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Transcript
Defenses Against Disease Chapter 36 Defending Against Pathogens • The world is teeming with microscopic organisms (microbes) – Some are parasites, live in or on the bodies of other living organisms, sometimes doing harm – When microbes cause disease they are called pathogens Basic Mechanisms of Defense • There are three basic lines of defense against disease • Vertebrate have all three lines of defense • The first line of defense: nonspecific external barriers – Prevent microbes from entering the body – Examples: skin and mucous membranes Skin and Mucous Membranes • The skin is important in blocking microbe entry and suppressing microbe growth – Skin is a barrier to microbes – Skin is continually shed, removing microbes that gain a foothold on skin – Many skin secretions contain natural antibiotics Skin and Mucous Membranes • Mucous membranes have effective microbe defense mechanisms – Mucous membrane secretions contain antibacterial enzymes (example: lysozymes) – Mucus traps microbes entering the nose or mouth – Respiratory tract cilia sweep mucus and microbes away from lungs Basic Mechanisms of Defense • The second line of defense: nonspecific internal barriers – Occurs when microbes breach nonspecific external barriers – Broad internal responses to microbe infection – Examples: phagocytic white blood cells, inflammation, fever Nonspecific Internal Defenses • Broad defenses that attack microbes that penetrate the skin • Three major categories of nonspecific internal defenses – Phagocytic cells and natural killer cells – The inflammatory response – Fever Phagocytic cells • Macrophages and neutrophils – White blood cells that ingest dead cells, cellular debris, and microbes by phagocytosis Natural Killer Cells • A type of white blood cell • Attack body cells that are cancerous or infected with virus – Secrete enzymes that poke holes in the cell membrane of virally-infected or cancerous cells The Inflammatory Response • Causes tissues to become warm, red, swollen, and painful • Functions – Attracts phagocytes to infected or injured tissue – Promotes clotting – Initiates protective behavior The Inflammatory Response • Tissue is damaged and bacteria enter body • Damaged cells produce chemicals that stimulate mast cells to release histamine – Capillary walls become "leaky" – Blood flow increases – Tissues become swollen, red, and painful to touch The Inflammatory Response • Macrophages are attracted to histamine – Consume bacteria and release cytokines that attract more white blood cells – Pus may be produced • Blood clots promote healing by isolating the site Fever • Helps combat large-scale infection by elevating body temperature • Some cells release cytokines in response to infection – Antibacterial cytokines • Macrophages release endogenous pyrogens: elevate body temperature • Other cytokines: decrease iron in the blood • Both act to slow bacterial reproduction – Antiviral cytokines: Interferon, which helps cells resist viral attack Basic Mechanisms of Defense • The third line of defense: specific immune response – Immune cells selectively destroy specific invading microbes and toxins – Invaders are “remembered,” allowing for a rapid future response to invasion Immune Response • 2 types: • Active Immunity – actively making antibodies in response to an antigen • Passive Immunity – receive antibodies and/or immune cells from someone else. – Short term immunity. Eventually “new “ cells are recognized as foreign & destroyed Immune Response • The immune response involves specialized white blood cells called lymphocytes • The immune system: lymphocytes, the chemicals they produce, and the organs that they live in Immune Response • Two major types of lymphocytes – B cells: formed and differentiate in the bone marrow – T cells: formed in the bone marrow; differentiate in the thymus Key Characteristics • An immune response has three steps – First: the immune system must recognize an invader – Second: the immune system must launch an attack – Third: the immune system must remember specific invaders to ward off future infections Detection of Invaders • Foreign invaders exhibit characteristic antigens – Foreign molecules that are particular to an invading microbe or toxin – Immune cells respond to the presence of antigens Antibodies and T-cell Receptors • Antibodies and T-cell receptors recognize and bind to foreign antigens • Antibodies are proteins that can be attached to B cells or free-floating in the blood • Antibodies – Y-shaped molecules made of light peptide chains and heavy peptide chains – Both chains have constant and variable regions that form highly specific antigen binding sites – Each type of antibody is unique to the B cell that makes them Antibodies • There are five different classes of antibodies(IgA, IgD, IgE, IgG, IgM), which perform various functions – Inactivate their antigens by binding them and causing them to clump together – Assist white blood cells to engulf microbes – Activate natural killer cells – Bind to blood proteins of the complement system… Antibodies – Some classes of antibodies can