Immunity. Chapter 38

Transcription

1 Immunity Chapter 38

2 Impacts, Issues Frankie s Last Wish Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers including the one that killed Frankie McCullogh

3 38.1 Integrated Responses to Threats Immunity The capacity to resist and combat infection by pathogens such as viruses, bacteria, and fungi In vertebrates, innate and adaptive immune systems work together to combat infection and injury

4 Evolution of the Body s Defenses Proteins in eukaryotic cell membranes have unique patterns that the body recognizes as self Cells of multicelled eukaryotes have receptors that recognize nonself cues (PAMPs) on or in pathogens, and trigger defense responses

5 Innate Immunity Binding of a receptor with a PAMP triggers immediate, general defense responses that are part of inborn innate immunity Complement Proteins that destroy microorganisms or flag them for phagocytosis An innate immune response

6 Adaptive Immunity Adaptive immunity is a system of defenses that specifically targets billions of different antigens an individual may encounter during its lifetime Antigen PAMP or other molecule the body recognizes as nonself that triggers an active immune response

7 Three Lines of Defense 1. Physical, chemical, and mechanical barriers Keep pathogens outside the body 2. Innate immunity General responses destroy invaders inside the body before they become established 3. Adaptive immunity Huge populations of white blood cells form to target and remember a specific antigen

8 Mucus and Cilia: Physical Barriers

9 Comparing Innate and Active Immunity

10 The Defenders White blood cells (leukocytes) specialized for different tasks carry out all immune responses Phagocytes (neutrophils, macrophages, dendritic cells) Secretory cells (eosinophils, basophils, mast cells Lymphocytes (B and T lymphocytes, natural killer cells)

11 The Defenders All white blood cells secrete chemicals, including cell-to-cell signaling molecules (cytokines) that coordinate all aspects of immunity Interleukins Interferons Tumor necrosis factors

12 White Blood Cells

13 Chemical Weapons of Immunity

14 38.1 Key Concepts Overview of Body Defenses The vertebrate body has three lines of immune defenses Surface barriers prevent invasion by ever-present pathogens General innate responses rid the body of most pathogens Adaptive responses specifically target pathogens and cancer cells

15 38.2 Surface Barriers Normal flora Billions of microorganisms normally live on human surfaces, including interior tubes and cavities of digestive and respiratory tracts A pathogen can cause infection only if it enters the internal environment by penetrating skin or other protective barriers at the body s surfaces

16 Some Normal Flora

17 Vertebrate Surface Barriers Physical, chemical, and mechanical barriers keep microorganisms outside body tissues Skin Mucus and cilia Lysozyme Gastric fluid and bile salts Normal flora Urination

18 Vertebrate Surface Barriers

19 Skin Healthy, intact skin is an effective surface barrier

20 38.3 Remember to Floss Dental plaque A thick, sticky biofilm of glycoproteins, bacteria, and their products that contribute to tooth decay and gum disease (periodontitis) Nine of every ten cardiovascular disease patients have serious periodontal disease Oral bacteria associated with periodontitis are also found in atherosclerotic plaque

21 Plaque

22 Key Concepts Surface Barriers Skin, mucous membranes, and secretions at the body s surfaces function as barriers that exclude most microbes

23 38.4 Innate Immune Responses Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established Phagocytes Complement Inflammation Fever

24 Phagocytes Macrophages Large phagocytes that patrol interstitial fluid and engulf and digest pathogens Secrete cytokines when receptors bind to antigen Cytokines attract more macrophages, neutrophils, and dendritic cells to infection site

25 Complement Complement proteins become activated when they encounter antigen Cascading enzyme reactions concentrate activated complement at infection site Complement attracts phagocytes to infection site and tags pathogens for destruction Forms attack complexes that puncture bacteria Helps mediate active immunity

26 Complement Attack Complexes

27 Inflammation Inflammation A local response to tissue damage characterized by redness, warmth, swelling and pain, triggered by activated complement and cytokines Mast cells release histamine, increasing capillary permeability Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris

28 Inflammation Response to Bacterial Infection

29 Fever Fever A temporary rise in body temperature above the normal 37 C (98.6 F) that often occurs in response to infection Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus Fever enhances the immune response by speeding up metabolism and phagocyte activity Fever over 40.6 C (105 F) can be dangerous

30 38.4 Key Concepts Innate Immunity Innate immune responses involve a set of general, immediate defenses against invading pathogens Innate immunity includes phagocytic white blood cells, plasma proteins, inflammation, and fever

31 38.5 Overview of Adaptive Immunity Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory

32 Self/Nonself Recognition Self versus nonself recognition Each kind of cell or virus has a unique identity MHC markers Plasma membrane self-recognition proteins T cell receptors (TCRs) Antigen receptors that recognize MHC markers as self, antigens as nonself

33 Specificity and Diversity Specificity Defenses are tailored to target specific antigens Diversity There are potentially billions of different antigen receptors on T and B cells

34 Memory Memory The capacity of the adaptive immune system to remember an antigen If the same antigen appears again, B and T cells make a faster, stronger response

35 First Step The Antigen Alert Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis All descendent cells recognize the same antigen T cells do not recognize an antigen unless it is presented by an antigen-presenting cell Macrophages, B cells, and dendritic cells digest particles and display antigen-mhc complexes

