Exam 4 New Material PDF

Terminology Host → larger organism supporting pathogenic microorganism growth Infection → microbe growth/multiplication on/within host, may or may not cause disease Infectious disease → health state change due to pathogen presence Pathogen → disease causing organism Pathogenicity → disease-causing a...

Terminology Host → larger organism supporting pathogenic microorganism growth Infection → microbe growth/multiplication on/within host, may or may not cause disease Infectious disease → health state change due to pathogen presence Pathogen → disease causing organism Pathogenicity → disease-causing ability (scale) Virulence → degree of harm caused to host Infectivity → ability to create a discrete point of infection Invasiveness → ability to spread to adjacent tissues Active penetration → lytic substances that alter host tissue Passive penetration → does not relate to pathogen itself (lesions or wounds) Types of Pathogens Extracellular → remain in tissue/fluids without entering host cells Intracellular → grow within host cells, -​ Facultative intracellular pathogen → can grow inside or outside host cells -​ Obligate intracellular pathogen → can grow only inside the host cells Disease Progression Stages 1.​ Incubation period → time between entry and symptom (subjective; pain) development 2.​ Prodromal stage → mild, non-specific symptoms 3.​ Illness period → Most severe stage; peak symptoms 4.​ Convalescence → recovery stage Methods of transmission Airborne → droplets (talking near someone), droplet nuclei (indirect - remain airborne for a while), dust particles Contact → direct (person to person) or indirect (fomites; door handle) Vehicle → surgical materials, food/water, biological materials - indirectly transmit pathogens Vector-borne → arthropods or vertebrates (highly virulent - do not harm vector) Vertical → mother to fetus -​ Pathogen’s virulence may be influenced by its ability to live outside its host -​ Exposure alone is not enough for infection to occur → tropism; determined by specific cell surface receptors Pathogen Survival Mechanisms 1.​ Protection from host defenses 2.​ Nutrient acquisition 3.​ Energy utilization 4.​ Adhesion mechanisms a.​ pili/fimbriae b.​ membrane/capsule materials c.​ Specialized adhesion molecules Host Defense Evasion 1.​ Biofilm formation 2.​ Immune system suppression 3.​ Capsule production → avoid phagocytosis 4.​ Genetic adaptation 5.​ Cell surface protein modification Phage variation → a reversible bacterial process that facilitates rapid genetic changes in response to changing environment Toxins and Damage Toxin → substance that disrupts the normal metabolism of host cells Toxigenicity → pathogen’s ability to produce toxins Intoxications → disease that results from entry of a specific preformed toxin into host Exotoxin → secreted proteins; site of infection into other body tissues or cells -​ Most lethal; encoded by genes on plasmids or prophages -​ Soluble, Heat labile -​ AB toxins → inhibition of protein synthesis → cell death -​ Clathrin dependent -​ pH 5 → dissociates A from B -​ A → catalyze toxicity reaction - NAD+ and EF-2 → Nicotinamide + ADP → inhibit protein synthesis -​ B → binds to host cell receptor → B recycled and dissociation from binding site when returned to surface -​ Membrane-destabilizing toxins → change osmolarity by forming pores on membrane -​ Superantigens → overstimulation of adaptive immune system -​ T cell overexpression (CD4 - MHC II)→ cytokines → pro-inflammation -​ Local effects Endotoxin -​ Heat stable -​ O-antigen in LPS of gram-negative bacteria - bound to bacteria and released when microorganism lyses -​ System effects → effect entire body rather than a single tissue or organ Mycotoxin -​ Produced by fungi -​ Common food crop contaminants -​ Cause liver disease and cancer Infectious dose 50 (ID50) → amount needed to infect 50% of hosts Lethal dose 50 (LD50) → amount needed to kill 50% of hosts Identification Methods Culture based methods -​ Selective → antibiotic plate supplemented for a specific type of bacteria -​ differential media → multiple organisms but able to differentiate between them -​ Hemolysis → patterns on blood agar -​ Gamma → no change -​ Alpha → partial breakdown -​ Beta → complete breakdown Immunomagnetic Based Technology -​ Antibody-coated magnetic particles to isolate specific microbes -​ Enabling pure culture isolation from mixed populations → only those with antibody attachment will be isolated with magnet - the rest is washed -​ Reduces contamination and increases accuracy Rapid identification systems -​ API 20E system → 20 biochemical tests -​ Identification code → automated systems (database for identification) Fungi identification → different from bacteria -​ Cultures → recover fungus from specimen -​ Evaluate growth rate and appearance on one selective and non-selective agar medium -​ Colonial morphology, color and dimorphism examined Microscopy -​ Wet Mount, heat or chemical fixation -​ Gram staining - peptidoglycan identification for appropriate antibiotic therapy -​ Fluorescence microscopy → visualization with fluorochrome staining Immunological Methods Immunofluorescence -​ Direct → uses fluorochrome-labeled antibodies directly on specimen - presence or absence of pathogen -​ Indirect → uses patient serum followed by labeled secondary antibodies - presence or absence of antibodies (secondary antibodies bind to) Molecular detection -​ PCR → DNA amplification -​ Real-time PCR → quantitative analysis -​ Ribotyping → bacterial identification using 16s rRNA -​ DNA fingerprinting for strain differentiation Serological Testing Serotyping → used to differentiate between strains (serotypes) that have different