Transcript for:
Overview of Skin and Infectious Diseases

Acne: not contagious, overgrowth, overproduction of sebum stimulated by hormones CC: Propionibacterium acnes (NF in small amounts) VF: Lipase Treatment: cleansing, topical antibiotics sometimes Boil: painful, purulent lesions (common for MRSA) CC: Staphylococcus aureus, VF: enzymes & toxins Dx: appearance & gram stain, Tx: topical/oral antibio. *MRSA: S.aureus gained meth. resist. via plasmid - use VANC!! Impetigo: scabs are picked, land, and spread CC: S. aureus or Streptococcus Pyogenes (GAS) VF: exoenzymes - break down skin * not huge bloodstream concern b/c superficial Dx: Gram stain, Tx: topical antibiotics Abscess: purulent, swelling, (result from boil/cellulitis) CC: S.aureus (~MRSA), GAS, VRE (vanc resistant) VF: exoenzymes & toxins, PVL toxin, Hemolysin (VRE) - kills WBCs, Dx: gram stain (VRE cocci short) Tx: antibiotics + open & drain Cellulitis: tight, hot, tender, pain, lymphangitis(track) CC: S.aureus, GAS, Pasteurella multocida, Bartonella henselae(rods) (ellas come from pet NF) VF: deeper tissue enzymes & toxins (MRSA&blood risk) Dx: Gram stain, Tx: antibiotics (oral or IV) SSSS: skin peeling, babies, bullous lesions CC: S.aureus, spread by adults who have S.a. in NF VF: exfoliative toxins (ET-A, ET-B) cause detachment within keratinized layers Tx: handwashing & antibiotics to prevent 2nd infect. Scarlet Fever: strawberry, pastia lines (creases), rash missing @mouth, rash - tiny red bumps CC: GAS (starts as strep throat) - your GAS must be able to produce SpeA toxin to cause scarlet fever VF: SpeA (erythrogenic toxin causes red. + inflam.) Dx: culture/gram stain, Tx: antibiotics Chickenpox: macule-papule-vesicle-scab (POX) Spread by aerosol (respiratory) or fluid (from spots) Shingles: virus enters nerves & becomes latent, banded, crust, more spots = higher chance of shingles CC: Varicella Zoster (VZV) > herpes virus VF: latency, Dx: appearance, Tx: vaccine Reye’s Syndrome: swelling in liver and brain Viral infection + aspirin = Reye’s, rare but serious S&S: encephalopathy, confusion, seizures, hypoglyc. Fifth Disease: slap cheek, lacy, low fever CC: Parvovirus B19, no VF, Dx: appearance, No Tx * concern for 5th & rubella is if spread to pregnant mother can & passed across placenta can cause birth defects or death Rubella: macular & mild, respiratory or urine, fever Teratogenic virus: transmitted in utero, persistent! CC: Rubella virus (Rubivirus, RNA), no VF, Dx: appearance, no treatment, covered in MMR vaccine Roseola: high fever, blanching, aerosol spread CC: Human Herpesvirus 6&7, no VF, Dx: fever & rash Measles: rubeola, dry cough, conjunctivitis, koplik’s spots, angry red rash, highly aerosol contagious CC: Measles Virus (helical RNA, Morbilliviridae) VF: cause syncytia, high risk of 2nd infection, treat symptoms, ~Vitamin A injections, MMR vaccine Hand, Foot, Mouth: blister rash, nail loss CC: Coxsackievirus A16, VF: viral, Tx: OTC Warts: benign squamous epithelial growths, plantar, seed, genital, contagious (not highly) CC: human papillomavirus (HPV 1,2,3,4) VF: cause unregulated cell growth Dx: appearance, Tx: cosmetic removal, biopsy? Molluscum contagiosum: pearly, plug, cheesy, waxy, can spread into “crops” CC: MCV (poxvirus family) VF: same as warts Tx: cosmetic removal *deeper than warts Ringworm (cutaneous mycoses (fungal)): scaly patches, circle, many diff. types CC: Dermatophytes - multiple funguses VF: eukaryotic, skin breakdown enzymes Dx: appearance or KOH test (will be mixed bag), Tx: antifungal antibiotic, hygiene Tinea Versicolor: discolored patches CC: Malassezia furfur (fungal) VF: eukaryotic, Dx: appearance, KOH test (will be one organism, not mixed bag) Tx: topical antifungals Leishmaniasis: eukaryotic w/ nucleus Cutaneous: infects capillaries-open,wet sore Mucocutaneous: nasal systems, oral/pharyngeal symptoms, can progress to ulcerative destruction of naso-oropharyngeal mucosa (perforation of the nasal septum) Systemic (visceral): affects organs & marrow, fever, weight loss, pancytopenia, discoloration CC: [Parasite] Leishmania spp. (L.donovani for systemic/visceral) VF: spread by sand flies, hides in host immune cells, endemic in tropical/equatorial Dx: culturing for parasite, Tx: antiparasitics Gas Gangrene: necrosis, anaerobic, crunchy “Anaerobic cellulitis” - so deep it has no O2 CC: Clostridium perfringens (rods) VF: multiple toxins, anaerobic growth, spores (post surgery) Dx: smell, appearance, gram stain Tx: aggressive antibiotics & HBO2 Anthrax: spores, black eschar, animal hide Lesion that is black w raised red outer ring Can be from contact with and animal hide CC: bacillus anthracis, G+ spore former & toxin producer, big risk is entering blood VF: glutamate capsule & 3-part toxin Dx: gram stain (G+ bamboo rods +/- spores) and medusa head colonies Tx: immediate antibiotics (PA-EF-LF) protective antigen: binder unit latches onto cell edema factor: cells push nutrients & fluid out & fluid builds up in outer tissue (edema) lethal factor: kills cells, shuts down protein synthesis & cell signaling = cell death (black) Styes: skin/eye, sebaceous/lacrimal glands Painful inflammation, purulent CC: S.aureus, VF: enzymes, Dx: gram stain Tx: antibiotics (often erythromycin), ~drainage Conjunctivitis: pink-eye, discharge, ~bloodshot Bacterial: milky, yellow discharge Viral: clear, liquid discharge CC: S.aureus, GAS, babies & adults = N.gonorrhoeae, Chlamydias (Gram N/A) Viral causes also, including adenovirus (newborn) Dx: appearance & discharge, gram stain Tx: varies based on type Keratitis: cornea, coldsore, gritty, dendrite Clear, tear-like discharge, pain & light sensitive CC: herpes simplex virus virus (type 1) VF: viral, latency, spread, Dx: appearance & discharge type (clear = viral), Tx: aggressive corticosteroids + antivirals Trachoma: not in US, scarring, scraping, blind Spread by fomites (towel, bucket of water) CC: Chlamydia trachomatis (type A,B,C) VF: intracellular bacterium, evades immune Dx: lash position, Tx: antibiotics Meningitis Overview: inflamation of meninges Headache, painful, stiff neck, ^# WBC in CSF Petechiae, intracranial pressure, necrosis Lumbar puncture = CSF, hard diagnoses infants Treatment: 3rd gen cephs! (for PPG), steroids - Ceftriaxone (Rocephin), Cefotaxime (Claforan) Sequelae: brain damage post meng - cognitive dysfunction, hearing loss, seizures, death Neisseria Meningitidis: letters, LPS, bacterial Most dangerous, kidney bean diplococci, VF: pili, capsule, LPS (leads to sepsis and DIC) Sudden high fever & flu-like Meningococcemia: systemic N.meng of blood = LPS, fever, rash, joint pain, diffuse intravascular coagulation (DIC), Waterhouse Friderichsen Syndrome = N.meng of adrenal glands Capsular type B = worst! Menactra MCV4 doesn't cover, Trumenba for type B Ceftriaxone for exposed Streptococcus pneumoniae: most common Bacterial lancet shaped diplococci Community-acquired, pneumonia, OM, sinusitis VF: capsule, NO LPS, no rash, Stereotype 3 is worse, developing resist to 3rd gen cephs Vaccine: Prevnar/Pneumovax, NUMBERS Haemophilus Influenzae: ear infection Bacterial tiny pleomorphic rods, VF: capsule Has LPS, not enough for rash, opportunistic(NF) Capsular type B was main but now HiB (vax) Listeria monocytogenes: food, diarrhea Affect elderly, immunocompromised, infants VF: invasion, listeriolysin (LLO), motility Enters host cells in gut, LLO to break & duplic. Neonatal Bacterial Meningitis: rapid deterior. Streptococcus agalactiae (GBS) - vaginal NF RDS, puerperal sepsis (childbed fever) in mom (purple spotted rash), skipped neo. visits Escherichia coli - fecal flora (ExPEC or NMEC) “KI” capsule type, endotoxin Cryptococcus neoformans: fungal meningitis S/S gradual onset, birds, decayed plant matter VF: large capsule, capsule stain on india ink Slow, chronic meng., respiratory, gummy rash Coccidioides Immitis: fungus > 2ndary meng. Pulmonary infection, soil, San Joaquin Valley VF: none (fungal), bag of coins, blocky spores Viral meningitis: common in kids Aseptic, rarely fatal w/ good immune Respiratory, mumps, EBV, HSV, VZV CC: enteroviruses = GI viruses VF: none (virus) CC: enterovirus-D68 = acute flaccid myelitis Naegleria fowleri: meningoenceph. Brain eating amoeba, water, head ache, fever, vomiting, confusion, coma, stupor Olfactory nerve > BBB > destroy frontal lobe, massive swelling, no cure or known treatments Generalized Acute Encephalitis: behavior Viral infections, VF: viral replication & immune response - immune influx, inclusions, no bacteria, NOT contagious Fever, behavior change, vision loss, confusion, seizures, paralysis, stiff neck Mild S/S: NSS fever, skin rash, swollen LN No symptoms in most, Tx: aggressive antivirals & treat symptoms immediately Arbovirus family: insects, mosquitoes WNV: most common, little or no flu-like S/S SLE: mosquitoes ^, midwest & south LaCrosse/Cali. Enceph: children, non-fatal Jamestown Canyon (JCV): deer/moose Powassan Enceph.: ticks/rodents Western & Eastern Equine: (WEE/EEE) = large hoofed animals (horse, cattle, ranches) *Tx: unresponsive to acyclovir but in case it is actually HSV, treat symptoms: monitor fever, reduce pain, identify source Other virus families: (no bite, think