Adaptive Immunity

Overview of Adaptive Immunity

Adaptive immunity is the body's highly specialized defense system that recognizes and responds to specific pathogens and their products. It is characterized by five key attributes: specificity, inducibility, clonality, unresponsiveness to self, and memory. The main cellular components are B lymphocytes (B cells) and T lymphocytes (T cells), which mature in the bone marrow and thymus, respectively. Adaptive immunity is divided into two main responses: cell-mediated and antibody-mediated (humoral) responses.

• Specificity: Targets specific antigens.

• Inducibility: Activated only in response to pathogens.

• Clonality: Generates clones of specific lymphocytes.

• Unresponsiveness to self: Prevents attack on the body's own cells.

• Memory: Remembers previous encounters for faster response.

Elements of Adaptive Immunity: The Lymphatic System

The lymphatic system is composed of vessels, cells, tissues, and organs that screen the body for foreign molecules. Lymphatic vessels conduct lymph in a one-way system, returning it to the circulatory system. Lymph is a fluid similar to blood plasma, arising from leaked blood vessel 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 and Epitopes

Antigens are molecules recognized as foreign and worthy of attack by the immune system. They are identified by three-dimensional regions called epitopes. Large foreign macromolecules, such as bacterial components and viral proteins, are the most effective antigens. Food and dust may also contain antigenic particles.

• Epitopes: Specific regions on antigens recognized by immune cells.

Types of Antigens

Antigens are classified based on their origin:

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

• Endogenous antigens: Produced by microbes reproducing 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 in the membranes of most vertebrate cells. MHC molecules hold and present antigenic epitopes to immune cells. There are two classes:

• 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 for MHC proteins to display epitopes. The process differs for endogenous and exogenous antigens:

• Endogenous processing: Antigens from within the cell are presented on MHC class I.

• Exogenous processing: Antigens from outside the cell are presented on MHC class II.

Immune Response Cytokines

Cytokines are soluble regulatory proteins acting as intercellular signals. They form a complex network among immune cells and include:

• Interleukins (ILs): Signal among leukocytes.

• Interferons (IFNs): Antiviral proteins acting as cytokines.

• Growth factors: Stimulate stem cell division.

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

• Chemokines: Signal leukocytes to move.

T Lymphocytes (T Cells)

Functions and Types of T Cells

T cells act against body cells harboring intracellular pathogens and abnormal antigens. Their activities are termed cell-mediated immune responses. T cells are produced in the bone marrow, mature in the thymus, and migrate to lymphoid organs. They possess T cell receptors (TCRs) on their membranes, which bind epitopes only when associated with MHC proteins.

• 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 types.

• Regulatory T lymphocytes: Repress adaptive immune responses and promote tolerance.

Clonal Deletion of T Cells

To prevent autoimmunity, self-reactive T cells are eliminated through apoptosis. Immature T cells undergo four possible fates:

• Failure to recognize MHC: apoptosis.

• Recognition of autoantigen: apoptosis.

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

• Recognition of MHC and foreign epitopes: become protective T cells.

Cell-Mediated Immune Responses

Cell-mediated responses target intracellular pathogens (viruses, protozoa, bacteria) and cancer cells. Activation of cytotoxic T cell clones involves several steps:

• Antigen presentation

• Helper T cell differentiation

• Clonal expansion

• Self-stimulation

Cytotoxic T Cell Killing Mechanisms

Cytotoxic T cells kill targets via two pathways:

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

• CD95 pathway: Activates apoptosis through cell surface glycoproteins.

Memory T Cells

Some activated T cells become memory T cells, persisting in lymphoid tissues for months or years. They respond rapidly upon re-exposure to their specific antigen-MHC complex, providing a more effective secondary response.

T Cell Regulation

Regulation prevents T cell responses to autoantigens. T cells require additional signals from antigen-presenting cells, and regulatory T cells moderate cytotoxic T cell activity.

B Lymphocytes (B Cells) and Antibodies

B Cell Function and Antibody Production

B cells are primarily found in the spleen, lymph nodes, and MALT. Their main function is the secretion of antibodies. Each B cell has a unique B cell receptor (BCR) that recognizes a specific epitope.

Antibody Structure and Diversity

Antibodies are immunoglobulins secreted by plasma cells. They have antigen-binding sites identical to the BCR of the activated B cell. The diversity of BCRs is generated by the recombination of gene segments (V, D, J) by the RAG enzyme.

Antibody Functions

Antibodies perform several functions:

• Activation of complement and inflammation

• Neutralization: Block pathogen activity

• Opsonization: Enhance phagocytosis

• Agglutination: Clump pathogens

• Antibody-dependent cellular cytotoxicity (ADCC): Target cells for destruction

Classes of Antibodies

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

• IgM: First antibody produced

• IgG: Most common and longest-lasting

• IgA: Associated with body secretions

• IgE: Involved in parasitic infections and allergies

• IgD: Function not well understood

Clonal Deletion of B Cells

Self-reactive B cells are deleted in the bone marrow, similar to T cells. Some may become inactive or alter their BCR instead of undergoing apoptosis.

Antibody Immune Responses

T-Dependent Antibody Immunity and Clonal Selection

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

Memory Cells and Immunological Memory

Memory B cells are produced during B cell proliferation and persist in lymphoid tissue. They initiate rapid antibody production upon re-exposure to the antigen.

• Primary response: Slow, produces small amounts of antibody.

• Secondary response: Rapid, produces large amounts of antibody.

Types of Acquired Immunity

Acquired Immunity: Active and Passive

Specific immunity is acquired during an individual's life and is classified as:

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

• Artificially acquired: Response to antigens introduced via vaccination.

• Each can be active (body produces its own antibodies) or passive (antibodies are received from another source).

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