1. I NFECTION AND D EFECTS IN D EFENSE Paula Ruedebusch, ARNP, DNP

2. 2 I MMUNE D EFICIENCY Defense system protects body Occasional breakdowns Mild defects or life-threatening defects

3. 3 M ICROORGANISM AND H UMAN R ELATIONSHIP Mutual relationship Normal flora Relationship can be breached by injury Leave their normal sites and cause infection elsewhere Opportunistic microorganisms

4. 4 O PPORTUNISTIC INFECTIONS

5. 5 I NFECTION Developed countries Sanitary living conditions, clean H20, uncontaminated food, vaccinations, antimicrobials US = heart disease and malignancies Deaths greatly surpass deaths from infectious disease Infectious disease India, Africa, Southeast Asia, etc. Vaccines and antimicrobials Alter prevalence of some infectious diseases New diseases Mutant stains and new diseases, drug-resistant TB, etc.

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9. 9 I NFECTIOUS DISEASE, MISC. https://www.youtube.com/watch?v=6xxd63o7Usg http://www.google.org/flutrends/about/how.html

10. 10 F ACTORS FOR I NFECTION Communicability Ability to spread from one individual to others and cause disease: measles and pertussis spread very easily, HIV is of lower communicability Immunogenicity Ability of pathogens to induce an immune response

11. 11 F ACTORS FOR I NFECTION ( CONT ’ D ) Infectivity Ability of pathogen to invade and multiply in the host Involves attachment to cell surface, release of enzymes, escape phagocytes, spread through lymph and blood to tissues Pathogenicity Ability of an agent to produce disease Success depends on communicability, infectivity, extent of tissue damage, and virulence

12. 12 F ACTORS FOR I NFECTION ( CONT ’ D ) Mechanism of action How the microorganism damages tissue Portal of entry Route by which a pathogenic microorganism infects the host Direct contact Inhalation Ingestion Bites of an animal or insect

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14. 14 F ACTORS FOR I NFECTION ( CONT ’ D ) Toxigenicity Ability to produce soluble toxins or endotoxins, factors that greatly influence the pathogen’s degree of virulence Virulence Capacity of a pathogen to cause severe disease; for example, measles virus is of low virulence; while rabies virus is highly virulent

15. 15 C LASSES OF I NFECTIOUS M ICROORGANISMS AND EXAMPLES Virus (poliomyelitis, influenza) Bacteria (Staph, Cholera, Strep pneumonia, TB) Fungi (tinea pedis, candidiasis) Protozoa (giardiasis, sleeping sickness) Chlamydia (Urethritis) Rickettsia (Rocky Mountain Spotted Fever) Mycoplasma (Atypical pneumonia) Helminths (Filariasis)

16. 16 P ATHOGEN D EFENSE M ECHANISMS Bacteria Produce surface coats that inhibit phagocytosis and toxins Viruses Many can mutate within cells where they are not available to immune and inflammatory mechanisms Not available to antibodies in circulation Antigenic variations: Antigenic drift Antigenic shifts http://www.cdc.gov/flu/about/viruses/change.htm

17. 17 B ACTERIA Prokaryotes Aerobic or anaerobic Motile or immotile Shapes: Spherical = cocci Rodlike – bacilli Spiral = spirochetes Gram stain

18. 18 B ACTERIAL V IRULENCE AND I NFECTIVITY Toxin production Exotoxins (cytotoxins, neurotoxins, pneumotoxins, enterotoxins, hemolysins) Enzymes released during growth, causing specific responses Immunogenic Antitoxin production Ex. Tetanus, diptheria, pertussis, group A streptococci (flesh eating bacteria) Endotoxins Lipopolysaccharides contained in the cell walls of gram- negative organisms released during cell destruction Pyrogenic effects

19. 19 E NDOTOXINS

20. 20 B ACTERIAL V IRULENCE AND I NFECTIVITY ( CONT ’ D ) Bacteremia (presence) or septicemia (growth) A result of a failure of the body’s defense mechanisms Usually caused by gram-negative bacteria Toxins released in the blood cause the release of vasoactive peptides and cytokines that produce widespread vasodilation leading to septic (endotoxic) shock https://depts.washington.edu/idhmc/guidelines/hospital /hmc_sepsis.html (UW Sepsis protocol) https://depts.washington.edu/idhmc/guidelines/hospital /hmc_sepsis.html

