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. Unlike innate immunity, adaptive immunity is characterized by its specificity, inducibility, clonality, unresponsiveness to self, and memory.

• Specificity: Targets unique antigens found on pathogens.

• Inducibility: Activated only in response to specific invaders.

• Clonality: Generates clones of immune cells specific to the antigen.

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

• Memory: Remembers previous encounters for faster future responses.

Comparison of Innate and Adaptive Immunity

Innate and adaptive immunity are two branches of the immune system, each with distinct characteristics and functions.

Lymphocytes and Types of Adaptive Immune Responses

Adaptive immunity involves the activity of specialized white blood cells called lymphocytes. There are two main types:

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

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

Adaptive immune responses are classified as:

• Cell-mediated immune responses: Involve T cells attacking infected or abnormal cells.

• Antibody immune responses: Involve B cells producing antibodies to neutralize pathogens.

Tissues and Organs of the Lymphatic System

The lymphatic system is composed of lymphatic vessels, lymphoid cells, tissues, and organs. It carries out immunosurveillance, screens tissues for foreign molecules, and provides sites for lymphocyte proliferation.

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

• Secondary lymphoid organs: Lymph nodes, spleen, tonsils, and mucosa-associated lymphoid tissue (MALT) (sites where lymphocytes reside and respond to antigens).

Lymphatic Vessels and Lymph Flow

Lymphatic vessels form a one-way system that conducts lymph from tissues and returns it to the circulatory system at the subclavian veins. Lymph is a fluid similar to blood plasma, arising from fluid leaked from blood vessels into surrounding tissues. Flow is aided by skeletal muscle contraction and breathing, and valves ensure unidirectional flow.

Lymphocyte Development

Lymphocytes originate in the red bone marrow. T cell precursors migrate to the thymus for maturation, while B cells mature in the bone marrow. Mature lymphocytes are seeded into secondary lymphoid organs, where they encounter antigens and undergo activation, proliferation, and differentiation.

Antigens and Their Types

Definition and Properties of Antigens

Antigens are molecules recognized as foreign and worthy of attack by the immune system. They are recognized by three-dimensional regions called epitopes or antigenic determinants. Large foreign macromolecules, such as bacterial components and proteins of viruses, fungi, and protozoa, make the best antigens. Food and dust can also contain antigenic particles.

Types of Antigens

• Exogenous antigens: Include toxins and components of microbial cell walls, membranes, flagella, and pili; present outside cells.

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

• Autoantigens: Derived from normal cellular processes; can trigger autoimmunity if not properly regulated.

Major Histocompatibility Complex (MHC) and Antigen Presentation

Roles of MHC Antigens and Antigen-Presenting Cells

MHC antigens are glycoproteins found in the membranes of most vertebrate cells. They are crucial for tissue compatibility and immune recognition. MHC molecules hold and position antigenic epitopes for presentation to immune cells.

Classes of MHC Proteins

• MHC class I: Present on all nucleated cells except red blood cells; display endogenous antigens.

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

Antigen Processing and Presentation

Antigens must be processed for MHC proteins to display epitopes on their surface. Endogenous antigens arise from inside body cells, while exogenous antigens are taken into APCs by phagocytosis. The steps of antigen processing and presentation involve loading epitopes onto MHC molecules and displaying them on the cell surface for recognition by T cells.

T Lymphocytes (T Cells)

Production, Maturation, and Migration

T cells are produced in the red bone marrow and mature in the thymus. They circulate in the lymph and blood, migrating to lymph nodes, spleen, and Peyer's patches (MALT). T cells have T cell receptors (TCRs) on their cytoplasmic membrane.

Specificity of T Cell Receptors (TCRs)

TCRs do not recognize epitopes directly; they only bind epitopes associated with an MHC protein. T cells act primarily against cells harboring intracellular pathogens or those producing abnormal cell-surface proteins (e.g., tumors).

Types of T Lymphocytes

• Cytotoxic T lymphocyte (Tc): Directly kills other cells; have CD8 glycoproteins.

• Helper T lymphocyte (Th): Regulate B cells and cytotoxic T cells; have CD4 glycoproteins; include Th1 and Th2 subtypes.

• Regulatory T lymphocyte (Treg): Downregulate adaptive immune responses; have CD4 glycoproteins.

