Overview. Barriers help animals defend against many dangerous pathogens they encounter.

Transcription

1 Immunity

2 Overview Barriers help animals defend against many dangerous pathogens they encounter. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins. Two major types of defence have evolved: Innate immunity and acquired immunity

3 Innate immunity Present before exposure to pathogens and is effective from birth. Involves nonspecific responses to pathogens. Innate immunity consists of external barriers plus internal cellular and chemical defences.

4 Acquired immunity Acquired or adaptive immunity develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens

5 Innate immunity Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Rapid response Acquired immunity Recognition of traits specific to particular pathogens, using a vast set of receptors Slower response Barrier defences: skin, mucous membranes, secretions Internal defences: Phagocytic cells, antimicrobial proteins, inflammatory response Natural killer cells Humoral response: Antibodies defend against infection in bodily fluids Cell-mediated resonse: Cytotoxic lymphocytes defend against infection in body cells

6 Barrier defences include the skin and mucus 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 microbes The low ph of skin and digestive system prevents growth of microbes

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8 White blood cells (leukocytes) engulf pathogens in the body Groups of pathogens are recognized by receptors After the WBC (white blood cell) engulfs a microbe, then it fuses with a lysosome to destroy the microbe

9 There are different types of phagocytic cells: Neutrophils engulf and destroy microbes Macrophages are part of the lymphatic system and are found throughout the body Eosinophils discharge destructive enzymes Dendritic cells stimulate development of acquired immunity These white blood cells engulf microbes, then to destroy the microbe they fuse with a lysosome

10 Antimicrobial peptides and proteins function in innate defence by attacking microbes directly or stopping their reproduction Interferon proteins provide innate defence against viruses and help activate microphages About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation

11 Inflammatory response occurs following an injury. Mast cells release histamine, which promotes changes in blood vessels. These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues Pus is a fluid filled with white blood cells, dead microbes, and cell debris, that builds up at the site of inflammation

12 Inflammatory response 1.Tissue injury -> release of histamine 2.Causes dilation and increased leakiness in local blood vessels and movement of phagocytes to area 3.Phagocytes consume bacteria and cell debris, and tissue heals

13 Inflammation can either be local or systemic (throughout body) Fever is a systemic inflammatory response triggered by macrophages (one type of WBC) and toxins from pathogens Septic shock is a life threatening condition caused by an overwhelming inflammatory response.

14 Natural Killer Cells Almost all cells in the body have a receptor on their surface Cancerous or infected cells no longer display this receptor, and natural killer cells attack these damaged cells Some pathogens avoid destruction by modifying their surface to prevent recognition or resisting breakdown by phagocytosis Tuberculosis is an example

15 Acquired immunity White blood cells called lymphocytes recognize and respond to antigens, or foreign molecules Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells.

16 Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously B cells and T cells have receptor proteins that can bind to foreign molecules

17 Each individual lymphocyte is specialized to recognize a specific epitope, or antigenic determinant, on an antigen An antigen is any foreign molecule to which a lymphocyte responds A single B or T cell has about 100,000 identical antigen receptors

18 Antigen binding site Antigen binding site Antigen receptor on a B cell Antigen receptor on a T cell

19 B cells give rise to plasma cells, which make proteins called antibodies or immunoglobulin Antibody 1 Antigen Antibody 2 Epitopes Antibody 4 Antigen binding sites Antibody 3

20 B cell receptors bind to specific, intact antigens Secreted antibodies, or immunoglobulins, are the same shape as B cell receptors and consist of two identical heavy chains and two identical light chains The tips of the chains form a constant (C) region, and each chain contains a variable (V) region.

21 T cells bind to antigen fragments presented on a host cell These antigen fragments are bound to special cell-surface proteins called MHC In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, called antigen presentation A nearby T cell can then detect the antigen fragment that is being displayed

22 If the MHC is presented on a normal body cell the antigen is displayed for cytotoxic T cells If the MHC is presenting on an immune system cell such as a macrophage, or B cell the antigen is displayed for cytotoxic T cells, and helper T cells

23 Normal body cell Immune cell

24 The acquired immune system has three important properties: 1. Receptor diversity (T cells and B cells can bind to any foreign particles) 2. A lack of reactivity against host cells (T cells and B cells never bind to normal cells, or proteins in the body) 3. Immunological memory (B cells remember coming in contact with a foreign particle)

25 Infected cell Antigen B cell Cytotoxic T cell Helper T cell Helper T cell Helper T cell Cytotoxic T cell Antibody production Plasma B cell Memory B cell

26 Antigen receptors are generated randomly As lymphocytes mature in bone marrow or thymus, they are tested for self reactivity Lymphocytes with receptors specific for the body's own molecules are destroyed by apoptosis

27 In the body there are a few lymphocytes with antigen receptors for any particular epitope The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly This is called clonal selection Two types of clones are produced: short-lived activated plasma cells and long-lived memory cells

