General Principles of Microbial Pathogenesis PDF

PATHOLOGY | TRANS #4 LE General Principles of Microbial Pathogenesis DR. ARLENE SANTOS | 09/28/2024 | Version...

PATHOLOGY | TRANS #4 LE General Principles of Microbial Pathogenesis DR. ARLENE SANTOS | 09/28/2024 | Version #1 02 OUTLINE B. CATEGORIES OF INFECTIOUS AGENTS I. Overview IV. Mechanism of Viral and Prions A. Definition of Terms Bacterial Injury → Infectious agents made up of the abnormal form of the B. Categories of Infectious A. Mechanism of Viral Injury prion protein Agents a. Types of Viral Infections → Can cause: II. How Microorganisms Cause b. Morphologic ▪ Bovine spongiform encephalopathies Disease Appearance A. Routes of Entry of B. Mechanism of Bacterial − Cause neuronal damage to the brain Microbes Injury ▪ Creutzfeldt-Jakob disease B. Entry, Spread and a. Bacterial Adherence to ▪ Kuru Dissemination of Microbes Host Cells − Associated with human cannibalism within the Body b. Bacterial Toxins Viruses C. Release from the Body c. Morphologic Bacteria and Transmission of Appearance of Bacterial Fungi Microbes Infections Protozoa III. Host-Pathogen Interactions V. Spectrum of Inflammatory A. Host Defense against Responses to infections Helminths Infection A. Suppurative Inflammation Ectoparasites B. Immune Evasion by B. Mononuclear Inflammation → Insects or arachnids that attach to or live on the skin Microbes C. Granulomatous → Ex. lice, bed bugs, fleas C. Injurious Effects of Host Inflammation II. HOW MICROORGANISMS CAUSE DISEASE immunity D. Infections in People w/ immunodeficiencies D. Cytopathic-Cytoproliferativ e Reaction E. Tissue Necrosis 📖 A. ROUTES OF ENTRY OF MICROBES [Robbins] Microbes can enter the host by breaching epithelial E. Mechanism by Which F. Chronic inflammation & surfaces, inhalation, ingestion, or sexual transmission Microbes Establish Scarring Respiratory, gastrointestinal, and genitourinary tract Infections & Damage VI. Special Techniques For Tissues Diagnosing Infections Agents infections (in healthy persons) VII. Review Questions → Caused by virulent microorganisms with the ability to VIII. References damage or penetrate the epidermis or mucosal IX. Appendix. epithelium Skin infections (in healthy persons) Must Lecturer Book Previous Youtube → Mainly caused by organisms that enter the skin through 💬 ❗️ superficial injuries ❗️ Know 📖 📋 Trans 🔺 Video Pathogens can establish infections if it possesses virulence factors that overcome normal host defenses or if SUMMARY OF ABBREVIATIONS the host defenses are overwhelmed UTI Urinary Tract Infection Host defenses include the following: TNF Tumor Necrosis Factor → Skin LEARNING OBJECTIVES ▪ Tough keratinized barrier ✔ Classify microorganisms/parasites into appropriate ▪ Low pH category ▪ Fatty acids ✔ Enumerate different mechanisms of host barriers to → Respiratory system infection ▪ Alveolar macrophages ✔ Discuss mechanisms of transmission and dissemination ▪ Mucociliary clearance by bronchial epithelium of microbes ▪ IgA ✔ Discuss general mechanisms by which infectious agents → GI system cause disease ▪ Gastric pH ✔ Enumerate and discuss the mechanism by which ▪ Viscous mucus infectious agents can evade immune system ▪ Pancreatic enzymes and bile ✔ Discuss mechanisms by which viruses and bacteria ▪ IgA and normal microbiota cause damage or kill cells → Urogenital tract ▪ Repeated flushing I. OVERVIEW ▪ Acidic environment created by commensal microbiota A. DEFINITION OF TERMS SKIN Invasion Intact keratinized skin protects against infection by serving → Process whereby microorganisms enter host cells & as a mechanical barrier, having a low pH, and by spread in the body producing antimicrobial fatty acids, and defensins Infection Most skin infections are initiated by mechanical injury of → Invasion & multiplication of microorganisms in body the epidermis tissues which may be clinically inapparent or result in → Mechanical defects local cellular injury ▪ Ex. ulcers → Used interchangeably with infectious disease → Needle stick injury → Intravenous catheters LE 2 TG 4 | Orge, Razon, Salanga, Verdillo TE | S. Reginaldo, J. Sim AVPAA | J. Tiongson PAGE 1 of 12 TRANS 4 VPAA | E. Punzalan PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos → Animal/insect bites GASTROINTESTINAL TRACT ▪ Vectors include fleas, ticks, mosquitoes, and lice Infections occur when local defenses are circumvented by ▪ Schistosoma larvae can traverse unbroken skin by a pathogen or when weakened, or when they are so releasing enzymes that dissolve the adhesive weakened that even normal flora produce disease proteins that hold keratinocytes together Most GI pathogens are transmitted by food or water → Direct penetrations on skin ❗️ contaminated with fecal material ▪ Fungi (dermatophytes) can cause superficial ↓ Hygiene = ↑ Diarrheal disease infections of the intact stratum corneum, hair, and Has multiple local defenses: nails → Acid