The Immune System: Structure and Function (Campbell Biology in Focus, Chapter 35)

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The Immune System

Introduction to the Immune System

The immune system is a complex network of cells, tissues, and molecules that protects organisms from disease-causing agents known as pathogens. These include bacteria, viruses, fungi, and other microorganisms. Specialized immune cells recognize and attack pathogens, enabling animals to avoid or limit infections.

Pathogen: Any disease-causing agent, such as a bacterium, fungus, or virus.
Immune System: The collection of defenses that enables an animal to avoid or limit many infections.
Adaptations: Protective mechanisms that have evolved to defend against pathogens.
Example: White blood cells attacking bacteria or viruses.

Recognition of Pathogens

How Immune Cells Recognize Pathogens

Immune cells identify pathogens by recognizing specific molecules associated with them. Recognition triggers a response that can eliminate or inactivate the pathogen. There are two main types of recognition: innate and adaptive.

Innate Recognition: Detects molecules common to groups of pathogens (e.g., dsRNA in viruses, flagellin in bacteria, mannan in fungi).
Adaptive Recognition: Detects unique molecules specific to individual pathogen strains (e.g., different strains of influenza virus).
Example: Toll-like receptors (TLRs) on immune cells bind to pathogen-associated molecular patterns (PAMPs).

Pathogen	Innate Recognition Molecule	Adaptive Recognition
Virus	dsRNA (nucleic acid in genome)	Strain-specific antigens
Bacterium	Flagellin (protein in flagella)	Strain-specific antigens
Fungus	Mannan (oligosaccharide in cell wall)	Strain-specific antigens

Innate Immunity

General Features of Innate Immunity

Innate immunity provides immediate, non-specific defense against pathogens. It relies on traits common to groups of pathogens and is found in all animals. Innate defenses include physical barriers, chemical secretions, and cellular responses.

Physical Barriers: Skin, shell, and mucous membranes prevent pathogen entry.
Chemical Barriers: Secretions such as saliva, mucus, and tears contain antimicrobial substances; low pH of skin and digestive tract inhibits microbial growth.
Cellular Defenses: Phagocytic cells ingest and destroy pathogens.
Example: Lysozyme in saliva breaks down bacterial cell walls.

Innate Immunity in Invertebrates

Invertebrates rely on physical barriers and immune cells for defense. Their exoskeleton acts as a barrier, and enzymes like lysozyme protect the digestive system. Immune cells produce proteins that recognize broad classes of pathogens.

Hemocytes: Immune cells in invertebrates that perform phagocytosis and release antimicrobial peptides.
Phagocytosis: The ingestion and breakdown of foreign substances, including bacteria.
Example: Hemocytes encapsulate large parasites and release peptides that disrupt pathogen membranes.

Innate Immunity in Vertebrates

Vertebrates have more complex innate defenses, including barrier defenses, phagocytosis, antimicrobial peptides, natural killer cells, interferons, and the inflammatory response.

Barrier Defenses: Mucous membranes and secretions trap and neutralize pathogens.
Phagocytic Cells: Neutrophils and macrophages ingest pathogens; dendritic cells stimulate adaptive immunity; eosinophils release destructive enzymes.
Natural Killer Cells: Detect and destroy abnormal cells, such as virally infected or cancerous cells.
Antimicrobial Peptides and Proteins: Cytokines and interferons interfere with pathogen replication; the complement system leads to cell lysis.
Inflammatory Response: Activated by injury or infection, involves cytokines, histamine, and increased blood flow, resulting in swelling, pain, and pus formation.

Adaptive Immunity

General Features of Adaptive Immunity

Adaptive immunity is a specific defense found only in vertebrates. It relies on lymphocytes (B cells and T cells) that recognize unique features of individual pathogens. The response is slower but highly specific and involves immunological memory.

Lymphocytes: White blood cells that mature in the thymus (T cells) or bone marrow (B cells).
Antigen: Any substance that elicits a response from B or T cells.
Antigen Receptor: Protein on B or T cells that binds to a specific part of an antigen (epitope).
Immunological Memory: The ability to respond more rapidly and effectively to previously encountered antigens.

B Cell and Antibody Recognition

B cells recognize antigens via Y-shaped receptors composed of heavy and light chains. Upon activation, B cells produce antibodies (immunoglobulins) that bind to pathogens and mark them for destruction.

Antibody Structure: Two identical heavy chains and two identical light chains; variable regions form the antigen-binding site.
Antibody Function: Neutralize pathogens, bind toxins, and activate the complement system.
Types of Immunoglobulins: Five classes (IgM, IgG, IgA, IgE, IgD) with different roles and locations.
Example: IgA is found in tears, saliva, and breast milk.