21. 21 S EPTIC S HOCK https://www.youtube.com/watch?v=NKtiC0HRrqc

22. 22 V IRAL I NFECTION Characteristics: Dependent on host cells No metabolism Simple organism Spreads cell to cell Usually a self-limiting infection

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24. 24 V IRAL R EPLICATION Not capable of independent reproduction Need permissive host cell Begins when virion binds to a specific receptor on the plasma membrane of a host cell penetrates the plasma membrane Virus then uncoats in cytoplasm DNA virus replicates in nucleus RNA virus replicates in cytoplasm

25. 25 V IRAL R EPLICATION ( CONT ’ D ) Copies of genetic material made New virions released from cell to infect other host cells Some remain latent in host cell until activated by stress, hormone changes, disease (e.g., herpes virus and cold sore)

26. 26 C ELLULAR E FFECTS OF V IRUSES Inhibition of host cell DNA, RNA, or protein synthesis Disruption of lysosomal membranes release enzymes that damage host cell Transformation of host cell to cancer cell Promotion of secondary bacterial infection

27. 27 S ECONDARY BACTERIAL INFECTIONS

28. 28 F UNGAL I NFECTION Large microorganisms with thick rigid cell walls without peptidoglycans (resist penicillin and cephalosporins) Eukaryotes Exist as single-celled yeasts, multi-celled molds, or both Reproduce by simple division or budding

29. 29 F UNGAL I NFECTION ( CONT ’ D ) Pathogenicity Adapt to host environment Wide temperature variations, digest keratin, low oxygen Suppress the immune defenses Usually controlled by phagocytes, T lymphocytes

30. 30 F UNGAL I NFECTION ( CONT ’ D ) Diseases caused by fungi are called mycoses Superficial, deep, or opportunistic Fungi that invade the skin, hair, or nails are known as dermatophytes The diseases they produce are called tineas (ringworm) Tinea capitis, tinea pedis, and tinea cruris

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32. 32 F UNGAL I NFECTION AND I NJURY Deep fungal infections are life threatening and are commonly opportunistic (e.g., with antibiotics or pH changes) Changes that alter normal flora foster fungal infections Candida albicans

33. 33 P ARASITIC I NFECTION Symbiotic Unicellular protozoa to large worms (helminths) Flukes, nematodes, tapeworms Protozoa include malaria, amoebae, flagellates More common in developing countries Spread human to human via vectors Usually ingested Tissue damage is secondary to infestation itself with toxin damage or from inflammatory/immune response

34. 34 P ARASITIC I NFECTION

35. 35 C LINICAL M ANIFESTATIONS OF I NFECTIOUS D ISEASE Variable depending on the pathogen Directly caused by the pathogen or indirectly caused by its products Fever

36. 36 C OUNTERMEASURES ( CONT ’ D ) Antimicrobials Bacteriocidal vs. bacteriostatic Inhibit synthesis of cell wall Damage cytoplasmic membrane Alter metabolism of nucleic acid Inhibit protein synthesis Modify energy metabolism

37. 37 C OUNTERMEASURES ( CONT ’ D ) Antimicrobial resistance Genetic mutations Inactivation Multiple antibiotic-resistance bacteria (e.g., MRSA) Can destroy normal flora Clostridum difficile Why? Overuse!

38. 38 C OUNTERMEASURES Vaccines Induction of long-lasting protective immune responses that will not result in disease in a healthy recipient Attenuated organism Killed organisms Recombinant viral protein Bacterial antigens Toxins

39. 39 C OUNTERMEASURES ( CONT ’ D ) Vaccines Biologic preparations of weakened or dead pathogens Long lasting immunity CDC schedules = http://www.cdc.gov/vaccines/ Development expensive Reluctance to vaccinate but complications rare

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41. 41 I MMUNE D EFICIENCIES Failure of immune mechanisms of self- defense Primary (congenital) immunodeficiency Genetic anomaly Secondary (acquired) immunodeficiency Caused by another illness More common

42. 42 I MMUNE D EFICIENCIES ( CONT ’ D ) Clinical presentation Development of unusual or recurrent, severe infections T cell deficiencies Viral, fungal, yeast, and atypical microorganisms B cell and phagocyte deficiencies Complement deficiencies

