Pathogens, Disease and Defense Against Disease

1. Pathogens, Disease and Defense Against Disease Pathogen – an organism that causes a disease Examples of organisms that cause disease: • viruses – influenza, chicken pox, AIDS, measles, common cold, polio • bacteria – cholera, diphtheria, pneumonia, meningitis, tuberculosis, tetanus, salmonellosis • fungi – athlete’s foot, ringworm, candidiasis, farmer’s lung, asparagillosis • protozoa – malaria, amoebiasis, trypansomiasis (sleeping sickness) • roundworms – elephantiasis, Ascaris, hookworms • flatworms – pork and beef tapeworms, liver fluke, schistosomiasis (bilharzias)

2. Pathogens gain entry to the body using one of the following methods: from the air (droplets) – diseases of the human respiratory system can be transmitted when an infected person coughs or sneezes out droplets containing pathogens, which are breathed in by an uninfected person (common colds, flu, diphtheria) direct contact – physical contact with an infected person carries the disease to an uninfected person through natural body openings (many diseases) food/water – pathogens in contaminated food or water enter the body through the digestive system (amoebiasis, tapeworm, salmonella poisoning) cuts in the skin – allows pathogen to gain entry to body (tetanus)

3. using infected needles – needle may contain pathogens in tiny drop of infected person’s blood left on needle – common mode of transmission in drug addicts (AIDS, blood carried diseases) blood transfusions – only occurs if blood supply is contaminated with a disease such as AIDS sexual intercourse – sexually transmitted diseases gain entry through the soft mucous membranes of the penis and vagina during sexual intercourse insects – blood-sucking insects inject their mouthparts though the skin and can transmit pathogens that they sucked out of an infected person (malaria)

4. The human body has three lines of defense against microbial attack: External barriers – skin and mucous membranes 1. intact skin acts as a barrier to entry and is inhospitable to microbial growth dry, dead skin does not contain moisture necessary for microbial growth and most will be ejected when skin cells are constantly soughed off skin is protected by secretions from sweat and sebaceous glands that contain natural antibiotics (lactic acid) that inhibit microbial growth

5. 2. membranes (in respiratory and digestive tracts) secrete mucus that contains antibacterial enzymes (destroy bacterial cell walls) the mucus also physically traps microbes that enter body through nose or mouth cilia on the membranes sweep up the mucus with microbes to be swallowed, coughed or sneezed out

6. Nonspecific internal defenses – effective against a wide range of pathogens – three categories: 1. Phagocytic cells and natural killer cells the body contains several types of amoeboid white blood cells that can engulf and digest microbes: macrophages (most important) - white blood cells that crawl around in the extracellular fluid ingesting microbes by phagocytosis, also act as “antigen presenting” cells (present parts of microbe to other cells of immune system) natural killer cells – another class of white blood cells, do not directly attack microbes, act by destroying the body’s own cells that have been invaded by viruses, also recognize and destroy cancerous cells

7. 2.Inflammatory response (localized injury) – results from injury and large-scale breaches of the skin such as a cut – inflammation occurs, phagocytes and killer cells are recruited, injured area is walled off to isolate infected tissue damaged cells release histamine into wounded area – makes capillary walls leaky and relaxes smooth muscle surrounding arterioles, wound becomes red, swollen, and warm chemicals are released to initiate blood clotting (helps to seal off wound and limit entry of more microbes) other chemicals (released by wounded cells and microbes themselves) attract macrophages to eat up microbes, dirt, and damaged cells

8. 3.Fever – results when population of microbes is sufficiently large enough to establish a major infection fever increases the activity of the phagocytic white blood cells fever slows down the reproduction of microbes fever also helps fight viral infections by increasing the production of interferon (increases resistance of surrounding cells to viral attack)

9. When non-specific defenses fail, the body launches an Immune Response (specific defense response to a particular microorganism) immune system consists of about 2 trillion lymphocytes (special type of white blood cell) distributed throughout body but clustered in thymus, lymph nodes, and spleen immune response results from interactions among the various types of lymphocytes and the molecules that they produce

11. A successful immune response involves recognizing an invader, launching a successful attack to overcome the invader, and retaining a memory of the invader to ward off future infections two key lymphocyte cells are involved in the immune response: B cells and T cells arise from precursor cells in bone marrow some of these cells are released into bloodstream and travel to the thymus and differentiate into T cells (for thymus) B cells differentiate in the bone marrow

12. Step 1: Recognition of the invasion of microbes antigens – markers on cells or materials in blood that are recognized by the immune system can be proteins on the cell surface of pathogens or toxins released by pathogens dissolved in blood (usually large proteins, polysaccharides, and glycoproteins) antigens on our own cells are recognized as “self” and do not stimulate an immune response the surfaces of the body’s own cells bear large proteins and polysaccharides just like microbes do these proteins are collectively called the major histocompatibility complex (MHC) MHCs are unique to each individual – one person’s MHCs would be recognized as foreign antigens in another person’s body (which is why tissue/organ transplants may be rejected)

13. any foreign material entering the body can act as an antigen and stimulate an immune response antigen – “anti” – means antibody, “-gen” – means generating, so an antigen is an antibody-generating agent

14. Antibodies • large proteins that are either attached to the surfaces of B cells or dissolved in the blood plasma (these are called immunoglobins, abbreviated Ig) – recognize and attach to foreign antigens • Y – shaped molecules made of 4 polypeptides (2 “heavy” chains and two “light” chains) • antibodies have two sites that stick out and constantly look for antigens (and attach to antigens) and one site that sticks to the surface of its lymphocyte • antibodies act in two ways: 1) act as receptors and bind to antigens triggering a response, and 2) act as effectors and circulate in bloodstream neutralizing poisonous antigens and destroying microbes bearing antigens • tips of antibodies form highly specific binding sites for antigens – each site has a specific shape and binds only to a specific type of antigen