antigenic compositions of a structure or product Agglutination Test -​ Blood typing and syphilis detection -​ Viral hemagglutination assays -​ Blood + measles virus → hemagglutination -​ Measles virus + antibodies from patient serum + blood → virus is neutralized due to antibody binding → inhibition of hemagglutination -​ Complement fixation tests for antibody detection Elisa -​ Direct (antigen trapped between two antibodies)→ detect protein antigens + protein enzyme = color change to yellow -​ Indirect (HIV testing) → detect antibodies → comparison between patient and control → indicator visualizes if there are antibodies attached to antigen = change color for positive results -​ Visualization → chromogen Lateral Flow assays → filter paper contains antigen -​ Test line → antibodies bind to antigen -​ Control line → excess antibody without antigen Western blot → protein analysis → lyme disease -​ Protein separation by electrophoresis -​ Primary and secondary antibodies → visualize amount of protein Flow cytometry → cell population → HIV monitoring (CD4+ and CD8+) -​ Fluorescently labeled stained cells + laser light = cell size and quantity Enveloped viruses can integrate their genome into host’s DNA (i.e. HIV) Non-enveloped - enter, replicate and lyse (i.e. poliovirus) Airborne Transmission → spread through respiratory droplets - cough, sneeze or speaking Chickenpox (varicella) → highly infectious DNA virus (uses host machinery to replicate viral genome) -​ Early genes → replication of viral genome -​ Late genes → transcription for assembly proteins - maturation -​ Preventable or shortening of illness from vaccine -​ Previous contraction = antibodies Shingles (herpes zoster) → reactivation of dormant chickenpox virus in cranial nerves -​ Vaccine available for individuals over 50 years -​ Immunocompromised person → virus migrates down sensory nerves → visual and auditory impairment COVID-19 → +RNA virus (direct translation of proteins) -​ Viral response phase → flu-like symptoms -​ Inflammatory response phase (cytokine storm) → shortness of breath, poor gas exchange -​ Mutations increase transmission not virulence -​ Higher risk for elderly, overweight and type II diabetics Influenza (A, B and C) → -RNA (replication needed for template mRNA translation) - lytic cycle by release of virions from infected cells -​ Viral particles → respiratory epithelium → nucleocapsid released into cytosol -​ Antigenic drift → small mutations -​ Antigenic shift → major changes Measles (Membrane - envelope) → -RNA *enveloped* -​ Red lesions (Koplik’s spots) -​ Progressive denaturation of CNS -​ Symptoms → fever, whooping cough, headache and conjunctivitis -​ MMR vaccine only - NO treatment Mumps (mumps virus - membrane) → -RNA *enveloped* -​ Transmission through saliva and respiratory droplets → swelling and tenderness of salivary glands (weeks after infection) -​ No cure just control symptoms -​ Pleomorphic (shape morphing) -​ Transmission through saliva and respiratory droplets Rubella (german measles) - enveloped +RNA -​ Red spot rash appears as immunity develops -​ Congenital rubella syndrome → vertical transmission → fetal death -​ MMR vaccine Smallpox (orthopox virus) → dsDNA -​ Malaise, body aches, high fever -​ Small red bumps filled with fluid -​ eradicated through vaccination Arthropod-borne Disease → fevers with/without rash, encephalitis and hemorrhagic fevers Dengue Fever → enveloped +RNA -​ 4 serotypes -​ Antibody-dependent enhancement (previous infection with different DENV) -​ Opsonize virus and hijack immune system West Nile Virus (flavivirus) → +RNA -​ Encephalitis -​ Mosquitoes that fed in infected birds -​ No treatment or vaccine Zika → enveloped +RNA -​ Can be transmitted person to person through bodily fluids (breastmilk or semen) -​ Birth Defects → microcephaly Direct Contact Transmission AIDS by HIV → Retrovirus (reverse transcriptase) HIV → bodily fluid transmission (blood, semen, vaginal secretions or breastmilk) -​ Viral protein attachment (gp120) → facilitates attachment to host cells -​ Macrophage infection → CCR5 → cross BBB -​ T-cell infection → CXCR-4 -​ Can integrate into host cell DNA and remain latent (asymptomatic) -​ Medication → suppress transcription of viral genome -​ Replication occurs in lymphoid tissue -​ T-helper cell reduction → opportunistic infections begin → CNS disease Cytomegalovirus (CMV) → enveloped dsDNA -​ Herpesviridae family -​ Can infect any cell of the body → cell swelling Genital Herpes → enveloped dsDNA -​ Active and latent disease with reactivations Mononucleosis (Epstein-Barr virus) → enveloped dsDNA -​ Mature virion → linear -​ Latent form → circular -​ Infect B cells -​ symptomatic/supportive therapy Hepatitis → infection and inflammation of liver  -​ A-E → fecal oral transmission -​ HEP B → enveloped dsDNA -​ Dane particle → mature virion Food and Waterborne Diseases Poliomyelitis → +RNA (enterovirus) -​ Infantile paralysis -​ nearly eradicated by vaccination -​ Multiplies in throat and small intestine -​ When persistent → enters CNS → paralytic polio Viral Gastroenteritis → food poisoning -​ Stomach and intestinal inflammation -​ F-O transmission -​ Norovirus -​ Rotavirus - vaccination Zoonotic Diseases Ebola → -RNA -​ Transmission through bodily fluids -​ Vector - bats -​ Viral hemorrhagic fever - vascular damage - blood blisters -​ No standard treatment - vaccination Rabies → -RNA -​ Neurotropic virus -​ Enters NS through acetylcholine receptors - clathrin dependent -​ Utilizes host ribosomes to translate viral proteins → negri bodies → spinal cord -​ Progressive encephalitis Diagnosis → Immunofluorescent antibody, serology for antibody or PCR Treatment → pre and post vaccination