Microbio Final Review PDF

**Chapter 14: Disorders in Immunity** **(Slide 4) Review: The Second Line of Defense: Formed Elements in Blood** **Hematopoiesis:** creation of cellular components of blood - All blood cells arise from stem cells **(Slide 5) Immune Response: A Two -Sided Coin** - Human immune system is powe...

**Chapter 14: Disorders in Immunity** **(Slide 4) Review: The Second Line of Defense: Formed Elements in Blood** **Hematopoiesis:** creation of cellular components of blood - All blood cells arise from stem cells **(Slide 5) Immune Response: A Two -Sided Coin** - Human immune system is powerful and a necessary system of defense, with the potential to cause injury and disease **Abnormal immune functions involved in:** - Ashma - Diabetes - Rheumatoid arthritis - Graft rejection **Immunopathology:** study of disease states associated with the over reactivity or under reactivity of the immune response **(Slide 6) Immune Response** **Hypersensitivity** (overreactivity) - Allergy and autoimmunity - The tissues are innocent bystanders attacked by immune components that CANNOT distinguish one's own tissues from foreign material **Hyposensitivity** (immunodeficiency) - Immune system is incompletely developed, suppressed, or destroyed **(Slide 7) Hypersensitivity: Four Types** **Type 1:** "common" allergy and anaphylaxis **Type 2:** IgG and IgM- mediated cell damage **Type 3:** Immune complex **Type 4:** T-cell response (cellular form of adaptive immune response) **Types I-III are B-cell-IgG type responses (antibody conditions)** **(Slide 8) Type I Allergic Reactions: Atopy and Anaphylaxis** **Allergy:** exaggerated immune response; causes inflammation **Allergens:** antigens that induce allergy in sensitive individuals **Atopy:** chronic local allergy (ex. Hay fever or asthma) **Anaphylaxis:** systemic, sometimes fatal, reaction that involves airway obstruction and circulatory collapse **(Slide 9) Who is Affected?** - Nearly half of US population is affected by airborne allergens (dust, pollen, mold) **Type I Allergies:** - Majority are relatively mild - Asthma and some food allergies may require hospitalization and can cause death - Some allergies last for a life, some are "outgrown" and others develop later in life **(Slide 10) Who is Affected?** **Generalized susceptibility to allergens:** inherited, not the allergy to a specific substance Ex.) parent with cat hair allergy may have child with pollen allergy Basically if parent has an allergy; greater chance that child will also acquire an allergy does not have to be the same exact one though - The prospect of a child developing an atopic allergy is 25%if parents are afflicted and 50% if siblings or grandparents are also afflicted **Genetic Basis for Atopy:** - Increased IgE production - Increased reactivity of mast cells (granular leukocyte) - Increased susceptibility of target tissue to allergic mediators **(Slide 11) Hygiene Hypothesis** - Immune systems need to be "trained" by interaction with microbes as we develop - But the industrialized world has created a hygienic environment (antimicrobial, well insulated homes, etc) - Children who grow up on farms have lower incidences of several types of allergies (do not live in as much of a hygienic environment so are introduced more to microbes than more people in "industrialized world" - Delivery by C section and maternal history of allergy elevates childhood risk of allergy by a factor of eight - Newborns only breast fed for the first four months have a lower risk of asthma and eczema a. Cytokines and growth factors in human milk act on the baby's gut mucosa to induce tolerance to allergens - 600 species of bacteria can be transferred to infants through breast milk a. Important role in the development of tolerance to foreign antigens **(Slide 13) Nature of Allergens and Entry Portals** As with all antigens, allergens have certain immunogenic characteristics - Proteins are more allergenic than carbohydrates, fats, or nucleic acids **Portals of entry** 1. Mucosa of the gut and respiratory tract a. Thin, moist surface that is normally penetrable 2. Skin (little more imperable compared to mucus) a. Dry, tough keratin is generally less permeable b. Access occurs through tiny breaks, gland, and hair follicles **(Slide 14) Common Allergens Classified by Portal of Entry** **Inhalants:** airbone environmental allergens such as: - Pollen - House dust - Dander - Fungal spores **Ingestants:** allergens that cause food allergies Ex.) peanuts, strawberries, shrimp **Injectants:** allergies triggered by: - Drugs - Vaccines - Bee venom **Contactants:** allergies that enter through the skin Ex.) detergent, lotion, latex gloves **(Slide 15) Role of Mast Cells in Type I Allergy** a. Located in all connective tissues - High numbers in lungs, skin, genitourinary and GI tracts b. After first allergen exposure (sensitization), mast cells bind IgE (antibody) c. In future exposures, allergen binds IgE, then mast cell **degranulates (releases cytokines)** d. Symptoms due to effects of host immune molecules on target organs (not the direct action of allergen) **(Slide 16) Cytokines, Target Organs, and Allergic Symptoms** **Cytokines:** - Histamine - Bradykinin - Serotonin - Leukotriene - Prostaglandins **(Slide 17) IgE- Mast-Cell-Mediated Allergic Conditions** - **Examples of Type 1 conditions** 1. **Hay Fever (allergic rhinitis)** - Seasonal reaction to inhaled plant pollen or molds - Chronic, year round reaction to airbone allergens or inhalants - Targets: respiratory membranes - Symptoms: nasal congestion; sneezing; profuse mucus secretion; itchy, red, and teary eyes; mild bronchoconstriction (**Slide 18) IgE-Mast-Cell-Mediated Allergic Conditions** 2. **Asthma (due to airway getting obstructed)** -respiratory disease characterized by episodes of impaired breathing due to severe bronchoconstriction -airways extremely sensitive to small amounts of inhalants, ingestants, or other stimuli, such as infectious agents -symptoms range from bouts of difficult breathing to fatal suffocation \~ **Rales**: clicking, bubbling, or rattling sounds in the lungs **(Slide 19) IgE-Mast-Cell-Mediated Allergic Conditions** 3. **Atopic Dermatitis/Eczema** - Intensely itchy skin inflammation - Sensitization occurs through ingestion, inhalation, and skin contact with allergens - Usually begins in infancy and is characterized by reddened, encrusted skin lesions - Progresses to a dry, scaly, thickened skin condition in adults - Scarring and thickened skin if chronic **(Slide 20) IgE-Mast-Cell-Mediated Allergic Conditions** 4. **Food Allergy** - Most common food allergens: peanuts, fish, cow's milk, eggs, shellfish, soybeans - Intestinal entry - Symptoms include vomiting, diarrhea, and abdominal pain - Other manifestations include hives, asthma, and occasionally anaphylaxis **(Slide 21) IgE-Mast-Cell-Mediated Allergic Conditions** 5. **Drug Allergy** - One of the most common side effects of treatment, affecting 5-10% of hospitalized patients - Reactions range from mild rash to fatal anaphylaxis - Compounds implicated a. Antibiotics: penicillin b. Synthetic antimicrobials: sulfa drugs c. Aspirin d. Opiates e. Contrast dye used in X rays **Outcome: rash** **(Slide 22) Anaphylaxis: An Overpowering IgE-Mediated Allergic Reaction** **Anaphylaxis/anaphylactic shock:** swift reaction to allergens: - **Cutaneous anaphylaxis:** wheal and flare inflammatory reaction to