cross the placenta and provide immunity to a developing child (IgG) – Another class is secreted in breast milk – Both help the newborn, whose immune system is not fully developed T-cell Receptors • T-cell receptors are attached to T cells • Consist of 2 polypeptide chains – Specific binding sites protrude from the T cell • Bind to antigen, which triggers a T-cell response • Response is triggered only when they encounter antigens – On the membranes of cancerous or infected cells – Presented on the membranes of macrophages that have ingested the invading microbes T-cell Receptors • Do not directly inactivate pathogens • Alter the activity of the T cell to which they are attached Millions of Antigens Recognized • The immune system can recognize millions of different antigens and responds by producing specific antibodies and Tcell receptors for each antigen • How does the immune system make so many specific antibodies and T-cell receptors? • There are no genes for entire antibody or receptor molecules Millions of Antigens Recognized • Antibodies and T-cell receptors are proteins encoded by a small number of genes that specify different versions of antibody regions • The different versions can be pieced together in millions of combinations Millions of Antigens Recognized • As each individual B cell develops, it retains only a few randomly selected genes • Thus, each B cell produces only a single type of antibody, specified by the chance recombination of antibody genes Millions of Antigens Recognized • NOTE: millions of different antibodies and T cell receptors are produced prior to infection – An invading antigen binds to a compatible antibody or T cell receptor by chance – The immune system does not design compatible antibodies and T cell receptors to bind to an invading antigen “Self” from “Non-self” • The immune system – Distinguishes “self” from “non-self” – Does not attack normal body cells • Due to major histocompatibility complexes (MHC) on body cells – Large protein and polysaccharide complexes – ID cells as being “of self” – Immune cells ignore these cells – Unique for everyone (except identical twins) Immune Cells Launch an Attack • Once an invading antigen has been detected, two forms of attack occur – Humoral immunity – Cell-mediated immunity Humoral Immunity • Provided by B cells and circulating antibodies • Attack antigens circulating in the bloodstream and lymph • Each B cell has a unique antibody attached to its surface that will only bind with properly shaped antigens Humoral Immunity • The mechanism of humoral immunity occurs in the following series of steps • Attached B cell antibodies bind to an invading antigen in the blood Bound B cell divides rapidly forming many identical copies (clonal selection) B cell clones differentiate to form memory B cells and plasma cells • • Humoral Immunity • Memory B cells: saved to fight future infection • Plasma cells: mass-produce the specific antibody into the blood Humoral Immunity • Antibody binding interactions promote destruction of the invader by – Neutralizing toxins – Promoting phagocytosis – Causing agglutination, which promotes phagocytosis – Activating of complement reactions, which promote phagocytosis Cell-Mediated Immunity • Provided by T cells, which attack cancer cells and cells that have been invaded by viruses • Three types of T cells are involved – Helper T cells – Cytotoxic T cells – Memory T cells Cell-Mediated Immunity • Helper T cells – Bind to antigens “presented” by a macrophage that consumed them • Helper T cells – Produce cytokines that stimulate T cell division and differentiation • Will form memory T cells and cytotoxic T cells • Will also stimulate division of B cells that are bound to an antigen Cell-Mediated Immunity • Cytotoxic T cells – Bind directly to cancerous or virally-infected cells – Release proteins that poke holes in cancer/infected cell membrane, killing the cell • Memory T cells – Dormant helper T cells that fight future infection by the antigen that produced it Memory • The immune system remembers past victories • Memory B and T cells remain long after the infection • Upon subsequent infection – Memory B cells form active plasma cells that quickly make many antibodies – Memory T cells form active cytotoxic T cells – The response is so rapid and strong that the repeat invader never gets a foothold Basic Mechanisms of Defense • Invertebrates lack immune defenses • Rely on non-specific defenses – External skeletons – Slimy secretions – Internal white blood cells that attack pathogens and secrete proteins to neutralize invaders and toxins – Proteins identified in horseshoe crabs are similar to those found in vertebrates Vaccinations • Vaccination involves the injection of weakened/killed microbes to confer immunity • Vaccination – Inactive antigens stimulate humoral and cellmediated immunity so memory cells form – Long term immunity results without having to be exposed to the disease – Examples: small pox, tetanus, mumps Antibiotics • Antibiotics may be administered if the infection is massive or unusually toxic • Effective on bacteria, fungi, and protists – Viruses are unaffected • Slow microbial reproduction • Give enough time for natural immunity to mobilize and remove invading microbes Allergies • Allergies are immune responses to antigens that are not harmful – Common “allergens” such as pollen, mold spores, dust, animal dander, and bee stings – Trigger an inflammatory response that produces allergy symptoms – An antigen enters the body and is recognized by a B cell with complementary antibody receptors The Allergic Reaction • “Allergy” plasma cells secrete “allergy antibodies” against the antigen • “Allergy antibodies” bind to mast cells – Mast cells become sensitized to the presence of the antigen • If re-exposed to the allergy-causing antigens, they bind to antibodies on the mast cells – The mast cell becomes stimulated The Allergic Reaction • The stimulated mast cells release histamine, which causes leaky capillaries and local inflammatory effects The Allergic Reaction • Respiratory allergy effects – Excess mucus production – Runny nose – Sneezing – Congestion • Food allergy effects – Nausea – Diarrhea Autoimmune Diseases • A condition where antibodies mistakenly attack the body’s own cells • Examples – Many cases of juvenile-onset diabetes – Multiple sclerosis – Rheumatoid arthritis • Treatments – Replacement therapy (example: transfusions) – Immune suppression (drugs) Immune Deficiency Diseases • The inability to mount an effective immune response to infection • Example: severe combined immune deficiency (SCID) – Genetic disorder resulting in few or no immune cells – Minor infections can be fatal – Can be treated by viral gene therapy AIDS • Acquired Immune Deficiency Syndrome (AIDS) is a devastating immune deficiency disease • Caused by human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) – Infect and destroy helper T cells • AIDS does not kill directly – Results in an increased susceptibility to disease as helper T cells decline HIV • Human Immunodeficiency Virus (HIV) is a retrovirus that infects and destroys helper T cells • HIV binds to a helper T cell and enters it • Then it hijacks the cell’s metabolic machinery, forcing it to make more HIV particles • The HIV particles emerge, taking an outer coating of T-cell membrane with them HIV • If untreated, helper T cell levels eventually diminish • Immune responses are weakened, and the person is diagnosed with AIDS • A person infected with AIDS is highly susceptible to other infections • The life expectancy for untreated AIDS victims is about 1 to 2 years. HIV • HIV does not survive long out of the body • Methods of transmission – Direct contact of broken skin or mucous membranes with virus-laden body fluids – Examples • • • • Blood Semen Vaginal secretions Breast milk Treatments of AIDS • Combinations of drugs targeting viral replication can disable HIV and slow the progress of AIDS, dramatically increasing life expectancy • However – HIV can mutate into forms resistant to the drugs – In some patients the drugs have severe side effects Treatments of AIDS • Development of a vaccine has not been successful – HIV disables the immune response that a vaccine depends on – HIV mutates rapidly Cancer • Cancer is a disease characterized by the unchecked growth of malignant tumor cells • Tumors are populations of cells that grow at abnormal rates • Two types of tumors – Benign: remain confined to one area – Malignant: grow uncontrollably and spread to other areas Cancer • Cancer cells form every day • Natural killer and cytotoxic T cells weed out most cells – Detect slight differences in cell membrane proteins as “non-self” antigens – Not all cancers are detected – Some lack “non-self” antigens – Some tumors grow too quickly for the immune system to handle • Some tumors attack the immune system, suppressing the immune response Medical Treatments for Cancer • Three main cancer treatments – Surgery – Radiation – Chemotherapy Medical Treatments for Cancer • Surgery – Actively removing tumors when located – Not all patches of cancer cells are detectable or removable by surgery – Remaining cancer cells can grow and spread Medical Treatments for Cancer • Radiation – Can be used to destroy microscopic clusters of cancer cells – Not useful for systemic cancers due to widespread tissue damage that would result Medical Treatments for Cancer • Chemotherapy (drug treatment) – Supplements surgery and radiation treatment – Attacks the machinery of cell division, suppressing cancer growth – Unfortunately, healthy cells divide too and are affected Monoclonal Antibodies • • • • • Process by which large quantities of antibodies (targeted against a particular antigen X) can be produced. A mouse is immunized by injection of an antigen X to stimulate the production of antibodies targeted against X. The antibody forming cells are isolated from the mouse's spleen. Monoclonal antibodies are produced by fusing single antibodyforming cells to tumor cells grown in culture. The resulting cell is called a hybridoma. Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell. Once a monoclonal antibody is made, it can be used as a specific probe to track down and purify the specific protein that induced its formation