Adaptive Immunity: Specific Defenses of the Host

Adaptive Immunity: Specific Defenses of the Host

Overview of Adaptive Immunity

Adaptive immunity is a specialized defense mechanism that targets specific pathogens. It is acquired through infection or vaccination and is characterized by a primary response (first exposure) and a secondary response (subsequent exposures), which is faster and more effective due to immunological memory.

• Adaptive immunity: Specific, acquired defense against pathogens.

• Primary response: Initial immune reaction to a new antigen.

• Secondary response: Enhanced response upon re-exposure to the same antigen.

Comparison: Adaptive vs. Innate Immunity

Adaptive immunity differs from innate immunity in its specificity and memory. Innate immunity is the body's immediate, non-specific defense, while adaptive immunity is slower but highly specific and capable of remembering past invaders.

• Innate immunity: Non-specific, immediate response.

• Adaptive immunity: Specific, acquired, and has memory.

Dual Nature of the Adaptive Immune System

Humoral vs. Cellular Immunity

The adaptive immune system consists of two main branches: humoral immunity and cellular immunity. Humoral immunity involves B cells and the production of antibodies, while cellular immunity involves T cells that target infected or abnormal cells.

• Humoral immunity: B cells produce antibodies to combat extracellular antigens.

• Cellular immunity: T cells recognize and destroy infected or abnormal cells.

B and T Cell Development

B cells mature in the bone marrow, while T cells mature in the thymus. Both migrate to lymphoid tissues where they encounter antigens.

Cytokines: Chemical Messengers of Immune Cells

Key Cytokines and Their Functions

Cytokines are signaling molecules that regulate immune responses. Different types include interleukins, chemokines, interferons, TNF, and hematopoietic cytokines.

• Interleukins (ILs): Communication between leukocytes.

• Chemokines: Induce migration of immune cells.

• Interferons (IFNs): Inhibit viral replication.

• Tumor necrosis factor alpha (TNF-α): Inflammation and autoimmune disease.

• Hematopoietic cytokines: Control blood cell development.

Cytokine	Source	Target Cells	Effect
IL-4	TH2	TH2, B cells	Proliferate TH2 cells, class switching to IgE
IL-12	Dendritic cells, macrophages	Naive T cells, NK cells	Stimulates growth/function of TH1 cells, stimulates NK cells
IL-17	TH17	Neutrophils	Stimulates epithelial cells to make antimicrobial proteins
IL-22	TH17	Epithelial cells	Stimulates epithelial cells to make antimicrobial proteins
Gamma interferon (IFN-γ)	TH1	CTL, macrophages	Promote phagocytosis, activate macrophages, enhance humoral response
Chemokines	Various	Neutrophils	Chemotaxis
TNF-alpha (TNF-α)	Macrophages, T cells, NK cells	Tumor cells	Inflammation
GM-CSF	Macrophages, T cells, NK cells	Myeloid stem cells	Increases macrophages and granulocytes

Antigens and Antibodies

Definitions and Functions

Antigens are substances that provoke an immune response, typically by causing the production of antibodies. Antibodies interact with specific regions on antigens called epitopes. Haptens are small antigens that require attachment to carrier molecules to elicit a response.

• Antigen: Substance that induces antibody production.

• Epitope: Specific region of an antigen recognized by antibodies.

• Hapten: Small molecule that becomes antigenic when attached to a carrier.

Antibody Structure and Classes

Antibodies (immunoglobulins) are Y-shaped proteins composed of two light and two heavy chains. The variable regions bind to epitopes, while the constant region determines the antibody class. There are five main classes: IgG, IgM, IgA, IgD, and IgE.

• IgG: Most abundant; crosses placenta; enhances phagocytosis.

• IgM: First response; causes agglutination.

• IgA: Found in mucous membranes and secretions.

• IgD: Assists in immune response on B cells.

• IgE: Allergic responses; defense against parasites.

Class	Structure	% Total Serum Antibody	Location	Known Functions
IgG	Monomer	80%	Blood, lymph, intestine	Enhances phagocytosis, neutralizes toxins/viruses, protects fetus
IgM	Pentamer	6%	Blood, lymph, B cell surface	First response, agglutination
IgA	Dimer (secretions), monomer (serum)	13%	Secretions, blood, lymph	Localized protection on mucosal surfaces
IgD	Monomer	0.02%	Blood, lymph, B cell surface	Serum function unknown, assists B cell response
IgE	Monomer	0.002%	Bound to mast cells, basophils, blood	Allergic reactions, defense against parasites

Humoral Immunity Response Process

Activation and Clonal Expansion of B Cells

B cells are activated when they encounter antigens. T-dependent antigens require T helper cells for activation, while T-independent antigens do not. Activated B cells undergo clonal expansion, differentiating into plasma cells (antibody producers) and memory cells.