the local injection of allergens skin abrasion or condition with break in the skin - **Systemic anaphylaxis:** characterized by sudden respiratory and circulatory disruption that can be fatal within minutes due to airway blockage excess of inflammatory molecules being released from reaction - often due to bee stings and injection of antibiotics or serum - Result of the sudden, massive release of chemicals into the tissues and blood, which act rapidly on target organs **(Slide 23) Diagnosis of Allergy: In Vitro Methods outside of organism** **Blood Testing** **Radioallergosorbent test:** measures levels of IgE to specific antigens **Tryptase test**: measures enzyme (tryptase) released by mast cells during allergic response **Differential blood cell count** **Leukocyte histamine-release test:** measures histamine released from basophils after allergen exposure **(Slide 24) Diagnosis of Allergy: In Vivo Method inside organism** **Skin Testing:** in vivo method to detect precise atopic or anaphylactic sensitivities - Skin is injected, scratched, or pricked with a small amount of pure allergen extract - A wheal and flare result 20 minutes after antigenic challenge is indicative of histamine release - Diameter of the wheal is measured and rated on a scale from 0 (no reaction) to 3 (greater than 15 mm) **(Slide 25) Treatment and Prevention of Allergy** - Take drugs that block the action of lymphocytes, mast cells, or chemical mediators **(Slide 26) treatment and Prevention of Allergy** - Avoid the allergen, although this may be difficult in many instances **(Slide 27) Treatment and Prevention of Allergy** **Desensitization:** controlled exposure to the antigen to reset the allergic reaction - IgE produced in response to allergen - In subsequent exposures, IgG binds allergen before it can bind to IgE on mast cells, stopping degranulation **(Slide 29) Type II Hypersensitivities: Reactions that Lyse Foreign Cells** Syndromes where host IgG and IgM antibodies target foreign cell surface antigens which results in complement-assisted destruction (lysis) of the targeted cells: - Transfusion reactions and organ donations - Hemolytic disease of the newborn - Some types of autoimmunities (body makes antibodies to own cells) **(Slide 30) Type II Hypersensitivities: Reactions that Lyse Foreign Cells** **Alloantigens:** Present in some, but not all members of the same species (can be variation between different species) - Donor cells may have different surface alloantigens that are recognized as foreign by host lymphocytes - Not an immune dysfunction; the immune system is functioning normally be reacting to foreign cells in an organ or tissue transplant **(Slide 31) Rh Factor and Its Clinical Importance** First discovered in experiments exploring genetic relationships among animals: - Monkey antigen (Rh for rhesus) present in \~85% of humans (absent in \~15%) - Rh+ is dominant gene; Rh- is recessive - Antibodies only develop against Rh through exposure to fetus's antigen or by transfusion **(Slide 32) Hemolytic Disease of the Newborn and Rh Incompatibility** Placental sensitization occurs when the mother is Rh- and unborn child is Rh+ - Fetal RBCs leak into mother's circulation during childbirth when placenta detaches - Mother's immune system detects foreign Rh factors on fetal RBCs antibodies start to be made against RBC of fetus - Does not usually affect the first child because process occurs so late in pregnancy **(Slide 33) Hemolytic Disease of the Newborn and Rh Incompatibility** In the next pregnancy with an Rh+ fetus: - Late in pregnancy, fetal blood cells escape into maternal circulation, eliciting a *memory response* - Maternal anti-Rh antibodies cross placenta and cause complement-mediated lysis of fetal RBCs - Causes potentially fatal **hemolytic disease of the newborn (HDN)** characterized by 1. Severe anemia 2. Jaundice **(Slide 34) Preventing Hemolytic Disease of the Newborn** - Once sensitization has occurred, all other Rh+ fetuses will be at risk - Prevention requires careful history of Rh- pregnant women - RhoGAM antiserum: 1. Must be given with each pregnancy with Rh- mother and Rh+ fetus 2. Sequesters (hides or isolates) fetal RBCs that have escaped into maternal circulation and prevents sensitization **(Slide 35) Type III Hypersensitivities: Immune Complex Reactions** Reaction of soluble antigen (not attached to cell surface) with antibody, and deposition of these complexes in various tissues in the body - **Immune complex reaction:** produces free-floating complexes that are deposited into tissues - **Arthus reaction and serum sickness:** associated with passive immunization (providing Ig from healthy patients to recipients) **(Slide 36) Mechanisms of Immune Complex Disease** 1. Large Quantities of antibodies are produced in response to large amounts of antigen 2. On second exposure, antigen-antibody complexes form and recruit complement and neutrophils to area - **Immune complex disease --** complexes deposited into basement membranes of epithelial tissues **\~** Neutrophils release granules that digest tissues and cause destructive inflammation **(Slide 37) Type IV Hypersensitivities: Cell-Mediated (Delayed) Reactions** - Results when T cells respond to antigens displayed on self tissues or transplanted foreign cells - Traditionally known as delayed hypersensitivity a. Symptoms arise one to several days following the second contact with antigen **(Slide 38) Infectious Allergy example of Type IV** **Tuberculin Reaction:** - Acute skin inflammation at the tuberculin extract injection site - Mainstay diagnostic tool for TB infections - Helper T cells release cytokines that recruit macrophages, neutrophils, and eosinophils to the site, causing a red bump **(Slide 39) Contact Dermatitis example of Type IV** - Allergen (i.e. poison ivy/oak) penetrates the outer skin layers: a. Processed by skin dendritic cells and presented to T cells b. Subsequent exposures attract lymphocytes and macrophages c. Cells release enzymes and cytokines that damage epidermis **(Slide 40) T Cells and Their Role in Organ Transplantation** - Transplantation or grafting of organs and tissues is a common medical procedure - Although it is life-giving, it is plagued with the natural tendency of lymphocytes to seek out and destroy foreign antigens - The bulk of the damage that occurs in graft rejections are attributed to cytotoxic T-cell action **(Slide 41) Genetic and Biochemical Basis for Graft Rejection** - MHC classes I and II are extremely important for regulating the immune response (and to get good match for donor organ) - People can exhibit variability in the pattern of these markers, but the pattern is identical in cells of the same person - Similarily is seen in related siblings and parents, but the more distant the relationship, the less likely that the MHC genes and markets will be alike - When a donor tissue (graft) displays varying/ different MHC molecules, T cells of the recipient (host) will react to graft as a foreign substance **(Slide 42) Host Rejection of Graft** - Cytotoxic T cells of host recognize foreign class I MHC markers on grafted cells - Helper and cytotoxic T cells bind grafted issue and begin rejection process (within 2 weeks) - Antibodies formed against the graft contribute to damage - Result is destruction of vascular supply and death of graft **(Slide 43) Graft Rejection of Host** - Some grafted tissues (bone marrow) contain