herpes) Herpesvirus: severe, aggressive enceph. Tx: acyclovir, cigarette burn baby possible JC Virus: “Progressive multifocal leuko- encephalopathy (PML), HIV/AIDS, twitching Demyelinizes cerebrum, bad if immunocomp Measles: two different forms PIE (post infection/immunization enceph): part of immune response, not virus related SSPE (subacute sclerosing panencephalitis): years post-measles from persistent virus Toxoplasma gondii: subacute encephalitis Flagellated parasite, severe in fetus or immunocompromised, CAT FECES, pregnant VF: eukaryotic. Teratogenic, birth defects Rabies: slow, progressive, zoonotic, fatal “Furious”: agitation, disorientation, seizures, twitching, foaming at mouth, spasms in neck and pharyngeal muscles = hydrophobia “Dumb”: paralyzed, disorientation, stupor CC: rabies virus (rhabdoviridae) VF: viral, enveloped, Tx: immediately administer antibodies then boost w vaccine NON-cellular neuro infectious agents: Prions: converting proteins, normal = PrPc, mutant = PrPp > refold normal into pathologic Bad prion enters, turns good to bad, buildup & deposits, cells die, holes in tissue (spongi.) Prion diseases: BSE (mad cow), Creutzfeldt-Jakob disease, Kuru, Scrapie Prion TSE’s: transmissible spongiform encephalopathies Neurodivergent, apoptosis, holes in brain Human TSE’s: mad cow - consumed/ exogenous prion, CJD - mutated normal prion VF: convert normal to PrPp Tetanus: lockjaw, toxin based, puncture Rigid paralysis disease: extreme clenching & contraction (Risus Sardonicus) CC: Clostridium tetani, spore forming, toxin gets to neurotract, VF: powerful neurotoxin called tetanospasmin, targets inhibitory motor neurons, blocks inhibition of muscle contraction, Dx: symptoms & lollipop Tx: antitoxin, then antibiotics, “tetanus shots”, vaccine (DaPT) & 10 year booster Botulism: flaccid paralysis, poorly preserved foods, double vision, difficulty swallowing, dizziness, descending (flaccid) muscular paralysis, respiratory compromise Food-borne botulism: ingestion of preformed toxin Infant botulism (floppy baby syndrome): entrance of botulinum toxin into blood, honey as major source of spores CC: Clostridium botulinum, spore forming anaerobe, VF: exotoxin that attacks acetylcholine neurotransmitter Dx: gram stain & appearance, Guillain- Barre, Tx: antitoxin, monitor for respiratory distress Urinary Tract Infections: *if virus, NOT UTI Bacterial VF: urease (breakdown urea into nitrites (G-) & CO2), flagella, pili Urinalysis: WBC, bacteria epithelial cells, nitrites, leukocyte esterase (= had WBC) - all bad to have Dx: colony counts in clean-catch sample (mid-flow) Start as urethritis: painful, burning urination Cystitis: bacteria in bladder - pubic pain, frequent urge to urinate, burning pain, cloudy urine, red/pink/orange, fever, nausea Pyelonephritis: kidneys - back pain @CVA E.coli UTI: most common, fecal strains, anal sex S/S: dysuria, increased frequency & urgency Reinfection/persistent UTI possible CC: Uropathogenic E.coli (UPEC) - bacillus (rods) VF: P-pili, flagella, Tx: Bactrim (can't use in pregnant women, & resistance is growing), Ciprofloxacin Proteus species UTI: kidney stone, catheter, sex CC: Proteus mirabilis or Proteus vulgaris VF: highly motile, potent urease, Dx: indole test to determine strain - P.m. = no ring, P.v. = red ring Tx P.m.: broad spec b-lactams or cephs, removal of stones Tx P.v.: resistant to b-lactams & cephs, use imipenem, 4th gen cephs, bactrim, or AGs Staphylococcus saprophyticus UTI: Frequently seen in younger (12-25) sex active females CC: Staphylococcus saprophyticus, VF: none known Dx: novobiocin, S.sapro = resistant to novo Tx: 1st/3rd gen cephs, Vanc if necessary (not first option), gaining resistance to Bactrim Vaginitis: itching, burning, white discharge CC: Candida albicans (fungus) - opportunistic Dimorphic (yeast & hyphae forms) yeast = budding fungus Dx: Sabouraud-Dextrose agar, egg-shaped, germ tubes Tx: Antifungal (fluconazole), (C.a. also = oral thrush, diaper rash) Vaginosis = overgrowth: CC: Gardnerella vaginalis - itching, fishy, gray/yellow VF: none, Dx: clue cells, Tx: broad spec antiribosomals (metronidazole) Multiple sex partners & frequent washing CC: Trichomonas vaginalis - green/white, frothy, foul smelling, strawberry cervix - can be asymptomatic VF: none, Dx: parasite w/ one eyespot & whiskers Tx: Flagyl (trichomonas is parasite), metronidazole ~ tight clothing Prostatitis: pain in pelvis/low back/genitals, hematuria, painful ejaculation, frequent urination, acute or chronic CC: unknown likely GI flora into urinary tract Homosexual men, anal sex, diapers for elderly Low testosterone, prostate damage/carcinoma Tx: mixed causes so very broad spec antibiotics for longer courses (often tetracycline 21-28 days) Gonorrhea: urethritis, purulent discharge, mucopurulent or bloody discharge, PID CC: Neisseria gonorrhoeae (diplococci), VF: pili w/ antigenic variation - always changing so not self limiting Dx: grows on Thayer-Martin, uses glucose only G=G *Ophthalmia Neonatorum: newborn eyes from birth *Can move to joints and cause arthritis Tx: 3rd gen ceph (ceftriaxone) NGU-2: burning but no gon. or chlamydia (mimics Chl.) CC: Mycoplasma species - Ureaplasma urealyticum VF: urease enzyme, Dx: NO CELL WALL Tx: erythromycin & tetracycline, azithromycin Chlamydia: most common, asymptomatic Urethra inflammation, watery discharge, epididymitis Watery discharge, cervicitis, salpingitis, can lead PID CC: Chlamydia trachomatis, stereotypes D-K (genital) VF: intracellular, Dx: bi-phasic life cycle = infectious form (elementary body evade), replication form (reticulate body replicate) *Stereotypes A,B,C = pinkeye, common in infants Lymphogranuloma venereum: L1, L2, L3 - ulcer on genitals > groin lymph nodes > buboes, painful, may rupture - mostly homosexual men Tx: Tetracycline & erythromycin (antiribosomals), azithromycin, doxycycline Syphilis: enters thru small abrasions & replicates CC: Treponema pallidum (spirochete) - no gram type VF: very smooth - antibodies cant stick (Teflon pathogen), motile, Dx: darkfield microscopy - appears white, won't gram stain so Giesma stain - pale pink Tx: penicillin (long-acting doses - Benzathine) Primary: small, hard chancre - painless, serous exudate – highly infectious *congenital syphilis starts as 2nd or 3rd Secondary: Spreading skin rash (palms & soles), mucous patches in/around mouth, condyloma lata (warts near chancre) Tertiary: due to immune response, gummas, necrotic soft palate, CNS involvement (dementia, ataxia, etc) Genital Herpes: malaise, anorexia, recurrent episodes CC: Herpes Simplex Virus (mostly HSV type 2) VF: viral, can be latent, can be transferred between oral and genital, Tx: Acyclovir or Valacyclovir (Valtrex) Genital Warts: most common, but not reported CC: Human papillomavirus (HPV) - papovaviridae family, icosahedral non enveloped, circular dsDNA VF: viral, HPV 6,11 = warts, HPV 16,18 = carcinoma, HPV 1-4 = skin and plantar warts, best prevention is to avoid contact, Vaccine: Gardasil = 6,11,16,18 No Tx, just cosmetic removal Oral Infections: Gingivitis: swelling, loss of color, redness, bleeding Necrotizing Ulcerative Gingivitis (NUG): severe pain, bleeding, necrosis (no oral hygiene) CC: Streptococcus mutans, VF: biofilms * trench mouth Mumps: fever, nasal discharge, muscle pain, malaise, AEROSOL risk, cheek swelling (parotitis) Virus multiplication in salivary glands - can spread to other organs, swelling of testes, ovaries, breasts CC: Mumps virus (orthomyxoviridae family) VF: forms syncytia to allow cell-cell spread Self limiting w/ normal tissue & hormone levels MMR vaccine, but can still get it (85/15) Gastritis: burning abdomen pain Gastric Ulcers: lesions in stomach mucosa (bloody stools, vomiting coffee grounds, upper GI bleed Can cause Gastric carcinoma from cell damage/repair CC: Helicobacter pylori (spirochete) VF: urease enzyme – urea + urease enzyme = ammonia + CO2, changes pH allowing survival Dx: ammonia breath test (urease detection) Tx: AMOX/TET/Flagyl/Clarithromycin + proton pump Intestinal Mucosa: absorb water & nutrients for body Enterocytes: cells w/villi, primary cells for adsorption Crypt cells: secrete hormones and Cl- for digestion, produce new enterocytes (renewal & maintenance) Goblet cells: secrete mucus M-cells & Peyer’s patches: intestinal immune lineages & outposts for immune cells Intestinal Mucosa: absorb water & nutrients for body Enterocytes: cells w/villi, primary cells for adsorption Crypt cells: secrete hormones and Cl- for digestion, produce new enterocytes (renewal & maintenance) Goblet cells: secrete mucus M-cells & Peyer’s patches: intestinal immune lineages & outposts for immune cells Foodborne Infections: live cells delivered by food, multiply in host once consumed, longer duration Food intoxications (food poisoning): food looks, tastes, smells normal, NOT from spoiled food Contains organism-produced molecules, but may not have live organisms, produced toxins, shorter duration Acute Diarrhea: 3+ loose stools in one day Bacterial, viral, & parasitic causes Characterize by: 1) type/description, 2) downstream consequences, most are self limiting w/ no Tx Rapid dehydration G(-) > multiple organ failure Reiter’s syndrome: urethritis, conjunctivitis, arthritis (can’t see/pee/climb tree) - from LPS Guillain-Barre syndrome: peripheral neuropathy (paralysis) - from LPS Typhoid fever: salmonella complication (S.typhi) Invasion of spleen and/or liver where large numbers of bacteria get to bloodstream – high fever, chills, abdominal rash, neurological symptoms Treat systemic = Ampicillin or Bactrim Salmonella: 2nd common, fecal-oral spread Linked to dairy or raw poultry products (milk, eggs, meat) CC: Salmonella spp. VF: invasive – enters/hides in cells after “membrane ruffling”, can enter bloodstream to cause shock, can invade bones (osteomyelitis) or liver, mostly self-limiting, hydrate/fluid replacement Shigella: highly contagious, DYSENTERY CC: Shigella sonnei, S.flexneri, Shigella dysenteriae VF: Shiga toxin: inhibits protein synthesis (cell death) VF: Invasive: replicates inside intestinal cells Tx: Ampicillin, Bactrim Azithro Complication: hemolytic uremic syndrome: Enterohemorrhagic (EHEC): O157:H7, O104:H4 STEC Complication: hemolytic uremic syndrome ^ Undercooked meat, spinach, apple juice, lettuce, etc VF: shiga toxin & effacing lesions Dx: can't use sorbitol for metabolism, grows on lactose Tx: supportive care & rehydrate, no antibiotics! Enteroinvasive (EIEC): significant fever Invades gut mucosa > cell destruction > diarrhea VF: I = invasive, Dx: grows on sorbitol, not lactose Self-limiting, fecal-oral spread, supportive treatment Enterotoxigenic (ETEC): travelers, water/ice Watery diarrhea, fever, nausea, vomiting Transmitted by fomites - dirty glasses, water, ice VF: 2 toxins - Heat stable toxin (ST) & heat labile toxin (LT), self-limiting Enteropathogenic (EPEC): infants & toddlers VF: causes intestinal cell membrane rearrangements by depolymerizing actin into “pedestal formations” Monitor patient, especially if young, rehydrate & supportive care Enteroaggregative (EAEC): chronic watery diarrhea in children & AIDS patients, associated w/ malnutrition VF: biofilm/clustering attachment to cell surface Supportive therapies & look for underlying issues Campylobacter jejuni: watery, yellow-green stools Most common bacterial diarrhea, symptoms can subside & recur, cooked poultry products VF: 2 toxins = enterotoxin (cAMP) & cytotoxin (PS) Microaerophilic spirochete organism, can cause Guillain-Barre syndrome from LPS, usually self-limiting Tx: rehydrate & electrolytes, erythromycin for severe Clostridium difficile: NF, nosocomial diarrhea VF: 2 enterotoxins (toxins A and B, not A-B!) Toxins > apoptosis/necrosis of tissues, sloughing Complication: pseudomembranous colitis VF: produce spores, Tx: discontinue ABX, use Flagyl, replacement therapy (yeasts/yogurt, FFRT, probiotics) Vibrio cholerae: comma-shaped bacterium Lives in water (halophilic > salt), replicates in humans Transmission = fecal-oral via water (fish, drinking, etc) Debilitating PROFUSE watery (Rice water) diarrhea VF: Cholera toxin – classic A/B cAMP regulator DEHYDRATION > MOF from lack of fluids!! Tx: REHYDRATE, Trimethoprim or ribosomal inhibitors for children, clean water supply > Vibrio parahaemolyticus: extreme watery diarrhea, linked to shellfish, invasive w low power enterotoxin Bacterial Food Poisoning: gut symptoms caused by preformed toxin, if symptoms are violent w/ very short incubation period intoxication rather than infection Staphylococcus aureus Exotoxin: unrefrigerated white foods (mayo, cream, meat, X salad) VF: Staph enterotoxin A (SEA) (can’t taste or smell toxin) Cramping, nausea, vomiting, diarrhea, rapid recovery Bacillus cereus: fried rice, cookmats, reheated foods Two exotoxins: cause diarrheal-type or emetic disease Parasitic Diarrhea: Cryptosporidium parvum: waterborne (fecal-oral) Ruminant wastes (sheep, cows, goats), also snakes and geese, in water – causes intense diarrhea Headache, sweating, vomiting, severe abdominal pain Immunocompetent: mild, self-limiting Immunocompromised: 50+ stools/day, extreme dehydration, nausea, vomiting, fatigue - may last years Dx: stains as “Acid-fast” & find oocysts in samples Giardia lamblia: flatulence, greasy/malodorous stools Fecal-oral transmission via water, backpackers, boy scout, beaver fever, parasite w/ 2 eyespots (monkey) + flagella, Tx: flagyl Entamoeba histolytica: Bloody diarrhea, weight loss “Non-bacillary dysentery”, hemorrhage, perforation, appendicitis, leaves erosive ulcerations VF: secretes enzymes that dissolve tissues Can spread from intestines to liver/spleen - Amoebic hepatitis (chocolate pus), fecal-oral transmission of cysts (found in pt samples) Tx: flagyl Cyclosporiasis: watery diarrhea, cramping, bloating Fresh produce, & water w fecal contamination CC: Cyclospora cayetanensis (protozoan) VF: parasitic, invasive; Dx: O&P (acid-fast staining) Tx: Bactrim Rotavirus: watery diarrhea, sudden onset/short incubation Infects & kills enterocytes > loss of microvilli Vaccine: RotaTeq Norovirus: vomit + diarrhea, self limiting Oysters, clams, seafood, highly contagious (airborne) CC: Norovirus (+) ssRNA, Caliciviridae family VF: CPE seen in both intestinal cell types Astrovirus: similar to norovirus, fecal-oral, (+)ssRNA Adenovirus: fecal-oral, longer incubation period Complications: respiratory symptoms, develop lactose intolerance CC: Adenovirus dsDNA w/ complex structural proteins “Sputnik virus” icosahedral virus w/ attachment spikes Gastroenteritis – serotypes 40,41,42 “Pharyngoconjunctival fever” – 3,7 VF: viral capsid spikes to attach, infects intestinal lining cells, (replication inhibits protein synthesis) Hepatitis: inflammation of liver, jaundice, dark urine, clay stool, antibodies are key to diagnosis Hep A/E: mild, Hep B/C: chronic, potentially carcinogenic Hep A: transmitted fecal-orally (usually by food) – contaminated water, milk, seafood, fruits/veggies CC: ssRNA genome, Picornaviridae family WHO: children, military, crowded living, homosexual Tx: Ribavirin Hep B: may cause chronic hepatitis leading to cirrhosis/cancer, transmitted thru body fluid exchange CC: partially dsDNA virus, Hepadnaviridae family “Balls & Sticks” appearance VF: hepatitis protein antigens (Ag) “Australia antigens” - HBsAg = [surface] forms a complex in liver leading to complexed deposits - HBcAg = [core] unknown fcn - HBeAg = unknown fcn VF: encodes an “RT”/RDDP enzyme > episomal latency (not integrated) WHO: IV drug users, healthcare workers, sexually promiscuity, TX: with IFN (interferon) and often combinations of valacyclovir or lamivudine Hep C: transmitted thru body fluids, primarily blood CC: (+)ssRNA, Flaviviridae family, multiple types VF: Hepatitis core protein (HCcAg) - immune suppression - HCV antibody Tx: Harvoni (2 antivirals in one pill), WHO: IV drug users, transfusion & organ transplant recipients Helminthic Intestinal Infections: Worms Mechanical blockage & tissue damage, Dx: discover eggs, larvae, or adult worms in stool/other tissues Tx: minimize human contact, physical removal, antihelminthic drugs Enterobius vermicularis (Pinworm): butthole worm Scotch tape test, lay eggs in anal folds Ascaris lumbricoides (Roundworms): intestinal, eggs consumed from environment (fecal-oral), hatch in large intestine, migrate thru liver & intestine to lungs, cough larvae/eggs to reswallow, causes distended belly, intestinal blockage, nutrient depletion, death. Affects humans & animals Necator americanus (Hookworm): tissue worm, uses teeth to burrow into skin from soil, “ground itch”, “larvae migrans” rash via circulation to lungs, coughing to swallow to intestines, direct infection leads to cyst in muscle/intestine/etc, nutrient depletion, failure to thrive, “blood sucking worm”, poor communities and developing countries Trichinella spiralis (Hunter’s worm): tissue worm, consumption of larvae in contaminated meat, likes wild game: bear/boar/deer/etc, nausea, vomiting, diarrhea, painful lesions, inflammatory response, migrates to other tissues, forms cysts in muscle or brain, characteristic lesions Neurocysticercosis: seizures, chronic headache, nausea, vomiting, impaired vision, mental status changes Taenia saginata (beef tapeworm): intestinal worm, consumption of eggs/cysts in contaminated meat, from undercooked BEEF, nausea, vomiting, painful bowels, intestinal blockage, inflammatory response, recognized by scolex with suckers only Taenia solium (pork tapeworm): intestinal worm, undercooked PORK, more dangerous due to auto-infectious cycle, cysticercosis: causes cysts (brain & muscle), same S&S as beef, recognized by scolex with suckers AND teeth Mechanism 1 - Cell wall level (narrow spec) Fam 1: Beta-Lactam antibiotics (cillin compounds) inhibit PPG synthesis, NAM/NAG subunite destabilize & lyse cell, Cillins: best effective against G(+), Penicillin=basic, amoxicillin & ampicillin=extended spectra, used in many infections, ox/clox/meth/naf= anti-staphylococcal, carbeni/pipera/ticar/mezlo= anti pseudomonas/resistant G+, carbepenem= good B-lac for G-, imipenem=similar to PEN, resistant to B-lactamase Fam 2: Non-B-lac Class, Vancomycin=against almost all G+, but not G-, last line, Red man syndrome - activates immune system (VANC IV pushed too fast), SJS/TEN - allergic reaction, Isoniazid & ethambutol= Gram NA, disrupts formation of mycolic acid, mycobacterium