gastric secretions ▪ Highly effective at killing certain organisms ▪ Impaired gastric acid secretions would increase the infectivity of Vibrio cholerae by 10,000-fold → Layer of mucus ▪ Prevents access of luminal pathogens to the surface epithelium → Pancreatic enzymes and bile detergents ▪ Can destroy organisms with lipid envelopes → Antimicrobial defensins ▪ Produced by gut epithelial cells → IgA antibodies ▪ Produced in mucosal lymphoid tissues such as Peyer patches and secreted into the gut lumen. → Peristalsis Figure 1. Layers of the skin[Lecture PPT] ▪ Can clear organisms, preventing their local overgrowth RESPIRATORY TRACT → Presence of normal gut microbiota A plethora of microorganisms, including viruses, bacteria, ▪ Competitively inhibits colonization and overgrowth by and fungi, are inhaled daily, mainly in dust or aerosol potential pathogens such as Clostridioides difficile particles. Many common GI pathogen are resistant to local defenses Microorganisms are trapped in the mucociliary blanket that → Norovirus lines the nose and the upper respiratory tract ▪ Scourge of the cruise ship industry → They are then transported by ciliary action to the back ▪ Nonenveloped virus that is resistant to inactivation by of the throat where they are swallowed and cleared acid, bile, and pancreatic enzymes → Particles smaller than 5 microns (< 5µm) are carried into ▪ Easily spreads where people are crowded together the alveoli where they are phagocytosed by leukocytes → Intestinal protozoa and helminths Microorganisms that infect the healthy respiratory tract ▪ Transmitted as cysts or eggs evade local defenses through several different ▪ Outer coats are acid-resistant mechanisms → Some respiratory viruses attach to and enter epithelial Table 1. Pathogenic Mechanism of GIT Diseases cells in the lower respiratory tract and pharynx Mechanism Description ▪ Influenza viruses Toxin Some organisms that contaminate food → Certain bacterial pathogens release toxins that enhance production can produce GI diseases without their ability to establish an infection by impairing ciliary establishing an infection activity → S. aureus can produce a powerful ▪ Mycoplasma pneumoniae and Bordetella pertussis exotoxin during its growth in contaminated food that is responsible for acute food poisoning Bacterial Establishes an infection and produces colonization and damaging toxins toxin production → V. cholerae and E. coli bind to intestinal epithelium and releases potent exotoxins responsible for symptomatic disease Adhesion and Invasion of intestinal mucosa and mucosal lamina propria invasion Causes ulceration, inflammation, and hemorrhage → Manifests as dysentery → Shigella spp., Salmonella enterica, Campylobacter jejuni, Entamoeba histolytica → Candida albicans invades oral and Figure 2. Cilia on the respiratory epithelium[Lecture PPT] esophageal squamous mucosa in immunocompromised patients to cause thrush PATHOLOGY General Principles of Microbial Pathogenesis PAGE 2 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos 📖 UROGENITAL TRACT C. RELEASE FROM THE BODY & TRANSMISSION OF Urine contains small numbers of low-virulence bacteria MICROBES [Robbins] Urinary tract is protected from infection by regular Microbes use a variety of exit strategies to ensure their emptying during micturition transmission from one host to the next Urinary tract pathogens (such as E. coli) Release may be accomplished by: → Gain access via urethra and must adhere to urothelium → Skin shedding to avoid being washed out → Coughing → Women have >10 times as many UTIs as men → Sneezing ▪ Female urethra is 5 cm while male urethra is 10 cm → Voiding of urine or feces → Obstruction of urinary flow or reflux of urine is a → During sexual contact major factor in susceptibility to UTI → Insect vectors Lactobacilli in the vagina causes low pH which protects it Some pathogens are released for only brief periods of time from pathogens or periodically during disease flares → Antibiotics can kill the lactobacilli and allow the → Others may shed for long periods by asymptomatic overgrowth of yeast, causing vaginal candidiasis carrier hosts MODES OF TRANSMISSION OF ORGANISMS 📖 B. ENTRY, SPREAD, & DISSEMINATION OF Direct and indirect contact MICROBES WITHIN THE BODY [Robbins] → Hepatitis B & C viruses can be transmitted through To enter the body, microbes penetrate the epithelial or needle stick injury or sharing of needles and syringes mucosal barriers through the skin, respiratory tract, GIT, or among drug users genitourinary tract. Respiratory route After entry, microbes may remain localized at the site of → Coughing, pathogens are aerosolized in droplets that entry can travel in long distances Some microbes may spread to other sites through: ▪ Transmitted through inhalation → Direct invasion ▪ E.g. M. tuberculosis, Varicella-zoster virus ▪ Pathogens secrete enzymes to break down tissues, Feco-oral