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29 Antigen Proliferation Memory B cell Plasma B cell

30 The first exposure to a specific antigen represents the primary immune response During this time, plasma cells are made, and T cells are activated In the secondary immune response, memory cells allow a faster, more efficient response to the same specific antigen

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32 Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells Helper T cells aid in both responses

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34 Helper T cells respond to nearly all antigen Helper T cells bind to antigen presenting cells Helper T cells secrete chemical messages that stimulate other lymphocytes

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36 Cytotoxic T cells interact the MHC on infected cells and become activated killer cells The activated cytotoxic T cell secretes proteins that destroy the infected target cell

37 Antibody Classes The five major classes of immunoglobulins (antibodies) differ in function and body location Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen Monoclonal antibodies are prepared from a single clone of B cells grown in culture

38 Fig a Class of Immunoglobulin (Antibody) Distribution Function IgM (pentamer) J chain First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutralization and crosslinking of antigens; very effective in complement system activation

39 Fig b Class of Immunoglobulin (Antibody) Distribution Function IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus

40 Fig c Class of Immunoglobulin (Antibody) IgA (dimer) J chain Distribution Present in secretions such as tears, saliva, mucus, and breast milk Function Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Secretory component Presence in breast milk confers passive immunity on nursing infant

41 Fig d Class of Immunoglobulin (Antibody) IgE (monomer) Distribution Present in blood at low concentrations Function Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions

42 Fig e Class of Immunoglobulin (Antibody) Distribution Function IgD (monomer) Transmembrane region Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection)

43 Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody Antibodies attached to antigen increase phagocytosis by macrophages called opsonization Antibodies together with the proteins of the complement system generate a membrane attack complex and cell lysis

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45 Fig Viral neutralization Virus Opsonization Bacterium Macrophage Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Foreign cell

46 Fig a Viral neutralization Virus

47 Fig b Opsonization Bacterium Macrophage

48 Fig c Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Foreign cell

49 Three types of immunity Innate immunity Everyone is born with a general type of protection. Many of the germs that affect other species don t harm us. For example the virus that causes leukemia in cats doesn t affect humans. Innate immunity includes the first line of defense external barriers of the body And non-specific defenses such as fever and inflammation.

50 Adaptive Immunity and Passive Immunity The second kind of defense is active immunity which develops through our lives. This involves lymphocytes and develops only as people are exposed to diseases or immunized by vaccines. Passive immunity is borrowed from another source and lasts for a short time. For example, antibodies in a mother s breast milk provide a baby with temporary immunity to diseases the mother has been exposed to.

51 Tissue and Organ Transplants MHC molecules are different among genetically non-identical individuals Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants Chances of successful transplantation increase in donor and recipient have MHC tissue types that are matched closely Immunosuppresive drugs facilitate transplantation

52 Immunity Everyone s immune system is unique. Some people never seem to get infections, whereas other seem to be sick all the time. As people become older they usually become immune to more pathogens. This is why adults and teens tend to get sick less often then kids.

53 Problems of the Immune System Disorders of the immune system fall into four main categories: 1. Immunodeficiency disorders (primary or acquired) 2. Autoimmune disorder (in which the body s own immune system attacks it own tissue as foreign matter) 3. Allergic disorders (in which the immune system overreacts in response to an antigen) 4. Cancers of the immune system

54 Immunodeficiency Disorders Immunodeficiencies occur when a part of the immune system is not present or is not working properly A person can be born with an immunodeficiency, although the symptoms might not occur until later in life, or it can be acquired through infection or produced by drugs Immunodeficiencies can affect B lymphocytes, T lyphocytes, or phagocytes.

55 Innate Immunodeficiency: Severe combined immunodeficiency (SCID) also known as bubble boy disease after a boy who lived in a microbe free bubble. SCID is a serious immune system disorder that occurs because of a lack of both B and T lymphocytes, which makes it almost impossible to fight infections.

56 Acquired Immunodeficiency Usually develop after a disease, although can also be the result of malnutrition, or medical problems. Can be caused by certain medications.

57 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

58 HIV Human immunodeficiency virus (HIV) infects helper T cells The loss of helper T cells impairs both the humoral and cell-mediated responses and leads to AIDS HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA

59 Immunodeficiency caused by medication Some medications suppress the immune system. One of the drawbacks of chemotherapy for treatment of cancer, is that it attacks many fast growing, healthy cells, including immune cells. As well people who have had organ transplants may need to take immunosuppresant medications.