TB, Pretomanid= inhibitory actions on bacteria cell wall mycolic acid biosynthesis, killing of active replicating M.tuberculosis bacteria, Fosfomycin =inhibits MurA enzyme, precursor step in PPG synthesis, single dose oral therapy for uncomplicated UTIs, G- enteroba Fam 3: Cephalosporins (better targeted than B-lactams) “2 R groups+house+garage” HEN PEcK (Haemophilus influenzae, enterobacter SPP, Neisseria SPP, Proteus, E.coli, Klebsiella) + Pseudomonas, 1st gen=Cephalexin(Keflex) - minor G- & HEN, 2nd gen=Cefuroxime(Zinacef)=fewer G+ & HEN PEcK=G-, 3rd gen=Ceftazidime(Fortaz), Ceftriaxone(Rocephin)=3G & up can cross BBB, fewer G+ & HEN PEcK, aggressive G-, 4th gen=Cefepime (Maxipime), rare G+, strong G- Bacitracin+ Polymyxin B(simple G+/-)=pore formers, Nephrotoxic (topical use only), Daptomycin=G+ effective vs staph Mechanism 2 (Protein synthesis) good to treat G N/A CLEAn TAG: Chloramphenicol= very broad spec, high side effects, only used when NO alternatives, Lincomycin & derivative CLindamycin(Cleocin)=used for anaerobic & severe aerobic infections (streptococcal TSS) adverse effect: pseudo colitis (C.diff), Erythromycin=G+,N/A, good for PEN allergies, chlamydia, syphilis, disrupts normal GI flora, diarrhea Azithromycin (Zithromax, Z-Pak), Tetracycline (Doxycycline, Minocycline) broad spec G+/-/NA - TERATOGENIC! Aminoglycoside=serious G-, IV use, must have oxygen, effects: nephrotoxicity (kidney failure), hearing loss, will cross placenta New Antiribosomals: Synercid= inhibits 50S ribosome, effective against Staphylococcus, Enterococcus, & resistant strains of streptococcus G-/+ secret last line Oxazolidones=Zyvox & Linezolid treat MRSA & Vanc Resistant Enterococcus, last line for G+, no G- activity Mechanism 3 (Metabolic Synthesis) mimics a natural compound, competitive inhibition, shuts down natural process (stops folic acid, folic acid is necessary for DNA replication), Sulfonamides(Sulfamethoxazole) & silver Sulfadiazine=G-, enteric bacteria, Shigellosis, acute UTI, Trimethoprim= otitis media, UTI, Brand names: Bactrim, Cotrim, Septra, NO PREGNANCY!! Sulf & Trim work better together = SYNERGISTIC, NEW Bedaquiline= antimycobacterial drug that inhibits the proton pump in M.tuberculosis Mechanism 4 (Nucleic Acid Str/Fcn: stops workers (Fluoro)Quinolones (-flox antibiotics)=stop replication(unwinding DNA) Ciprofloxacin= prophylaxis, anthrax (weakest) Norfloxacin= G+/-, pseudomonas, UTI Levofloxacin= many STD organisms, skin/systemic infection (strongest) Nalidixic acid=UTIs (especially G+ for pregnant women, doesn’t stop VF or protein synthesis, just stops duplication) Rifampin= inhibit action of bacterial RNA polymerase during transcription (G+/-, mycobacterium tuberculosis) treats pneumonia, UTI, gastroenteritis, can cause tendon rupture Antivirals: DNA polymerase synthesis inhibitors: Cyclovir compounds=mimic nucleotides to chain terminate, Foscarnet may be added when resistance to cyclovirs occurs, Trifluridine=virus infection of eye RNA polymerase synthesis inhibitors: Ribavirin=tries to stop RDRP, doesnt stop every RDRP, limited usagem useless against common cold, flu, polio, measles Remdesivir= NEW, attacks RDRP, Covid19 polymerase version. Nucleoside Reverse Transcriptase Inhibitors: NRTIs= competitive inhibition of RT, need host phosphorylation pathways to work (going after RDDP) -vudine compounds (zidovudine- AZT, stavudine, lamivudine) Retro/RDDP -avir compounds (abacavir, entecavir) competitive inhibitors, get across BBB Non-Nucleoside Reverse Transcriptase Inhibitors= non-competitive inhibitors of RT (bind away from active site) Unconventional namings (efavirenz/nevirapine) taken less frequently & does not inhibit human DNA polymerase, can be teratogenic Fungal Infections: Synthetic Azoles (-azole) broad spec antifungal agents (ringworm) Clotrimazole/Miconazole=mainly topical ointments for infections in skin/mouth/vagina (monistat) Ketoconazole =oral & topically for cutaneous mycoses, vaginal/oral candidiasis, & some systemic mycoses (higher power) Fluconazole=used in selected patients for AIDS-related mycoses, get CSF (brain fluid)(highest power!) good choice for yeast infection Amphotericin B=attack fungal membranes by binding fungal sterols (ergosterol) & form pores, can react w/ human cholesterol if overdosed, high toxicity Terbinafine (Lamisil)=topical ointments for skin (used for nails) Nystatin= oral thrush Antiparasitic compounds: Quinine & Artemisinin as anitmalarials(keeps parasite contained) Chloroquine & Primaquine=less toxic to humans, both slow parasitic growth, commonly used as combo therapy (include Bactrim) Metronidazole(Flagyl)=-dazole works best on parasites, usually for protozoan infections, causes DNA & protein damage Amoebicide/Giardia Lamblia/ Trichomonas Vaginalis=good for anaerobic Antihelminth compounds: energy drainers for worm infections, leads to paralysis or death or worm expulsion from body, ion channel blockers/membrane permeabilizing/cytoskeletal depolarizers/nicotinic acid inhibitors Pyrantel Pamoate (Pinworms), Mebendazole & Thiabendazole=good for pinworm & hookworm, and flat (tape) worms Ivermectin=good on other worms such as lice, scabies, and rosacea Immunity 1 & 2: 1st line defense, no memory, always same Cytokines IL: cell communication, interleukins (IL) & interferons (IFN) Actions: “Come” =chemotaxis, “Do”=activation, “Become”=differentiate, “Go”=amplification IL-1: recruits cells to site - chemotaxis, fever & inflammation, “GET HERE NOW” IFN-a/B: Antiviral response (defense/alert), activate NK cells, increase antigen presentation, signals neighboring cells, slows metabolic activity & therefore viral replication IFN-y: innate cell activation, signaling, turn B-cells to T-cells IL-2: T-cell growth Innate& replication, stimulates T-cell survival & growth(especially CD4+ & CD8+) IL-4,5,6: signals class switching from IgM to IgG/IgA (4=maybe IgE) IL-10: Anti-inflammatory, reduces cytokine production, T-reg cells, “STOP” IL-17,22: Produced by CD4 TH17, recruit neutrophils, promote inflammation, bouncer BAFF: B-cell activation factor, survival, differentiation, & maturation, involved in autoimmune when dysregulated (lupus), tells 4/5/6 to class switch TNF-a: pro-inflammatory cytokine, activates macrophages & T-cells, rheumatoid arthritis TNF-B: immune regulation & inflammation, redundancy in activation signals (only a few) 1st line defense: physical barriers - skin, mucous, body temp, pH, microflora 2nd line defense: antigen (Ag)=foreign & causes immune response, epitope=part of antigen that immune response recognizes, PAMPS (molecular patterns), APC=antigen present. Cells C1:Granulocytes (BOMB): large granule, PYOgenic=pus-forming, PYROgenic=fever forming - Neutrophils=first responders, most common wbc, trap (NETs) & bomb (granules), short life - Basophils=blue/purple staining granules, B=blue=barbell, MAST cells w/ allergies - Eosinophils= red/pink staining granules, fights worms & parasites C2:Agranulocytes (EAT): APCs, monocytes, single nucleus - Macrophages=big cell eaters, APC - Dendritic cells=octopus shape, best APC b/c of superior antigen capture C3:Lymphocyte: rbc, B-cells, T-cells Seek & destroy: (MØ/DC mechanism) 1)binding, 2)recognition by PRR (engulf), 3)fusion (phagosome+lysosome=phagolysosome), 4)digestion, T-cell development: presentation, B-cell activation: poop Agranulocytes: primary phagocytic or specialized functions Monocytes: become MØ or DC (phagocytes & APCs) PAMP: short fragments that aren’t “self” shared among antigens, non-clonal distribution (multiple recognitions on each cell), multifunctional, activate MØ, NØ, DC PRR: pattern recognition receptor, common type = toll-like receptor (TLR) TLR2: LTA/PPG in G+, G- proteins; TLR4: LPS, cover cell surface & scans impact shaping of immune response, guides & produces only needed cells Complement cascade: set of soluble serum proteins (C1-C9), assemble stepwise (1 thru 9) on antigen surface similar to bomb, forms membrane attack complex (MAC) C3a: inflammation & recruit, C3b: opsonization/phagocytosis Inflammation: second line response/defense, redness(vasodilation), swelling(edema), heat (fever), pain(damage & mediators) - arrival of neutrophils, macrophages, dendrites, recognition of antigen by innate cells, activation - trapping antigen, eliminate antigen, amplification specialization of response, win or death B-cells: made & trained in bone marrow, makes antibodies, specific response, memory cells, secrete antibodies, best against EXTRAcellular Good-Naive cell: immune cell ready to be used, never encountered antigen before, “less than perfect response”, Better-Activated effector cell: immune cell that has encountered antigen, now react to cause an effect, Best-Memory cell: veteran cell that responds as effector faster/more efficiently to previously encountered antigen Positive selection: “do you have a receptor & work”, Negative selection: “do you hurt self” Adaptive cell responses: 1) find specific epitope, 2) bind antigen & activate adaptive cell, 3)do effector function & duplicate, 4) specialize response based on affinity & performance, 5)either memory cells form or apoptosis, WIN! Activated B-cells = plasma cell (clock face nuclei) make & secrete antibodies Humoral immunity - each B-cell produces ONE antibody that recognizes ONE epitope T independent antigen (Ti-Ag): acute, antigen that stimulate B-cells w/out co-stimulation by helper T-cells, IgM only, cross link antigen receptors on surface T dependent antigen (Td-Ag): response to protein & most antigens, interaction of B-cells & helper T-cells, CD40 & CD40L (need T) humoral Y shaped arrangement: variable antigen binding sites on top ends Class Switch: convert antibody from IgM to IgG or IgA, requires help from T-cells, IL-4,5,6 B-cell memory: memory B-cells reverted to inactive no Ig release, carry IgG IgG= Great, crosses placenta, blood responses (monomer) IgA= Mucosal responses (dimer), breast milk, GI IgM= Meh, initial naive response, switches to G/A as response narrows, rookie IgE= Parasitic response & allergies, binds & activates mast cells, T1 HB reaction IgD= Don't care, naive response, B-cell receptor, surface bound T-cells: made in thymus, coordination & killing cells, INTRAcellular, virus T-cell receptor (TCR): on surface exposed to antigen, +/- selections till used CD4 with MHC-2: Helper or protein marker, MHC-2 binds/shows extracellular antigen for helper T-cell response, release IL-4,5,6 - class switching! TH1= help innate & killer T-cells to improve responses, release IFN-y TH2= help B-cells differentiate/class switch, release IL-4,5,6, BAFF, & CD20 TH17= promotes/regulates, inflammation, BOUNCER, IL-17,22 CD8 with MHC-1: KILLER, only needs signal 2 once, professional, MHC-1 binds/shows intracellular antigen for killer T-cell response, lyse cells, DESTROY Cytotoxic T lymphocytes(CTL): apoptotic(cell suicide), granules(bomb), 1) Perforin: granule, stabs tiny holes in cell, gets granzyme inside 2) Granzyme: granule/apo, activate target caspases > apoptosis(guts) 3) Fas-FasL: apoptosis, death receptor that doubles caspase action/no ls > release IFN-y for innate to clean up the mess, collateral damage possible T-cell Activation: APC presents to T-cell using MHC, move MHC+antigen to surface to interact with T-cell and CD4/CD8, co-stimulation Signal 1: TCR>MHC+antigen // CD4/8>MHC2/1, recognition Signal 2: CD28>B7 - ½ full activation, CD8 only once/4 every time Activated T-cell function: 1)produces IL02 (CLONE) & others to give orders, 2)TOUCH: only after signal 1+2, CD40(ear) molecule on the surface of immune cells, CD40L(hook) molecule on the surface of T-cell = pass signals Treg cells: (CD4), IL-10, hippies, reduce inflammation, slow response, CD25 or FOXp3 surface markers, autoimmunity, CTLA-4 contact regulation Natural Killers (NK): recognize like MØ, kill like CD8 CTL T-cell, cancer - Lazy T-cells>tolerance/anergy Hypersensitivity: response to foreign antigen hurts self antigens, damage host Type 1: “immediate” or “allergic” rxn, allergies, wrong antibody type Intolerance vs allergy: intolerance is host can’t use or process a compound bc of genetic mutation, allergy: immune system is directly targeting something Localized or systemic rxns from release of inflammatory molecules, FAST! 1. Atopic: chronic local allergy (hay fever, asthma, etc) 2. Anaphylaxis: systemic, sometimes fatal reaction, low bp, & airway constriction, BAD, anaphylactic shock, mast cells everywhere Formation of IgE antibody type, IgE binds & activates mast cells/basophils, mast cells= granulocytes, granules=HISTAMINE Empty IgE coats mast cell=SENSITIZATION, immediate release after bind Dx: wheal/flare rxn, skin testing=patients skin injected with allergen, look for wheel response in skin, common/fast, in vitro: IgE blood levels Tx: antihistamines, epinephrine (EpiPen), cromolyn new, homeopathic Asthma: severe bronchoconstriction, antigen unknown nut histamine releases Tx=steroids(Flovent), bronchodilators(Albuterol), combo drugs(Advair) Atopic Dermatitis: Eczema, intensely itchy inflammatory on skin, Food/Drug Allergies: peanuts, fish, cows milk, eggs, shellfish, soybeans * mucosal/intestinal absorption, vomiting, diarrhea, abdominal pain, hives Red Man Syndrome: VANC, pruritus itch, red rash, antihistamines tx no vanc, side effect not allergy Type 2 (cytotoxic): “antibody-mediated” rxn, B-cell misrecognition of self vs foreign, should be treated as self, but targeted for destruction, IgG Binding of antibody to “self” antigen patterns that are confused, antibody binds & activates innate/complement, MAC & innate responses = destruction Transfusion Rxn: binding of antibody to RBC, hemolysis, + has RH Hemolytic Disease of Newborn: administer Rhogam to RH- pregnant women, only RH- mothers with RH+ fathers, mom could attack baby RH+ if no Rhogam Drug-Induced Rxn: PEN(cillins) act as haptens, appears foreign w/ self-protein contact, can produce autoimmune diseases - ITCP Immune Thrombocytopenic Purpura: destruction of platelets & decreased # of circulating platelets, easy bruising (purpura), caused by quinidine/quinine Autoimmune Hemolytic Anemia(AIHA): destruction of RBCs, two variants (immune & idiopathic) “sore tongue”, blue sclera, fever, headaches * Warm: autoantibody IgG attacks RBC, 50+ age, corticosteroids * Cold: IgM & C3d coat RBC triggering hemolysis, 50+ age, avoid cold Type 3: “Complexing” rxn, wrong clearance (too much trash left over), autoimmune diseases, complexes accumulate & cause new reactions Systemic: Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), serum sickness rxn to vaccine after exposure (baby rash), blotchy/veiny pruritus red rash Localized: HS pneumonitis, kidney failure, arthus rxn to vaccine after exposure, hot/tight/knotted red tissue, painful to touch, can become necrotic Type 2/3 Tx: limit inflammation by corticosteroids, plasmapheresis: replace anti (specific), biologics: anti-CD40 or anti-CD19 or 20 (B-cell surface marker) Type 4: Delayed or cell-mediated or CMI rxn, T-cell, wrong response, didn't need T-cells but they came and caused damage Antigens attach to cells, targets for intracellular (CMI) responses, T-cells! Typically chronic, progressive disease, T+MØ cycles = epitope spread Tx: corticosteroids, anti-B7 (Costim), anti-IL-2, TNF antagonists, cyclosporin (prevent organ rejection) and limit inflammation Allergic Contact Dermatitis: intense irritating skin rash, foreign haptens, poison ivy, PPD serum, formaldehyde, used for TB testing, blisters develop Graft Rejection: when CTLs recognize foreign MHC-1 on graft, slow rejections, ends in graft death, graft vs host disease - 30% of grafts, slow * Hyperacute rejection: takes minutes, type 2, Ab-related 1. Autograft: tissue transplanted from one site on body to another site 2. Allografts: (common), cadaver grafting, tissue exchange between people 3. Xenograft: tissue exchange between different species, pig heart valve Stevens Johnsons Syndrome (SJS): serious, painful red or purplish rash that spreads & blisters causing top layer of skiing to die/shed, B-lactams cause, NSAIDS, not true allergy Autoimmunity: immune response mistargeted against self, attacks self antigen Adaptive process, recognizes self vs foreign, DAMP vs PAMP, type 2 or 3 Failures in self tolerance, inheritable genes/errors environmental stimuli Tx: immune suppression (corticosteroids, NSAIDs, TNF-inhibitor, biologics * Personalized immunotherapy: infusions of needed molecules, short-term * Immune replacements: bone marrow, costly, risk of rejection T-cell: TCR/Antigen/MHC+Costim vs TCR/Antigen?=/MHC only, different presentation = different response, tolerance major way to control immunity and keep safe * Responses: productive response, tolerance (ignore), ignorance(no response) B-cell: autoantibody production, antibodies mark self & response follows * Negative selection primary for B-cell tolerance, receptor editing, 2nd recombination of light chain variable rxns, control by BAFF/CD20 protein Primary IA: self antigen is recognized during generative lymph process, (BM/Thymus) * Most likely, MHC haplotypes may be more likely to present as a self antigen Negative Selection development: AIRE gene mutation, lack/failure of control mechanisms, tolerance errors, bad signal 2 (CD28/B97), wrong # of Tregs Peripheral: previously controlled mature lymphocytes mis-activated 1. Molecular mimicry: PAMP patterns mimic self patterns, confusion 2. Bystander activation: bad orders given, wrong MHC, superantigens 3. Epitope spreading: frees self antigen not normally seen > foreign & destroy Type 1 Diabetes (Mellitus): immune cells (B) vs insulin-producing cells, genetic Multiple Sclerosis: CD8 & CD4 T-cells attack myelin sheath insulating brain and spinal cord neurons, deficits in speech, vision, muscle function Myasthenia Gravis: Autoantibodies target ACh receptors, Ddx for Guillain-Barre, botulism, weakening/paralysis of muscles as synapses fail Hashimoto’s Thyroiditis: target thyroid hormones, T3/4, puffy face, tongue enlargement, Tx: anti-inflammatory + thyroid replace (levothyroxine) SLE: Produce antibodies against DNA fragmentation, T3, rash, arthritis, kidney failure, butterfly rash, spring break disease Rheumatoid arthritis: attacks joints/cartilage or uncleared Ig+Ag in joints, related to TNF amounts in synovial, anti-inflammatories (TNF-inhibitors), advi Celiac Disease: spure, autoantibodies against gluten, NOT