17. T-cell receptors – T-cells also have receptors on their surfaces also have highly specific binding sites for particular antigens act only as receptors to trigger an immune response in T-cell (as compared to antibodies that act as receptors to trigger a response AND function in destroying foreign antigens)

18. Step 2: Overcoming the microbial invasion – the immune system mounts two types of attack: humoral immunity is provided by B cells and circulating antibodies; invaders are attacked before they can enter body cells, and cell- mediated immunity is produced by T cells which attack invaders that have made their way into body cells

19. Humoral immunity • produced by antibodies in the blood – because antibodies circulate in the bloodstream, humoral immunity can only defend against invaders in blood and extracellular fluid • B cells with specific antibodies on their surfaces bind to antigens on the invader • binding causes B cells to divide rapidly – clonal selection (resulting population of cells are genetic clones of original parent B cell “selected” by binding to particular antigen) • daughter cells differentiate into two cells types: memory cells and plasma cells

21. memory cells do not release antibodies but play an important role in future immunity plasma cells become enlarged and make huge quantities of their own specific antibodies that are released into bloodstream

22. antibodies destroy microbes in four ways: 1. neutralization – antibody may combine with or cover up the binding site of a toxic antigen such as a bacterial toxin, thereby preventing the toxin from harming the body 2. promotion of phagocytosis – antibody may coat surface of microbe and identify it as a target for circulating phagocytic white blood cells to engulf

23. 3. agglutination – antibodies have multiple binding sites and may bind to antigens on two different microbes holding them together more and more antibodies link up with antigens on different microbes clumping them together this enhances phagocytosis complement reactions – the antibody-antigen complex on the surface of an invading cell may trigger a series of reactions with blood proteins called the complement system these complement proteins bind to antibodies and attract phagocytic cells or may directly destroy invaders by creating holes in their plasma membranes (similar to natural killer cells)

25. Cell-mediated immunity • produced by T cells, primary defense against body’s own cells when they have become cancerous or have been infected by viruses • also important in overcoming infection by fungi or protists • three types of T cells contribute to cell-mediated immunity: 1. Cytotoxic T-Cells 2. Helper T-Cells 3. Suppressor T-Cells

26. Cytotoxic T cells • release proteins that disrupt the infected cell’s membrane • this attack is activated when receptors on the cytotoxic T cell’s membrane bind to antigens on surface of infected cell – create giant holes in target cell’s membrane

27. Helper T cells • when receptors of these cells bind to antigen, the cells release chemicals (hormone-like) that assist other immune cells in their defense of the body • chemicals stimulate cell division and differentiation in both B cells and cytotoxic T cells • very little immune response (cell-mediated or humoral) can occur without the boost provided by helper T cells (reason why AIDS is so deadly)

28. Suppressor T cells • act after an infection has been conquered – help to shut off the immune response in both B cells and cytotoxic T cells • after infection is over, some suppressor T cells and helper T cells remain and function as memory T cells to help protect the body against future exposure to the same antigen

29. Step 3: “Remembering” the antigen for protection against future exposure to the same pathogen/antigen memory cells allow us to retain immunity to antigens B and T memory cells survive for many years if body is exposed to antigens to which the immune system as previously mounted a response, the appropriate memory cells recognize the invaders – they begin to multiply rapidly and produce a second immune response by generating huge populations of plasma cells and cytotoxic T cells second immune response is very rapid – invasion is overcome so fast, there may be no noticeable symptoms of infection

30. Secondary Immune Response

32. Summary of Humoral and Cell-Mediated Immune Responses

33. AIDS – Acquired Immune Deficiency Syndrome • caused by two viruses – human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) • viruses undermine the immune system by infecting and destroying helper T cells (responsible for stimulating both cell-mediated and humoral immune responses • AIDS does not directly kill its victims, they become increasingly susceptible to opportunistic diseases as the helper T cell population declines – these other diseases finally kill them

34. HIV is a retrovirus – contains RNA as its genetic material reproduce by transcribing RNA to DNA (using reverse transcriptase) and then inserting the DNA into the chromosome of a host cell eventually the infected cell begins transcribing and translating the viral DNA and more viruses are produced that enter into the bloodstream proliferating viruses eventually kill the host helper T cell as the number of helper T cells decline, the lymphocytes are no longer signaled to act during an invasion and the victim no longer produces sufficient antibodies to fight diseases

36. HIV infected Helper T cell

37. people become infected with HIV in several ways: 1. sexual intercourse – virus is present in semen and vaginal secretions 2. in traces of blood on a hypodermic needle that is shared by IV drug abusers 3. across the placenta from a mother to a baby, or through cuts during childbirth or in milk during breast-feeding 4. in transfused blood or with blood products such as Factor VIII used to treat hemophiliacs 5. accidents causing blood contamination – the disease can be transmitted between a patient and a surgeon during operations, and between a patient and a dentist through cuts in the skin 6. tattoos and ear piercing with infected needles

38. Social implications of AIDS: due to ignorance about the methods of transmission, some people feel uncomfortable in the company of HIV positive people HIV positive people may have difficulty obtaining health insurance, finding jobs, having friends and building normal social relations sexual life styles have changed due to the awareness of and education about AIDS – use of condoms has become prevalent