• Major histocompatibility complex (MHC): Molecules on cell surfaces identifying self and presenting antigens.

• Clonal selection: Process by which B cells differentiate into plasma and memory cells.

• Clonal deletion: Removal of self-reactive B cells.

Results of the Antigen-Antibody Interaction

Protective Mechanisms

Antigen-antibody complexes protect the host by tagging foreign molecules for destruction. The main outcomes include agglutination, opsonization, antibody-dependent cell-mediated cytotoxicity, neutralization, and activation of the complement system.

• Agglutination: Clumping of antigens.

• Opsonization: Coating antigens to enhance phagocytosis.

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

• Neutralization: Blocking pathogen attachment.

• Complement activation: Lysis of pathogens.

Cellular Immunity Response Process

Key Cells and Functions

Cellular immunity involves T cells, which mature in the thymus and migrate to lymphoid tissues. M cells in the gut facilitate antigen transfer to immune cells. Antigen-presenting cells (APCs) such as dendritic cells and macrophages present antigens to T cells.

• M cells: Transfer antigens from gut to immune cells.

• Dendritic cells: Present antigens to T cells.

• Macrophages: Engulf pathogens and present antigens.

Classes of T Cells

T cells are classified by clusters of differentiation (CD) markers. CD4+ T helper cells interact with MHC class II molecules, while CD8+ cytotoxic T lymphocytes (CTLs) interact with MHC class I molecules.

• TH cells (CD4+): Activate B cells, CTLs, and macrophages.

• CTLs (CD8+): Destroy infected or abnormal cells.

• Treg cells: Suppress immune responses.

Cytotoxic T Lymphocytes and Apoptosis

CTLs recognize and kill infected cells by inducing apoptosis, a programmed cell death process that prevents the spread of infection.

• Apoptosis: Programmed cell death; prevents viral spread.

Nonspecific Cells and Extracellular Killing

Natural Killer (NK) Cells and ADCC

NK cells destroy cells lacking MHC class I molecules, such as virus-infected or tumor cells. In antibody-dependent cell-mediated cytotoxicity (ADCC), immune cells target large pathogens coated with antibodies.

• NK cells: Kill cells without MHC class I; attack viruses, tumors, parasites.

• ADCC: Immune cells lyse antibody-coated target cells.

Cell	Function
T Helper (TH1) Cell	Activates cells related to cell-mediated immunity
T Helper (TH2) Cell	Stimulates production of eosinophils, IgM, IgE
T Helper (TH17) Cell	Recruits neutrophils; stimulates antimicrobial proteins
Cytotoxic T Lymphocyte (CTL)	Destroys target cells by inducing apoptosis
T Regulatory (Treg) Cell	Regulates immune response, maintains self-tolerance
Activated Macrophage	Enhanced phagocytic activity; attacks cancer cells
Natural Killer (NK) Cell	Attacks and destroys target cells; participates in ADCC

Immunological Memory

Primary vs. Secondary Immune Response

The primary immune response occurs upon first exposure to an antigen, while the secondary response is faster and stronger due to memory cells. Class switching allows the production of different antibody types.

• Primary response: Initial IgM production.

• Secondary response: Rapid IgG, IgE, or IgA production.

• Antibody titer: Measurement of antibody concentration in serum.

Types of Adaptive Immunity

Four Types of Adaptive Immunity

Adaptive immunity can be acquired naturally or artificially, and can be active or passive.

• Naturally acquired active immunity: Infection-induced antibody production.

• Naturally acquired passive immunity: Antibodies transferred from mother to child.

• Artificially acquired active immunity: Vaccination-induced antibody production.

• Artificially acquired passive immunity: Injection of preformed antibodies.

Summary: Dual Nature of the Adaptive Immune System

The adaptive immune system is divided into humoral and cellular branches, each responsible for dealing with different types of pathogens. Humoral immunity targets extracellular pathogens, while cellular immunity targets intracellular pathogens.