indigenous populations of lymphocytes a. Make it possible for graft to reject the host **Graft versus host disease:** - Graft attacks host tissue bearing foreign MHC markers - Effects are systemic and toxic - Most common symptom: **popular, peeling skin rash; other organs also affected** - Occurs within 100 to 300 days of the graft **(Slide 44) Classes of Grafts** **Autograft:** transplant from one body site to another on same individual **Isograft:** tissue from an identical twin is used **Allograft:** between genetically different individuals of **same** species; most common graft **Xenograft:** tissue exchange between individuals of **different** species **(Slide 45) Inappropriate Response to Self: Autoimmunity** **Autoimmune disease:** individuals develop hypersensitivity to themselves **Autoantibodies,** T cells, or both, mount an abnormal attack against self-antigens *Systemic:* involves several major organs *Organ specific:* involves only one organ or tissue **(Slide 46) Possible Causes of Autoimmune Disease** **Genetics:** cases cluster in families, and even unaffected members tend to develop autoantibodies for the disease - Rheumatoid arthritis is more common in persons with particular genes for Class I and II MHC **Molecular mimicry:** microbial antigens have similar molecular structures as host; antibodies made against microbe antigen will also react with host **Infection:** virus infection alters cell receptors causing attack of infected cells/tissues **Gut Microbiome:** healthy biome trains immune system **(Slide 47) Examples of Autoimmune Diseases: Systemic Autoimmunities** **Systemic lupus erythematosus (SLE or lupus):** - Autoantibodies against organs, tissues, or intracellular materials **Rheumatoid arthritis** - Progressive, debilitating damage to joints, sometime to lungs, eyes, skin, and nervous system - Autoantibodies form complexes that bind membranes of joints, activating cytokine release by macrophages **(Slide 48) Autoimunities of the Endocrine Glands** **Graves Disease:** - Attachment of autoantibodies to receptors on cells of the thyroid gland - Causes over-production of thyroid hormone and symptoms of hyperthyroidism **Type I Diabetes:** - Cytotoxic T cells attack and lyse insulin-producing cells - Reduced amount of insulin underlies disease symptoms **(Slide 49) Neuromuscular Autoimmunities** **Myasthenia gravis:** - Autoantibodies bind to receptors for muscle stimulation - Progresses to complete loss of skeletal muscle function and death - Immunosuppressive drugs and therapy used to remove autoantibodies from circulation **(Slide 50) Neuromuscular Autoimmunities** **Multiple Sclerosis:** - Paralyzing neuromuscular disease associated with lesions on myelin sheath that surrounds neurons of central nervous system - T cell and autoantibody-induced damage compromise the capacity of neurons to send impulses - Symptoms include: - Muscle weakness - Tremors - Difficulties in speech and vision - Paralysis **(Slide 51) Immunodeficiency Diseases:** Hyposensitivities - Occasionally, an individual is born with or develops weakened immune responses - Predominant consequences of **immunodeficiencies** are recurrent, overwhelming infections with opportunistic microbes **Primary Diseases:** present at birth (congenital), usually stemming from genetic errors **Secondary Diseases:** acquired after birth and caused by natural or artificial agents **(Slide 52) Primary Immunodeficiency Diseases** - Often due to inherited abnormality - Can lack either B or T cells, or both - Lymphocytes may be - Absent, or present at low levels - Present, but not functioning normally **Chapter 15: Diagnosing Infections** **(Slide 3) What is Causing this Condition?** How to identify bacteria in patient specimens or in samples from nature: **Phenotypic:** macroscopic and microscopic morphology, physiology, and biochemistry - Observation of microbe's microscopic and macroscopic morphology, physiology, and biochemical properties **Immunologic:** serological analysis - Analysis of microbe using antibodies, or of patient's antibodies using prepacked antigens **Genotypic:** genetic techniques - Analysis of microbe's DNA or RNA **(Slide 4) Phenotypic Methods** Observation of traits that an organism is expressing - Involves examining microbe appearance and behavior: - Types of enzymatic activities it can carry out - Physical conditions it thrives in - Antibiotics it is susceptible to - Chemical composition of its walls and/or membranes **(Slide 5) Immunologic Methods** - Patient sample is tested for the presence of specific antibodies to a suspected pathogen - Often easier than testing for the microbe itself - Lab kits are available for immediate identification of a number of pathogens **(Slide 6) Genotypic Methods** Advantages of genomic methods over phenotypic methods: - Culturing of microorganisms is not always necessary - Genotypic methods are increasingly automated, producing **rapid** results that are often **more precise** than phenotypic methods **(Slide 7) First Steps: Specimen Collection** Success of identification and treatment depends on how specimens are collected, handled, stored, and cultured: 1. Aseptic technique is imperative 2. Sterile sample containers and other tools prevent contamination from the environment or the patient 3. Only the infected site should be sampled; not surrounding areas - Labeling and identifying specimens, as well as providing accurate patient history, are crucial to obtaining timely and accurate results **(Slide 8) First Steps: Specimen Collection** 1. **Saliva samples:** spit or drool into container 2. **Sputum samples:** discharged by coughing or collected with a catheter 3. **Fluids:** blood taken by sterile needle aspiration **(Slide 9) First Steps: Specimen Collection** 4. **Skin Samples:** swabbed or scraped with a scalpel; wounds are swabbed or punched with biopsy tool 5. **Fluids:** cerebrospinal and tissue fluids taken by sterile needle aspiration **(Slide 10) First Steps: Specimen Collection** 6. **Urine samples:** a. Aseptically from bladder with catheter b. "clean catch"- washing external urethra and collecting urine midstream c. "dirty catch" -- first-voided urine - Urethra, vagina, or cervix sampled with swab or applicator stick Other specimen sources: \~ eye (swab) \~ ear canal (swab) \~ nasal cavity (swab) \~ diseased tissue (biopsied) **(Slide 11) Overview of Lab Techniques** **First:** Patient analysis for signs of infection Look for fever, wound exudate, mucus production, abnormal lesions, etc) **Second:** specimen collection and analysis - **Testing time** a. Few minutes (tests like rapid strep test) b. Several weeks (tests like tuberculosis infection) **Third:** Results are entered into patient chart **(Slide 12) Phenotypic Methods: Methods Requiring Growth** Selective and differential growth: 1. **Specialized media:** used to enrich a pathogen present in small numbers or easily overgrown 2. **Selective media:** used for nonsterile specimens containing a diversity of bacterial species to encourage the growth of only the suspected pathogen 3. **Differential media:** used to identify definitive characteristics and fermentation patterns **(Slide 13) Phenotypic Methods: Methods Requiring Growth** 4. **Dichotomous Key:** flowchart used to identify specimens - Combines results of Gram staining, growth on differential media, and simple enzymatic tests **(Slide 14) Phenotypic