The Immune System PDF

The Immune System  The Immune System The immune system is a complex network of cells and proteins that defends the body against infection Pathogens, agents that cause disease, infect a wide range of animals, including humans The immune system recognizes foreign bodies and res...

The Immune System  The Immune System The immune system is a complex network of cells and proteins that defends the body against infection Pathogens, agents that cause disease, infect a wide range of animals, including humans The immune system recognizes foreign bodies and responds with the production of immune cells and proteins All animals have innate immunity, a defense active immediately upon infection Vertebrates also have adaptive immunity  Innate immunity is present before any exposure to pathogens and is effective from the time of birth It involves nonspecific responses to pathogens Innate immunity consists of external barriers plus internal cellular and chemical defenses Adaptive immunity, or acquired immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens Figure 43.2 Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY Barrier defenses: (all animals) Skin Recognition of traits shared Mucous membranes by broad ranges of Secretions pathogens, using a small Internal defenses: set of receptors Phagocytic cells Rapid response Natural killer cells Antimicrobial proteins Inflammatory response ADAPTIVE IMMUNITY Humoral response: (vertebrates only) Antibodies defend against Recognition of traits infection in body fluids. specific to particular pathogens, using a vast Cell-mediated response: array of receptors Cytotoxic cells defend against infection in body cells. Slower response  In innate immunity, recognition and response rely on traits common to groups of pathogens Innate immunity is found in all animals and plants In vertebrates, innate immunity is a first response to infections and also serves as the foundation of adaptive immunity  Innate Immunity of Invertebrates In insects, an exoskeleton made of chitin forms the first barrier to pathogens The digestive system is protected by a chitin-based barrier and lysozyme, an enzyme that breaks down bacterial cell walls Hemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria Pathogen PHAGOCYTIC CELL Vacuole Lysosome containing enzymes  Hemocytes also secrete antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria Antimicrobial peptides, also called host defence peptides are part of the innate immune response found among all classes of life  The immune system recognizes bacteria and fungi by structures on their cell walls An immune response varies with the class of pathogen encountered  Innate Immunity of Vertebrates The immune system of mammals is the best understood of the vertebrates Innate defenses include barrier defenses, phagocytosis, antimicrobial peptides Additional defenses are unique to vertebrates: natural killer cells, interferons, and the inflammatory response  Barrier Defenses Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts Mucus traps and allows for the removal of microbes Many body fluids including saliva, mucus, and tears are hostile to many microbes The low pH of skin and the digestive system prevents growth of many bacteria  Cellular Innate Defenses Pathogens entering the mammalian body are subject to phagocytosis Phagocytic cells recognize groups of pathogens by TLRs, Toll-like receptors NB. Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and play a critical role in innate immune responses  There are different types of phagocytic cells Neutrophils engulf and destroy pathogens Macrophages are found throughout the body Dendritic cells stimulate development of adaptive immunity Eosinophils discharge destructive enzymes  Cellular innate defenses in vertebrates also involve natural killer cells These circulate through the body and detect abnormal cells They release chemicals leading to cell death, inhibiting the spread of virally infected or cancerous cells  Antimicrobial Peptides and Proteins Peptides and proteins function in innate defense by attacking pathogens or impeding their reproduction Interferon proteins provide innate defense, interfering with viruses and helping activate macrophages About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation  Inflammatory Responses The inflammatory response, such as pain and swelling, is brought about by molecules released upon injury or infection Mast cells, a type of connective tissue, release histamine, which triggers blood vessels to dilate and become more permeable Activated macrophages and neutrophils release cytokines, signaling molecules that enhance the immune response  Pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues Pus is the result of the body's natural immune system automatically responding to an infection  Inflammatory Response Pathogen Splinter Macro- Movement Signaling phage of fluid Mast molecules cell Capillary Phagocytosis Red Neutrophil blood cells  Inflammation can be either local or systemic (throughout the body) Fever is a systemic inflammatory response triggered by pyrogens released by macrophages and by toxins from pathogens Septic shock is a life-threatening condition caused by an overwhelming inflammatory response  Evasion of Innate Immunity by Pathogens Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis Tuberculosis (TB) is one such disease and kills more than a million people a year ADAPTIVE IMMUNITY  Adaptive immunity In adaptive immunity, receptors provide pathogen-specific recognition The adaptive response relies on two types of lymphocytes, or white blood cells Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells  Antigens are substances that can provoke a response from a B or T cell In adaptive immunity, recognition happens when a B or T cell binds to an antigen via a protein called an antigen receptor The small accessible part of an antigen that binds to an antigen receptor is called an epitope A single antigen usually has several different epitopes, each binding a receptor with a different specificity  All of