5. UNDERSTANDING PATHOGENESES OF INFECTIOUS AGENTS 1. Enumerate the categories of Infectious agents and their general features 2. Know the different human barriers against infectious agents 3. To enumerate and understand the Transmission & Dissemination of microbes 4. To know how microbes cause disease A. VIRAL INJURY B. BACTERIAL INJURY C. INJURIOUS EFFECTS OF HOST IMMUNITY COURSE OUTLINE
6. KNOW DISEASES PRODUCED BY SOME OF THE INFECTIOUS AGENTS A. VIRAL INFECTION B. BACTERIAL INFECTION C. PARASITES D. FUNGAL COURSE OUTLINE
9. PRIONS Nucleic acid free Spontaneous mutation or Inherited Mutation in PrP Cause Transmissible Spongiform Encephalitis
10. Pathophysiology Abnormal PrP promotes transformation of normal PrP to abnormal forms EXPLAINING THE INFECTIOUS NATURE OF THESE DISEASE
11. Cause Transmissible Spongiform encephalitis Kuru ( Human Cannibalism ) Bovine Spongiform Encephalitis ( Mad Cow Disease ) Creutzfeldt-Jacob Disease (Spontaneous - Sporadic/ Inherited -Familial) Transmitted From corneal/ organ transplant BSE infected cattle Blood Transfusion Vacuolization of gray matter but no inflammation Clinical presentation
12. Obligate Intracellular 20-300nm May aggregate forming inclusion bodies CMV – large eosinophilic inclusion Nucleic acid core surrounded by capsid Cause Transient illness ( colds, influenza) Not eliminated persist w/in cells Continue to multiply ( HEPATITIS B ) Non-replicating OR Latent ( chickenpox shingles) May transform host cell tumor / cancer cell ( Human papilloma virus ) VIRUSES
13. Mobile genetic elements that infect bacteria Indirectly cause human diseases Encodes virulence factor Exchange of these elements between bacteria Bacteriophages/ plasmids Converts Nonpathogens Pathogens Plasmids/ Transposons Encode antibiotic resistance Eg. Vancomycin – resistant enterococci BACTERIOPHAGE, PLASMIDS, TRANSPOSONS
14. Bacteria Prokaryotes – have cell membrane Gram positive - thick wall surrounding the cell membrane (stain violet ) Gram negative - thin cell wall sandwich between 2 phospholipidbilayer membranes ( stain red ) Lack Nuclei Most synthesize their own DNA/RNA Depend on host for Favorable Environment Intracellular or Extracellular
15. CHLAMYDIA, RICKETTSIAE, MYCOPLASMA Divide by binary fusion Mycoplasma Lack cell wall Mycoplasma are tiniest living organism Airborne transmission Binds surface epithelial cells in airway Chlamydia Lack metabolic capabilities (ATP) Chlamydia & Rickettsia Obligate intracellular organism Mulitply in vacuoles inside the cell
17. HELMINTHS ECTOPARASITES Multicellular organism Life cycle Roundworms- Nematodes ASCARIS FILARIA/ TRICHINELLA Flatworms- Cestodes Tapeworms Flukes – Trematode Schistosoma Arthropods Lice Ticks Bedbugs Live on the skin May be vectors for other pathogens Lyme disease by ticks
18. TRANSMISSION & DISSEMINATION OF MICROBES ROUTES OF ENTRY Spread & Dissemination Release of Microbes Sexually Transmitted Infection
29. Respiratory Pathogens Influenza Virus (+) Hemagglutinin proteins on surface bind sialic acid on epithelium of host engulf by cell virus replicate inside cell (+) Neuramidase Cleaves sialic acid – Allow viral release from cell Lowers the viscosity of the mucus facilitates viral transit Staphyloccoci ( Secondary Infection ) Gain access to host cell after viral infxn cause loss of ciliated epithelium
32. 1. Proliferate Locally at the site Adhere & Proliferate in/on Epithelial Cells HPV , Dematophytes Confined to Lumen of Hallow Viscera Cholera Spread & Dissemination of Microbes
33. Spread & Dissemination of Microbes 2. Penetrate the epithelial barrier Spread via Hematogenous or Lymphatic or Nerve Invasiveness Due to: Motility Secrete Lytic enzymes- Hyaluronidase Degrades extracellular matrix between cells Strep & Staph Initial spread Follow tissue Planes of Least Resistance Regional LN Blood Stream Distant organs Abscess Regional LNs Bacteremia Colonize distant organs
35. Spread & Dissemination of Microbes 3. Viral Propagation A). Propagate from Cell to Cell by replication B). Propagate By Fusion or Transport within Nerves – Rabies, VZV 4. Placental – Fetal Route Bacterial / MycoplasmaPlacentitis Premature delivery Maldevelopment - Rubella Severe in Early trimester Syphilis affect mother late in 2nd Trimester Passage to birth canal- Gonococcal, Chlamydia Maternal Milk – CMV, HBV, HTLV-1
36. Maternal transmission HIV – Major cause of AIDS in children HBV – Can later cause Chronic Hepatitis & Liver Ca Notes:
39. Respiratory Viruses & Bacteria Infectious only when lesions are open to AIRWAYS Fecal-oral Water-borne viruses HAV, HEV, Polio, Rotaviruses Saliva EBV, CMV, Mumps Larval penetration Hookworms, Schistosomiasis Transmission- Person to Person
40. Sexual / Prolonged Intimate or Mucosal Contact Viruses - HPV, HSV, HBV, HIV Bacteria – Syphilis, Gonorrhea, Chlamydia Protozoan – Trichomonas Candida Blood & Blood products/ Needle pricks, etc HBV, HCV, HIV Transmission- Person to Person