Methods: Methods Requiring Growth** 5. **Biochemical Testing** - Physiological reactions of bacteria to nutrients and other substrates - Provides evidence of enzyme systems present in a species - Based on enzyme-mediated metabolic reactions visualized by a color change (**Slide 15) Phenotypic Methods: Methods Requiring Growth** **Biochemical testing -- basic procedure** - Microbe is cultured in media with a special substrate, then tested for a particular end product - Enzyme expression made visible by a colored dye; no color means no enzyme to act on substrate **Unknown microbe + substrate** 1. enzyme present in microbe - Product forms - Color changes - \+ result 2. Enzyme absent in microbe - No product formed - No color change - (- ) Result **(Slide 16) Phenotypic Methods: Antimicrobial Susceptibility Testing (5)** Useful in determining drugs to select in treatment - Especially important to determine susceptibility with critical increase in antimicrobial resistance Most automated phenotypic systems incorporate antimicrobial susceptibility testing during pathogen identification **(Slide 17) Phenotypic Methods: Miscellaneous Tests** 6. **Phage Typing** - Bacteriophage infect bacteria in a species-specific and strain-specific way - Useful in identifying some bacteria 1. Bacterial lawn is inoculated onto agar 2. mapped off into blocks 3. phage are exposed to each block - cleared areas corresponding to lysed cells **indicate sensitivity to that phage** - bacteriophage specificity has been used to create sensitive and rapid diagnostic tests **(Slide 18) Determining Clinical Significance of Cultures** Rapid determination of whether isolate is clinically important, a contaminant, or normal biota is critical: - A few colonies of E. coli in a urine sample can indicate normal biota, but several hundred can mean an active infection - Isolation of a single colony of a true pathogen (i.e. M. tuberculosis) from any sample is highly suggestive of disease - Repeated isolation of a relatively pure culture of any microorganism can mean it is an agent of disease **(Slide 18) Phenotypic Methods** **Drawbacks** - When the microbe must be cultured, it takes a minimum of 18 to 24 hours and often longer - Many infectious conditions may be caused by nonculturable organisms, leaving open the possibility that the organism that we do culture is simply a bystander **(Slide 19) Immunologic Methods: Serology** **Serology:** involves **in vitro testing** (tests performed on a sample taken from the body) of serum, urine, cerebrospinal fluid, whole tissues, and saliva for the presence of specific antibodies Based on the principle that antibodies have an extreme specificity for antigens: - Their presence can reveal the history of a patient's contact with microorganisms or other antigens **(Slide 20) Immunologic Methods: Serology** - Visualization of the interaction of antigens and antibodies macroscopically or microscopically provides a powerful tool for detecting, identifying, and quantifying them Used to determine - Immunologic status of patients - Confirm a suspected diagnosis - Screen individuals for disease **(Slide 21) Whole Blood, Plasma, and Serum** **Blood Plasma** - Liquid component of whole blood (no blood cells) containing proteins and other soluble components of whole blood a. 95% H2O and contains dissolved proteins, glucose, clotting factors, electrolytes, hormones, CO2 and O2 - Keeps electrolytes balanced and protects body from infection and other blood-related disorders - Blood plasma is separated from whole blood by centrifugation of fresh blood containing an anticoagulant - Blood cells fall to the bottom of the tube - Blood plasma is poured or drawn off **(Slide 22) Whole Blood, Plasma, and Serum** **Blood Serum** - Blood with all cells and clotting factors removed Ex.) no WBC, RBCs, platelets, or clotting factors - Includes all proteins not used in blood clotting Ex.) electrolytes, antibodies, antigens, hormones and external substances (i.e. drugs or microbes) - Used in numerous diagnostic tests and as treatment - Antibodies in serum from convalescent (recovering) patients **Blood Serum Collection** - Allow blood to clot (coagulate) - Centrifuge to remove clot and blood cells - Remaining liquid supernatant is serum **(Slide 23) Different Kinds of Antigen- Antibody Interactions** - **At molecular level, immunological tests are based on antibody binding to specific epitopes of antigen** - **Binding reaction is not visible to the naked eye or light microscopy** - Antibody/antigen interaction must be confirmed indirectly - Observed as clumps in the solution(precipitations) or color changes **(Slide 24) Serology: Agglutination and Precipitation Reactions** - In both, one antigen is interlinked with several antibodies to form insoluble aggregates (settle out in solution) **Agglutination:** antigens are whole cells or organisms such as red blood cells, bacteria, or viruses displaying surface antigens - Forms visible clumps of cells \*clumping of whole bacteria **(Slide 25) Serology: Agglutination and Precipitation Reactions** **Agglutination** **Antigen-** same per well **Antibody-** diluted by half per well **Agglutinated:** significant antibody titer links antigen **Nonagglutinated:** not enough antibody to link antigen **(Slide 26) Serology: Agglutination and Precipitation Reactions** **Hemagglutination (blood coming from RBC)** - Agglutination of RBC surface antigens and complementary antibodies; used in blood typing **(Slide 27) Serology: Agglutination and Precipitation Reactions** - Viral hemagglutination occurs when viruses agglutinate RBCs without an antigen-antibody reaction - Mumps, measles, influenza **(Slide 28) Serology: Agglutination and Precipitation Reactions** **Indirect (passive) agglutination tests** **Ex.) put on latex bead** - Use antigens/ antibodies attached to particles **Detect antibodies:** free antibodies react with antigens bound to particles (often latex beads) OR **Detect Antigens:** free antigens react with antibodies bound to particles **(Slide 29) Serology: Agglutination and Precipitation Reactions** **Precipitation Reactions** - Reaction of **soluble antigens** with antibodies to form large, aggregates called latices - Antigen-antibody complex forms, followed by the formation of a lattice that precipitates from solution - More difficult to visualize because precipitates are easily disrupted in liquid media **(Slide 29) Serology: Agglutination and Precipitation Reactions** **Precipitation Reactions** - **Precipitation ring test:** a cloudy line forms where there is the optimal ratio of antigen and antibody **(Slide 30) Serology: Immunochromatography (Lateral Flow Test)** - **Plastic cartridge contains porous material that directs fluid flow in one direction** - A fluid patient sample is added to the sample well - Fluid flows to test line that contains antibodies matching antigens bind antibodies and flow continues - Control line contains a stripe of molecules that change color when bound Antigen-antibody technique for identifying, classifying, and subgrouping certain bacteria into categories called serotypes: - Employs antisera against cell antigens such as the capsule, flagellum, and cell wall - Basis for differentiating pneumococcal and streptococcal serotypes **(Slide 32) Serology: Western Blot** - Cell proteins are separated by electrical charge in a gel - Proteins are then transferred from gel to a special