MOD II Midterm 1.1

primary infection vs secondary/re-infection?

• primary: 1st infection w/ pathogen, stages= microbe entry → incubation → prodromal stage → symptoms → convalescent period

• secondary: repeat infection w/ same microbe

latent infection? subclinical infection and carrier?

• latent → pathogen dormant after primary infection, reactivate later (e.g immunocompromised)

• subclinical → no overt signs/symptoms (asymptomatic)

  • carrier → host unable to clear infection but not signs (can still transmit)

stages of microbial infection? bacterial port of entry? attachment?

• enter host → attach cell → invade/establish → survive host defense → damage + disease → exit host → spread

• POE → ingest, inhale, trauma, needlestick, arthropod bite, sexual

• attachment → fimbriae, flagella, spike, barb

direct transmission? indirect transmission?

• direct → physical, respiratory, vertical, bio vector

  • vector → bio (participate in pathogen life cycle) OR mechanical (transport infectious agent w/o being infected)

• indirect → fecal-oral (fomites or food/water) + aerosols (resp., animal waste, soil)

stages of immune response? molecular mimicry?

• invasion → innate immune response → APC (i.e DC) deliver to LN → adaptive immune response → B + T cells

• pathogen produce molecules similar to host → host makes Ab → Ab cross react w/ host tissue = autoimmune

  • e.g group A strep. M protein similar to cardiac muscle = rheumatic fever

exotoxin types? endotoxin MOA?

• AB toxins → A= action portion (injury) + B= binding portion (entry)

  • ex: cholera toxin, tetanus toxin, diphtheria toxin, botulism toxin

• lipid A portion of LPS + LOS found in gram (-) bacteria (E. coli, P. aeruginosa, Klebsiella)

  • MOA: lipid A binds CD14 + TLR4 on MO + B cells → stim. prod. + release acute-phase cytokines (IL-1+6, TNFa, PG)

superantigen function?

• stimulate T cells → release large amt. TNF WITHOUT classic antigen presentation

  • ex: staphylococcal toxic shock syndrome (TSST-1) → fever, hypotension, erythematous rash

adherence molecule types?

• adhesin molecules + pili/fimbriae

  • ex: Mycoplasma pneumoniae P1 adhesin, MSCRAMM of Staph aureus (adhesin), E. coli type 1 pili, N. gonorrhoeae type IV pili

capsule function? biofilm function?

• capsule → loose polysaccharide or protein layer around bacteria = protect from phagocytosis

  • ex: staph aureus, strep pneumo, strep pyogenes, neisseria gonorrhea, e coli

• biofilm → bacteria communities made of polysaccharides = prevent Ab binding, complement action, phagocytosis

  • ex: staph epi

sepsis vs septic shock?

• sepsis → infection + organ dysfxn

  • inc. WBC, CRP, procalcitonin

• septic shock → sepsis + persistent hypotension w/ vasopressors (MAP> 65 mmHg)

  • lactate > 2 mmol/L, inc. WBC, tachycardia

  • possible late stage refractory response to vasopressors

what causes metabolic acidosis in septic shock?

• hypovolemia → dec. perfusion (dec. O2)

• anaerobic met. → inc. lactate

• = inc. H (dec. pH) → dec. HCO3 (buffers H) + inc. CL (replace lost HCO3)

  • late inc. K

lab panels for organ dysfxn?

• kidney → inc. creatinine, dec. urine output

• liver → inc. AST/ALT, bilirubin

• coagulation → inc. PT/INR, aPTT, dec. platelet

• heme → inc. WBC/low WBC

• metabolic acidosis

cardiovascular effect of septic shock?

• >50 PP

• early → reflex tachy (inc. CO)

• late (cool/clammy, inc. lactate) → dec. CO

• massive VD → dec. SVR (always below normal but inc. in comparison late stage)

• vol. leak/hypovolemia → dec. CVP/preload + PCWP

  • vol. overload (JVP, edema) → opp.

cardiovascular effect of hypovolemic shock?

• <30 PP

• low CO, PCWP, CVP/preload

• inc. SVR (comp)

steps of viral infection? tissue tropism?

• POE → attach to host → invade + establish → survive defense → damage + disease → exit

• affinity for viruses for specific tissue due to receptor distribution

viruses with animal resevoirs?

• rabies → bat bites

• hantavirus → rodent feces

• yellow fever/dengue/zika → mosquito

• SARS3 → cat aerosol droplets

• avian flu → bird feces

viruses with the following routes of entry (resp. tract, GIT, skin)?

• resp. tract → influenza, RSV, measles, CMV, parovirus B19

• GIT → HAV, polio/rota/norovirus

• skin → rabies, dengue, zika, HPV

viruses with the following routes of entry (genital tract, blood, transplacenta, breastfeeding)?

