Adaptive Immunity: Structure, Function, and Mechanisms

Adaptive Immunity

Overview and Comparison with Innate Immunity

Adaptive immunity is the body's highly specific defense mechanism against distinct invaders and their products. It is distinguished from innate immunity by its specificity, inducibility, clonality, unresponsiveness to self, and memory. The following table compares innate and adaptive immunity:

Feature	Innate Immunity	Adaptive Immunity
Distribution	Almost all multicellular eukaryotes	Only in vertebrates
Targets	Limited number of key structures (PAMPs)	Antigens (billions of types)
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

Key Attributes of Adaptive Immunity

• Specificity: Targets unique antigens.

• Inducibility: Activated only in response to specific pathogens.

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

• Unresponsiveness to Self: Prevents attack on self-antigens.

• Memory: Remembers previous encounters for faster response.

Lymphocytes in Adaptive Immunity

Lymphocytes are central to adaptive immunity. There are two main types:

• B lymphocytes (B cells): Mature in the bone marrow; responsible for antibody production.

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

Adaptive immunity involves two main responses:

• Cell-mediated immune responses: Target intracellular pathogens and abnormal cells.

• Antibody (humoral) immune responses: Target exogenous pathogens and toxins.

The Lymphatic System

Tissues and Organs of the Lymphatic System

The lymphatic system screens the tissues of the body for foreign molecules and is composed of lymphatic vessels, lymphoid cells, tissues, and organs.

• Lymphatic vessels: One-way system conducting lymph from tissues back to the circulatory system.

• Lymph: Fluid similar to blood plasma, arising from leaked blood vessel fluid.

• Primary lymphoid organs: Red bone marrow and thymus.

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

Antigens and Their Properties

Definition and Structure

Antigens are molecules recognized as foreign and worthy of attack. They are identified by three-dimensional regions called epitopes.

• Best antigens: Large foreign macromolecules.

• Sources: Bacterial components, proteins of viruses, 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 reproducing inside body cells.

• Autoantigens: Derived from normal cellular processes.

Major Histocompatibility Complex (MHC) and Antigen Presentation

MHC Proteins

MHC proteins are glycoproteins found in the membranes of most vertebrate cells. They hold and position antigenic epitopes for presentation to immune cells.

• MHC class I: Present on all 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 are processed for MHC proteins to display epitopes. The process differs for endogenous and exogenous antigens.

T Lymphocytes (T Cells)

Production, Maturation, and Migration

T cells are produced in the red bone marrow, mature in the thymus, and migrate to lymph nodes, spleen, and Peyer's patches. They possess T cell receptors (TCRs) on their membrane.

Specificity of TCR

• TCRs bind only epitopes associated with MHC proteins.

• T cells act primarily against cells harboring intracellular pathogens or abnormal cell-surface proteins.

Types of T Lymphocytes

• Cytotoxic T lymphocyte (Tc): Directly kills other cells.

• Helper T lymphocyte (Th): Regulates B cells and cytotoxic T cells; includes Th1 and Th2.

• Regulatory T lymphocyte (Tr): Represses adaptive immune responses.

Lymphocyte	Site of Maturation	Representative Cell-Surface Glycoproteins	Notable Secretions
Helper T cell type 1 (Th1)	Thymus	CD4, distinctive TCR	Interleukin 2, IFN-γ
Helper T cell type 2 (Th2)	Thymus	CD4, distinctive TCR	Interleukin 4, 5
Cytotoxic T cell (Tc)	Thymus	CD8, CD95L, distinctive TCR	Perforin, granzyme
Regulatory T cell (Tr)	Thymus	CD4, CD25, distinctive TCR	Interleukin 10

Clonal Deletion of T Cells

Clonal deletion is vital to prevent immune responses against autoantigens. Self-reactive lymphocytes are eliminated by apoptosis.

• T cells not recognizing MHC protein undergo apoptosis.

• T cells recognizing autoantigen die by apoptosis.

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

• T cells recognizing MHC protein and foreign epitopes become protective T cells.

B Lymphocytes (B Cells) and Antibodies

Production and Function

B cells are found primarily in the spleen, lymph nodes, and MALT. Their major function is the secretion of antibodies.

Specificity of B Cell Receptor (BCR)

• Each B cell generates a single BCR.

• Two variable regions form antigen-binding sites.

• Each BCR recognizes only one epitope.

• The repertoire of BCRs can recognize millions of different epitopes.

Lymphocyte Receptor Diversity

Genes for constant and variable regions of BCRs occur at discrete loci. The RAG enzyme combines different variable region gene segments to generate antibody diversity.

Antibody Structure and Function

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

• Functions: Activation of complement and inflammation, neutralization, opsonization, agglutination, antibody-dependent cellular cytotoxicity (ADCC).

Classes of Antibodies

• 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: Exact function unknown.

Clonal Deletion of B Cells

Clonal deletion occurs in the bone marrow. Self-reactive B cells may become inactive or change their BCR rather than undergo apoptosis.

Immune Response Cytokines

Cytokine Types and Functions

Cytokines are soluble regulatory proteins acting as intercellular signals. They are secreted by various leukocytes and form a complex network of signals.

• Interleukins (ILs): Signal among leukocytes.

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

• Growth factors: Stimulate stem cells to divide.

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

• Chemokines: Signal leukocytes to move.

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 of Cytotoxic T Cell Clones

Cell-mediated responses target intracellular pathogens and abnormal body cells. Activation of cytotoxic T cells involves four steps:

1. Antigen presentation

2. Helper T cell differentiation

3. Clonal expansion

4. Self-stimulation

Mechanisms of Cytotoxic T Cell Killing

• Perforin-granzyme pathway: Synthesis of killing proteins.

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

Memory T Cells

Some activated T cells become memory T cells, persisting for months or years in lymphoid tissues. They respond immediately upon subsequent contact with the specific epitope-MHC complex.

T Cell Regulation

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

Antibody Immune Responses

T-Dependent Antibody Immunity and Clonal Selection

T-dependent antibody immunity depends on 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 and Memory Cells

• Plasma cells: Secrete antibody molecules complementary to the specific antigen; short-lived but their antibodies and progeny persist.

• Memory B cells: Produced by B cell proliferation; do not secrete antibodies but initiate antibody production if antigen is encountered again.

Primary and Secondary Immune Responses

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

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

Types of Acquired Immunity

Active vs. Passive Immunity

Specific immunity is acquired during an individual's life and can be:

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

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

• Active: Body produces its own antibodies.

• Passive: Antibodies are received from another source.