the antigen receptors made by a single B or T cell are identical and thus bind to the same epitope Each B or T cell display specificity for a particular epitope, enabling it to respond to any pathogen that produces molecules containing the same epitope Exposure to the pathogen activates B and T cells with antigen receptors specific for parts of that pathogen  Antigen receptors Mature B cell Mature T cell 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 Disulfide bridges link the chains together A transmembrane region near one end of each heavy chain anchors the receptor in the cell’s plasma membrane A short tail region at the end of the heavy chain extends into the cytoplasm B-cell receptor The light and heavy chains each have a constant region (C) Within the two tips of the Y shape, the light and heavy chains each have a variable region (V) The constant regions of the chains vary little among the receptors on different B cells, whereas the variable regions differ greatly from one B cell to another Together, the variable regions of the light and heavy chains provide antigen-binding sites  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 receptor called an antibody or immunoglobulin (Ig) Secreted antibodies are similar to B cell receptors, by having the same Y-shaped organization but lack transmembrane regions that anchor receptors in the plasma membrane Figure 43.10 Antigen receptor Antibody B cell Antigen Epitope Pathogen (a) B cell antigen receptors and antibodies Antibody C Antibody A Antibody B Antigen (b) Antigen receptor specificity Antigen Recognition by T Cells Each T cell antigen receptor consists of two different polypeptide chains (called  and  chains) linked by a disulfide bridge Near the base of the T cell antigen receptor is a transmembrane region that anchors the molecule in the cell’s plasma membrane The outer tips of the chains form variable (V) regions, together forming a single antigen-binding site the remainder of the molecule is made up of constant (C) regions T cell and B cell antigen receptors are functionally different  T cells bind only to antigen fragments displayed or presented on the surface of host cells These antigen fragments are displayed by host cell-surface proteins called MHC (major histocompatibility complex) molecules  When a host cell is infected, enzymes inside the cell cleave the antigen into small peptides called antigen fragments MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation A rightly specific T cell can then bind both the antigen fragment and the MHC molecule This interaction is necessary for the T cell to participate in the adaptive immune response B Cell and T Cell Development The adaptive immune system has four major characteristics Diversity of lymphocytes and receptors Self-tolerance; lack of reactivity against an animal’s own molecules B and T cells proliferate after activation Immunological memory Generation of B and T Cell Diversity By combining variable elements, the immune system assembles a diverse variety of antigen receptors The immunoglobulin (Ig) gene encodes one chain of the B cell receptor 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 formed 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, or programmed cell death Proliferation of B Cells and T Cells In the body there are few lymphocytes with antigen receptors for any particular epitope In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made This 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 This proliferation of lymphocytes is called clonal selection Two types of clones are produced: short-lived activated effector cells that act immediately against the antigen and long-lived memory cells that can give rise to effector cells if the same antigen is encountered again Figure 43.14 B cells that Antigen differ in Antigen antigen receptor specificity Antibody Memory cells Plasma cells  Immunological Memory Immunological memory is responsible for long-term protections against diseases, due to either a prior infection or vaccination 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, more efficient response Figure 43.15 Primary immune response Secondary immune response to to antigen A produces antigen A produces antibodies to A; antibodies to A. primary immune response to antigen B produces antibodies to B. 104 Antibody concentration (arbitrary units) 103 Antibodies to A 102 Antibodies to B 101 100 0 7 14 21 28 35 42 49 56 Exposure Exposure to to antigen A antigens A and B Time (days) Adaptive immunity defends against infection of body fluids and body cells Acquired immunity has two branches: the humoral immune response and the 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 affected host cells Helper T Cells: A Response to Nearly All Antigens A type of T cell called a helper t cell triggers both the humoral and cell-mediated immune responses Signals from helper T cells initiate production of antibodies that neutralize pathogens and activate T cells that kill infected cells Antigen-presenting cells have class I and class II MHC molecules on their surfaces  Class II MHC molecules are the basis upon which antigen- presenting cells are recognized Antigen receptors on the surface of helper T cells bind to the antigen and the class II MHC molecule; then signals are 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 Figure 43.16 Antigen- presenting Antigen fragment cell Pathogen Class II MHC molecule 1 Accessory protein Antigen receptor Helper T cell  Cytokines  2 Cell- Humoral   mediated immunity immunity 3 B cell Cytotoxic T cell Cytotoxic T Cells: A Response to Infected 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 Figure 43.17-1 Cytotoxic T cell An activated cytotoxic T cell binds to a class Accessory I MHC –antigen fragment complex on an protein Antigen infected cell via its antigen receptor and an Class I MHC receptor accessory protein (called CD8) molecule Infected cell Antigen 1 fragment Figure 43.17-2 The T cell releases Cytotoxic T cell perforin molecules, which form pores in the infected cell Accessory protein Antigen