The Immune System: Overview

General Functions and Organization

The immune system provides resistance to disease-causing microorganisms and is a functional system composed of molecules and immune cells, especially lymphocytes. It is not an anatomical organ system but operates throughout the body, using lymphoid tissues and circulating immune cells. The immune system is often compared to a medieval castle, with multiple lines of defense acting independently and cooperatively to resist invasion.

• Three lines of defense: Surface barriers, innate internal defenses, and adaptive defenses.

• Surface barriers: Intact skin and mucosae act as the first line of defense, keeping invaders out.

• Innate internal defenses: Second line, activated when surface barriers are breached; includes inflammation, antimicrobial proteins, and phagocytes.

• Adaptive defenses: Third line, highly specific and slower to respond; includes humoral and cellular immunity.

Innate Defenses

Surface Barriers: First Line of Defense

Surface barriers include the skin and mucous membranes, along with their secretions. These barriers are present at birth and provide mechanical and chemical protection against pathogens.

• Keratinized epidermis: Highly effective against most microbes; keratin resists acids, bases, enzymes, and toxins.

• Mucosae: Line internal tracts and provide similar mechanical barriers.

• Protective chemicals:

  • Acid mantle: Acidity of skin, vaginal, and stomach secretions inhibits bacterial growth.

  • Enzymes: Lysozyme in saliva, mucus, and tears kills microbes; stomach enzymes digest pathogens.

  • Mucin: Sticky mucus traps microbes in digestive and respiratory tracts.

  • Defensins: Antimicrobial peptides secreted in response to barrier breach.

  • Other chemicals: Sebum lipids and dermcidin in sweat are toxic to bacteria.

• Respiratory tract: Mucus-coated hairs and cilia trap and sweep out pathogens.

Innate Internal Defenses: Second Line of Defense

If pathogens breach surface barriers, innate internal defenses are activated. These include nonspecific cellular and chemical mechanisms such as phagocytes, natural killer cells, antimicrobial proteins, inflammation, and fever.

• Pattern recognition receptors: Identify pathogens by recognizing specific molecular patterns (e.g., carbohydrates).

• Toll-like receptors (TLRs): Central in triggering immune responses; humans have 11 TLRs, each recognizing a different class of microbe.

Phagocytes

Phagocytes are white blood cells that ingest and digest foreign invaders and debris. The main types are neutrophils and macrophages.

• Neutrophils: Most abundant; phagocytize infectious material.

• Macrophages: Most voracious; can be free (wandering) or fixed (resident in organs).

• Phagocytosis: Process by which phagocytes engulf and digest pathogens.

• Steps of phagocytosis:

  1. Phagocyte adheres to pathogen/debris using receptors.

  2. Phagocyte forms pseudopods to engulf particles, forming a phagosome.

  3. Phagosome fuses with lysosome, forming a phagolysosome.

  4. Toxic compounds and lysosomal enzymes destroy pathogens.

  5. Exocytosis removes indigestible material.

Natural Killer (NK) Cells

NK cells are large granular lymphocytes that police blood and lymph, targeting cells with abnormal surface proteins (e.g., lacking MHC). They induce apoptosis in cancer and virus-infected cells and secrete chemicals to enhance inflammation.

Inflammation: Tissue Response to Injury

Inflammation is a nonspecific response to tissue injury, preventing spread of pathogens, disposing of debris, alerting the adaptive immune system, and setting the stage for repair. The four cardinal signs are redness, heat, swelling, and pain.

• Inflammatory chemical release: Histamine, kinins, prostaglandins, and cytokines dilate arterioles and increase capillary permeability.

• Vasodilation and permeability: Brings more immune cells and chemicals; causes redness, heat, swelling, and pain.

• Phagocyte mobilization: Steps include leukocytosis, margination, diapedesis, and chemotaxis.

Antimicrobial Proteins

Antimicrobial proteins enhance innate defenses by attacking microbes or hindering their reproduction. The most important are interferons and complement proteins.

• Interferons (IFNs): Immune-modulating proteins produced by virus-infected cells; block viral replication and activate NK cells and macrophages.

• Complement system: At least 20 plasma proteins, activated via classical, lectin, or alternative pathways; amplifies inflammation, promotes phagocytosis, and causes cell lysis.

Fever

Fever is a systemic response to infection, triggered by pyrogens released by leukocytes and macrophages. It increases metabolic rate, enhances immune response, and suppresses bacterial growth.

Adaptive Defenses

General Features

The adaptive immune system is a specific defense system that targets and eliminates pathogens and abnormal cells. It consists of two overlapping arms:

• Humoral immunity: Antibody-mediated, targets extracellular pathogens.

• Cellular immunity: Cell-mediated, targets infected, cancerous, or foreign cells.