route allowing the organisms to spread contiguously in the → Ingestion of food or water contaminated by fecal tissue material → The lymphatics → Most enteric pathogens are spread through this ▪ Allows travel to regional lymph nodes, allowing them → Some parasitic helminths shed eggs in stools that hatch to reach the bloodstream as larvae that are capable of penetrating the skin of the → The bloodstream next host ▪ Pathogens may produce a systemic inflammatory Sexual transmission response syndrome called sepsis → Requires prolonged intimate or mucosal contact − Manifests as fever, low BP, and coagulopathies → E.g. HSV, HIV, HPV, Treponema pallidum, Neisseria that may result in organ failure and death if left gonorrhoeae, Trichomonas vaginalis, Phthiris pubis unchecked Vertical transmission → The nerves → Mode of transmission of infectious agents from mother ▪ Certain viruses can spread to the CNS by infecting to fetus peripheral nerves then traveling along axons ▪ Placental transmission ▪ E.g. Rabies virus, poliovirus, varicella-zoster virus − Most likely to occur when mother is infected during pregnancy − Can interfere with fetal development − E.g. Rubella during 1st trimester can cause mental retardation, cataract, and deafness ▪ Transmission during birth − Caused by contact of newborn with infected birth canal − E.g. Neisseria gonorrhoeae, Gonococcal conjunctivitis ▪ Postnatal transmission in perinatal milk − E.g. Cytomegalovirus, HIV, Hepatitis B Insect/arthropod vectors → Spreads through blood meals of arthropod vectors such as mosquitoes, ticks, and mites → E.g. Malaria transmitted by female Plasmodium malariae and Dengue transmitted by Aedes aegypti Figure 3. Routes of entry and dissemination of microbes[Robbins] PATHOLOGY General Principles of Microbial Pathogenesis PAGE 3 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos III. HOST-PATHOGEN INTERACTIONS − Increases susceptibility to infections caused by After bypassing host tissue barriers, infectious extracellular bacteria and viruses (ex. S. aureus) microorganisms must also evade innate & adaptive ▪ Deficiency of the late MAC components are immunity of the host to proliferate & be transmitted to the associated with Neisseria infections next host. → Defects in neutrophil function The host immune response to microbes can be a major → Defects in TLR signaling pathway cause of tissue injury. → T-cell defects Inherited or acquired defects in innate & adaptive immunity → Immunosuppression in organ transplant or during bone often impair the immune system, rendering the affected marrow engraftment individual susceptible to infections → Lack of splenic function in sickle cell disease increases 📋 risk of infection by encapsulated bacteria (ex. S. A. HOST DEFENSE AGAINST INFECTION (2026) pneumoniae) Factors affecting the outcome of an infection: E. MECHANISMS BY WHICH MICROBES ESTABLISH → Virulence of a microbe INFECTIONS & DAMAGE TISSUES ▪ Degree of pathogenicity of the microbe 1. Infectious agent → contact/enter host cells → directly lead ▪ Ability to invade tissues of the host to cell death or change in cell metabolism and proliferation → Nature of the host’s immune response that can lead to transformation ▪ May either eliminate or exacerbate the infection 2. Infectious agents may: ▪ May be the principle cause of tissue damage → Release toxins that kill cells → Release enzymes that degrade tissue components B. IMMUNE EVASION BY MICROBES → Damage blood vessels → ischemic necrosis Antigenic Variation 3. Infectious agents → elicits host immune response → Inactivating antibodies principal cause of tissue damage (e.g. M. tuberculosis Resisting phagocytosis (e.g. by producing a capsule) granuloma) Suppressing the host’s adaptive immune response → Granulomatous inflammatory reaction Establishing latency during which viruses survive in a silent ▪ Sequesters the TB bacilli & prevents their spread state in infected cells ▪ produces tissue damage (caseation necrosis) & Infecting and disabling or killing immune cells fibrosis C. INJURIOUS EFFECTS OF HOST IMMUNITY 📖 (Robbins) GRANULOMATOUS INFLAMMATION The host immune response to microbes can sometimes be the cause of a tissue injury Granulomatous inflammation → Infection with M. tuberculosis results in a delayed hypersensitivity response and the formation of granulomas, producing tissue damage (caseous necrosis) and fibrosis. T-cell–mediated inflammation → Damage from HBV and HCV infection of hepatocytes. Innate immune inflammation → Pattern recognition receptors bind to pathogen-associated molecular patterns (PAMPS) and to damage-associated molecular patterns (DAMPS) released from damaged host cells, leading to inflammation Figure 4. Macroscopic Pathology of Granulomatous Inflammation. Humoral immunity Section of the lung with multiple coalescent granulomas, which → Poststreptococcal glomerulonephritis can develop after appear on