filter - Filter is incubated with antibody solutions labeled with radioactive, fluorescent, or luminescent molecules - Sites of specific antigen-antibody binding will appear as a pattern of bands that can be compared to known positive and negative controls - Verifies microbial-specific antigens or antibodies in a patient sample **(Slide 33) Serology: Immunofluorescence Testing** - Combines fluorescent dyes with antibodies - **Direct fluorescent-antibody tests (using known antibodies, looking for antigens)** - Unknown specimen is fixed to slide and exposed to Ab solution - Antibodies bound to sample will be visualized by fluorescence microscopy - Valuable for identifying infectious organisms and locating microbial antigens on cells **(Slide 34) Serology Immunofluorescence Testing** **Indirect fluorescent-antibody tests (antigen is known; searching for antibody)** - Known antigen is added to the patient test serum - Next, anti-human serum antibody (fluorescent) is added and binds to any patient antibodies bound to antigen - Binding visualized through fluorescence microscopy - Detects specific antibodies in serum; indicates presence of current or previous infection - Used to diagnose \_\_\_ and various viral infections **(Slide 35) Serology: Enzyme-Linked Immunosorbent Assay (ELISA)** - **Uses an antibody with a linked enzyme ( and the enzyme reaction) to detect antigens and antibodies** - Indirect or direct ELISA - Use shallow well microtiter plates - Easy to interpret; clearly positive and clearly negative results **(Slide 36) Serology: Enzyme- Linked Immunosorbent Assay (ELISA)** **Direct ELISA: detects antigens** -sample containing antigens is mixed with antibody \- enzyme-linked antibodies react with the antigen \- detected by adding a substrate for the linked enzyme; a color is produced **(Slide 37) Enzyme-Linked Immunosorbent Assay (ELISA)** **Indirect ELISA: detects antibodies** -serum added to plate that contains antigen \- bound antibody detected with anti-human antibody (with linked enzyme) -addition of substrate causes color change - Common test used for antibody screening for HIV - False positives can occur; verification by Western blot may be necessary **(Slide 38) In Vivo Testing** Similar principles as serological tests, but antigen or antibody is introduced directly to patient **Tuberculin Reaction:** - Small amount of purified protein derivative from Mycobacterium tuberculosis is injected into the skin - Appearance of a red, raised, thickened lesion in 48 to 72 hours can indicate previous exposure to tuberculosis (**Slide 39) General Features of Immune Testing** The most effective diagnostic tests have a high degree of specificity and sensitivity **Specificity:** property of a test to focus only on a certain antibody or antigen and not react with an unrelated or distantly related antigen **Sensitivity:** detection of even minute quantities of antibodies or antigens in a specimen; reflects the degree to which a test will detect every positive person **(Slide 41) Genotypic Methods: Polymerase Chain Reaction (PCR)** - PCR results in the production of numerous identical copies of DNA or RNA molecules within hours - Can amplify even minute quantities of nucleic acids present in a sample **(Slide 43) Genotypic Methods: Polymerase Chain Reaction (PCR)** **Real-Time PCR (**aka qPCR q=quantitative) - Uses fluorescent labeling during amplification - Level of fluorescence is measured in real time as reaction is running - Fully automated and faster than traditional PCR, because analysis of the DNA after the reaction is finished is not necessary - Often assess the antimicrobial susceptibilities at the same time as identifying the organism **Multiplex PCR:** - Contains primers for multiple organisms in the differential diagnosis for the patient's symptoms - Most often, multiplex PCR is also known as real-time PCR **(Slide 44) Genotypic Methods: Hybridization** Identifies microbes by analyzing segments of genetic material **Probes:** small segments of DNA or RNA that are complementary to specific sequences of nucleic acid from a microbe - Probes are fluorescently labeled to an enzyme that triggers a color change when hybridization occurs - Base-pairing of probes to nucleic acids can provide evidence of a microbe's identity **(Slide 45) Genotypic Methods: Hybridization** **Fluorescent (in situ) hybridization (FISH):** - Fluorescently labeled probes are applied to cells within a sample - Glowing cells are located and microbe identity can be concluded Used to: - Confirm a diagnosis - Identify microbial components in biofilms - Cancer diagnoses (patient DNA examined to design treatment) **(Slide 46) Genotypic Methods: Hybridization** **Microarrays ("Chips")** - Absorbent plates containing gene sequences from potentially thousands of different possible infectious agents - Chosen based on a large differential diagnosis - Designed to contain bacterial, viral, and fungal genes in a single test - Matching sequences hybridize in the chip and fluorescence is detected by a computer program **(Slide 47) Genotypic Methods: Whole- Genome Sequencing** - Useful for rapid analysis of outbreaks and drug-resistant organsism - Deep sequencing -- single genome scanned and analyzed multiple times; minimizes errors - Method is becoming inexpensive and routine may soon become the preferred technique to diagnose illness **(Slide 48) Genotypic Methods: Pulsed-Field Gel Electrophoresis** - **Separates DNA fragments that are too large for conventional gel electrophoresis** - DNA is cut with restriction enzymes; results in different sized fragments - Fragments separate in gel due to alternating voltage applied from three different directions - Often used in acute outbreaks of foodborne and other infections **PulseNet:** CDC program that investigates possible foodborne disease outbreaks **(Slide 50) Additional Diagnostic Technologies** Chips (integrated circuits) - Miniaturized genetic tests that require few supplies and little technical training Imaging - X rays have been used for centuries in TB diagnosis - MRI, CT scans, and PET scans are increasingly used to find areas of localized infection in deep tissue - Can save patients from an invasive biopsy **(Slide 51) Additional Diagnostic Technologies** Mass Spectrometry - Rapid and highly accurate microbial identification within minutes; can also detect antibiotic susceptibilities - Analyzes proteins within a sample - Involves ionizing the sample with a laser and ions are identified by their mass-to-charge ratio **Chapter 20: Infectious Diseases Affecting the Gastrointestinal Tract** **(Slide 1) Gastrointestinal Tract and its Defenses** - The gastrointestinal (GI) tract can be thought of as a long tube, extending from mouth to anus - Often called the digestive tract or the enteric tract - **Eight main sections:** - Mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, and anus - Four accessory organs add digestive fluids and enzymes to assist in digestion and processing food: a. Salivary glands, liver, gallbladder, pancreas **(Slide 2) Gastrointestinal Tract and Its Defenses** - The GI tract contains a tremendous amount of microorganisms and encounters millions of new ones each day **Defenses include:** - Mucus - Secretory IgA - Peristalsis: keeps food and microorgansisms moving through tract - Saliva (contains lysozyme and lactoferrin) - Stomach fluid (highly acidic) - Bile (antimicrobial) **(Slide 