membrane, and Class I MHC receptor Perforin Gran- molecule zymes granzymes, enzymes Pore Infected that break down cell Antigen proteins. Granzymes 1 fragment 2 enter the infected cell by endocytosis Figure 43.17-3 Cytotoxic T cell Released cytotoxic T cell Accessory protein Antigen Dying receptor Perforin infected cell Class I MHC Gran- molecule zymes Pore Infected cell Antigen 1 fragment 2 3 The granzymes initiates apoptosis within the infected cell, leading to fragmentation of the nucleus and cytoplasm and eventual cell death. The released cytotoxic T cell can attack other infected cells B Cells and Antibodies: A Response to Extracellular Pathogens The humoral response is characterized by secretion of antibodies by B cells Activation of B Cells Activation of the humoral immune response involves B cells and helper T cells as well as proteins on the surface of pathogens In response to cytokines from helper T cells and an antigen, a B cell proliferates and differentiates into memory B cells and antibody secreting effector cells called plasma cells Figure 43.18-1 Antigen-presenting Pathogen cell Antigen After an antigen-presenting cell fragment engulfs and degrades a Class II pathogen, it displays an antigen MHC Accessory molecule protein fragment complexed with class II Antigen receptor MHC molecule. A helper T cell that recognizes the complex is Helper T cell 1 activated with the aid of cytokines secreted from the antigen-presenting cell Figure 43.18-2 Antigen-presenting Pathogen cell When a B cell with receptor for Antigen B cell fragment the same epitope internalizes the antigen, it displays an Class II antigen fragment on the cell MHC  molecule Accessory surface in a complex with a protein Cytokines Antigen class II MHC molecule. An receptor activated helper T cell bearing Activated receptors specific for the Helper T cell helper T cell 1 2 displayed fragment bind to the B cell. This interaction , with the aid of cytokines from the T cell, activates the B cell Figure 43.18-3 Antigen-presenting Pathogen cell Antigen B cell fragment Class II Memory B cells MHC  molecule Accessory protein Cytokines Antigen receptor Activated Helper T cell helper T cell Plasma cells Secreted 1 2 3 antibodies The activated B cell proliferates and differentiates into memory B cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same antigen that initiated the response. Antibody Function 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  In opsonization, antibodies bind to antigens on bacteria creating a target for macrophages or neutrophils, triggering phagocytosis Antigen-antibody complexes may bind to a complement protein—which triggers a cascade of complement protein activation Ultimately a membrane attack complex forms a pore in the membrane of the foreign cell, leading to its lysis Figure 43.19 Activation of complement system and pore Neutralization Opsonization formation Complement proteins Antibody Formation of membrane attack complex Bacterium Virus Flow of water and ions Pore Foreign Antigen Macrophage cell Active and Passive Immunization Active immunity develops naturally when memory cells form clones in response to an infection It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory  Passive immunity provides immediate, short-term protection It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person Immunoglobulin (Ig) - any of a class of proteins present in the serum and cells of the immune system, which function as antibodies. Figure 43.20 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure)  Stimulates Engulfed by Gives rise to Antigen-  presenting cell   B cell Helper T cell Cytotoxic T cell   Memory helper T cells    Antigen (2nd exposure)  Memory Active Plasma cells Memory B cells cytotoxic T cells cytotoxic T cells Secreted antibodies Defend against extracellular Defend against intracellular pathogens pathogens and cancer Autoimmune Diseases In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, insulin- dependent diabetes mellitus, and multiple sclerosis  Exertion, Stress, and the Immune System Moderate exercise improves immune system function Psychological stress has been shown to disrupt immune system regulation by altering the interactions of the hormonal, nervous, and immune systems Sufficient rest is also important for immunity Immunodeficiency Diseases Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses Acquired immunodeficiency develops later in life and results from exposure to chemical and biological agents Evolutionary Adaptations of Pathogens That Underlie Immune System Avoidance Pathogens have evolved mechanisms to prevent immune responses Antigenic Variation Through antigenic variation, some pathogens are able to change epitope expression and prevent recognition The human influenza virus mutates rapidly, and new flu vaccines must be made each year Human viruses occasionally exchange genes with the viruses of domesticated animals This poses a danger as human immune systems are unable to recognize the new viral strain Latency Some viruses may remain in a host in an inactive state called latency Herpes simplex viruses can be present in a human host without causing symptoms Attack on the Immune System: HIV Human immunodeficiency virus (HIV) infects helper T cells The loss of helper T cells impairs both the humoral and cell-mediated immune responses and leads to AIDS HIV escapes the immune system because of antigenic variation and an ability to remain dormant while integrated into host DNA  People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse The spread of HIV is a worldwide problem The best approach for slowing this spread is education about practices that transmit the virus END  QUIZ 4 (20) 1. List the two types of immunities in vertebrates (2) 2. List two types of barrier defences (2) 3. Name the two lymphocytes that mature in the bone marrow and thymus respectively (2) 4. Name the two divisions of adaptive immunity (2) 5. Differentiate between neutralisation and opsonisation by antibodies (2) 6. How does HIV affect you immune system until it becomes AIDS (10)