gross examination as fairly defined gray-white areas, infection with S. pyogenes. usually with a central area of necrosis Chronic inflammatory diseases → In the development of inflammatory bowel disease, it enables the entry of both pathogenic and commensal microbes resulting in inflammation. Cancer → Viruses, such as HBV and HCV, and bacteria, such as H. pylori, that are not known to carry or to activate oncogenes are associated with cancers, presumably because these microbes trigger chronic inflammation with subsequent tissue regeneration, which provides fertile ground for the development of cancer 📋 D.INFECTIONS IN PEOPLE WITH IMMUNODEFICIENCIES (2023) Nature of infection depends on which effector mechanisms are impaired Figure 5. Microscopic Pathology of Granulomatous Inflammation. → Genetic immunodeficiencies Central area of necrosis in a caseating granuloma. Composed of a ▪ Antibody deficiencies (X-linked agammaglobulinemia) central area of necrosis with aggregates of epithelioid cells, Langhans giant cells, and lymphocytes. PATHOLOGY General Principles of Microbial Pathogenesis PAGE 4 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos IV. MECHANISMS OF VIRAL AND BACTERIAL INJURY ▪ Produces degradative enzymes and toxic proteins A. MECHANISMS OF VIRAL INJURY ▪ Inducing cell death by activating “death receptors” (in Viruses the TNF receptor family) on the plasma membrane → Size: less than ½ micron, usually much less and triggering the intracellular apoptotic machinery. → Has a central core that contains DNA or RNA ▪ Metabolic derangements such as activation of → Surrounded by a protein known as capsid endoplasmic reticulum stress response → Sometimes has a lipid envelope ▪ Cell lysis or fusion, and formation of viral inclusions → Limited number of genes coding for all the other → Antiviral immune response structures ▪ Cytotoxic T lymphocytes (CTLs) destroy virus-infected cells, thus may also cause tissue injury MECHANISMS OF CELL DAMAGE → Malignant transformation of infected cells Tropism ▪ Oncogenic viruses can stimulate cells growth and → Predilection of viruses to infect certain cells and not survival by different mechanisms such as: others − Expression of virus-encoded oncogenes and viral → Determined by: proteins that inactivate key tumor suppressors ▪ Physical factors o Hepatitis B and C viruses are associated with ▪ Surface proteins the development of hepatocellular carcinoma − Required for viral entry known as viral receptors o Human papillomavirus (HPV) associated with 📖 − Major determinant of tissue tropism is the the development of cervical carcinoma presence of viral receptors on host cells (Robbins) − Other factors that are required for viral replication TYPES OF VIRAL INFECTION 📖 → Physical barriers can contribute to tissue 1. Abortive infection tropism (Robbins) → An infection in which some or all viral components have ▪ Enteroviruses replicate in the intestine in part been synthesized but no infective virus is produced because they can resist inactivation by acids, bile, → Results from: and digestive enzymes ▪ Infection with defective virus ▪ Host cell is nonpermissive ▪ Prevents replication of virus 2. Acute (Transient) Infection → Infection of few days duration 3. Latent infection → An infection that is asymptomatic but is capable of manifesting symptoms under particular circumstances if the virus is activated ▪ Virus latency − Ability of a pathogenic virus to lie dormant within cells − Can be reactivated under particular circumstances 4. Chronic productive/Transient infection → Virus is not cleared but remains in specific cells of the host ▪ Hepatitis B − If Hep B is not eliminated from the body, it will continuously injure the liver causing liver cirrhosis and increase the risk of hepatocellular carcinoma 5. Transforming infection → Malignant or oncogenic transformation of infected cells in which cell proliferation is genetically modified ▪ HPV − Oncogenic virus causing the development of cervical cancer and B cell malignancies MORPHOLOGICAL APPEARANCE OF VIRAL INFECTIONS No characteristic gross or clinical appearance Figure 6. Mechanisms by which viruses cause injury to Microscopically: cells[Robbins] → Cell lysis → Interstitial lymphocytic infiltration Virus gains entry into the host cells by binding to viral → Characteristic viral cytopathic effect such as: receptors ▪ Multinucleation Once viruses are inside host cells, they can damage or kill − Warthin-Finkeldey syncytial giant cell the cells by: o Multinucleated giant cells with eosinophilic → Direct cytopathic effects nuclear & cytoplasmic inclusions ▪ Prevents the synthesis of critical host ▪ Inclusion bodies macromolecules − Intranuclear (DNA) − E.g. Host cell DNA, RNA, or proteins − Intracytoplasmic (RNA) PATHOLOGY General Principles of Microbial Pathogenesis PAGE 5 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos − Negri body → Exotoxin o