Immune System and the Body’s Defense

Chapter 22: Immune System and the Body’s Defense

22.1 Introduction to the Immune System and Infectious Agents

  • The immune system differs fundamentally from other body systems as it is not composed of distinct organs.

  • It consists of cellular and molecular structures dispersed throughout the body.

  • The primary function of the immune system is to provide immunity, offering protection against harmful agents.

  • Infectious agents that can damage or kill a host include five major categories:

    • Bacteria:

    • Defined as single-celled prokaryotes.

    • Characterized as small cells lacking a nuclear envelope, enclosed by a cell wall.

    • Viruses:

    • Composed of pieces of DNA or RNA encased in a protein shell.

    • Viruses are much smaller than cells, approximately one-hundredth of a micrometer.

    • Classified as obligate intracellular parasites, which must enter a host cell to reproduce.

    • They direct infected cells to replicate their nucleic acids and capsid, potentially destroying the host cell.

    • Fungi:

    • Eukaryotic organisms that possess both a membrane and a cell wall, including molds and yeasts.

    • Release proteolytic enzymes that induce inflammation.

    • Protozoans:

    • Eukaryotic, unicellular organisms that lack a defined cell wall.

    • Disease-causing forms are termed parasites. Examples include malaria and trichomoniasis.

    • Multicellular Parasites:

    • Nonmicroscopic organisms such as parasitic worms that derive nourishment from their hosts.

    • Example includes tapeworms.

    • Prions:

    • Defined as fragments of infectious proteins, neither cellular nor viral in nature.

    • Capable of causing diseases in nervous tissue, such as Variant Creutzfeldt-Jakob disease, also known as “mad cow disease.”

    • Prions can transmit disease from cows to humans through consumption of infected meat.

22.2 Overview of the Immune System

  • The immune system is composed of various cellular and molecular structures that function to protect the body from infection and harmful substances.

  • Immune Responses:

    • The term "immune response" refers to all physiological processes executed by immune system components.

    • Innate Immune Response: Provides immediate, non-specific defense against pathogens without prior exposure.

    • Adaptive Immune Response: Offers specific and delayed protection that develops only after exposure to an antigen.

22.2a Immune Cells and Their Locations

  • Leukocytes (White Blood Cells): Formed in red bone marrow, includes:

    • Granulocytes: Neutrophils, eosinophils, basophils.

    • Monocytes: Transform into macrophages when migrating from blood into tissues.

    • Lymphocytes: Include B-lymphocytes, T-lymphocytes, and natural killer (NK) cells.

  • Locations of immune cells:

    • Most leukocytes reside in body tissues rather than circulating in the blood.

    • Secondary Lymphoid Structures: Where T- and B-lymphocytes, macrophages, dendritic cells, and NK cells are found; examples include lymph nodes, spleen, tonsils, and mucosa-associated lymphoid tissue (MALT).

    • Macrophages: May be permanent residents of specific organs or migrate.

    • Dendritic Cells: Located within epithelial layers of skin and mucosal membranes; perform antigen processing.

    • Mast Cells: Found in connective tissues, especially near blood vessels; play a role in inflammatory responses.

22.2b Cytokines

  • Cytokines: Small proteins regulating immune activity.

    • Produced by both innate and adaptive immune cells.

    • Function as chemical messengers released from one cell and bind to receptors on target cells.

    • Modes of action include:

    • Autocrine (acting on the same cell that releases them).

    • Paracrine (acting on local cells).

    • Endocrine (acting on distant cells after blood circulation).

    • Characteristics:

    • Short biological half-life.

    • Regulates the development and behavior of immune cells and inflammatory response.

22.2c Antigens

  • Antigens: Unique molecules, typically proteins or polysaccharides, that bind to components of the adaptive immune system. Examples include:

    • Virus capsids, bacterial/fungal cell walls, bacterial toxins, and tumor antigens.

  • Epitope: Specific region of an antigen where lymphocytes or antibodies attach.

  • Immunogens: Antigens that induce an immune response; immunogenicity depends on factors like foreignness, size, complexity, and quantity.