3) Gastrointestinal Tract and its Defenses** **70% of immune system is located in intestinal tract** - Gut- associated lymphoid tissue (GALT) - Lymph nodes - Peyer's patches **Other organs:** - Tonsils and adenoids in the oral cavity and pharynx - Small areas of lymphoid tissue in the esophagus - Appendix **(Slide 4) Normal Biota of the Gastrointestinal Tract** **The oral cavity** - More than 600 known species of microorganisms including bacteria, fungi, and protozoa - **Dental plaque:** synergistic community of bacteria on teeth; a type of biofilm **Stomach** - Previously thought sterile due to very low pH - Evidence for \~128 different species of microbes found **Large intestine** - Haven for billions of microbes (bacteria, fungi, protozoa, and archaea) - 10\^11 microbes per gram of contents **(Slide 5) Normal Biota of the Gastrointestinal Tract** - Provides a protective function - Helps with digestion - Provides nutrients that we cannot provide ourselves a. E.coli synthesizes vitamin K - "Teaches" the immune system to react to microbial antigens - Composition can influence host's chances for obesity or autoimmune diseases **(Slide 6) Diseases of the Gastrointestinal Tract** - Typically two types of digestive system diseases **Infections:** pathogens enter GI tract and multiply **\~** typically delay in GI disturbance as bacteria grow **\~ fever is common** **Intoxications:** ingestion of preformed toxin - Sudden symptoms and GI disturbance - **Fever not as common** **Associated terms:** **Dysentery:** severe diarrhea containing blood and/or mucus **Gastroenteritis:** inflammation of the stomach and intestinal mucosa **[(Slide 7) Acute Diarrhea ]** - **Three or more loose stools in a 24-hr period** - Often accompanied by fever, abdominal pain, cramping, nausea, vomiting, and dehydration - 1.2 to 1.9 cases per person per year in U.S. (rate doubles in children) **\> 10 episodes per year for children in developing countries** **-** children who survive dozens of bouts of diarrhea are likely to have permanent physical and cognitive defects \- more than 700,000 infants a year die from diarrhea **[(Slide 8) Acute Diarrhea ]** - In U.S., \~1/3 of cases due to contaminated food - \~48 million people are sickened each year by a foodborne illness and 3,000 die - Most cases are self-limiting and do not require treatment - Antibiotic treatment typically avoided but quick treatment with antibiotics is sometimes necessary (ex. Shigellosis) - For public health reasons, it is important to know cause; but in most cases identification is not performed **[(Slide 9) Acute Diarrhea: Salmonella ]** Very large genus of bacteria; disease caused by **Salmonella enterica** - Bacteria are further divided into subspecies and further into serogroups - Salmonella enterica subspecies enterica serovar Typhi or Salmonella typhi - Normal intestinal biota in cattle, poultry, rodents, and reptiles - Survives outside the host in inhospitable environments **[(Slide 10) Acute Diarrhea: Salmonella ]** **Salmonellosis:** - Severe forms can include elevated body temperatures and septicemia - Vomiting, diarrhea, and mucosal irritation - Blood can appear in the stool - In healthy adults, symptoms subside within 2 to 5 days - Death is infrequent, except in debilitated patients **[(Slide 11) Acute Diarrhea: Salmonella ]** **Transission:** **ID50:** measurement of how many organisms must be ingested to cause disease Salmonella has a high 1D50, meaning a lot of organisms must be ingested for disease to result - Animal products such as meat and milk can be readily contaminated with Salmonella during slaughter, collection, and processing - Most cases are traceable to a common food source such as milk or eggs **Prevention:** avoiding contact with the bacterium **Treatment:** fluid and electrolyte replacement for mild cases **[(Slide 12) Acute Diarrhea: Shigella (another genus that can cause diarrhea) ]** Primarily human parasites but can infect apes - All produce similar disease that varies in intensity - Resemble some types of pathogenic E.coli **Signs and symptoms:** - Frequent watery stools, fever, intense abdominal pain - Nausea and vomiting are common **Dysentery: diarrhea containing blood** - In Shigella, stools often contain obvious blood and even more often found to have occult blood (not visible to naked eye) **[(Slide 13) Acute Diarrhea: Shigella ]** - Invades cells of the large intestine and initiates an inflammatory response that causes extensive tissue destruction - Orally and through direct person-to-person contact - Small infectious dose: 10 to 200 bacteria - Disease mostly associated with lax sanitation, malnutrition, and crowding - Spread epidemically in day care centers, prisons, mental institutions, nursing homes, and military camps - Some people may become chronic carriers for several months **Prevention:** good food hygiene **Treatment:** fluid and electrolyte replacement for mild cases **[(Acute Diarrhea: Shiga-Toxin-Producing E. Coli (STEC) ]** - **Virulence due to Shiga Toxin** - Identical exotoxin as in Shigella species - Toxin genes due to prophage (integrated bacteriophage) - Destroys cells in the large intestine, resulting in bloody diarrhea **Transmission:** ingestion of contaminated or undercooked beef - Other foods and beverages can be contaminated as well **Culture and Diagnosis:** - Confirm infection with stool culture and test for Shiga Toxin - Positive specimens should be sent to state or local health departments for characterization and outbreak monitoring **Prevention: good food hygiene** - Shiga toxin is heat-labile and E.coli is killed by heat **Treatment** - Antibiotics are contradicted; may increase pathology by releasing more toxin - Supportive therapy (i.e. plasma transfusions to dilute toxin) is a good option **[(Slide 14) Acute Diarrhea: Other E.coli ]** **At least five other categories of E.coli can cause diarrheal diseases"** - Entertoxigenic E.coli (ETEC) - Enterinvasive E.coli (EIEC) - Enteropathogenic E.coli (EPEC) - Diffusely adherent E.coli (DAEC) - Enteroaggregative E.coli (EAEC) **In clinical practice, most physicians are interested in differentiating STEC from the others** **[(Slide 15) Acute Diarrhea: Campylobacter ]** **One of the most common bacterial causes of diarrhea in the US** Campylobacter jejuni is the most common cause - Inhabits intestinal tract, genitourinary tract, and oral cavity of humans and animals - Transmission by ingestion of contaminated beverages and food, especially water, milk, meat, and chicken - Once ingested, C. jejuni enters last segment of the small intestine near its junction with the colon **Signs and Symptoms** - Frequent watery stools, fever, vomiting, headaches, abdominal pain a. Enterotoxin causes diarrhea similar to cholera - Symptoms may last longer than 2 weeks: a. May subside and then recur over a period of weeks **Infection can lead to a rare, serious neuromuscular paralysis called Guillain-Barre syndrome (GBS)** - 20% to 40% of GBS cases preceded by Campylobacter infection **Prevention:** rigid sanitation of water and milk supplies and care in food prep **Treatment:** rehydration and electrolyte balance therapy **[Acute Diarrhea: Clostridioides difficile ]** - Gram-positive, endospore-forming anaerobe - Normal biota of the intestine - Causes pseudomembranous colitis (antibiotic-associated colitis) a. Due to therapy with broad-spectrum antibiotics b. Able to superinfect the