Eosinophilic inclusion found in pyramidal ▪ proteins secreted by the bacterium which cause neurons of hippocampus and Purkinje cells of cellular injury and disease. cerebellum of patients with rabies ▪ Categories of Exotoxins: o Rabies virus detected within Negri bodies by − Enzymes ultrastructural and immunohistochemical o Has a role in tissue destruction and abscess methods. formation. o Ex. S. aureus produces exfoliative toxin → degrades proteins holding the keratinocytes together → causes epidermis to detach from deeper skin (Staphylococcal Scalded skin syndrome). − Toxins that alter intracellular signaling or regulatory pathways o Most of these are toxins w/c are composed of an active A subunit w/ enzymatic activity & a Figure 7. Morphology of viral infections. Negri body pointed binding B subunit. by arrow (L) Warthin-Finkeldey syncytial giant cell (R)[Lecturer] o ex. Bacillus anthracis; Vibrio cholerae − Neurotoxins B. MECHANISMS OF BACTERIAL INJURY o produced by Clostridium tetani → inhibit Bacteria damage host cell based on its ability to: release of neurotransmitters → paralysis → Adhere to host cell − Superantigens → Invade cells and tissues o produced by S. aureus → cause release of → Deliver toxins high levels of cytokines → capillary leak & shock. BACTERIAL ADHERENCE TO HOST CELLS MORPHOLOGICAL APPEARANCE Bacterial damage to host tissue depends on several factors. Bacteria use various surface structures to attach to Gross findings: redness, swelling, purulent exudate, host cells, these include: necrosis. Adhesins Microscopic findings: primary cellular response is the → Bacterial surface proteins that bind bacteria to host cells predominance of neutrophils. or extracellular matrix. Clinical findings: fever, pain, increased WBC count with → Ex. Streptococcus pyogenes – uses adhesins proteins neutrophilia. F & teichoic acid to bind to fibronectin on the surface of host cells & in the extracellular matrix. Pili → Filamentous structures on the surface of bacteria which act as adhesins. → Ex. E.coli which causes urinary tract infection ▪ Expresses a pilus which binds to a urothelial glycoprotein receptor → causes Urinary tract Infection. ▪ Has a stalk which is composed of repeating subunits ▪ Has tip fibrillum which determines the tissue binding specificity of the bacteria and binds to the D-mannosylated receptors of the bladder epithelium and the globus containing glycosphingolipids of the epithelium. Figure 8. Abscess, a gross finding. Purulent inflammatory tissue buried in a tissue, organ or confined space. Note the BACTERIAL TOXINS presence of redness, swelling, and underneath this Any bacterial substance that contributes to illness can be swollen area is a presence of pus or purulent exudate. considered toxins. [Lecture PPT] → Endotoxins ▪ Components of the gram-negative bacterial cell wall. ▪ A lipopolysaccharide (LPS) found in cell wall of gram-negative bacteria ▪ Stimulates host immune response & injures host cell; − Host immune response to lipid A (responsible for endotoxin activity of LPS) o production of cytokines & chemoattractants by immune cells o enhance T-lymphocyte activation.. − Injurious effect of high levels of endotoxin o induces increased levels of cytokines (TNF, IL-1, IL-12) causing septic shock, disseminated Figure 9. Characteristic microscopic findings are the intravascular coagulation (DIC) & adult presence of neutrophils. Neutrophils are seen within the respiratory distress syndrome. alveoli of patients w/ Pneumococcal pneumonia. [Lecture PPT] PATHOLOGY General Principles of Microbial Pathogenesis PAGE 6 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos V. SPECTRUM OF INFLAMMATORY RESPONSES TO HISTOPATHOLOGY INFECTION Which mononuclear cell predominates within the A. SUPPURATIVE (PURULENT) INFLAMMATION inflammatory lesion depends on the host immune Histologic pattern of tissue reaction to acute tissue response to the organism. damage. Secondary syphilis in the dermis Characteristics: Perivascular inflammatory infiltrate → Increased vascular permeability → Lymphocytes & plasma cells around the blood vessels. → Neutrophilic infiltration Endothelial proliferation Evoked by extracellular gram-positive cocci and → Proliferation of cells lining the blood vessels gram-negative rods. Plasma cells They release chemoattractants which attract neutrophils to → Mononuclear inflammatory cell the site of infection. → Abundant in lesions seen in the primary stage and Dead and dying neutrophils plus liquefactive necrosis form secondary stages of syphilis. pus. Lymphocytes → predominant inflammatory cell in HIV infection & viral infections of the brain. Figure 12. Mononuclear inflammation seen in the dermis of secondary syphilis highlighting the plasma cells and the [Lecture PPT] Figure 10. Process of pus formation. lumen of the blood vessel [Lecture PPT] HISTOPATHOLOGY C. GRANULOMATOUS INFLAMMATION A polymorphonuclear