  • Haptens: Small molecules that are not antigens on their own but can become immunogenic when attached to larger molecules.

22.2d Comparison of Innate Immunity and Adaptive Immunity

  • Key Differences:

    • Types of cells involved.

    • Specificity of response to an antigen.

    • Mechanisms used for elimination of harmful substances.

    • Response time:

    • Innate Immunity: Immediate response, present at birth, protects against various substances without prior exposure.

    • Adaptive Immunity: Takes days to develop, responds specifically to antigens through T- and B-lymphocytes.

22.2e Features of Innate Immunity

  • First Line of Defense: Skin and mucosal membranes prevent entry of pathogens.

  • Second Line of Defense: Engages various internal defenses, including cellular and molecular components such as neutrophils, macrophages, and NK cells, among others.

22.3 Innate Immunity

  • Characteristics:

    • Prevents entry of harmful substances and responds nonspecifically. The first line of defense is the skin and mucosal membranes.

    • Second line of defense includes activities of immune cells (neutrophils, macrophages, etc.), chemicals (e.g., interferon, complement), and physiological responses (e.g., inflammation, fever).

22.3a Preventing Entry

  • Skin as a Barrier:

    • Physical barriers formed by epidermis and dermis. Keratinized stratified squamous epithelium increases defense.

  • Mucous Membranes: Lining body openings release mucus and antimicrobial substances (defensins, lysozyme). Their functions involve removal and neutralization of pathogens.

    • The microbiome of nonpathogenic microorganisms helps compete against pathogenic organisms.

22.3b Second Line of Defense: Nonspecific Internal Defenses

  • Initiation of this response occurs when the first line of defense is breached, employing selected immune cells, antimicrobial proteins, inflammation, and fever.

22.3c Nonspecific Internal Defenses: Cells

  • Phagocytic Cells: Such as neutrophils and macrophages that engulf pathogens. Examples of processes include:

    • Phagocytosis: ingestion of unwanted substances, formation of phagolysosome for digestion, respiratory burst for microbial destruction.

  • Proinflammatory Cells: Basophils and mast cells that release chemicals promoting inflammation and attract leukocytes. Specific roles include:

    • Histamine for increasing blood flow.

    • Heparin as an anticoagulant.

  • NK Cells: Patrol and destroy unhealthy cells, inducing apoptosis by releasing perforin and granzymes.

  • Eosinophils: Attack multicellular parasites, releasing cytotoxic substances during allergic reactions and asthma.

22.3d Nonspecific Internal Defenses: Antimicrobial Proteins

  • Interferons: A class that interferes with the spread of intracellular pathogens. Key actions:

    • Trigger neighboring cells to produce enzymes that degrade viral nucleic acids and inhibit protein synthesis.

    • Activating NK cells to destroy virus-infected cells.

  • Complement System: About 30 plasma proteins involved in pathogen recognition and elimination. Activation via:

    • Classical Pathway: Antibody binding to substrate.

    • Alternative Pathway: Direct binding to microbial cell walls.

    • Functions:

    • Increasing inflammation.

    • Opsonization for phagocytosis.

    • Cytolysis through the membrane attack complex (MAC).

22.3e Nonspecific Internal Defenses: Inflammation

  • Inflammation: A localized response to injury characterized by redness, heat, swelling, and pain. Involves several stages:

    1. Release of chemical signals (histamine, prostaglandins).

    2. Vasodilation and increased capillary permeability to recruit leukocytes.

    3. Delivery of plasma proteins and formation of exudate aids in cleansing and healing of the area.

22.3f Nonspecific Internal Defenses: Fever

  • Fever: An elevation in normal body temperature driven by pyrogens affecting the hypothalamic set point. Important stages include the onset of temperature rise, maintenance at peak levels, and eventual decline. Benefits include:

    • Inhibiting pathogen reproduction.

    • Accelerating tissue repair.
      Risks include possible distress and damage to host.

22.4 Adaptive Immunity: An Introduction

  • Adaptive immunity involves lymphocyte responses to specific antigens, leading to clonal proliferation and a longer response time than innate immunity, constituting the body’s third line of defense.

  • It comprises:

    • Cell-mediated immunity: predominated by T-lymphocytes.

    • Antibody-mediated immunity: predominated by B-lymphocytes and plasma cells that produce antibodies.

22.4a General Structure of Lymphocytes

  • T- and B-lymphocytes have unique receptor complexes: about 100,000 per cell, with specificity for a single antigen.

  • T-Lymphocytes: possess T-cell receptors (TCR) and are defined by CD molecules (CD4 and CD8).

  • B-Lymphocytes: feature B-cell receptors (BCR) but lack CD molecules because they can bind antigens directly.

22.4b Antigen-Presenting Cells and MHC Molecules

  • Antigen Presentation: Critical for T-cell recognition of antigens and facilitated by Major Histocompatibility Complex (MHC) proteins. There are two classes:

    • MHC Class I: Found on all nucleated cells, interacts with CD8 cytotoxic T-cells.

    • MHC Class II: Restricted to APCs (like dendritic cells and B-cells), interacts with CD4 helper T-cells.

22.4c Overview of Life Events of Lymphocytes

  • Life Cycle: Encompasses formation and selection, activation upon encountering antigens, and effector response in eliminating antigens.

22.5 Activation and Clonal Selection of Lymphocytes

  • Clonal Selection: Upon exposure to an antigen, lymphocytes proliferate to form clones that recognize that antigen. This can happen in secondary lymphoid structures like lymph nodes or spleen.

  • Activation of T-lymphocytes: Involves recognizing MHC-antigen complexes presented by APCs using their TCR and undergoing proliferation and differentiation.

  • Activation of B-lymphocytes: Binding of free antigens to BCR leads to engulfing, processing and presentation of the antigen to a helper T-cell.

22.5b Selection and Differentiation of T-Lymphocytes

  • Positive Selection: Enables T-cells that successfully bind MHC proteins to survive.

  • Negative Selection: Eliminates T-cells that recognize self-antigens to maintain self-tolerance.

22.6 Effector Response at Infection Site

  • Effector Response: Mechanisms utilized by T-lymphocytes, B-lymphocytes, and plasma cells for antigen elimination. They can be further broken down into:

    • Helper T-lymphocytes: Regulate immune responses through cytokine release.

    • Cytotoxic T-lymphocytes: Directly destroy infected or abnormal cells.

    • B-lymphocytes: Produce antibodies.

22.6a Activation of T-Lymphocytes

  • Helper T-cell Activation: Requires recognition of MHC class II molecules with antigen presented on an APC.

  • Cytotoxic T-cell Activation: Involves interaction with MHC class I molecules presented by infected cells.

22.6b Activation of B-Lymphocytes

  • Initial antigen binding to BCR, leading to helper T-cell interaction and subsequent proliferation into plasma cells and memory B-lymphocytes.

22.6c Lymphocyte Recirculation

  • Lymphocytes exit secondary lymphoid structures and circulate through the body to enhance opportunities for encountering specific antigens.

22.6d Characteristics of Lymphocyte Activation

  • The role of T lymphocytes in activating B lymphocytes, correlating with antibody production and memory cell formation.

22.7 Effector Response at Infection Site

  • Effector functions of lymphocytes provide mechanisms for eliminating pathogens, regulated through cytokines and immune cell communication.

22.8 Structure and Functions of Antibodies

  • Immunoglobulins: Antibodies structured as Y-shaped proteins composed of heavy and light chains with variable and constant regions.

  • Mechanisms of action include:

    • Neutralization, agglutination, precipitation, complement activation, opsonization, and NK cell activation.

22.9 Immunologic Memory

  • Active Immunity: Formation of memory lymphocytes post-exposure to pathogens.

  • Passive Immunity: Transfer of antibodies from one individual to another without memory formation.

  • Vaccination: Triggers adaptive immunity contributing to herd immunity concepts.

Clinical Views and Complications

  • Summary of various immunological disorders such as hypersensitivities, HIV, and autoimmune diseases, emphasizing the dual nature of immune responses.