large intestine when drugs have disrupted the normal biota Severe cases exhibit abdominal cramps, fever, and leukocytosis - Colon is inflamed and gradually sloughs off membranelike patches called **pseudomembranes** - If not stopped, perforation of the cecum and death can result Difficult to eradicate; stubborn infections decrease patient's quality of life **66% of C. diff cases are healthcare-associated** - C. diff releases endosprores which contaminate the environment: - Hospitalized patients must be put in isolation conditions, and constant attention to disinfection and infection control is required **[Acute Diarrhea: Vibrio Cholerae ]** **Slightly curved, gram negative rod with single flagellum** - Associated with salty waters - Produces the choltera toxin toxin causes the host cells to secrete electrolytes and water causes "rice water stools" - Can lose 12 to 20 liters of fluid per day (blood can then start to clot) - Treatment includes IV fluid replacement **[Acute Diarrhea: Cryptosporidium (protozoa) ]** **Intestinal protozoan that infects a variety of mammals, birds, and reptiles** Transmitted through drinking water or food contaminated by feces from infected animals - Half the outbreaks of diarrhea associated with swimming pools are caused by Cryptosporidium Invade intestinal epithelium Mimic other types of gastroenteritis: **headache, sweating, vomiting, severe abdominal cramps, and diarrhea** **Treatment not usually required for otherwise healthy patients** **[Acute Diarrhea: Norovirus and Rotavirus ]** **Viral Gastroenteritis** - One of the most common diseases in humans - \~90% caused by Rotavirus or Norovirus **Rotavirus** - Common in children; low mortality - 2 to 3 day incubation; low grade fever, diarrhea, vomiting - Prevented with a live oral vaccine **Norovirus** - Fecal- oral transmission - Low infectious dose - 18-48 hour incubation; diarrhea and vomiting **[Food Poisoning ]** - Severe nausea and frequent vomiting accompanied by diarrhea - Others sharing meal have same symptoms - Onset within 1-6 hours - Symptoms in the gut are caused by a preformed toxin of some sort from: Staphylococcus aureus, Bacillus cereus, Clostridium perfringens - Nonmicrobial sources such as fish, shellfish, or mushrooms can cause **intoxication** **[Food Poisoning: Staphylococcus aureus Exotoxin ]** Toxins produced when the organism is allowed to incubate in food - S. aureus outgrows most bacteria in environments with high temperature and high osmotic pressure - Exotoxin is heat-stable; inactivation requires 100 degrees Celsius for at least 30 mins Ingested toxin acts on the gastrointestinal epithelium: - Stimulates nerves causing symptoms of cramping, nausea, vomiting, and diarrhea Recovery is rapid, usually within 24 hours **[Food Poisoning: Clostridium perfringens and Bacillus cereus ]** **Clostridium Perfringens** - Forms endospores, produces an exotoxin acute abdominal pain, diarrhea, and nausea in 8 to 16 hours **Bacillus cereus** - Forms endospores---spores survive heating, germinate, and produce toxins one causes a diarrheal-type disease other cause an **emetic** or vomiting disease (found a lot in rice) **[Chronic Diarrhea ]** **Diarrhea lasting longer than 14 days** - Can have infectious causes or can reflect noninfectious conditions **Irritable bowel syndrome and ulcerative colitis:** - Neither caused by a microorganism - Increasing evidence that a chronically disrupted intestinal biota can contribute to these conditions AIDS patients suffer from chronic diarrhea caused by opportunistic microorganisms: - HIV status should be considered if a patient presents with chronic diarrhea **[Chronic Diarrhea: Cyclospora ]** **Cyclospora cayetanesis protozoan:** - Since 1990 has become very common **Fecal oral transmission** - Most cases associated with consumption of fresh produce and water contaminated with feces Disease occurs worldwide and is not spread from person to person **[Chronic Diarrhea: Giardia]** - **Caused by Giardia duodenalis** - Flagellated protozoan - Typically transmitted in contaminated water - Attaches to the intestinal wall - Prolonged diarrhea, abdominal pain, and flatulence a. Stools have a greasy, foul-smelling quality to them **[Tooth and Gum Infections: Dental Caries ]** **Dental caries or tooth decay** **Dental plaque:** biofilm involved in the formation of **dental caries** (tooth decay) - 700 species of bacteria in the oral cavity Streptococcus mutans is an important cariogenic organism \~gram-positive coccus \~converts sucrose to lactic acid \~produces sticky polysaccharides that contribute to biofilm formation \*pretty good at generating biofilm **\*\*\*\* the most common infectious disease of human beings:** - Involves the dissolution of solid tooth surface due to the metabolic action of bacteria - Caries penetrate from enamel into the dentin **Decay can reach the pulp, which contains the blood supply and nerve cells** - May advance to soft tissues, leading to abscesses **Introduction of table sugar in the diet is correlated with the level of dental caries** **[Tooth and Gum Infections: Periodontitis ]** Several conditions characterized by the inflammation and degeneration of structures that support teeth **Gingivits:** inflammation and infection of the gums **Periodontitis:** bone and tissue surrounding the teeth are destroyed **Calculus:** hard, porous substance produced above and below gingival margin; induces varying degrees of periodontal damage **[Mumps]** **Mumps virus targets the parotid salivary glands** - Fever, nasal discharge, muscle pain, and malaise - Painful swelling may occur 16 to 18 days after exposure **(parotitis)** **Most infections are self-limiting with complete, uncomplicated recovery and permanent immunity** - **Transmitted through salivary and respiratory secretions** - **Symptomatic treatment to relieve fever, dehydration, and pain** - **Prevented with MMR vaccine** **[Gastritis and Gastric Ulcers ]** **Helicobacter Peptic Ulcer Disease** - Caused by Helicobacter pylori - Infects 30-50% of the population in the developed world - Grows in the stomach acid by producing urease converts urea to alkaline ammonia - Disrupts stomach mucosa, causing inflammation **[Hepatitis ]** - Inflammatory disease marked by necrosis of hepatocytes and an inflammatory response that swells and disrupts the liver architecture: **Jaundice:** yellow tinge in the skin and eyes caused by bilirubin accumulation in the blood and tissues - Can be caused by a variety of different viruses: **Cytomegalovirus, Epstein-Barr virus, and GBV-C** - Noninfectious conditions that cause hepatitis include autoimmune diseases, drugs, and alcohol abuse **[Hepatitis: Hepatitis C Virus ]** Parental transmission; often blood transfusions - Destroys the liver by using genetic variaton to evade the immune response - Kills more in the U.S. than AIDS - 85% of cases become chronic 25% develop liver cirrhosis or cancer - **Treatment but [no] vaccine** **[Gastrointestinal Tract Diseases Caused by Helminths ]** **Helminths that parasitize humans are amazingly diverse:** - Barely visible roundworms (0.3mm) - Huge tapeworms (25m) **Three categories:** Nematodes (roundworms) Trematodes (flukes) Cestodes (tapeworms) **Helminthic diseases are usually accompanied by an additional set of symptoms that arise from the host response to the helminth** **[Eosinophilia ]** - Increase in granular leukocytes called **eosinophils** - Have