exudate which is composed of Form of mononuclear inflammation usually evoked by neutrophils within the alveoli. infectious agents that resist eradication & capable of Intact alveolar septa. stimulating a strong cell mediated immunity. Ex. Mycobacterium tuberculosis Characterized by aggregates of (+) activated macrophages known as epithelioid cells → Epithelioid cells may form multinucleated giant cells → Multinucleated giant cells seen in TB granuloma are known as Langhans giant cells. TB granuloma may contain a central area called caseous necrosis Figure 11. Suppurative inflammation seen in Pneumococcal pneumonia [Lecture PPT] B. MONONUCLEAR INFLAMMATION Mononuclear inflammation is a pattern of tissue reaction in infection. Common finding in chronic inflammatory processes. Mononuclear inflammatory infiltrates, when they develop acutely are usually a response to: → Viruses → Intracellular bacteria → Intracellular parasites Figure 13. Granulomatous inflammation. Type of mononuclear inflammatory cell predominant in the Arrow: Epithelioid histiocytes. Arrowhead: Langhans giant lesion-depends on the host immune response. cells (multinucleated giant cells composed of epithelioid histiocytes). Asterisk: Caseation necrosis. [Lecture PPT] PATHOLOGY General Principles of Microbial Pathogenesis PAGE 7 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos D. CYTOPATHIC-CYTOPROLIFERATIVE RESPONSE Produced by viruses The lesions are characterized by cell necrosis or cellular proliferation, usually with scanty inflammatory cells. Viral infection can result to: → Inclusion bodies ▪ Characteristic of a viral infection ▪ Some viruses replicate within cells and make viral aggregates → Multinucleated cells ▪ Other viruses induce cells to fuse and form multinucleated cells called polykaryons ▪ Examples: − In viral infections specifically Herpes Zoster viral infection Figure 15. Gas gangrene showing myonecrosis and gas in − Measles virus tissues [Lecture PPT] → Epithelial cell detachment F. CHRONIC INFLAMMATION AND SCARRING ▪ Blisters ▪ May occur due to focal damage in the skin Many infections elicit chronic inflammation. Chronic ▪ Seen in Herpes Zoster infection inflammation may lead to either: → Epithelial cell proliferation → Complete healing → Development of malignant neoplasms → Extensive scarring Example: CHARACTERISTICS OF VIRAL INFECTIONS → Note the calcified eggs of Schistosoma haematobium in Cell necrosis bladder wall Cellular proliferation usually with few inflammatory cells → Extensive scarring manifested as fibrosis of the bladder → Inclusion bodies wall cause dysfunction of the bladder ▪ Visible form of viral aggregates ▪ Example: Herpes Virus → Multinucleated cells ▪ Due to fusion of cells ▪ Example: Measles Virus → Epithelial cell proliferation ▪ Example: Genital warts caused by HPV Figure 16. Calcified eggs of Schistosoma haematobium in the bladder wall. [Green arrow] calcified eggs. [Blue arrow] dense fibrous tissue [Lecture PPT] VI. SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIONS AGENTS Gold standards for the diagnosis of infections: → Culture Figure 14. Herpes Zoster virus blister in mucosa[Lecture PPT] → Biochemical identification E. TISSUE NECROSIS → Serologic identification Causative agents: → Molecular diagnosis → Clostridium perfringens, Corynebacterium diphtheriae Table 2. Other Techniques for Diagnosing Infectious Agents and other organisms that secrete powerful toxins Techniques Infectious agents → Entamoeba histolytica Gram stain Most bacteria → Viruses: Herpes simplex virus, Hepatitis B virus Acid-Fast stain Mycobacteria, Nocardiae Example: → Clostridium perfringens secrete many toxins Silver stain Fungi, Legionellae, ▪ Alpha toxins - most powerful Pneumocystis → Gangrenous necrosis - manifestation of tissue damage Periodic-Acid Schiff Fungi, amebae → Necrotic muscle cells stain ▪ Note that darker color (markedly eosinophilic) of the Mucicarmine Cryptococcus ❗ cell and loss of cross-striations Giemsa Campylobacter, Gas Formations - gas bubbles appearing as clear or Leishmania, malaria empty space between 2 necrotic muscle cells parasites ▪ Distinctive histologic finding in gas gangrene caused Antibody stains All classes by Clostridium perfringens. Culture All classes DNA Probes All classes PATHOLOGY General Principles of Microbial Pathogenesis PAGE 8 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos 4. All of the following infectious agents can be TREPONEMA PALLIDUM transmitted through maternal milk EXCEPT: A. Hepatitis B B. HIV C. Epstein-Barr virus D. Cytomegalovirus 5. Bacteria can damage host cells through: A. Prevention of host cell protein synthesis B. Activation of death receptors C. Production of toxins D. Neoplastic transformation of infected cells 6. Which of the following are local defenses of the gastrointestinal tract against microbial infections? A. Normal flora of the gastrointestinal