The Immune System

Overview: Recognition and Response

  • Pathogens are agents that cause disease and infect a wide range of animals, including humans.

  • The immune system enables animals to avoid or limit many infections.

  • All animals possess innate immunity, a defense active immediately upon infection.

  • Vertebrates also have adaptive immunity.

Innate vs. Adaptive Immunity

  • Innate Immunity:

    • Includes barrier defenses.

    • Involves receptor proteins that bind to molecules or structures common to viruses, bacteria, or other microbes.

    • Binding activates internal defensive responses to a broad range of pathogens.

  • Adaptive Immunity:

    • Develops after exposure to agents like microbes, toxins, or other foreign substances.

    • Involves a very specific response to pathogens.

Concept 35.1: Innate Immunity

  • Innate immunity is found in all animals and plants.

  • In vertebrates, it's an immediate response to infections and the foundation of adaptive immunity.

Innate Immunity of Invertebrates

  • Insects use their exoskeleton as a physical barrier against infection.

  • Lysozyme in the digestive system breaks down bacterial cell walls.

  • Immune cells recognize pathogens by binding to specific molecules.

  • Each recognition protein recognizes a broad class of pathogens.

  • Hemocytes circulate within hemolymph and carry out phagocytosis (ingestion and breakdown of foreign substances).

  • Hemocytes release antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria.

Innate Immunity of Vertebrates

  • Mammalian immune system is the best understood among vertebrates.

  • Innate defenses include barrier defenses, phagocytosis, and antimicrobial peptides.

  • Additional defenses unique to vertebrates: natural killer cells, interferons, and the inflammatory response.

Barrier Defenses

  • Skin and mucous membranes of respiratory, urinary, and reproductive tracts.

  • Mucus traps and allows removal of microbes.

  • Body fluids like saliva, mucus, and tears are hostile to microbes.

  • Low pH of skin and digestive system prevents bacterial growth.

Cellular Innate Defenses

  • Pathogens entering the mammalian body are subject to phagocytosis.

  • Phagocytic cells recognize pathogens by Toll-like receptors (TLRs).

  • Each mammalian TLR binds to fragments of molecules characteristic of a set of pathogens.

  • Types of Phagocytic Cells:

    • Neutrophils: circulate in blood and are attracted by signals from infected tissues.

    • Macrophages: found throughout the body.

  • Additional Cell Types:

    • Dendritic cells: stimulate development of adaptive immunity in cells contacting the environment (e.g., skin).

    • Eosinophils: discharge destructive enzymes.

  • Cellular innate defenses involve natural killer cells that detect abnormal cells and release chemicals leading to cell death.

Antimicrobial Peptides and Proteins

  • Pathogen recognition triggers release of peptides and proteins that attack pathogens or impede reproduction.

  • Interferons provide innate defense by interfering with viruses and activating macrophages.

  • The complement system consists of about 30 proteins activated by substances on microbe surfaces, leading to lysis of invading cells.

Inflammatory Response

  • Brought about by molecules released upon injury or infection, leading to pain and swelling.

  • Activated macrophages and neutrophils release cytokines that modulate the immune response and promote blood flow.

  • Mast cells release histamine, causing blood vessels to dilate and become more permeable.

  • Enhanced blood flow delivers antimicrobial peptides, resulting in pus accumulation (white blood cells, dead pathogens, and cell debris).

  • Inflammation can be local or systemic.

    • Fever is a systemic inflammatory response triggered by substances released by macrophages.

    • Septic shock is a life-threatening condition due to an overwhelming inflammatory response.

    • Chronic inflammation can threaten health.

Evasion of Innate Immunity by Pathogens

  • Adaptations have evolved in some pathogens to avoid destruction by phagocytic cells.

  • The outer capsule of some bacteria interferes with molecular recognition.

  • Tuberculosis (TB) resists breakdown within lysosomes after being engulfed.

Concept 35.2: Adaptive Immunity

  • Adaptive response relies on two types of lymphocytes (white blood cells):

    • T cells mature in the thymus.

    • B cells mature in bone marrow.

Antigen Recognition

  • Antigens are substances that elicit a response from B or T cells.

  • Recognition occurs when a B or T cell binds to an antigen via an antigen receptor.

  • The immune system produces millions of different antigen receptors, but receptors on a single B or T cell are identical.

  • The small accessible part of an antigen that binds to a receptor is called an epitope.