43. 43 P RIMARY I MMUNE D EFICIENCIES Most are the result of a single gene defect Five groups: B lymphocyte deficiencies T lymphocyte deficiencies Combined T and B cell deficiencies Complement defects Phagocyte defects

44. 44 B L YMPHOCYTE D EFICIENCIES Hypogammaglobulinemia or agammaglobulinemia Bruton agammaglobulinemia Autosomal agammaglobulinemia X-linked hyper-IgM syndrome IgG subclass deficiency Selective IgA deficiency Common variable immune deficiency

45. 45 T L YMPHOCYTE D EFICIENCIES DiGeorge syndrome Partial or complete absence of T cell immunity Chronic mucocutaneous candidiasis

46. 46 S ECONDARY D EFICIENCIES Also referred to as acquired deficiencies Far more common than primary deficiencies Often not clinically relevant

47. 47 S ECONDARY D EFICIENCIES ( CONT ’ D ) Causes: Normal physiology conditions Psychologic stress Dietary insufficiencies Malignancies Physical trauma Medical treatments Infections Acquired immunodeficiency syndrome (AIDS)

48. 48 A CQUIRED I MMUNODEFICIENCY S YNDROME (AIDS) Syndrome caused by a viral disease Human immunodeficiency virus (HIV) Depletes the body’s Th cells Incidence: Worldwide: 33.4 million (2008) United States: about 56,000 (2008)

49. 49 A CQUIRED I MMUNODEFICIENCY S YNDROME (AIDS) ( CONT ’ D ) Effective antiviral therapies have made AIDS a chronic disease Epidemiology Blood-borne pathogen Heterosexual activity is most common route worldwide Increasing faster in women than men especially in adolescents

50. 50 A CQUIRED I MMUNODEFICIENCY S YNDROME (AIDS) ( CONT ’ D ) Pathogenesis Retrovirus Genetic information is in the form of RNA

51. 51 H UMAN I MMUNODEFICIENCY V IRUS (HIV)

52. 52 H UMAN I MMUNODEFICIENCY V IRUS (HIV) ( CONT ’ D ) Structure protein binds to the CD4 molecule found primarily on surface of helper T cells Destroys CD4+ Th cells Typically 800 to 1000 cell/mm 3 Reverses CD4/CD8 ratio AIDS = < 200 cell/mm 3 of CD4 + T cell

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54. 54 H UMAN I MMUNODEFICIENCY V IRUS (HIV) ( CONT ’ D ) Clinical manifestations Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS Window period Th cells <200 cells/mm 3 diagnostic for AIDS Diagnosis of AIDS is made in association with various clinical conditions and lab tests: Atypical or opportunistic infections, and cancer Presence of antibodies against HIV (4 to 7 weeks after blood transmission, 6-14 months after sexual intercourse) Western blot analysis

55. 55 H UMAN I MMUNODEFICIENCY V IRUS (HIV) ( CONT ’ D ) Treatment and prevention Highly active antiretroviral therapy (HAART) Reverse transcriptase inhibitors Protease inhibitors New drugs Entrance inhibitors Integrase inhibitors Vaccine development Genetically and antigenically variable Antibodies may not be protective

56. 56 H YPERSENSITIVITY Altered immunologic response to an antigen that results in disease or damage to the host

57. 57 H YPERSENSITIVITY ( CONT ’ D ) Allergy Deleterious effects of hypersensitivity to environmental (exogenous) antigens Autoimmunity Disturbance in the immunologic tolerance of self- antigens Alloimmunity Immune reaction to tissues of another individual

58. 58 H YPERSENSITIVITY ( CONT ’ D ) Characterized by the immune mechanism: Type I IgE mediated Type II Tissue-specific reactions Type III Immune complex mediated Type IV Cell mediated

59. 59 H YPERSENSITIVITY ( CONT ’ D ) Immediate hypersensitivity reactions Anaphylaxis Types I, II, III Delayed hypersensitivity reactions Type IV reactions

60. 60 T YPE I H YPERSENSITIVITY IgE mediated Against environmental antigens (allergens) IgE binds to receptors on surface of mast cells Food allergies Kids: Milk, chocolate, citrus fruits, eggs, wheat, nuts, peanut butter, fish Adults: shellfish Urticaria Histamine release H 1 and H 2 receptors Antihistamines

