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 specific antigens, generate tailored responses, and remember previous encounters for faster future responses.

• 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 antigens for faster secondary responses.

Cells Involved in Adaptive Immunity

Adaptive immunity primarily involves lymphocytes, which are a type of white blood cell. The two main types are:

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

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

Types of Adaptive Immune Responses

• Cell-mediated immune responses: Involve T cells that directly attack infected or abnormal cells.

• Antibody (humoral) immune responses: Involve B cells that produce antibodies to neutralize pathogens.

Elements of Adaptive Immunity

The Lymphatic System

The lymphatic system is composed of lymphatic vessels, cells, tissues, and organs. It screens the body's tissues for foreign antigens and returns lymph to the circulatory system.

• Lymphatic vessels: One-way system conducting 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 microbes.

• Sources: Bacterial components, viral proteins, fungi, protozoa, food, and 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 body cells.

• Autoantigens: Derived from normal cellular processes.

Major Histocompatibility Complex (MHC) and Antigen-Presenting Cells

The MHC is a group of glycoproteins found on the membranes of most vertebrate cells. They are essential for antigen presentation and determining 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 and dendritic cells.

Antigen Processing and Presentation

Antigens must be processed and presented by MHC molecules to be recognized by T cells. The process 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 Specificity

T cells are produced in the red bone marrow and mature in the thymus. They circulate in the lymph and blood and migrate to secondary lymphoid organs. Each T cell has 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 Tc cells; include Th1 and Th2 subtypes.

• Regulatory T lymphocytes (Tr): 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. T cells that react to self-antigens undergo apoptosis, while those that recognize foreign antigens survive.

• T cells not recognizing MHC undergo apoptosis.

• T cells recognizing autoantigens die by apoptosis or become regulatory T cells.

• Surviving T cells form the repertoire of protective T cells.

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.

B Cell Receptor (BCR) Specificity

Each B cell expresses a unique BCR capable of recognizing a specific epitope. The diversity of BCRs allows the immune system to recognize millions of different antigens.

• Two variable regions form the antigen-binding sites.

• Each B cell produces only one type of BCR.

Generation of Antibody Diversity

The diversity of BCRs is generated by the recombination of gene segments (V, D, J) through the action of the RAG enzyme.

Antibody Structure and Function

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

• IgM: First antibody produced during an immune response.

• IgG: Most common and long-lasting; provides the majority of antibody-based immunity.

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

• IgE: Involved in allergic responses and defense against parasitic infections.

• 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 rather than undergo apoptosis.

Immune Response Cytokines

Cytokines are soluble regulatory proteins that act as intercellular signals in the immune system. 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: Signal leukocytes to move (chemotaxis).

Cell-Mediated Immune Responses

Activation of Cytotoxic T Cells

Cell-mediated immunity targets intracellular pathogens and abnormal body cells. The activation of cytotoxic T cells involves:

1. Antigen presentation

2. Helper T cell differentiation

3. Clonal expansion

4. Self-stimulation

Mechanisms of Cytotoxic T Cell Killing

• Perforin-granzyme pathway: Cytotoxic T cells release perforin and granzymes to induce apoptosis in target cells.

• CD95 pathway: Involves interaction with CD95 on target cells, leading to apoptosis.

Memory T Cells

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

T Cell Regulation

Regulation is essential to prevent T cell responses against self-antigens. Regulatory T cells and additional signals from antigen-presenting cells help maintain self-tolerance.

Antibody Immune Responses (Humoral Immunity)

T-Dependent Antibody Immunity and Clonal Selection

Most antibody responses require the assistance of helper T cells (T-dependent). The process 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

• Primary response: Initial exposure to antigen; slower and produces less antibody.

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

Types of Acquired Immunity

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

• Naturally acquired: Through natural exposure to antigens (e.g., infection).

• Artificially acquired: Through medical intervention (e.g., vaccination).

• Active immunity: The body produces its own antibodies.

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