allergy, IgA, damage to intestines (shag vs tile), tense vesicles, mouth ulcers Immunodeficiency: reduced or no functional immune response * Increased susceptibility to infectious diseases, reduced immune potency 1. Primary: resulting from a genetic defect 2. Secondary: acquired resulting from an environmental cause, cancer, HIV Congenital: primary, naturally occurring genetic errors/defects, 3 types * TLR defects, no PRR recognition, complement defects (C2-C5), slow innate Chronic Granulomatosis Disease: MØ form granulomas, staphylococci, skin infections, fungal, pneumonia, diarrhea, Tx = antibiotics & IFN-y Hyper IgE Syndrome (Job’s): lack of fever, lots of histamine, bone fragments, cuts behind ear, eczema, dental abnormalities, Tx = antibiotics & immunosuppressives Lymphocyte Maturation: defects in B, T, or both maturation 3rd line SCID (severe combined immunodeficiency): bubble boy, no B or T cells, no + selection, mutations in RAG recombinase Bruton’s Agammaglobulinemia: No B cell maturation, lack of Ig, extracellular, BM transplant, not fatal DiGeorge’s Syndrome: thymus no function, no T cell maturation, cardiac, abnormal face, thymic aplasia, cleft palate, hypocalcemia, chromosome 22 (Catch 22) Lymphocyte Activation: normal maturation, bad effectors (can't do job) X-linked Hyper IgM syndrome: No B class switching, defects in contact molecules/T-cells, only produces IgM, extracellular infections like bacteria/fungus Common variable immunodeficiency: environmental cause, design/intended as therapy (corticosteroids), cancer/treatments, HIV Designed Immunodeficiency: corticosteroids = compounds that reduce immune function, works through multiple methods Cancer: Tx=destruction on tissue via chemo drugs/radiation, anti-inflammatory (corticosteroids), protein calorie malnutrition (replication blocks, terminal illness) HIV: retrovirus, uses RDDP to get to host, stage 3=AIDS, integrate to host * Infects T-cells, uses MØ & DCs as reservoirs, CD4 for entry, then turn on & clone & kill * GP41 & GPI20 (capsid molecules), results in SLOW T-cell death Stage 1: vague, flu-like symptoms, T-cell count 500+, asymptomatic Stage 2: chronic HIV infection, more numerous mild opportunistic infections, lasts 2-15 years, T-cell count 200-500, low HIV in blood Stage 3: AIDS, rare infections, neoplasms, gateway to other infections like cancer or meningitis, T-cell count below 200 Kaposi’s Sarcoma: papular rash from HHV-8, tumors in endothelial cells B-cell Lymphoma: tumors form B-cells from EBV HIV/AIDS Tx: start antiretroviral therapy ASAP if expected, life-long treatment, maintain T-cells, Atripla or PrEP/PEP, inhibit RT/integrase/protease Serology (Vaccines): immunology that deals with in vitro diagnostic testing of the serum, presence/absence of antibodies and type/tiered, TITER detection Sensitivity: how well does the test detect people with the condition vs Specificity: how does the test determine people that do NOT have the condition Agglutination: binding whole cells together, clumping Precipitation: binding epitope molecules in solution * Positive: clumping, precipitate, color change, etc * Negative: milky or uniform, both by immunoassay tests (ELISA used for HIV testing & can see multiple antigens at a time and changes color Antigen Testing: must have detectable amount of antigen, need universally good antibody that binds antigen, detects infectious agents, no info on immune response, known antibody given, covid or pregnancy test Antibody testing: needs immunocompetent patient, recent analysis, detects immune response to antigen, but not directly detect the antigen (unknown antibody) * E.coli on plate, if sample binds than yes E.coli antigen Hybridomas: generate designer B-cells to recognize antigens for research/tests Anti-toxin: inject specific antibodies, protection needed NOW, neutralizing Immune Serum Globulin: Ig extracted from pooled blood, lab-made, polyclonal Ig, hyperimmune people, replacing antibodies immunodeficiency, lots of cloning, nurse-saver, not a long term solution for immunodeficiency Biologics: lab made monoclonal Ig, bind to specific antigen & block it, mAbs, targeted immunotherapy, antibodies block one process, CD28, turns cell quiet NO LIVE VACCINE: pregnant, immunodeficient, cancer, can’t make memory cells Herd immunity: collective immunity through mass immunization makes indirect protection on the non immune members(umbrella) one protects lots Types of immunity: Active immunity: person is challenged with antigen that stimulates, production of antibodies, creates memory, takes time, lasting Passive immunity: molecules are donated to an individual, no memory, acts immediately, short-term Natural immunity: through normal life experiences (chickenpox) Artificial immunity: through a medical procedure/protection (vaccine) Combinations: Active natural immunity: disease & develop natural protection/memory Active artificial Immunity: vaccination & experience “practice” antigen to develop memory from known set of antigens Passive natural immunity: molecules are donated to provide protection until system(breastfeed) Passive artificial immunity: you get a shot to neutralize an antigen, develop no memory (gamma globulin, antitoxins) Live vaccine: M(mumps), Y(yellow fever), R(rubella), O(oral polio & oral typhoid) M(measles), E(endemic typhus), T(TB=BCG), I(nasal influenza=LAIV), P(plague) Live attenuated vaccines: uses living pathogens with reduced virulence (harm) - stronger immune potential but less safe for immunocompromised Subunit vaccines: antigen/epitope fragments, safest vaccine class, (B)TH2 response, no live or whole organism, weak, booster/conjugate good Genetic engineered recombinant vaccines: DNA/RNA/plasmid from infectious agent, expressed foreign antigen inside cells, adaptive response, MRNA makes protein ans body makes epitopes, uses BOTH B & T cells Sign: measurable (102 fever) vs Symptom: subjective to patient (pain scale) Disease stages: incubation=time w/out S&S, prodromal=generic S&S & lots of spread, illness=specific S&S, convalescent=recovery Infection classification: Common source=from shared source, propagated=person-person Acute=rapid onset/short duration, persistent=chronic/latent/slow Focal=infectious agent left and turned into something else (i.e. sore throat to heart problem), mixed=more than one pathogen/infection Primary=starting infection, secondary=occurs after primary Infectious dose=# of organisms needed to infect (lower ID=more virulent) Mortality rate: total # of deaths in population due to disease Morbidity rate: # of persons afflicted with infectious disease Reservoir: water sources, soil, Vector: drinking, fleas/ticks/mosquitos Sporadic: occasionally or irregular from contact w reservoir Endemic: native to a region at constant % from related organism Outbreak: sudden unexpected occurrence (often from travel) Epidemic: outbreak affecting multiple populations, above expected levels Pandemic: world-wide, linkages across continents Identification methods: staining(gram=PPG/acid fast=lipid) based on pathogen structure, growth/colony morphology colony size/odor/color, slow physiological/biochemical traits traditional, metabolic/chemical analysis (sorbitol/indole), serology & genetic detection faster, better, more accurate Mutations: point mutant=single base change, silent=base change that does not change AA codon, nonsense=stop codon, ends protein early, missense= changes codon to different AA, frameshift=disrupts normal triplet reading by insert or delete Bacterial DNA movement: transformation=free acquisition & recombination transduction=phage shuttling, conjugation=pilus-mediated transfer of plasmids, transposons=jumping genes, + all mutations/natural changes PCR: best for genetic diagnosis, very sensitive, 16S RNA(if protein is made, there is 16S), no growth needed, form sample to DNA in 4-6 hours 1. Pick a DNA sequence that is unique(16S RNA) to what you want to detect 2. Take sample and harvest DNA out of it (@30min) 3. RUn PCR rxn to detect that unique thing (@3hrs) 4. Evaluate PCR result (if +(has a band), the sequence is there RFLP: restriction, fragment, length, pattern - compare (paternity testing) Gene therapy: replacing bad gene with a good copy, gene inserted in viruses for infection, delivery into host tissues, expression of new copy RESPIRATORY TRACT: most common place for infectious agent access URT: mouth, nose, nasal cavity, sinuses, pharynx, epiglottis, larynx LRT: trachea, bronchi, bronchioles, lungs, alveoli (U&L divided at voicebox) Defenses: cilia, mucus(catch&trap), coughing, sneezing, swallowing Rhinitis(common cold): sneezing, scratchy throat, runny nose(rhinorrhea) CC: rhinoviruses, coronaviruses (can be RSV/pertussis/EBV/ED68,hMPV,etc) VF: penetrate mucus&attach to cells, use sialic acid - specific bind molecule, no IL1, highly mutable, Dx: appearance, Tx: droplet control, “chicken soup & rest” Enterovirus D68: summer cold, pre-flu, CCS, low grade fever CC: Enterovirus strains(primarily ED68), VF: viral, 100 serotypes Dx: appearance, Tx: CCTx, warn abt respiratory collapse, supportive care *AFM:acute flaccid myelitis=slow, likely reversible paralysis, can cause encephalitis if crosses BBB Sinusitis(sinus