36 Cell Types Effector cells Differentiated lymphocytes (B and T cells) that act at once to fight infection Memory cells Long-lived B and T cells reserved for future encounters with the same antigen

37 Antigen Processing

38 Two Arms of Adaptive Immunity Antibody-mediated immune response B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid Cell-mediated immune response Cytotoxic T cells and NK cells detect and destroy infected or altered body cells

39 Interactions Between Antibody-Mediated and Cell-Mediated Responses

40 Intercepting and Clearing Out Antigen After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses During an infection, lymph nodes swell due to accumulation of T cells Antibody-antigen complexes bound by complement are cleared by the liver and spleen

41 The Lymphatic System

42 38.6 Antibodies and Other Antigen Receptors Antigen receptors on B and T cells have the potential to recognize billions of different antigens Antibody Y-shaped antigen receptor (protein), made only by B cells, that binds only to the antigen that prompted its synthesis Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins

43 Antibody Structure

44 Five Classes of Antibodies Constant regions determine 5 classes of antibodies (immunoglobins IgG, IgA, IgE, IgM, and IgD), each with different functions B cell receptors are membrane-bound IgM or IgD antibodies

45 Five Classes of Antibodies

46 Making Antigen Receptors Genes that encode antigen receptors occur in several segments on different chromosomes Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations T cells mature in the thymus, which stimulates production of MHC and T cell receptors

47 Antigen Receptor Diversity

48 38.7 The Antibody-Mediated Immune Response Antibody-mediated immune response Antigen activates naïve B cells and dendritic cells Naïve T cell binds to APC and differentiates into effector and memory helper T cells Helper T cells bind antigen-mhc complexes on activated B cell and secrete cytokines B cell differentiates into effector B cells, which produce antibodies targeting a specific antigen, and memory B cells

49 Antibody-Mediated Immune Response

50 Clonal Selection and Memory Cells Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster

51 Clonal Selection and Memory Cells

52 Primary and Secondary Immune Response

53 38.8 The Cell-Mediated Response Cell-mediated immune response Dendritic cell ingests altered body cell, displays antigen-mhc complexes, migrates to lymph node Naïve helper T and cytotoxic T cells bind to APC Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells Cytotoxic T cells circulate and touch-kill altered body cells

54 Primary Cell-Mediated Response

55 Cytotoxic T Cells Cytotoxic T cells touch-kill cells displaying antigen-mhc markers; perforin and proteases puncture cells and kill them by apoptosis

56 Natural Killer Cells Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers

57 Key Concepts Adaptive Immunity In an adaptive immune response, white blood cells destroy specific pathogens or altered cells Some make antibodies in an antibody-mediated immune response; others destroy ailing body cells in a cell-mediated response

58 38.9 Allergies Allergy An immune response to a typically harmless substance (allergen) First exposure stimulates production of IgE, which becomes anchored to mast cells and basophils Later exposure stimulates secretion of histamine and cytokines that initiate inflammation Anaphylactic shock is a severe and potentially fatal allergic reaction

59 Allergies: Annoying or Life-Threatening

60 38.10 Vaccines Immunization The administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease Vaccine (active immunization) A preparation containing an antigen that elicits a primary immune response Passive immunization Administration of antibodies; no immune response

61 Smallpox Vaccine Edward Jenner created the first vaccine against smallpox, which has now been eradicated

62 Recommended Immunizations

63 38.11 Immunity Gone Wrong Misdirected or compromised immunity is sometimes the result of mutation or environmental factors The outcome is often severe or lethal

64 Autoimmune Disorders Sometimes lymphocytes and antibodies fail to discriminate between self and nonself Autoimmune response An immune response that is misdirected against the person s own tissues Rheumatoid arthritis, Graves disease, multiple sclerosis

65 Immunodeficiency In immunodeficiency, the immune response is insufficient to protect a person from disease Primary immune deficiencies are present at birth SCIDs, ADA Secondary immune deficiency results from exposure to an outside agent, such as a virus AIDS

66 Gene Therapy Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy

67 38.12 AIDS Revisited Immunity Lost Acquired immune deficiency syndrome (AIDS) A group of disorders resulting from a failure of the immune system due to HIV infection Includes rare cancers and infections caused by normally harmless microorganisms Human immunodeficiency virus (HIV) A retrovirus that attacks specific cells of the immune system, including helper T cells

68 T Cells and AIDS

69 Global HIV and AIDS Cases

70 Transmission and Treatment Common modes of HIV transmission Unprotected sex, mother to child, shared syringes HIV testing Antibodies are found in blood, saliva or urine Drugs There is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress

71 Prevention Vaccines Experimental vaccines are mostly ineffective or risky; the virus high mutation rate is an obstacle Education The best option for preventing the spread of HIV is teaching people how to avoid being infected

72 The Global AIDS Program The global battle continues; researchers are using several strategies to develop an HIV vaccine

73 Key Concepts Immunity In Our Lives Vaccines are an important part of any health program Failed or faulty immune mechanisms can result in allergies, immune deficiencies, or autoimmune disorders The immune system itself is a target of human immunodeficiency virus (HIV)