T Cell Recognition

T cells recognize antigen fragments presented on host cell surfaces by major histocompatibility complex (MHC) molecules. The interaction between T cell receptors and MHC-antigen complexes is essential for adaptive immunity.

T Cell Receptor: Composed of alpha and beta chains; variable regions form the antigen-binding site.
MHC Molecules: Host proteins that display antigen fragments on cell surfaces.
Antigen Presentation: Process by which MHC molecules transport antigen fragments to the cell surface.
Example: Cytotoxic T cells recognize and kill infected cells displaying foreign antigens with class I MHC.

Development and Diversity of Lymphocytes

The adaptive immune system generates a vast diversity of lymphocytes and receptors through gene rearrangement. Self-tolerance is ensured by eliminating or inactivating self-reactive cells during maturation.

Clonal Selection: Activation and proliferation of lymphocytes specific to an encountered antigen.
Memory Cells: Long-lived cells that enable a rapid secondary immune response.
Gene Rearrangement: Variable (V), joining (J), and constant (C) segments recombine to produce diverse receptors.
Equation:
Example: Human B cells can generate over different receptors.

Immune Responses

Humoral and Cell-Mediated Responses

Adaptive immunity includes two main responses: humoral (antibody-mediated) and cell-mediated. Helper T cells activate both responses.

Humoral Response: B cells produce antibodies that neutralize or eliminate extracellular pathogens.
Cell-Mediated Response: Cytotoxic T cells destroy infected host cells.
Helper T Cells: Activate B cells and cytotoxic T cells by recognizing antigens presented by antigen-presenting cells (APCs).
Example: Helper T cells use CD4 accessory protein to bind class II MHC molecules on APCs.

Immunological Memory

Immunological memory ensures long-term protection. The primary immune response occurs upon first exposure to an antigen, while the secondary response is faster and stronger due to memory cells.

Primary Response: Initial activation of B and T cells; slower and less robust.
Secondary Response: Rapid and enhanced response upon re-exposure to the same antigen.
Example: Vaccination induces immunological memory against specific diseases.

Immunization and Vaccines

Principles of Immunization

Immunization uses antigens to stimulate adaptive immunity and memory cell formation. Vaccines may contain inactivated toxins, killed or weakened pathogens, or genetic material encoding pathogen proteins.

Types of Vaccines: Inactivated, attenuated, subunit, mRNA, and DNA vaccines.
Example: mRNA vaccines for SARS-CoV-2 encode the viral spike protein.
Booster Doses: Additional doses may be required to maintain immunity.

Active and Passive Immunity

Active immunity arises from infection or immunization, while passive immunity results from the transfer of antibodies from another individual.

Active Immunity: Long-lasting protection due to memory cell formation.
Passive Immunity: Temporary protection from transferred antibodies (e.g., maternal antibodies crossing the placenta or present in breast milk).
Artificial Passive Immunization: Injection of antibodies from immune animals (e.g., antivenom for snake bites).

Disorders and Avoidance of Immune System

Allergies and Autoimmune Diseases

Immune system dysfunction can lead to exaggerated responses (allergies) or self-targeting (autoimmune diseases).

Allergies: Hypersensitive responses to harmless antigens (allergens); may cause anaphylactic shock.
Autoimmune Diseases: Immune system attacks self-molecules (e.g., lupus, type 1 diabetes, multiple sclerosis, rheumatoid arthritis).
Example: Antihistamines block histamine receptors to reduce allergy symptoms.

Pathogen Evasion of Immunity

Some pathogens evade immune responses through latency, antigenic variation, or direct attack on immune cells.

Latency: Viruses remain inactive in host cells (e.g., herpes simplex virus).
Antigenic Variation: Pathogens change their surface epitopes to avoid recognition (e.g., influenza virus).
HIV/AIDS: HIV attacks helper T cells, leading to acquired immune deficiency syndrome (AIDS).
Example: HPV vaccine protects against virus-associated cancers.

Immune Rejection and Medical Applications

Transplanted cells or tissues may be rejected by the recipient's immune system. Matching MHC molecules and immunosuppressive drugs help minimize rejection. Antibodies are also used as diagnostic and therapeutic tools.

Monoclonal Antibodies: Produced from a single clone of B cells; used in medical diagnosis and treatment.
Blood Transfusion: Requires matching blood types to avoid immune reactions.
Example: Antibody tests can identify past viral infections.