a specialized. Capacity to destroy helminths - Hallmark of helminthic infection **Helminthic infections acquired through:** - Fecal oral route - Penetration of the skin **Most organisms spend part of their lives in the intestinal tract:** - While in the intestine, helminths run the gamut of intestinal symptoms - Some produce symptoms outside of the intestines **Chapter 21: Infectious Diseases Affecting the Genitourinary System** **Genitourinary Tract and Its Defenses** - The structures in the genitourinary tract are really two distinct organ systems: **Males:** urethra is terminal organ of reproductive tract **Females:** urethra is separate from the vagina **Urinary system** - **Two kidneys** - **Two ureters** - **One urinary bladder** - **One urethra** **Infection prevented by:** - Valves that prevent backflow to the kidneys - Acidity of urine - Mechanical flushing **Genitourinary Tract and Its Defenses** **Male Reproductive System** - **Two testes** - **System of ducts** \*Epididymis \*Ductus (vas) deferens \*Ejaculatory duct \*Urethra \- **Accessory glands** **- penis** **[Female Reproductive System ]** - **Two ovaries** - **Two uterine (fallopian) tubes** - **The uterus, including the cervix** - **The vagina** - **External genitals (vulva)** **Major defense:** changes vaginal pH of the vagina due to estrogen release: - Stimulates glycogen secretion by vaginal mucosa; certain bacteria ferment into acid, lowering vaginal pH to between 4.2-5 **Normal Biota of the Genitourinary Tract** Contrary to popular belief, urine is not sterile - Contains low levels of microbes (even within bladder) - Becomes contaminated with skin microbiota closer to end of urethra - Microbiome is active area of research **Lactobacillus are predominant genus (especially in females)** - Produce lactic acid (lowers pH) - Estrogen promotes growth higher UTI rate during pregnancy and menopause Lower estrogen levels = higher pH (leads to higher UTI, etc) **Candida albicans yeast** - 10-25% of women **[Urinary Tract Infections ]** **Urethritis:** inflammation of the urethra may progress to: **cystitis** **Cystitis:** inflammation of the urinary bladder may progress to: **ureteritis** **Ureteritis:** infection of the ureters left untreated, infection may progress to... : **pyelonephritis** **Pyelonephritis:** inflammation of one or both kidneys **8 million urinary tract infections annually** - Most due to Escherichia coli **[Urinary Tract Infections (bacteria) ]** **Cystitis:** inflammation of the urinary bladder - Commonly caused by E.coli **Dysuria:** difficult or painful urination - Eight times more common in women than men due to the short length of the urethra and its proximity to the anal opening **Pyelonephritis:** inflammation of one or both kidneys - 75% of cases caused by E.coli - Fever and back or flank pain - Generally results in bacteremia - Can form scar tissue in kidneys and become life-threatening **[Reproductive Diseases Caused by Microorganisms ]** **Sexually transmitted infections (STIs)** - Formerly termed sexually transmitted diseases (STDs) - Often no signs or symptoms - Over 30 types of infections - \~20 million new cases annually in US half occur in 15 to 24 year olds - Most prevented with condoms **[Discharge Diseases: Gonorrhea ]** **Caused by Neisseria gonorrhoeae** gram-negative diplococcus - Attaches to epithelial mucosa using fimbriae - Invades spaces between epithelial cells \~ causes inflammation \~ forms pus acquired at point of sexual contact - Pharyngeal gonorrhea and anal gonorrhea **Symptoms:** **Men:** painful urination and discharge of pus **Women:** fewer symptoms; pelvic inflammatory disease If left untreated, may disseminate and become systemic - Endocarditis - Meningitis - Arthritis **Opthalmia neonatorum:** acquired during birth from mother; may cause infant blindness due to eye infection **[Discharge Diseases: Chlamydia ]** **Nongonococcal Urethritis** - **Nonspecific urethritis** - Any inflammation of the urethra not caused by N. gonorrhoeae - Commonly caused by Chlamydia trachomatis - Painful urination and watery discharge; often asymptomatic; pelvic inflammatory disease (PID) in women **Pelvic Inflammatory Disease (PID)** - Extensive bacterial infection of the female pelvic organs - N. gonorrhoeae and C. trachomatis - Chronic abdominal pain **Pelvic Inflammatory Disease (PID)** **Salpingitis:** infection of uterine tubes - Most serious form of PID - Scarring can cause infertility or ectopic pregnancy (fertilized egg grows outside of uterus) **[Vaginitis and Vaginosis]** **Vaginitis:** inflammation of the vagina due to infection - pH above 4.5, fishy odor, copious frothy discharge **Vaginosis:** no sign of inflammation **[Candida albicans ]** - Fungus that grows on the mucosa of the mouth, intestinal tract, and genitourinary tract - Due to opportunistic growth caused by: antibiotic use diabetes hormones **Oral candidiasis: thrush** **Vulvovaginal candidiasis: vaginitis** **Yeasty, thick, yellow discharge** **[Gardnerella Species]** **Bacterial vaginosis** - Caused by Gardnerella vaginalis Pleomorphic gram-negative rod **Clue cells** - Sloughed-off vaginal epithelial cells covered with a biofilm of G. vaginalis **[Genital Ulcer Diseases ]** Three common infectious conditions can result in lesions on the genitals: - Syphilis - Chancroid - Genital herpes infection with an ulcer disease increases the chances of infection with HIV because of open lesions **[Genital Ulcer Diseases: Syphilis ]** **Caused by Treponema pallidum** - Gram-negative spirochete - Grows slowly in cell culture - Invades the mucosa or through skin breaks and enters the bloodstream - Induces an inflammatory response **Primary stage:** **Chancre:** at sight of infection; \~ 3 weeks after exposure - Painless and highly infectious - Disappears after 2 weeks **Secondary stage:** - Several weeks later - Skin and mucosal rashes (esp on palms and soles) - Due to inflammatory response **Latent period** - Occurs after secondary stage with or without treatment - No symptoms - Found in spleen and lymph nodes **Tertiary stage** - Appear years after latency - Due to cell-mediated immune reactions **Gummatous syphilis: gummas** (inflamed masses of tissue) on many organs **Cardiovascular syphilis:** weakens the aorta **Neurosyphilis:** affects the CNS; dementia **Congenital syphilis (mother to newborn)** - Transmitted through placenta to fetus - Neurological damage to the fetus **[Genital Ulcer Diseases: Genital Herpes ]** - **Caused by Herpes simplex virus type 2 (HSV-2)** ¼ over age 30 infected in US - Painful vesicles on the genitals; painful urination - Heals within 2 weeks Recurrent infection from viruses latent in nerve cells - Due to menstruation, emotional stress, or illness No cure; suppression and management with antivirals **[Neonatal Herpes ]** - Herpesvirus crosses the placental barrier and infects the fetus damages the CNS, developmental delays, blindness, hearing loss - Newborns may be infected from HSV exposure during delivery - Treatment with intravenous acyclovir - Survival rate of 40% **[Wart Diseases: Human Papillomaviruses Infection ]** **Genital Warts** - Caused by human papillomaviruses - \~5 million new cases occur in US each year - Visible warts caused by serotypes 6 and 11 serotypes 16 and 18 cause cervical cancer - Kills 4000 women annually in US **Treatment via removal of warts and antivirals** - Prevention with HPV vaccines