Antigen Recognition by B Cells and Antibodies

  • Each B cell antigen receptor is a Y-shaped molecule with two identical heavy chains and two identical light chains.

  • Constant (C) regions vary little, while variable (V) regions differ greatly among B cells.

  • V regions of heavy and light chains form an antigen-binding site.

  • Binding of a B cell antigen receptor to an antigen is an early step in B cell activation.

  • This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig).

  • Secreted antibodies are similar to B cell receptors but are not membrane-bound and defend against pathogens.

Antigen Recognition by T Cells

  • Each T cell receptor consists of two different polypeptide chains (α and β).

  • The tips of the chain form a variable (V) region; the rest is a constant (C) region.

  • The V regions of the α and β chains together form an antigen-binding site.

  • T cells bind only to antigen fragments displayed on a host cell.

  • MHC (major histocompatibility complex) molecules are host proteins that display antigen fragments on the cell surface.

  • In infected cells, antigens are cleaved into smaller peptides by enzymes.

  • MHC molecules bind and transport the antigen fragments to the cell surface (antigen presentation).

  • A T cell can then bind both the antigen fragment and the MHC molecule, necessary for the adaptive immune response.

B Cell and T Cell Development

  • Four major characteristics:

    • Diversity of lymphocytes and receptors.

    • Self-tolerance; lack of reactivity against an animal’s own molecules.

    • Proliferation of B and T cells after activation.

    • Immunological memory.

Generation of B Cell and T Cell Diversity

  • Combining variable elements assembles millions of different receptors.

  • Capacity to generate diversity is built into the structure of Ig genes.

  • Many different chains can be produced from the same gene by rearrangement of the DNA.

  • Rearranged DNA is transcribed and translated, and the antigen receptor is formed.

  • Example: A receptor light-chain gene contains a variable (V) segment, a joining (J) segment, and a constant (C) segment.

  • The gene contains one C segment, 40 different V segments, and 5 different J segments. These can be combined in 200 different ways.

  • The number of heavy-chain combinations is even greater.

Origin of Self-Tolerance

  • Antigen receptors are generated by random rearrangement of DNA.

  • As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity.

  • Some B and T cells with receptors specific for the body’s own molecules are destroyed by apoptosis (programmed cell death), and the remainder are rendered nonfunctional.

Proliferation of B Cells and T Cells

  • Only a tiny fraction of antigen receptors are specific for a given epitope.

  • In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made.

  • Binding of a mature lymphocyte to an antigen initiates events that activate the lymphocyte.

  • Once activated, a B or T cell undergoes multiple cell divisions to produce a clone of identical cells (clonal selection).

  • Some cells become short-lived activated effector cells that act immediately against the antigen.

  • For B cells, the effector forms are plasma cells, which secrete antibodies.

  • Long-lived memory cells give rise to effector cells if the same antigen is encountered again.

Immunological Memory

  • Responsible for long-term protection against diseases due to prior infection.

  • The first exposure to a specific antigen represents the primary immune response.

  • During this time, selected B and T cells give rise to their effector forms.

  • In the secondary immune response, memory cells facilitate a faster, stronger, and longer response.

  • Immunological memory can span many decades.

Concept 35.3: Adaptive Immunity Defends Against Infection

  • B and T lymphocytes produce a humoral immune response and a cell-mediated immune response.

  • In the humoral immune response, antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph.

  • In the cell-mediated immune response, specialized T cells destroy infected host cells.

Helper T Cells: Activating Adaptive Immunity

  • A type of T cell called a helper T cell triggers both the humoral and cell-mediated immune responses.

  • A foreign molecule must be bound by the antigen receptor of the helper T cell.

  • An antigen must be displayed on the surface of an antigen-presenting cell.

  • Antigen-presenting cells have class I and class II MHC molecules on their surfaces.

  • Antigen-presenting cells are recognized based on their class II MHC molecules.

  • Antigen receptors on the surface of helper T cells bind to the antigen and the class II MHC molecule.

  • Signals are then exchanged between the two cells.

  • The helper T cell is activated, proliferates, and forms a clone of helper T cells, which then activate the appropriate B cells.

B Cells and Antibodies: A Response to Extracellular Pathogens

  • The humoral response is characterized by secretion of antibodies by clonally selected B cells.

  • Activation of B cells involves helper T cells and proteins on the surface of pathogens.

  • A single activated B cell gives rise to thousands of identical plasma cells.

  • Antibodies do not kill pathogens; instead, they mark pathogens for destruction.