tract Figure 17. Spirochetes on Warthin Silver Stain (L). Dark B. Peristalsis field microscopy (R). Both are for presumptive diagnosis C. Layer of the mucus on the surface of the mucosa of T. pallidum[Lecture PPT] D. All of the above Treponema pallidum Answer Key: 1B, 2A, 3D, 4C, 5C, 6D → Causative agent of syphilis → Spiral-shaped III. REVIEW QUESTIONS(2022) Warthin-starry stain & Dark field microscopy 1. Which of the following viruses can produce chronic → Used for presumptive diagnosis of T. pallidum productive/persistent infection Fluorescent treponemal antibody test (serologic A. Dengue virus test) B. Herpes Simplex Virus → Used for diagnosis of T. pallidum C. Cytomegalovirus ▪ More sensitive since it detects antibodies to T. D. Hepatitis B Virus pallidum 2. All of the following are mechanisms by which infectious agents can evade local defenses and cause respiratory tract infections ЕХСЕРТ: III. REVIEW QUESTIONS(2021) A. Resistance to killing by phagocytes 1. A 30-year-old female sought consultation because of B. Attachment and local proliferation of microbes multiple vesicles on her external genitalia. The vesicles C. Ciliary paralysis by toxins have an erythematous base. Microscopic examination of D. Uptake through M cells the fluid from the vesicles showed cells with glassy 3. Epstein-Barr virus has a tropism for: intranuclear inclusions. The most probable diagnosis of A. T-cells this patient is: B. B-cells A. Chicken pox C. Plasma cells B. Genital herpes D. Macrophages C. Lymphogranuloma venereum 4. Viruses can cause damage to or kill host cells by: D. Condyloma acuminatum A. Prevention of synthesis of host cell DNA or RNA 2. An autopsy was done on a renal transplant patient B. Production of degradative enzymes who died from a disseminated infection. Pathologic C. Production of toxic proteins examination of the lungs showed an interstitial D. All of the above mononuclear infiltrate, foci of necrosis, and the presence 5. All of the following are mechanisms by which bacteria of markedly enlarged alveolar macrophages and can damage host tissues EXCEPT: epithelial cells of the airways with large "owl's eye" A. Production of toxins nucleus. The most probable causative agent of this B. Production of pro-apoptotic proteins infection is: C. Adherence to host cells A. Cytomegalovirus D. Invasion of host cells B. Epstein-Barr virus C. Varicella zoster virus Answer Key: 1D, 2D, 3B, 4D, 5B D. Mumps virus 3. A child was brought to the OPD because of a reddish-brown rash on his face, trunk, and extremities of several days duration. The rash initially appeared on the face and spread downward to the trunk and extremities. A few days before the rash appeared, he had fever, cough, colds, and red, watery eyes. Sputum examination showed multinucleated giant cells with eosinophilic intranuclear inclusions. These giant cells are called A. Langhans giant cells B. Tzank giant cells C. Reed-sternberg cells D. Warthin-Finkelday cells PATHOLOGY General Principles of Microbial Pathogenesis PAGE 9 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos III. REVIEW QUESTIONS(2024) 7. Epstein-Barr Virus has a tropism for: 1. A nurse sought consultation at the infirmary because A. T cells of a painful, erythematous vesicle on her right thumb. B. B cells Drainage of the fluid from the vesicle was done. C. Plasma cells Microscopic examination of the fluid showed Cowdry D. Macrophages type A inclusions. The nurse most likely has: 8. Choose the best statement that describes an HIV A. Fever blister infection: B. Paronychia A. Acute HIV syndrome seen at the onset of C. Herpetic whitlow candidiasis D. Onychomycosis B. Spread of infection to lymphoid tissues started late in the course of disease C. Establishment of chronic infection occurs during 2. A postmortem exam was done on a liver transplant clinical latency period patient who died from a disseminated infection. D. CD4+ T-cell count can predict progression of Pathologic examination of the colon showed the disease presence of markedly enlarged cells lining the colonic 9. Marks hepatocellular damage in HBV infection glands. These cells each have a purple nuclear inclusion A. Natural Killer Cells surrounded by a clear halo. Extensive areas of the colon B. Plasma Cells showed intestinal necrosis, ulceration and C. CD4+ T-cells pseudomembrane formation. In this case, the most likely D. CD8+ T-cells infectious agent is: A. Herpes Zoster virus Answer Key: 1C, 2D, 3A, 4D, 5D, 6D, 7B, 8D, 9D B. Epstein-Barr virus III. REVIEW QUESTIONS(2025) C. Herpes Simplex virus 1. What type of viral infection is a Human D. Cytomegalovirus papillomavirus? 