Adaptive Immunity: Structure, Function, and Mechanisms

Adaptive Immunity: Overview

Introduction to Immunity

The immune system protects the body from pathogens through two main strategies: innate immunity (nonspecific defenses) and adaptive immunity (specific defenses). Adaptive immunity is characterized by its ability to recognize specific antigens and mount a targeted response, involving both humoral and cellular components.

• Innate immunity: Immediate, nonspecific defense against pathogens.

• Adaptive immunity: Induced, specific resistance to particular pathogens, involving memory for faster secondary responses.

Dual Nature of Adaptive Immunity

Humoral and Cellular Immunity

Adaptive immunity is divided into two interdependent branches: humoral immunity and cellular immunity. Each branch is specialized for dealing with different types of pathogens.

• Humoral immunity: Mediated by antibodies produced by B cells; effective against extracellular pathogens.

• Cellular immunity: Mediated by T cells; effective against intracellular pathogens such as viruses and some bacteria.

Development of T and B Cells

Both T and B lymphocytes originate from stem cells in the bone marrow. Their maturation sites differ:

• B cells: Mature in the bone marrow (or bursa of Fabricius in birds).

• T cells: Mature in the thymus.

After maturation, these cells migrate to lymphoid tissues such as the spleen and lymph nodes, where they encounter antigens.

Antigens and Antibodies

The Nature of Antigens

An antigen (Ag) is any substance that provokes an immune response, leading to the production of specific antibodies or sensitized T cells. Antigens possess distinct regions called epitopes (antigenic determinants) that are recognized by antibodies.

• Hapten: A small molecule that becomes antigenic only when attached to a larger carrier molecule.

The Nature and Structure of Antibodies

Antibodies, or immunoglobulins (Ig), are Y-shaped globular proteins that specifically bind to antigens. Each antibody has two antigen-binding sites, determining its valence.

• Structure: Composed of two heavy and two light chains, with variable regions forming the antigen-binding sites.

• Fc region: The stem of the Y, important for effector functions.

Classes of Antibodies

There are five main classes of immunoglobulins, each with distinct structures and functions:

• IgG: Monomer; most abundant in serum; crosses placenta; fixes complement; half-life = 23 days.

• IgM: Pentamer; first antibody produced in response to infection; fixes complement; half-life = 5 days.

• IgA: Dimer; found in secretions (mucosal protection); half-life = 6 days.

• IgD: Monomer; found on B cells; initiates immune response; half-life = 3 days.

• IgE: Monomer; involved in allergic reactions and defense against parasitic worms; half-life = 2 days.

B Cells and Humoral Immunity

Activation of B Cells

B cells can be activated by two types of antigens:

• T-dependent antigens: Require cooperation with T helper (TH) cells. The antigen is presented with MHC class II on the B cell surface to a TH cell, which then provides cytokines to activate the B cell.

• T-independent antigens: Can directly stimulate B cells to produce antibodies without T cell help (often polysaccharides).

Clonal Selection and Differentiation

Upon activation, B cells undergo clonal selection, proliferating and differentiating into:

• Plasma cells: Produce and secrete antibodies specific to the antigen.

• Memory cells: Provide long-term immunity by responding rapidly to subsequent exposures.

Antigen–Antibody Binding and Its Effects

Binding of antibodies to antigens leads to several protective mechanisms:

• Agglutination: Clumping of pathogens, enhancing phagocytosis.

• Opsonization: Coating of antigens to enhance phagocytosis.

• Activation of complement: Leads to cell lysis and inflammation.

• Antibody-dependent cell-mediated cytotoxicity (ADCC): Destruction of target cells by immune cells.

• Neutralization: Blocking of pathogen attachment or toxin activity.

T Cells and Cellular Immunity

T Cell Maturation and Selection

T cells mature in the thymus, where thymic selection eliminates many immature or self-reactive T cells, ensuring self-tolerance.

Principal Cells in Cell-Mediated Immunity

Several types of T cells and related cells function in cellular immunity:

Cell	Function
T Helper (TH1) Cell	Activates cells related to cell-mediated immunity: macrophages, T cells, and natural killer cells
T Helper (TH2) Cell	Stimulates production of eosinophils, IgM, and IgE
Cytotoxic T Lymphocyte (CTL)	Destroys target cells on contact; generated from T cytotoxic (TC) cell
T Regulatory (Treg) cell	Regulates immune response and helps maintain tolerance
Activated Macrophage	Enhanced phagocytic activity; attacks cancer cells
Natural Killer (NK) Cell	Attacks and destroys target cells; participates in antibody-dependent cell-mediated cytotoxicity

Antigen-Presenting Cells (APCs)

APCs such as dendritic cells, macrophages, and B cells digest antigens and present antigen fragments on their surface with MHC molecules, facilitating T cell activation.

T Helper Cells (CD4+)

CD4+ T helper cells recognize antigens presented with MHC class II on APCs. Upon activation, they secrete cytokines and differentiate into various subtypes:

• TH1 cells: Activate macrophages and promote cell-mediated immunity.

• TH2 cells: Stimulate B cells and eosinophils.

• TH17 cells: Stimulate innate immune responses.

• Treg cells: Suppress immune responses to maintain tolerance.

Cytotoxic T Cells (CD8+)

CD8+ T cells recognize antigens presented with MHC class I on infected or abnormal cells. Once activated, they become cytotoxic T lymphocytes (CTLs) that induce apoptosis in target cells by releasing perforin and granzymes.

Natural Killer (NK) Cells and ADCC

NK cells destroy cells lacking MHC I, such as virus-infected or tumor cells, and participate in antibody-dependent cell-mediated cytotoxicity (ADCC), especially against large parasites.

Cytokines and Immune Communication

Role of Cytokines

Cytokines are chemical messengers that regulate the intensity and duration of immune responses. Overproduction can lead to a cytokine storm, causing tissue damage.

• Interleukins (IL): Mediate communication between leukocytes.

• Interferons (IFN): Inhibit viral replication and activate immune cells.

• Tumor necrosis factor (TNF): Promotes inflammation.

• Chemokines: Induce migration of leukocytes.

Immunological Memory

Primary and Secondary Immune Responses

The primary response occurs after the first exposure to an antigen, with a lag phase before antibody production. The secondary (anamnestic) response is faster and more robust due to memory cells.

Types of Adaptive Immunity

Acquisition of Immunity

• Naturally acquired active immunity: Resulting from infection.

• Naturally acquired passive immunity: Transfer of antibodies from mother to fetus or infant.

• Artificially acquired active immunity: Vaccination with antigens.

• Artificially acquired passive immunity: Injection of antibodies (antiserum).

Terminology of Adaptive Immunity

• Serology: Study of antigen-antibody reactions.

• Antiserum: Serum containing antibodies.

• Globulins: Serum proteins, including immunoglobulins (antibodies).

• Gamma globulin: Serum fraction containing antibodies.