    • In neutralization, antibodies bind to viral surface proteins, preventing infection of a host cell.

    • Antibodies may also bind to toxins in body fluids and prevent them from entering body cells.

  • Antigen-antibody complexes may bind to a complement protein, leading to formation of a pore in the membrane of the foreign cell and its lysis.

  • B cells can express five different forms (or classes) of immunoglobulin (Ig) with similar antigen-binding specificity but different heavy-chain C regions.

    • One type, the B cell antigen receptor, is membrane bound.

    • The others are soluble and include those found in blood, tears, saliva, and breast milk.

Cytotoxic T Cells: A Response to Infected Host Cells

  • Cytotoxic T cells are the effector cells in the cell-mediated immune response.

  • Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells and possess an accessory protein that binds to class I MHC molecules.

  • The activated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis.

Summary of Humoral and Cell-Mediated Immune Responses

  • Both the humoral and cell-mediated responses can include primary and secondary immune responses.

  • Memory cells enable the secondary response.

Active and Passive Immunity

  • Active immunity occurs naturally when a pathogen infects the body.

  • Passive immunity provides immediate, short-term protection.

    • It is conferred naturally when antibodies cross the placenta from mother to fetus or pass from mother to infant in breast milk.

  • Active immunity is induced when antigens are introduced into the body in vaccines.

    • In this process of immunization, inactivated bacterial toxins or weakened or killed pathogens are introduced.

  • Passive immunity can be conferred artificially by injecting antibodies into a nonimmune person.

Antibodies as Tools

  • Polyclonal antibodies, produced following exposure to an antigen, are products of many different clones of plasma cells, each specific for a different epitope.

  • Monoclonal antibodies are prepared from a single clone of B cells grown in culture.

  • Monoclonal antibodies have provided the basis for many recent advances in medical diagnosis and treatment.

Immune Rejection

  • Cells transferred from one person to another can be destroyed (rejected) by the recipient’s immune defenses.

  • To minimize rejection, physicians use donor tissue that closely matches the MHC molecules of the recipient.

  • Recipients also take medicines that suppress their immune responses.

Disruptions in Immune System Function

  • Adaptive immunity protects against many pathogens but isn't fail-safe.

Allergies

  • Allergies are exaggerated (hypersensitive) responses to antigens called allergens.

  • In localized allergies like hay fever, plasma cells secrete antibodies specific for antigens on the surface of pollen grains.

  • This triggers immune cells in connective tissue to release histamine and other inflammatory chemicals.

  • Antihistamines block receptors for histamine and diminish allergy symptoms.

  • An acute allergic response can lead to anaphylactic shock, a life-threatening reaction.

  • Substances that can trigger anaphylactic shock include bee venom, penicillin, peanuts, and shellfish.

  • People with these hypersensitivities often carry epinephrine to counteract the allergic response.

Autoimmune Diseases

  • In individuals with autoimmune diseases, the immune system targets certain molecules of the body.

  • Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.

  • Genes, heredity, and environment all influence susceptibility to autoimmune disorders.

Immune System Avoidance

  • Mechanisms to thwart immune responses have evolved in pathogens.

  • A pathogen may alter how it appears to the immune system by changing the epitopes it expresses (antigenic variation).

  • This mechanism is seen in the parasite that causes sleeping sickness and in the influenza virus.

  • Some viruses avoid an immune response by infecting cells and then entering an inactive state called latency.

  • The virus (such as herpes simplex) remains latent until a stimulus reactivates it.

  • Stimuli include stress, fever, or menstruation.

  • Acquired immunodeficiency syndrome (AIDS) is caused by HIV (human immunodeficiency virus), which both attacks and escapes the immune system.

    • It infects helper T cells with high efficiency.

    • It escapes the immune system through its high mutation rate, which reduces the ability of the immune system to eliminate the infection.

    • It also can undergo latency.

  • People with AIDS are highly susceptible to infections and cancers that a healthy immune system would normally defeat.

  • Unprotected sex and transmission via HIV-contaminated needles account for the majority of HIV infections.

  • HIV cannot be cured, but drugs have been developed to slow HIV replication and progression to AIDS.

Cancer and Immunity

  • The frequency of certain cancers increases when adaptive immunity is impaired.

  • 15–20% of all human cancers involve viruses.

  • The immune system can act as a defense against viruses that cause cancer and against cancer cells that harbor viruses.

  • In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer.