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INFECTION AND DEFECTS IN DEFENSE Paula Ruedebusch, ARNP, DNP IMMUNE DEFICIENCY Defense system protects body Occasional breakdowns Mild defects or life-threatening defects 2 MICROORGANISM AND HUMAN RELATIONSHIP Mutual relationship Normal flora Relationship can be breached by injury Leave their normal sites and cause infection elsewhere Opportunistic microorganisms 3 OPPORTUNISTIC INFECTIONS 4 INFECTION Developed countries US = heart disease and malignancies India, Africa, Southeast Asia, etc. Vaccines and antimicrobials Deaths greatly surpass deaths from infectious disease Infectious disease Sanitary living conditions, clean H20, uncontaminated food, vaccinations, antimicrobials Alter prevalence of some infectious diseases New diseases Mutant stains and new diseases, drug-resistant TB, etc. 5 6 7 8 INFECTIOUS DISEASE, MISC. https://www.youtube.com/watch?v=6xxd63o7Usg http://www.google.org/flutrends/about/how.html 9 FACTORS FOR INFECTION 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 10 FACTORS FOR INFECTION (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 11 FACTORS FOR INFECTION (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 12 13 FACTORS FOR INFECTION (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 14 CLASSES OF INFECTIOUS MICROORGANISMS 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) 15 PATHOGEN DEFENSE MECHANISMS 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 16 BACTERIA Prokaryotes Aerobic or anaerobic Motile or immotile Shapes: Spherical = cocci Rodlike – bacilli Spiral = spirochetes Gram stain 17 BACTERIAL VIRULENCE AND INFECTIVITY 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 gramnegative organisms released during cell destruction Pyrogenic effects 18 ENDOTOXINS 19 BACTERIAL VIRULENCE AND INFECTIVITY (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) 20 SEPTIC SHOCK https://www.youtube.com/watch?v=NKtiC0HRrqc 21 VIRAL INFECTION Characteristics: Dependent on host cells No metabolism Simple organism Spreads cell to cell Usually a self-limiting infection 22 23 VIRAL REPLICATION 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 24 VIRAL REPLICATION (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) 25 CELLULAR EFFECTS OF VIRUSES 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 26 SECONDARY BACTERIAL INFECTIONS 27 FUNGAL INFECTION 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 28 FUNGAL INFECTION (CONT’D) Pathogenicity Adapt to host environment Wide temperature variations, digest keratin, low oxygen Suppress the immune defenses Usually controlled by phagocytes, T lymphocytes 29 FUNGAL INFECTION (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 30 31 FUNGAL INFECTION AND INJURY 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 32 PARASITIC INFECTION 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 33 PARASITIC INFECTION 34 CLINICAL MANIFESTATIONS OF INFECTIOUS DISEASE Variable depending on the pathogen Directly caused by the pathogen or indirectly caused by its products Fever 35 COUNTERMEASURES (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 36 COUNTERMEASURES (CONT’D) Antimicrobial resistance Can destroy normal flora Genetic mutations Inactivation Multiple antibiotic-resistance bacteria (e.g., MRSA) Clostridum difficile Why? Overuse! 37 COUNTERMEASURES 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 38 COUNTERMEASURES (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 39 40 IMMUNE DEFICIENCIES Failure of immune mechanisms of selfdefense Primary (congenital) immunodeficiency Genetic anomaly Secondary (acquired) immunodeficiency Caused by another illness More common 41 IMMUNE DEFICIENCIES (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 42 SECONDARY DEFICIENCIES (CONT’D) Causes: Normal physiology conditions Psychologic stress Dietary insufficiencies Malignancies Physical trauma Medical treatments Infections Acquired immunodeficiency syndrome (AIDS) 43 ACQUIRED IMMUNODEFICIENCY SYNDROME (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) 44 ACQUIRED IMMUNODEFICIENCY SYNDROME (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 45 ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) (CONT’D) Pathogenesis Retrovirus Genetic information is in the form of RNA 46 HUMAN IMMUNODEFICIENCY VIRUS (HIV) 47 HUMAN IMMUNODEFICIENCY VIRUS (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/mm3 Reverses CD4/CD8 ratio AIDS = < 200 cell/mm3 of CD4 + T cell 48 49 HUMAN IMMUNODEFICIENCY VIRUS (HIV) (CONT’D) Clinical manifestations Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS Window period Th cells <200 cells/mm3 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 50 HUMAN IMMUNODEFICIENCY VIRUS (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 51 HYPERSENSITIVITY Altered immunologic response to an antigen that results in disease or damage to the host 52 HYPERSENSITIVITY (CONT’D) Allergy Autoimmunity Deleterious effects of hypersensitivity to environmental (exogenous) antigens Disturbance in the immunologic tolerance of selfantigens Alloimmunity Immune reaction to tissues of another individual 53 HYPERSENSITIVITY (CONT’D) Characterized by the immune mechanism: Type I Type II Tissue-specific reactions Type III IgE mediated Immune complex mediated Type IV Cell mediated 54 HYPERSENSITIVITY (CONT’D) Immediate hypersensitivity reactions Anaphylaxis Types I, II, III Delayed hypersensitivity reactions Type IV reactions 55 TYPE I HYPERSENSITIVITY 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 H1 and H2 receptors Antihistamines 56 TYPE I HYPERSENSITIVITY (CONT’D) Manifestations: Itching Urticaria Conjunctivitis Rhinitis Hypotension Bronchospasm Dysrhythmias GI cramps and malabsorption 57 TYPE I HYPERSENSITIVITY (CONT’D) Genetic predisposition- atopic Tests: Food challenges Skin tests Laboratory tests Desensitization Cautiously 58 TYPE I HYPERSENSITIVITY (CONT’D) 59 TYPE II HYPERSENSITIVITY Tissue specific Specific cell or tissue (tissue-specific antigens) is the target of an immune response 60 TYPE II HYPERSENSITIVITY (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) 61 TYPE III HYPERSENSITIVITY 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 62 TYPE IV HYPERSENSITIVITY Does not involve an antibody! Cytotoxic T lymphocytes or lymphokine producing Th1 cells Examples: Acute graft rejection Skin test for TB Some autoimmune disorders Contact allergic reactions (chemicals, cosmetics, detergents, clothing, food, metals, topical meds) 63 PPD TEST Intradermal injection of tuberculin antigen Delayed hypersensitivity skin test (24-72 hours) Influx of T lymphocytes and macrophages Induration (clear hard center) Erythema (surrounding) 64 ALLERGY 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 65 EPIPENS 66 AUTOIMMUNITY 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) 67 AUTOIMMUNE EXAMPLES Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Autoantibodies against: Nucleic acids Erythrocytes Coagulation proteins Phospholipids Lymphocytes Platelets, etc. 68 AUTOIMMUNE EXAMPLES (CONT’D) Systemic lupus erythematosus (SLE) Deposition of circulating immune complexes containing antibody against host DNA More common in females 69 SYSTEMIC LUPUS ERYTHEMATOSUS Clinical manifestations: Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70%-80%) Renal disease (40%-50%) Hematologic changes (50%) Cardiovascular disease (30%-50%) 70 SYSTEMIC LUPUS ERYTHEMATOSUS (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 71 ALLOIMMUNITY 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 72 GRAFT REJECTION 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 73 GRAFT REJECTION (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 74 GRAFT-VERSUS-HOST DISEASE (GVHD) Immunocompromised individuals are at risk for GVHD T cells in the graft are mature and capable of cellmediated destruction tissues within the recipient Not a problem if patient is immunocompetent 75 QUESTIONS? Thank you for a fantastic quarter!! Study hard, you can do it!! 76