41. Direct Contact or Consumption of Animal products Indirectly via an Invertebrate vectors Insects, Ticks, Mites Transmission – Animals to HumanZOONOTIC INFECTIONS
58. VIRULENCE Ability of microbe to infect , colonize, damage host tissues HOST RESISTANCE Ability of host defense mechanisms to eradicate infection – Innate & Adaptive Immune Defenses Outcome of Infection – Determined
59. INNATE DEFENCES Physical Barriers Macrophages NK cells Plasma Proteins – Complement , Cytokines, Acute phase reactants Adaptive Immune response Are stimulated by exposure to microbes Increase in magnitude, speed & effectiveness with successive exposure Mediated by T & B lymphocytes and their products Immune Defenses
60. HOW MICROORGANISMS CAUSE DISEASE DIRECT LY CAUSE CELL DEATH TOXIN / ENZYME RELEASE INDUCE CELLULAR RESPONSES
62. Tissue Tropism Predilection of virus to infect certain cells and not others. Tropism Determined : HOST CELL RECEPTOR- MAJOR DETERMINANT CELLULAR TRANSCRIPTION FACTORS That Recognize Viral Enhancer & Promoter Sequences Allow Viral replication inside the cell ANATOMIC BARRIER LOCAL TEMPERATURE pH HOST DEFENSE
63. 1. Binding to host cell surface proteins Viruses possess specific cell-surface PROTEINS Viruses may use Normal Cellular Receptors of Host Host Proteases are Needed For Binding Host Proteases Cleaves & Activates Influenza Hemagglutinin 2. Translocation into cytosol 3. Replication via virus specific enzymes Viruses Enter Host (+) Hemagglutinin proteins on surface bind sialic acid on epithelium of host engulf by cell virus replicate inside cell (+) Neuramidase– lowers the viscosity of the mucus facilitates viral transit
66. Inducing Host immune response to virus – infected cells Host (CTL) Lymphocytes attack virus-infected cells FAS Ligand on CTL binds FAS receptor in liver cells Eg. Hepatitis B virus Virus Damage Cell involved in Host Antimicrobial Defense Secondary Infections Viral killing of one cell type cause the death of the other cells Motor denervation atrophy of the muscles Antiviral Immune responses
70. Virulence genes Plasmids & Bacteriophage Mobile genetic elements Spread between bacteria Encode virulence factors – Abtic resistance, toxins Quorum sensing Induce expression of virulence factor as their concentration in tissues increases Eg. Staph aureus - abscess Biofilm formation Live in viscous layer of extracellular material Enhance adherance & Inaccesible IV catheters, Artificial joints Bacterial Virulence
81. Exotoxin- Secreted proteins 1. ENZYME - Protease staph. Split epidermis from dermis 2. TOXINS – with A-B toxins A subunit – enzymatic activity INACTIVATES HOST PROTEINS – Cholera/Diptheria DEGRADES HOST PROTEINS - Botulinum B-subunit – binding receptor & delivers A subunit to the cell
82. 3. Neurotoxins – Clostridium botulinum & tetani Inhibit release of neurotransmitters But do not kill neurons 4. Superantigens – staph aureus, strep pyogenes Stimulate very large T-lymphos Lead to very high lymphocyte proliferation and cytokine release Capillary leak shock Exotoxin
86. Remaining inaccessible to host immune response Varying or shedding antigens Resisting innate immune defenses Preventing T-cell activation Impairing effective T-cell antimicrobial responses by specific or non-specific immunosuppression Mechanism of Immune evasion by Microbes
87.
88. Propagate in the lumen of Intestine – Clostridium difficile Gallbladder – Salmonella typi Shed from luminal surface of epithelial cells CMV- urine, milk Polio – stool Infect the keratinized skin – Pox virus Infect Host cell – malaria Encyst in tissues – tapeworms Viral Latency – many viral genes are not expressed Inaccessible to Host Immune
89. Varying antigens / Shedding antigens Low fidelity of Viral RNA polymerases HIV Reassortment of viral genomes Influenza virus Different capsular polysaccharides Strep Pneumoniae Shed antigens w/in minutes of penetrating the skin Preventing recognition by antibodies Schistosomamansoni
90. Resisting Innate Immune Response CAMP Resistance Cationic antimicrobial peptides ( CAMP ) Defensin, Cathelicidins Initial defense against invading microbes Enabling them to avoid killing by pmns & macropahges Carbohydrate Capsule Pneumococcus, Meningococcus, Hemophilus PREVENTI PHAGOCYTOSIS K1 capsule containing sialic acid E. coli- meningitis Sialic acid will not bind C3b ( alternate complement pathway)
91. Covering them with host proteins Staph aureus covered by A molecules that bind Fc portion inhibit Phagocytosis Protease Degrade antibodies Neisseria, Hemophilus, Streptococcus Replicating w/in phagocytic cells Mycobacterium, cryptococcus Resisting Innate Immune Response
92. Some viruses block complement activation HERPESVIRUSES, POXVIRUS Produce homologues of IFN/ IFN receptors INHIBIT THE ACTION OF SECRETED IFN Produce cytokine mimics EBV – homologue of IL 10 ( Bind & Inhibit secreted IFN ) Resisting Innate Immune Response