3. An elementary student was brought to the hospital A. Abortive because of fever and a vesicular rash of several days B. Transforming duration. The rash started on the trunk and then spread C. Chronic productive/persistent outward to the head and the extremities. A biopsy of the D. Latent rash was done. Histologic examination of the rash 2. It is a type of viral infection in which some or all viral showed intraepithelial vesicles with intranuclear components have been synthesized but no infective inclusions in the epithelial cells at the base of the virus is produced. vesicle. The most likely causative agent of this infection A. Abortive infection is: B. Transforming infection A. Varicella Zoster virus C. Chronic productive/persistent infection B. Herpes Simplex Virus Type I D. Latent infection C. Herpes Simplex Virus Type 2 3. This category of exotoxin plays a role in tissue D. Measles Virus destruction and abscess formation 4. A 10-year old child was brought to the ER because of a A. Superantigens rash and high grade fever of a few days duration. Prior to B. Neurotoxins the appearance of the rash, the child had colds and C. Enzymes watery eyes. The blotchy, reddish brown rash initially D. Toxins that alter intracellular signaling or regulatory appeared on the head then spread downward to the trunk pathway and upper extremities. PE revealed a generalized 4. T/F. Suppurative (purulent) inflammation is a reaction maculopapular, erythematous eruption and a palpable to chronic tissue damage cervical lymph node. Histologic exam of the lymph node 5. Common route of transmission used by showed follicular hyperplasia and multinucleated giant Mycobacterium tuberculosis cells that are called: A. Feco-oral A. Reed-Sternberg cells B. Vertical B. Langhans giant cells C. Respiratory C. Touton giant cells D. Urogenital D. Warthin-Finkeldey cells 6. Define invasion 5. In mumps parotitis, the clinical findings of 7. All of the following are characteristics of microbial enlargement and pain of the parotid gland are most likely defenses in the GIT, EXCEPT: due to which of the following microscopic findings? A. Epidermal barrier A. Desquamation of the ductal epithelial cells B. Peristalsis B. Edema C. Normal microbiota C. Inflammation D. None of the above D. All of the above 8. T/F. Horizontal transmission reflects infection from 6. Which of the following viruses can produce chronic mother to fetus or newborn child. productive/persistent infection? 9. Infections due to encapsulated bacteria are due to? A. Dengue virus A. Antibody deficiencies B. Herpes Simplex virus B. Complement proteins C. Cytomegalovirus C. Neutrophil functions D. Hepatitis B virus D. T-cell deficiencies PATHOLOGY General Principles of Microbial Pathogenesis PAGE 10 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos 10. T/F. Inclusion bodies are characteristics of a viral V. REFERENCES infection. 2021, 2022, 2023, 2024, 2025, 2026 Transes 11. Technique for diagnosing Pneumocystis Kumar, V., Abbas A., Aster, J., Deyrup, A., & Das, A.(2023). Robbins & A. Silver stain Kumar: Basic Pathology. (11th ed.). Elsevier, Inc. B. Gram stain C. Mucicarmine D. Acid-fast stain Answer Key: 1B, 2A, 3C, 4F, 5C, 6. Invasion is the process whereby organisms enter host cells and spread in the body, 7A, 8F, 9B, 10T, 11A4 PATHOLOGY General Principles of Microbial Pathogenesis PAGE 11 of 12 PATHOLOGY | LE 2 General Principles of Microbial Pathogenesis | Dr. Arlene Santos VII. APPENDIX Table X. Routes of Microbial Infection[Robbins] Site Major Local Defense/s Basis for Failure of Local Defense Pathogens (Examples) Skin Epidermal barrier Mechanical defects (punctures, burns, S. aureus ulcers) C. albicans P. aeruginosa Needle sticks HIV Hepatitis viruses Arthropods and animals bites Yellow fever Plague Lyme disease Malaria Rabies Direct penetration Schistosoma spp. Gastrointestinal Epithelial barrier Attachment and local proliferation of V. cholerae tract microbes G. duodenalis Attachment and local invasion of microbes Shigella spp. Salmonella spp. Campylobacter spp. Uptake through M cells Poliovirus Shigella spp. Salmonella spp. Acidic secretions Acid resistant cysts and eggs Many protozoa and helminths Peristalsis Obstruction, ileus, postsurgical adhesions Mixed aerobic and anaerobic bacteria (E. coli, Bacteroides spp.) Bile and pancreatic enzymes Resistant microbial external coats Hepatitis A Rotavirus Norovirus Normal protective microbiota Broad-spectrum antibiotic use Clostridioides difficile Respiratory Mucociliary clearance Attachment and local proliferation of Influenza viruses tract microbes Ciliary paralysis by toxins H. influenzae M. pneumoniae B. pertussis Resident alveolar Resistance to killing by phagocytes M. tuberculosis macrophages Urogenital tract Urination Obstruction, microbial attachment, and E. coli local proliferation Normal vaginal microbiota Antibiotic use C. albicans Intact epidermal/epithelial Microbial attachment and local proliferation N. gonorrhoeae barrier Direct infection/local invasion Herpes virus Syphilis Local trauma Various sexually transmitted infections (E.g. Human papillomavirus) PATHOLOGY General Principles of Microbial Pathogenesis PAGE 12 of 12