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, residing in lymphoid tissues and circulating in body fluids. The immune system is often compared to a medieval castle, with multiple lines of defense acting both independently and cooperatively to resist invasion. There are three main lines of defense:

• Surface barriers (first line): Intact skin and mucosae act as structural barriers to keep invaders out.

• Innate internal defenses (second line): Includes inflammation, antimicrobial proteins, and phagocytes that inhibit the spread of invaders.

• Adaptive (specific) defense system (third line): Targets identified enemies with specialized responses, taking longer to mount.

Innate Defenses

Surface Barriers: First Line of Defense

Surface barriers include skin and mucous membranes, along with their secretions. The heavily keratinized epidermis is highly effective against most microbes. Protective chemicals produced by these barriers include:

• Acid: Acid mantle inhibits bacterial growth.

• Enzymes: Lysozyme in saliva, mucus, and lacrimal fluid 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: Lipids in sebum and dermcidin in sweat are toxic to bacteria.

Respiratory tract modifications include mucus-coated hairs in the nose and cilia in the upper tract that sweep dust and bacteria-laden mucus toward the mouth.

Innate Internal Defenses: Second Line of Defense

If microbes breach surface barriers, the second line of defense is activated. This includes nonspecific cellular and chemical means such as phagocytes, natural killer cells, antimicrobial proteins, inflammation, and fever. These defenses recognize pathogens by binding to specific-shaped molecules (e.g., carbohydrates) not found on normal human cells, using pattern recognition receptors like Toll-like receptors (TLRs).

Phagocytes and Phagocytosis

Phagocytes are white blood cells that ingest and digest foreign invaders and debris. Types include:

• Neutrophils: Most abundant, phagocytize infectious material.

• Macrophages: Most voracious, derived from monocytes (free or fixed in tissues).

Phagocytosis involves several steps:

• Phagocyte adheres to pathogen/debris using receptors.

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

• Lysosome fuses with phagosome, forming a phagolysosome.

• Toxic compounds and lysosomal enzymes destroy pathogens.

• Exocytosis removes indigestible material.

Natural Killer (NK) Cells

NK cells are large granular lymphocytes that police blood and lymph, killing cancer and virus-infected cells by inducing apoptosis and secreting 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. Four cardinal signs: redness, heat, swelling, pain.

• Inflammatory chemicals (e.g., histamine, kinins, prostaglandins) released by injured cells.

• Vasodilation and increased capillary permeability bring immune cells and proteins to the site.

• Phagocyte mobilization involves leukocytosis, margination, diapedesis, and chemotaxis.

Antimicrobial Proteins

Antimicrobial proteins enhance innate defenses by attacking microbes or hindering their reproduction. Key proteins:

• Interferons (IFNs): Produced by virus-infected cells, interfere with viral replication in neighboring cells, activate NK cells and macrophages.

• Complement proteins: At least 20 plasma proteins, activated via classical, lectin, or alternative pathways, amplify inflammation, promote phagocytosis, and cause cell lysis.

Fever

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

Adaptive Defenses

General Features

The adaptive immune system is a specific defense system targeting almost any pathogen. 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 provoke an immune response. They can be complete (immunogenic and reactive) or incomplete (haptens, which require a carrier protein). Antigenic determinants are specific parts of antigens recognized by antibodies or lymphocyte receptors.

Self-Antigens: MHC Proteins

MHC proteins are glycoproteins unique to each individual, displaying self or foreign peptides. T lymphocytes can only bind antigens presented on MHC proteins.

B and T Lymphocytes and Antigen-Presenting Cells

Three crucial cell types in adaptive immunity:

• B lymphocytes: Provide humoral immunity.

• T lymphocytes: Provide cellular immunity.

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

Lymphocyte Development, Maturation, and Activation

Lymphocytes undergo five general steps:

• Origin: Hematopoietic stem cells in red bone marrow.

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

• Seeding: Colonize secondary lymphoid organs.

• Antigen encounter and activation: Clonal selection upon first antigen encounter.

• Proliferation and differentiation: Formation of effector and memory cells.

Humoral Immunity

Activation and Differentiation of B Cells

B cells are activated by antigen binding, followed by endocytosis and proliferation into plasma cells (antibody-secreting) and memory cells. Antibodies circulate in blood and lymph, marking antigens for destruction.

Immunological Memory

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

Active and Passive Humoral Immunity

Active immunity involves B cells producing antibodies (naturally via infection or artificially via vaccination). Passive immunity involves receiving antibodies (naturally from mother or artificially via injection), but does not generate memory cells.

Antibody Structure and Classes

Antibodies (immunoglobulins, Ig) are proteins with a basic Y-shaped structure, composed of heavy and light chains, variable and constant regions. Five major classes: IgG, IgA, IgM, IgE, IgD.

Antibody Targets and Functions

Antibodies inactivate and tag antigens for destruction via:

• Neutralization: Block binding sites on pathogens.

• Agglutination: Clump antigens together.

• Precipitation: Form complexes that settle out of solution.

• Complement activation: Trigger cell lysis and enhance inflammation.

Cellular Immunity

T Lymphocytes and Their Roles

T cells provoke cellular immune responses when presented with antigens. Major types:

• Helper T cells (CD4): Activate B cells, other T cells, and macrophages; direct adaptive response.

• Regulatory T cells: Moderate immune response.

• Cytotoxic T cells (CD8): Destroy infected, abnormal, or foreign cells.

MHC Proteins and Antigen Presentation

T cells respond only to processed antigen fragments displayed by MHC proteins. CD4 cells bind antigens on MHC II proteins (on APCs), CD8 cells bind antigens on MHC I proteins (on all body cells except RBCs).

Activation and Differentiation of T Cells

T cell activation requires antigen binding and co-stimulation by APCs. Activated T cells proliferate and differentiate into effector and memory cells. Cytokines (e.g., interleukins, interferons) regulate immune responses.

Roles of Specific Effector T Cells

• Helper T cells: Central role in mobilizing humoral and cellular immunity, activating B and T cells, and recruiting other immune cells.

• Cytotoxic T cells: Directly attack and kill infected or abnormal cells using perforins and granzymes to induce apoptosis.

• Regulatory T cells: Suppress immune responses, prevent autoimmunity.

Immune System Disorders

Immunodeficiencies

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

Autoimmune Diseases

Autoimmune diseases result from the immune system failing to distinguish self from foreign antigens, producing autoantibodies and self-reactive T cells. Examples: rheumatoid arthritis, multiple sclerosis, type 1 diabetes, lupus.

Hypersensitivities

Hypersensitivities are immune responses to harmless threats causing tissue damage. Types include:

• Immediate (acute) hypersensitivity: Allergies, mediated by IgE and histamine release.

• Subacute hypersensitivity: Mediated by IgM and IgG, slower onset.

• Delayed hypersensitivity: Mediated by T cells, takes 1–3 days to appear.

Developmental Aspects of the Immune System

Immune system stem cells develop in liver and spleen during early weeks, then bone marrow becomes primary source. With age, immune efficiency wanes, increasing susceptibility to infection, cancer, and autoimmune diseases.

Summary Table: Immunoglobulin Classes

Summary Table: Lines of Defense

Additional info: These notes provide a comprehensive overview of Chapter 21, suitable for exam preparation in Anatomy & Physiology courses, covering both innate and adaptive immune responses, key cell types, mechanisms, and clinical relevance.