Clonal Deletion of T Cells

To prevent autoimmunity, T cells undergo clonal deletion. T cells that do not recognize self MHC proteins undergo apoptosis (positive selection). T cells that recognize autoantigens die by apoptosis (negative selection). Some self-recognizing T cells become regulatory T cells, while those that recognize MHC protein and foreign epitopes become protective T cells.

B Lymphocytes (B Cells) and Antibodies

Location and Function

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

Specificity of B Cell Receptors (BCRs)

Each B lymphocyte has multiple copies of the B Cell Receptor (BCR), which is unique to each cell. The two variable regions of the BCR form the antigen-binding sites, and each BCR recognizes only one epitope. The collection of BCRs in an individual can recognize millions of different epitopes.

Antibody Structure and Function

Antibodies are immunoglobulins similar to BCRs, secreted by activated B cells called plasma cells. They have antigen-binding sites and specificity identical to the BCR of the activated B cell. Antibodies function in several ways:

• Activation of complement and inflammation

• Neutralization

• Opsonization

• Agglutination

• Antibody-dependent cellular cytotoxicity (ADCC)

Classes of Antibodies

The immune system uses different classes of antibodies depending on the type of antigen, portal of entry, and function needed. There are five classes:

• IgM: First antibody produced

• IgG: Most common and longest-lasting antibody

• IgA: Associated with body secretions

• IgE: Involved in response to parasitic infections and allergies

• IgD: B cell receptors; exact function unknown

Clonal Deletion of B Cells

Clonal deletion of B cells occurs in the bone marrow. Self-reactive B cells may become inactive or change their BCR rather than undergo apoptosis. Self-tolerant B cells are seeded out to secondary lymphatic tissue.

Cytokines and Immune Regulation

Cytokines

Cytokines are soluble regulatory proteins that act as intercellular signals, secreted by various leukocytes. The cytokine network is a complex web of signals among immune cells.

• Interleukins (ILs): Signal among leukocytes

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

• Growth factors: Stimulate stem cells to divide

• Colony stimulating factors

• Tumor necrosis factor (TNF): Secreted by macrophages and T cells to kill tumor cells and regulate immune responses

• Chemokines: Signal leukocytes to move

Cell-Mediated Immune Responses

Overview and Functions

Cell-mediated immunity responds to intracellular pathogens and abnormal body cells, such as viruses, cancer cells, intracellular protozoa, and bacteria. Some T cells directly kill cells, while others release chemicals that regulate immune responses.

Activation of T Cells

Helper T cells play a central role in adaptive immune response. Activation is a two-step process involving antigen binding and co-stimulation on the surface of the same APC, required for clonal selection and proliferation.

Activation of Cytotoxic T Cells

Adaptive immune responses are initiated in lymphoid organs. Steps involved in activation of cytotoxic T cells:

1. Antigen presentation

2. Helper T cell differentiation

3. Clonal expansion

4. Self-stimulation (IL-2)

Functions of Cytotoxic T Cells

Cytotoxic T cells kill targets through two pathways:

• Perforin-granzyme pathway: Release of perforins and granzymes

• CD95 pathway: Mediated through glycoprotein receptor on body’s cells

Memory T Cells

Some activated T cells become memory T cells, persisting for months or years in lymphoid tissues. They immediately become functional upon subsequent contact with the specific epitope-MHC complex, providing a more effective response than the primary response.

T Cell Regulation

Regulation is needed to prevent T cell responses to autoantigens. T cells require additional signals from an antigen-presenting cell (costimulation). Regulatory T cells also moderate cytotoxic T cell activity.

Antibody Immune Responses

Inducement of T-Dependent Antibody Immunity

T-dependent antibody immunity depends on the function of helper T cells. 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 and Memory Cells

• Plasma cells: Majority of cells produced during B cell proliferation; secrete antibody molecules complementary to the specific antigen; short-lived but their antibodies and progeny can persist.

• Memory cells: Produced by B cell proliferation; have BCRs complementary to the epitope that triggered their production; do not secrete antibodies; long-lived and initiate antibody production if antigen is encountered again (immunological memory).

Primary and Secondary Immune Responses

• Primary immune response: Small amounts of antibodies produced; may take days to produce enough antibodies to eliminate the antigen.

• Secondary immune response: Memory cells respond to another exposure to the antigen; much faster than the primary response.

Types of Acquired Immunity

Classification

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

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

• Artificially acquired: Response to antigens introduced via a vaccine.

Both types can be distinguished as either active (body produces its own antibodies) or passive (antibodies are received from another source).

Summary Table: Role of MHC Proteins in Cellular Immunity