infection): congestion, pressure, head/toothache, swelling, following CC, opaque discharge=bacterial, clear=viral CC: mixed bacterial/fungal/viral agents, likely NF (explains recurrence) VF: biofilms, persistence, mixed infections, Dx:appearance, can use radiology Tx: broad spec ABX, alternate ABX to prevent resistance Otitis Media(ear infection): URT infection reaches eustachian tubes, CCS, fullness/pain in ear, hearing loss, pus/inflammatory fluid in middle ear AOM (acute otitis media)=bulge, loss of landmarks, CC: streptococcus pneumoniae, Haemophilus influenzae OM w/ effusion=retraction of eardrum, CC: viruses (rhinovirus, RSV, etc) VF: capsule for bacteria, variance(mutations), Dx: appearance, screaming, Tx: 72hr watchful waiting, B-lactams(not preferred bc increasing resistance), vax(HiB, pneumovax/Prevnar) *severe infx can eardrum rupture(tubes), meng Pharyngitis(strep throat-sometimes): inflammation, pain/swelling, reddened mucosa, bad breath, white packets/pus, may affect speech & swallowing *can be non infectious-yelling/vocal cord strain, post-nasal drip CC1: often viral caused, less severe, rhinovirus, RSV, influenza, EBV, ED68... CC2: Streptococcus pyogenes(GAS)(true strep throat), causes ⅓, some NF VF: surface antigens: lipoteichoic acid(LTA), M protein, hyaluronic acid (HA) *M protein=adhesin&WBC evasion, type (1,5,etc) tell what VFs are coming Linked to strain serotype&sequelae determinate(scarlet fever, AGN & RA, rheumatic fever, etc), true strep give PEN extracellular toxins: streptolysins (SLO&SLS) for hemolysis, erythrogenic toxin responsible for rash/fever typical of scarlet fever, superantigens: SpeA, SpeC activate Tcells & induce tumor necrosis factor(TNF) cytokine damage CC3: fusobacterium necrophorum, rare, identical to GAS, can lead to Lemierre’s syndrome: bacteria spreads from throat to jugular vein, clumps of bacteria travel thru bloodstream S.pyogenes complications: scarlet fever(sandpaper-like rash,high fever), rheumatic fever(damage to heart valves, arthritis in multiple joints), glomerulonephritis(kidney function/failure), TSS & necrotizing fasciitis Diphtheria: sore throat, lack of appetite, low-grade fever, pseudomembrane forms on tonsils/pharynx, asphyxiation, systemic diphtheria=toxin attacks CNS & cardiac tissue - extreme fatigue, dementia, death that looks like MI CC: corynebacterium diphtheriae(rods), gram stain “chinese character” or “XY” VF: toxin(no invasion) A/B toxin attacks protein synthesis, ELEK test, tinsdale agar(black colonies), Dx: appearance, rapid strep testing(serological), Tx: antitoxin + PEN or ERY, vax (DPT) Pertussis(whooping cough)(U/LRT): CCS, paroxysmal(comes&goes), severe cough with “whoop” sound, burst blood vessels in eyes, vomiting, cracked ribs Long recovery(convalescent) phase of weeks/months, secondary infections CC: bordetella pertussis, VF: tracheal toxin(CT) - AB toxin, kills ciliated nasopharynx cells, pertussis toxin(PT) - upregulate cAMP (EXPORT) in cells *toxins enter cells, kill cells, dead cells slough off=airway full of dead cells & debris, @ same time PT enters cell & turns on cAMP, causes cell export(mucus), now mucus & dead cells fill airway, Dx: sound, throat culture, Tx: erythromycin, vax(DPT) - 5x boosters *highly contagious, aerosol transmis. Croup(U/LRT): CCS, inflamed voice box & windpipe, can spread to bronchi, barking cough, stridor w/ inhalation, worse at night, CC: parainfluenza virus, VF: viral, Dx: sounds, CXR steeple sign, Tx: cool mist, outdoors, monitor RSV(U/LRT): fever, rhinitis, pharyngitis, otitis, can lead to wheezing, rales, etc, blueing from airway inflammation(LRT involvement-pneumonia) CC: respiratory syncytial virus (RNA virus), VF: syncytia, triple RSV: syncytial (no O2 transfer)+inflammation+remodeling, Dx: bronchial or nasal wash to find syncytial cells, Tx: self-limiting, severe=O2, IV fluids, ventilation, Ribavirin Influenza(U/LRT): rapid onset, headache, chills, dry cough, body ache, fever (but H1N1 variable), extreme fatigue can last days/weeks, cytokine storm responsible for systemic symptoms, largest cause of death - second bacterial infections(pneumonia), epidemic CC: influenza virus(orthomyxovirus) types A&B, “subclasses”=HxNx typing differences but still usually A strain VF: mutability, Hemagglutinin(HA) & Neuraminidase(NA) capsid proteins bind to host cell, spikes for attachment&entry to host cells, Dx: symptomatic, rapid testing, Tx: self limiting, severe=may give antivirals(relenza, Tamiflu-placebo at this point), “best guess” vaccine yearly for anyone +6mo (inactive), or LAIV(live attenuated)(FluMist, 5yr+) for mucosal protection Best prevention: hygiene+vaccine, Other antivirals: entry/exit blockers- Zanamivir(Relenza), SpOA=influenza virus(HxNx) Influenza variation: segmented genome of 8 RNA strands-allows for reassortment&mutations, yearly strain mutations=antigenic DRIFT, epidemic strain changes(reassortment)=antigenic SHIFT Coronaviruses(U//LRT): CCS, swift severe acute respiratory collapse, fever, cough, SOB, progression to pneumonia, zoonotic SARS(sudden acute respiratory syndrome),MERS(middle east resp. syndrome) CC: coronaviruses - 1. SARS(not seen since 2005), 2. Novel coronavirus (nCov) or MERS-CoV, VF: unknown, super spreaders, rapid transmission Dx: lab tests(PCR) for MERS-CoV, Tx: supportive to relieve symptoms Metapneumovirus(hMPV)(U/LRT): influenza symptoms, found as influenza & RSV negative, CC: metapneumovirus(paramyxovirus), VF: unknown Dx: DFA, PCR, Tx: treat symptoms not virus, self-limiting Tuberculosis: mycobacterium tuberculosis (#1 cause) or mycobacterium avium intracellulare (MAC) + *NEW* mycobacterium bovis, organism w/ heavy lipid content, need acid-fast staining - shows slim red-snapper rods w/ segments Positive ID typically requires culture, (M.tb vs MAC) very slow growing(weeks), produces breadcrumb colonies, VF: cord factor & proton pump=allow intracellular growth, very low infectious dose (ID= ~10) M∅ ingest M.tb(eaten but not killed), killing by CD8+ Tcells needed, leaves cell debris, need for more M∅, leads to stalemate, formation of granulomas/tubercules & M.tb(dormancy/latency)=Primary TB Reactivation/escape causes large immune response by Tcells, Secondary TB= destructive pneumonia(consumption), CTLs & cytokine release from Tcells results in caseous necrosis(cottage cheese lung) Primary=infection>trap>latency, Secondary=death Tuberculosis Dx: tuberculin testing(PPD)=T4HS(delayed rxn)-inject very small amount that doesn't get large rxn but if you had TB before, memory Tcells will cause rxn, if + PPD test then: CXR, AFB, culture isolation Quant-iFeron GOLD=new TB blood test(take Tcells out & stimulate w/ epitope to see if they produce IFN-y) Primary TB: goes dormant, flu-like, + PPD, - infiltrates, not highly contagious Secondary TB: active, contagious, fever, blood tinged sputum, night sweat, weight loss, caseous necrosis, + PPD & infiltrates Miliary(disseminated/Potts)TB: spread out of lungs to other tissues High level of ABX resistance due to long tx & pt noncompliance, MDR-TB= multidrug-resistant TB, XDR-TB= extensively drug-resistant TB, TDR-TB= totally drug-resistant TB Tx: heat & UV sensitive(sun&outdoors), cocktail tx=long term(mo-yrs) ABX, RIPESAg= Rifampin, Isoniazid, Pyrazinamide, Ethambutol, Streptomycin, & Aminoglycosides, Prevention: education & detection, monitor primary TB Vaccine: BCG - ineffective & not used in U.S., NEW XDR-TB Tx= NixTB Bronchitis: extreme cough, congestion, chest pain, fever, fatigue, as inflammation of bronchial tubes progressive=excessive mucus, chest pains, SOB Chronic if >3mo, watch for pneumonia, CC: virus(influenza,RSV,hMPV), bacterial(S.pneumoniae,H.influenzae,Mycoplasma,Klebsiella), environmental/ immunological(smoke,allergens,pollutants), Dx: bronchial wash to find agent, CXR, Tx: self-limiting, may need O2,IV,vent., treat symptoms(inhaler, albuterol) Pneumonia: fluid in alveoli of lung, begin w URT symptoms, then chest pain, fever, cough, discolored sputum, hypoxia, SOB, tachypnea, hyponatremia(loss of sodium) common bc of fluid imbalances w Na/K pump, possible septic spread Dx: CXR & physical exam w auscultation-crackles, rales, 99 speech, egophony CC: wide variety, almost any bacteria, but fungal/viral/parasitic forms exist too Classifiers: lobar=lower lobes,unilateral CAP-community-acquired(walking): most common CC: streptococcus pneumoniae(lancet shaped diplococci) VF:capsule, string test, rust sputum, Tx: cephalosporins, Other CC: H.influenzae,Neisseria spp,viral pneumonia HAP-hospital acquired(nosocomial): S.pneumoniae stays at top, then S.aureus/MRSA(common VAP-ventilator associated),P.aeruginosa(common VAP), Klebsiella pneumoniae(CRKP)-gut surgery,catheter, bacillus NF of gut & feces Atypical(interstitial)pneumonia: walking pneumonia, infection of interstitial space & alveolar walls, bi-lateral, wispy fluid, young&college-age, CC: chlamydia pneumoniae(intra) or mycoplasma pneumoniae(extracellular fried egg colonies), Tx: macrolides or tetracyclines Fungal: Aspergillus fumigatus “black mold” can be NF or opportunistic, breathe in over time=SLOW, AIDS patients, black lesions, “lightning/broccoli” Pneumocystis jirovecii (PCP): cold-like, lower septum, HIV/AIDS