Antigens

Antigens are substances that trigger adaptive defenses. Most are large, complex molecules foreign to the body. They possess antigenic determinants—specific regions recognized by antibodies or lymphocyte receptors.

Self-Antigens: MHC Proteins

All body cells display self-antigens, including MHC proteins (major histocompatibility complex), which are unique to each individual. T lymphocytes can only bind antigens presented on MHC proteins.

B and T Lymphocytes and Antigen-Presenting Cells

Three crucial cell types are involved in adaptive immunity:

• B lymphocytes: Provide humoral immunity.

• T lymphocytes: Provide cellular immunity.

• Antigen-presenting cells (APCs): Present antigens to T cells; include dendritic cells, macrophages, and B cells.

Lymphocyte Development, Maturation, and Activation

Lymphocytes undergo a five-step process: origin, maturation, seeding secondary organs, antigen encounter and activation, and proliferation/differentiation.

• Origin: Hematopoietic stem cells in red bone marrow.

• Maturation: In bone marrow (B cells) or thymus (T cells); involves immunocompetence and self-tolerance.

• Seeding: Naive cells colonize secondary lymphoid organs.

• Activation: Antigen encounter triggers clonal selection.

• Proliferation: Activated cells form clones; most become effector cells, some become memory cells.

T Cell Education in the Thymus

T cells undergo positive and negative selection in the thymus to ensure self-tolerance and immunocompetence.

Humoral Immunity

Activation and Differentiation of B Cells

B cells are activated by antigen binding, followed by endocytosis and proliferation. Most become plasma cells that secrete antibodies; some become memory cells.

Immunological Memory

Primary immune response occurs upon initial antigen exposure, with a lag period. Secondary response is faster and stronger due to memory cells.

Active and Passive Humoral Immunity

Immunity can be acquired actively (via infection or vaccination) or passively (via maternal antibodies or injection of antibodies). Passive immunity provides immediate but temporary protection.

Antibodies: Structure and Classes

Antibodies (immunoglobulins, Ig) are proteins secreted by plasma cells. They have a basic Y-shaped structure with variable and constant regions. Five major classes: IgG, IgA, IgM, IgE, and IgD.

• IgG: Most abundant; crosses placenta.

• IgA: Found in secretions; protects mucosal surfaces.

• IgM: First antibody released; potent agglutinating agent.

• IgE: Involved in allergic responses and defense against parasites.

• IgD: Functions as B cell receptor.

Antibody Targets and Functions

Antibodies inactivate and tag antigens for destruction via neutralization, agglutination, precipitation, and complement activation.

Cellular Immunity

T Lymphocytes: Types and Functions

T cells provoke cellular immune responses. Major types include CD4 (helper and regulatory T cells) and CD8 (cytotoxic T cells). Helper T cells activate B cells, other T cells, and macrophages; cytotoxic T cells destroy infected and abnormal cells.

MHC Proteins and Antigen Presentation

T cells respond only to antigens presented on MHC proteins. CD4 cells bind antigens on MHC II (APCs), CD8 cells bind antigens on MHC I (all body cells except RBCs).

Activation and Differentiation of T Cells

T cell activation requires antigen binding and co-stimulation. Activated T cells proliferate and differentiate into effector and memory cells.

Helper T Cells: Central Role

Helper T cells mobilize both humoral and cellular immunity, activate B and T cells, and secrete cytokines to recruit other immune cells.

Cytotoxic T Cells

Cytotoxic T cells directly attack and kill infected, cancerous, or foreign cells by releasing perforins and granzymes or binding to membrane receptors to induce apoptosis.

Regulatory T Cells

Regulatory T cells suppress immune responses, preventing autoimmunity and maintaining tolerance to self-antigens.

Immune System Disorders

Immunodeficiencies

Immunodeficiency is a condition where immune function is impaired. Examples include severe combined immunodeficiency (SCID), Hodgkin’s lymphoma, and AIDS (caused by HIV).

Autoimmune Diseases

Autoimmune diseases occur when the immune system attacks self-antigens, leading to conditions such as rheumatoid arthritis, type 1 diabetes, and lupus. Treatments include immunosuppressive drugs and therapies targeting specific immune pathways.

Hypersensitivities

Hypersensitivities are immune responses to harmless antigens that cause tissue damage. Types include immediate (allergies), subacute, and delayed hypersensitivities.

Developmental Aspects of the Immune System

Immune system stem cells develop in the liver and spleen during early development, then in bone marrow. With age, immune efficiency declines, increasing susceptibility to infections, cancer, and autoimmune diseases.

Key Tables

Immunoglobulin Classes

*Additional info: Academic context and explanations have been expanded for clarity and completeness. Images included are directly relevant to the adjacent content and reinforce key concepts visually. Tables have been recreated and summarized for study purposes.*