• genital → HSV2, HPV, HBV, zika, HIV

• blood → HBV, HCV, HIV, CMV, HTLV

• transplacenta → CMV, HSV, HIV, rubella, zika, parovirus B19

• breastfeeding → HIV, CMV, HBV

HSV1 (oral) family, viral protein, symptoms? latency?

• herpesviridae

• heparan sulfate

• vesicular lesions on mouth + encephalitis

• latent in trigeminal (V) sensory ganglia

HSV2 (genital) family, viral protein, symptoms? latency?

• herpesviridae

• heparan sulfate

• vesicular lesions on genitals + viremia

• latent in sacral ganglia

varicella zoster (VZV) family, viral protein, symptoms? latency?

• herpesviridae

• heparan sulfate

• chicken pox → acute, asynch, derm rash

  • shingles → reactivate latent, painful lesion

• latent in CN/dorsal root ganglia, retrograde axonal transport

CMV family, viral protein, symptoms? latency?

• herpesviridae

• heparan sulfate

• hearing loss, chorioretinitis, microcephaly

• persistent or latent infection, mimic EBV

EBV (mono) family, viral protein, symptoms? latency?

• herpesviridae

• gp350/220 → CD21 (CR2)

• fever, pharyngitis, lymphadenopathy

• latent in B cells

hepatitis B family, viral protein, symptoms? Antibody levels?

• hepadnaviridae

• NTCP + EGFR

• hepatitis, cirrhosis, cancer (edema/jaundice)

• Ab levels

  • window → HBcAb (IgM)+, HBeAg+

  • acute → HBsAg+, HBcAb (IgM)+, HBeAg+

  • chronic → HBsAg+, HBcAb (IgG)+, HBeAb±

  • recovery → HBsAg+, HBsAb

HIV family, viral protein, symptoms? progress into?

• retroviridae

• gp1120/41 → CD4 + CCR5

• thrush, lymphadenopathy, opportunistic infections

• progress to AIDs; encodes proaptotic Vpr

SARS-CoV-2 family, viral protein, symptoms? diagnosis?

• coronoaviridae

• spike protein → ACE-2

• cold-like, ARDS, sepsis, organ failure, MIS-C

• Dx w/ RT-PCR or antigen test

poliovirus family, viral protein, symptoms? transport? vaccine?

• picornaviridae

• VP1 → CD155 (PVR)

• fever aspetic meningitis, flaccid paralysis (bc destruction of ant. horn motor cells)

• retrograde axonal transport; fecal oral route

  • killed/inactive vaccine to prevent mutation

rhinovirus family, viral protein, symptoms?

• picornaviridae

• VP1 → ICAM1 (CD54)

• sneezing, congestion, sore throat

  • common cold; acid labile

influenza family, viral protein, symptoms? action?

• orthomyxoviridae

• HA → sialic acid

• fever, myalgia, cough

• segmented genome, steals host mRNA 5’ cap

  • HA (enter) + NA (exit)

RSV family, viral protein, symptoms?

• paramyxoviridae

• F protein → GAGs

• upper resp/lower tract- bronchiolitis, pneumonia

• helical capsid + uses RT+ HA/NA

measles family, viral protein, symptoms? invasion?

• paramyxoviridae

• HA → CD46

• cough, coryza (runny nose), conjunctivitis, maculopapular rash + koplik spots (mouth)

• direct invasion via capillary endothelium SSPE (neurodegeneration due to latency)

rabies family, viral protein, symptoms? transport?

• rhabdoviridae

• G protein → NCAM

  • negri bodies → viral factories

• hydrophobia, agitation, coma

• retrograde axonal transport

maraviroc MOA? target? enfuvirtide?

• both → attachment (entry/fusion) inhibitors

• maraviroc: CCR5 (stability) → HIV

• enfuvirtide: gp41 → HIV

amantadine + rimantadine MOA? target?

• uncoating

• M2 → influenza A (no longer recommended)

acyclovir, zidovudine, penciclovir, famciclovir MOA? target?

• genome replication (DNA synth)

• thymidine kinase + DNA polymerase → HSV, VZV

ganciclovir, valganciclovir, foscarnet (CMV/HSV resistant), cidofovir MOA? target?

• genome replication (DNA synth)

• thymidine kinase, UL97 kinase, DNA polymerase → CMV

remdesivir MOA? target?

• genome replication (DNA synth)

• RNA polymerase → coronavirus

paxlovid (nirmatrelvir + ritonavir) MOA? target?

• protease inhibitor (PI)

• post-translational modification inducer → COVID-19

oseltamavir + xanamivir MOA? target?

• release (NA)

• sialic acid → influenza (therapy not indicated past 48 hrs)

cabotegravir, raltegravir, elvitegravir MOA? target?

• integrase inhibitor (INSTI)

• HIV