patients, AIDS-defining illness, “ping pong balls” on a methenamine silver stain, Tx: Bactrim(only immunocompetent!) Histoplasma capsulatum: bird dropping, bat caves, soil locations, endemic in MO rural populations & midwest, small oval budding yeasts in M∅, snowstorm, slow progress fungus Legionella pneumophila: water, A/C cooling towers, chlorine resistant, cough, chest pain, vomiting, delirium, diarrhea, shock, MOF, death Pontiac fever: breathing weak or dead L.pneumo bacteria, Tx: immediate ABX, environmental H2O control/sourcing, grow on CYBE agar Hantavirus: environmental virus, rodents poop>dry up>air currents>inhaled, starts w/ flu-like symptoms+pneumonia, recovery begins then SUDDEN, MASSIVE, UNEXPLAINABLE inflammation, bleeding into lungs, often fatal CARDIOVASCULAR & LYMPHATIC SYSTEMS: SIRS(systemic inflammatory respiratory syndrome): pre-sepsis, defined as two or more of: fever(>100.4), heart rate(>90bpm), resp rate(>20), abnormal WBC count, main issue: MOF, highly dangerous, may need both suppression (corticosteroids) & ABX (ABX cant stop toxins&VFS) >SEPSIS: 2 SIRS+confirmed/suspected infection >SEVERE SEPSIS: sepsis + signs of end organ damage, hypotension >SEPTIC SHOCK: severe sepsis w/ persistent hypotension, signs of end organ damage, lactate >4mmol Endocarditis: endocardium inflammation, infection of heart valves, microbe attachment & growth(“vegetations”), fever, anemia, abnormal heartbeat, petechiae rash, Osler’s nodes/Janeway lesions, splinter hemorrhage CC: staphylococcus epidermidis (coag-negative Staph-won’t clump w/ antibodies), skin NF, cocci in clusters CC2: oral streptococci (S.mutans or S.oralis) CC3: high power pathogens like S.aureus, GAS, etc VF: biofilm formation - has to stick & stay to form vegetation Negative for coagulase enzyme, may follow infection of prosthetic devices or IV drug use, Tx: complete removal of prosthetic, long-term ABX, possibly VANC Toxic Shock Syndrome: sudden high fever & low bp (hypotension), vomiting/ diarrhea, confusion, seizures, head/muscle aches, rash resembling sunburn on palms & soles, peeling of hands/feet, boiled lobster rash, can lead to MOF CC: almost any bacteria, Staph aureus(toxemia)-staph can release TSST-1(superantigen) w/out entering bloodstream, tampon usage, Strep pyogenes(bacteria+toxemia)-often introduced w/ puncture wounds, SpeA & SpeC toxins(superantigens), Gram(-) bacteria from LPS release (septic shock) endotoxin Necrotizing Fasciitis (NF): flesh eating disease, use bloodstream to move, death & necrosis of tissue requires debridement, often after trauma CC: streptococcus pyogenes or staphylococcus aureus, toxin mediated Tx: debridement>removal of tissue(cutting margins, possible amputation) NEW emerging causes= Vibrio vulnificus(waterborne), Aeromonas hydrophila(waterborne) Septicemias: organisms actively replicating in blood, fever & hypotension, very ill, altered mental state, shaking, chills, GI symptoms, increased respiratory Many different bacteria & a few fungi can cause this - NOT viruses Favorites: GAS & pseudomonas aeruginosa - NF, grows anywhere w/ O2, grows on almost any media, greenish color, fruity/grape-like odor, identify by fluorescence (+) and oxidase testing (+)(purple color), ENDOTOXIN (LPS), lots of adhesion molecules, alginate capsule, elastase destroys connective tissues, Exotoxin A & Exoenzyme S for direct tissue damage(protein synthesis inhibitors, highly multi-drug resistant, prefers wet/moist, hot tub bug, burn wounds, cystic fibrosis, swimmers ear Plague: bubonic plague, black death, flea bite, causes necrosis of lymph nodes, swollen bubo in groin/axilla, fever, chills, nausea, headache, DIC, subcutaneous hemorrhage/purpura, tissue necrosis, HIGH mortality Septicemic plague form:progresses to massive bacterial growth(blood&lymph) Pneumonic plague form: respiratory disease- attacks lungs CC: Yersinia pestis, VF: low ID(3-50), Yop T3SS(stabs immune cells, injects toxins), ENDEMIC to West/SW US, from fleas, contact w wild animals Tx: aminoglycoside ABX, vax available for high risk individuals Tularemia: lawn mower fever, rabbit fever, headache, fever, chills, malaise, progresses to ulcerative lesions, swollen LN, sore throat, intestinal disrupt, debilitating, fatal if inhalation exposure, vector=tick(open sore @tick bite) CC: Francisella tularensis, VF: intracellular, highly infectious (ID=1-10) Tularemia cont. Potential bioweapon CatA, Tx: Aminoglycosides (Gent, Kan) Lyme Disease: rash spread by tick,mimics neuromuscular&rheumatoid condit. “Post lyme disease syndrome”=headache, fatigue, arthralgias 6mo to 1 year CC: Borrelia burgdorferii (spirochete), VF: motility, adhesion, antigen shifting Tx: doxycycline or b-lactams(1st), cefotaxime or ceftriaxone(2nd), over 3-4 weeks, corticosteroids for inflammatory Early localized (EM): bullseye rash, not painful Early disseminated: acute neurologic or cardiac involvement usually weeks to months after bite, meningitis, cranial neuropathy, motor/sensory radiculo- neuropathy- facial nerve is most often affected cranial nerve, Lyme can cause bilateral cranial nerve palsies, occasional conjunctivitis Late disease: months to years later, arthritis, mild neurologic syndrome Lyme encephalopathy Rock Mountain Spotted Fever(RMSF): tick, fever, chills, headache, muscle pain, spotted rash from extremities to trunk, CV disruption, restlessness, delirium, convulsion, tremor, coma CC: Rickettsia rickettsii, VF: obligate intracellular pathogen, replicates in endothelial cells, these are killed, blood system compromised, kidney failure, GI problems, heart complications, Tx: Tetracycline, limit tick exposure Ehrlichiosis: RMSF w/ no rash, tick, no rash bc infects WBC CC: E.chaffiensis(HME)-Human Monocytic Ehrlichia(M∅, DC) or E.equi (HGE)- Human Granulocytic Ehrlichia(N∅, Masts, etc) both are identical infections but infect different immune cell types, VF: intracellular pathogen, Tx: Tetracycline, limit tick exposure CSF & CBC: animal wound, start as classic cellulitis, moves to capillaries or lymphatics-LN swell & become pus-filled, track lines, CC: CSF= Bartonella henselae(intracellular bacterium), CBC= Pasteurella multocida(safety pin stain, capsule, P.multocida toxin(PMT) destroys connective tissue & allows invasion Tx: self-limiting, possible ABX, immunocompromised=aggressive therapy Ebola: hemorrhagic fever, headache, weakness, vomiting, zoonotic, chest pain, impaired kidney/liver function, rash, red eyes, CC: ebola virus, Marburg virus, VF: aggressive viremia, clotting leading to internal/external bleeding, Tx: unknown, treat symptoms if possible, spread by blood and close contact Vax: rVSV-ZEBOV, hemorrhagic fever variants, 6/U shape, bud from host cells Infectious Mononucleosis: mono, kissing disease, sore throat, grey/white color, swelling, CC: Epstein-Barr virus(EBV human herpesvirus 4), infects bcells, can be latent, no Tx, could lead to spleen rupture-internal bleeding Dengue Fever: mosquito, sudden high fever(104-5), flat red rash w second rash on top, bonebreak fever, CC: dengue virus, puerto rico, VF: viremia Zika Virus: mosquito, similar to dengue, fever, rash, conjunctivitis, joint pain, treat symptoms-no aspirin, not deadly, Guillain-Barre, if pregnant risk of microcephaly during 1st trimester=lack of brain development, small head Malaria: mosquitos, cyclic fevers, anemia, fatigue, neurological damage, abnormal posturing, CC: plasmodium falciparum(parasite), circles/rings, Dx: thick & thin blood smears, Tx: quinine ABX, mosquito repellent & water source cleanup HIV: retrovirus, uses RDDP to get to host, 1: flu-like, Tcell 500+, asymptomatic, 2: chronic, 2-15yrs, Tcell 200-500, 3: AIDS, gateway to infection(cancer/meng), Tcell <200, Tx: antiretroviral therapy ASAP, life-long, Atripla or PrEP/PEP, HAART:highly active antiretroviral therapy, cART, combination antiretroviral therapy, cocktail therapy for life COVID: zoonotic RNA virus, spikes as main epitope, frequent mutations, COHABITATION is our goal, ARDS as main killer event>immune based response fills alveoli & leads to fibrosis(non-elastic), Tx as RDRP inhibitors (remdesivir), combo of B&T responses, long covid: microvascular clot issues, taste/smell, SOB/scarring, neuropathy, cardiac damage, stroke, seizure, Guillain-Barre, spike glycoprotein(S) binds ACE2, TMPRSS cleaves S & starts membrane fusion & virus entry, infection of T2 pneumocytes/surfactant, cytokine storm, PCR, antigen/antibody serology testing, herd immunity Antigenic Original Sin(AOS): responses based on memory(as opposed to modifying ABX)work fastest, so Bcells get to work pumping out antibodies of shapes they’ve seen before=imprinting, neither good nor bad, simply reflects that a person’s first exposure to a virus can have a noticeable effect on their later responses to variants of that same virus. In AOS, prior memory can interfere or even prevent you from generating antibodies against new variants. Not currently seen in COVID, but carefully watching “you can’t teach an old dog new tricks” old dog is your immune memory. Extra Notes: Rapid strep test: serology of Ig’s against outer Lancefield group antigens of GAS Streptococcal Pharyngitis Tx: b-lactams Diphtheria cases increasing bc less children receiving DPT vax