60 Autoimmune Disorders In an autoimmune disorder, the immune system mistakenly attacks the body s healthy organs and tissues as though they were foreign invaders. Examples: Lupus chronic disease marked by muscle and joint pain and inflammation (may involve attacks on kidneys and other organs) Juvenile rheumatoid arthritis a disease in which the immune system attacks certain body parts ( such as joints of the knee, hand, and foot)

61 Allergic Disorders Occur when the immune system overreacts to exposure to antigens in the environment. The substances that provoke such attacks are called allergens. The immune response can cause symptoms such as swelling, inflammation, watery eyes, sneezing. Medications that are antihistamines can relieve symptoms. In some cases, allergies can be life threatening if they cause anaphylaxis which is a systemic allergic response. Allergic disorders include asthma, eczema, and allergies

62 In localized allergies, including hay fever IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells The next time the allergen enters the body, it binds to mast cell-associated IgE molecules Mast cells release histamine and other mediators causing vascular changes leading to typical allergy symptoms

63 Cancers of the immune system Cancer occurs when cells grow out of control. This can happen with cells of the immune system. Lymphoma involves the lymphoid tissue. Leukemia involves abnormal growth of leukocytes, is the most common childhood cancer. Both types of cancer in kids are curable.

64 Vaccines A vaccine is a biological preparation that provides active acquired immunity to a particular disease. Vaccines are typically made of an agent that resembles the disease causing microorganism, or its toxins, or one of its surface proteins. The agent stimulates the body s immune system, to produce B memory cells, so that if the immune system encounters these microorganisms in the future it will easily recognize and destroy them.

65 What are vaccines made of? There are several types of vaccines: Inactivated a previously virulent microorganism that has been destroyed with chemicals, heat, radioactivity or antibiotics. Examples: Influenza vaccine, bubonic plague

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67 Attenuated live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions to disable their virulent properties, or that are closely related but less dangerous organism that produce a broad immune response. Examples: viral measles, bacterial - typhoid Typically produce more durable immunological response, but may not be safe for immunocompromised individuals. (May rarely mutate to a virulent form and cause disease.)

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70 Toxoid made from inactivated toxic compounds that cause illness rather than the microorganism. Examples: tetanus and diptheria

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72 Subunit protein subunit Rather than introducing a whole-agent vaccine, a fragment can be used to create an immune response. Example: Hepatitis B virus only the surface proteins of the virus

73 Conjugate Certain bacteria have polysaccharide outer coats that are not good at causing an immune response. But, by linking these outer coats to proteins (e.g. toxins) the immune system can be led to recognize the polysaccharide as a protein antigen. Example Haemophilus influenzae type B vaccine

74 How the vaccine works The agent stimulates the body s immune system, to produce B memory cells, so that if the immune system encounters these microorganisms in the future it will easily recognize and destroy them.

75 Schedule For the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to the particular vaccines. Later on booster shots are required to achieve full immunity.

76 History Edward Jenner (1700s) learned that dairy workers never got the disease small pox, which was deadly and disfiguring. Instead the dairy workers got cowpox, a much milder disease.

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78 Jenner took pus from the hand of a milkmaid with cowpox and scratched it into the arm of an 8-yearold boy. Six weeks later he inoculated (inserted smallpox fluid) the boy with smallpox, but the boy did not catch smallpox.

79 Smallpox was eradicated worldwide by the 1960s and 70s. There are no human cases, and smallpox is not found in any other organisms. This achievement was hoped to be the first for many disease s eradication.

80 Herd Immunity The form of immunity that occurs when a significant proportion of the population is vaccinated. Provides a measure of protection for individuals who have not developed immunity, such as babies, and immunocompromised individuals.

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84 Are vaccines harmful?

85 Myth: MMR causes autism MMR is a vaccine for mumps measles and rubella given to toddlers. Symptoms of autism usually become apparent around the same time as MMR is given no causality proven. Autism probably has multiple components including genetics.

86 Myths about vaccines Myth: Thimerosal causes autism Thimerosal is a compound that contains mercury, and was used as a preservative in vaccines There was no evidence of harm, but it has been taken out of vaccines as a precaution Thimerosal has not been used in any routinely recommended childhood vaccines since 2001

87 Multiple studies have shown that thimerosal in vaccines does not cause autism when comparing children who received thimerosal-containing vaccines and those who received thimerosal free vaccines.

88 Myth: vaccines contain harmful chemicals Vaccines contain aluminum as an adjuvant an ingredient that improves immune response. This allows for less antigen to be used. Aluminum is a very common metal found in nature, and infants get more of it through breast milk than in vaccines.

89 Continued chemicals Formaldehyde used to detoxify diphtheria and tetanus toxins or to inactivate a virus. There is a very small amount left over in the vaccine, but it is safe. Humans normally have formaldehyde in their bloodstream at levels higher than found in vaccines.

90 Myth Vaccines are not effective Most childhood vaccines are very effective when properly administered (~80% - 100%), but no vaccine claims to be 100% effective. Some adult vaccines are not as effective as childhood vaccines.

91 Myth: Natural Infection is better than immunization Natural infection usually does cause better immunity than vaccination. However the price paid for natural disease can include paralysis, permanent brain damage, liver failure, liver cancer, deafness, blindness, pneumonia or death.