Elements of Adaptive Immunity

The 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 immune surveillance and response.

• Lymphatic vessels: One-way system that returns lymph from tissues to the circulatory system.

• Lymph: Fluid similar to blood plasma, derived from interstitial fluid.

• 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. They are identified by specific regions called epitopes.

• Best antigens: Large, complex macromolecules such as proteins from bacteria, viruses, fungi, and protozoa.

• Other sources: Food and dust can also contain antigenic particles.

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.

• Autoantigens: Derived from normal cellular processes.

Major Histocompatibility Complex (MHC) and Antigen-Presenting Cells

The major histocompatibility complex (MHC) consists of glycoproteins found on the membranes of most vertebrate cells. MHC molecules hold and present antigenic epitopes to immune 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 on antigen-presenting cells (APCs) such as macrophages, B cells, and dendritic cells.

Antigen Processing

Antigens must be processed and presented by MHC molecules for recognition by T cells. The processing pathway differs for endogenous and exogenous antigens.

T Lymphocytes (T Cells)

Development and Specificity

T cells are produced in the red bone marrow and mature in the thymus. They circulate in the lymph and blood, migrating to secondary lymphoid organs. Each T cell expresses a unique T cell receptor (TCR) that recognizes specific antigen-MHC complexes.

• TCRs: Bind only to epitopes presented by MHC molecules.

• Function: Primarily act against cells harboring intracellular pathogens or abnormal proteins.

Types of T Lymphocytes

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

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

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

Clonal Deletion of T Cells

To prevent autoimmunity, self-reactive T cells are eliminated in the thymus through clonal deletion. Immature T cells undergo apoptosis if they recognize self-antigens or fail to recognize MHC proteins.

• T cells that do not recognize MHC proteins die by apoptosis.

• T cells that recognize autoantigens die by apoptosis.

• Some self-recognizing T cells become regulatory T cells.

• T cells that recognize MHC and foreign epitopes become the protective repertoire.

B Lymphocytes (B Cells) and Antibodies

Location and Function

B cells are primarily found in the spleen, lymph nodes, and MALT, with a small percentage circulating in the blood. Their main function is the secretion of antibodies.

B Cell Receptor (BCR) Specificity

Each B cell expresses multiple copies of a unique B cell receptor (BCR), which binds to a specific epitope. The diversity of BCRs allows the immune system to recognize millions of different antigens.

Antibody Structure and Function

Antibodies, or immunoglobulins, are secreted by activated B cells (plasma cells) and have antigen-binding sites identical to the BCR of the parent B cell. Antibodies mediate several immune functions:

• Activation of complement and inflammation

• Neutralization

• Opsonization

• Agglutination

• Antibody-dependent cellular cytotoxicity (ADCC)

Classes of Antibodies

There are five main classes of antibodies, each with distinct roles:

• IgM: First antibody produced during an immune response.

• IgG: Most common and long-lasting antibody in serum.

• IgA: Associated with body secretions (e.g., mucosal immunity).

• IgE: Involved in responses to parasitic infections and allergies.

• IgD: Function not fully understood.

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

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

• Interleukins (ILs): Signal among leukocytes.

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

• Growth factors: Stimulate stem cell division.

• Tumor necrosis factor (TNF): Kills tumor cells and regulates immune responses.

• Chemokines: Induce chemotaxis of leukocytes.

Cell-Mediated Immune Responses

Activation of Cytotoxic T Cell Clones

Cell-mediated responses target intracellular pathogens and abnormal cells. The activation of cytotoxic T cells involves several steps:

1. Antigen presentation

2. Helper T cell differentiation

3. Clonal expansion

4. Self-stimulation

Mechanisms of Cytotoxic T Cell Killing

Cytotoxic T cells kill target cells via two main pathways:

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

• CD95 pathway: Involves interaction with a glycoprotein on target cells to trigger apoptosis.

Memory T Cells

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

T Cell Regulation

Regulation is essential to prevent inappropriate T cell responses. T cells require additional signals from antigen-presenting cells, and regulatory T cells help moderate cytotoxic T cell activity.

Antibody Immune Responses

T-Dependent Antibody Immunity and Clonal Selection

Antibody responses are mounted against exogenous pathogens and toxins, and are activated only in response to specific antigens. T-dependent antibody immunity requires helper T cells and involves four steps:

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

Plasma Cells

Plasma cells are the main antibody-secreting cells produced during B cell proliferation. They are short-lived but their antibodies and progeny can persist in the body.

Memory Cells and Immunological Memory

Memory B cells are long-lived cells that do not secrete antibodies but can rapidly initiate antibody production upon re-exposure to the antigen. The primary immune response is slower and produces fewer antibodies, while the secondary response is faster and more robust due to memory cells.

Types of Acquired Immunity

Acquired immunity develops during an individual's life and can be classified as:

• Naturally acquired: Response to antigens encountered in daily life.

• Artificially acquired: Response to antigens introduced via vaccination.

Each type can be further divided into active (immune response generated by the host) or passive (antibodies received from another source).

Type	Active	Passive
Naturally Acquired	Immune response to infection	Maternal antibodies transferred to offspring
Artificially Acquired	Vaccination	Antibodies from immune serum