61. 61 T YPE I H YPERSENSITIVITY ( CONT ’ D ) Manifestations: Itching Urticaria Conjunctivitis Rhinitis Hypotension Bronchospasm Dysrhythmias GI cramps and malabsorption

62. 62 T YPE I H YPERSENSITIVITY ( CONT ’ D ) Genetic predisposition- atopic Tests: Food challenges Skin tests Laboratory tests Desensitization Cautiously

63. 63 T YPE I H YPERSENSITIVITY ( CONT ’ D )

64. 64 T YPE II H YPERSENSITIVITY Tissue specific Specific cell or tissue (tissue-specific antigens) is the target of an immune response

65. 65 T YPE II H YPERSENSITIVITY ( CONT ’ D ) Five mechanisms: Cell is destroyed by antibodies and complement Cell destruction through phagocytosis Soluble antigen may enter the circulation and deposit on tissues; tissues destroyed by complement and neutrophil granules Antibody-dependent cell-mediated cytotoxicity (ADCC) Causes target cell malfunction (e.g., Graves)

66. 66 T YPE III H YPERSENSITIVITY Immune complex mediated Antigen-antibody complexes are formed in the circulation and are later deposited in vessel walls or extravascular tissues Not organ specific Serum sickness Raynaud phenomena Arthrus

67. 67 T YPE IV H YPERSENSITIVITY Does not involve antibody! Cytotoxic T lymphocytes or lymphokine producing Th1 cells Direct killing by Tc or recruitment of phagocytic cells by Th1 cells Examples:  Acute graft rejection  Skin test for TB  Some autoimmune disorders  Contact allergic reactions (chemicals, cosmetics, detergents, clothing, food, metals, topical meds)

68. 68 PPD T EST Intradermal injection of tuberculin antigen Delayed hypersensitivity skin test (24-72 hours) Influx of T lymphocytes and macrophages Induration (clear hard center) Erythema (surrounding)

69. 69 A LLERGY Most common hypersensitivity and usually type I Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals Pollens, molds and fungi, foods, animals, etc. Often allergen is contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat Bee stings

70. 70 E PIPENS

71. 71 A UTOIMMUNITY Breakdown of tolerance Body recognizes self-antigens as foreign Self-antigens not normally seen by the immune system Infectious disease (e.g., rheumatic fever, glomerulonephritis)

72. 72 A UTOIMMUNE E XAMPLES Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Autoantibodies against: Nucleic acids Erythrocytes Coagulation proteins Phospholipids Lymphocytes Platelets, etc.

73. 73 A UTOIMMUNE E XAMPLES ( CONT ’ D ) Systemic lupus erythematosus (SLE) Deposition of circulating immune complexes containing antibody against host DNA More common in females

74. 74 S YSTEMIC L UPUS E RYTHEMATOSUS Clinical manifestations: Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70%-80%) Renal disease (40%-50%) Hematologic changes (50%) Cardiovascular disease (30%-50%)

75. 75 S YSTEMIC L UPUS E RYTHEMATOSUS ( CONT ’ D ) Eleven common findings:  Facial rash (malar rash)  Discoid rash  Photosensitivity  Oral or nasopharyngeal ulcers  Nonerosive arthritis  Serositis  Renal disorder  Neurologic disorder  Hematologic disorders  Immunologic disorders  Presence of antinuclear antibodies (ANA)  Serial or simultaneous presence of at least four indicates SLE

76. 76 A LLOIMMUNITY Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species Transplant rejection and transfusion reactions: Major histocompatibility complex (MHC) Human leukocyte antigens (HLA) Transfusion reactions ABO blood groups Rh incompatibility Hemolytic disease of newborn

77. 77 G RAFT R EJECTION Transplant rejection is classified according to time Hyperacute Immediate and rare Preexisting antibody to the antigens of the graft Acute Cell-mediated immune response against unmatched HLA antigens

78. 78 G RAFT R EJECTION ( CONT ’ D ) Transplant rejection is classified according to time Chronic Months or years Inflammatory damage to endothelial cells of vessels as a result of a weak cell-mediated reaction against minor HLA antigens

79. 79 G RAFT -V ERSUS -H OST D ISEASE (GVHD) Immunocompromised individuals are at risk for GVHD T cells in the graft are mature and capable of cell- mediated destruction tissues within the recipient Not a problem if patient is immunocompetent