lec 13 (?) bacterial, viral, and fungal respiratory infections

anatomy of respiratory tract

upper:

• nasal passages

• sinuses

• nasopharynx

• larynx

lower:

• trachea

• bronchi

upper + lower = conducting system (passageway to transport air)

bronchioles = transitional system

alveoli = exchange system

mechs of defense of respiratory tract

conducting system: anatomical barriers, mucociliary appratus, antbds, lysozyme, mucus

transitional system: club cells, antioxidants, lysozyme, antbds, mucociliary apparatus

exchange system: alveolar macrophages, antbds, surfactant (carpet surface of alveoli to protect from microbes), antioxidants

mucociliary apparatus/escalator

cilia + mucus (produced by goblet cells)

ciliar beat to move mucus and entrapped material to the pharynx

• up from lungs

• down from nasal passages

alveolar macrophages

phagocytose particles/organisms that reach the alveoli

organisms are “killed” inside the macrophages

initiate and regulate immune response

granuloma

bacteria has been phagocytosed but survives degradation inside macrophage

produces inflammatory cytokines

bordetella pertussis: whooping cough

gram negative, non-enteric, aerobic

source: other infected humans

transmitted via aerosols

highly contagious (>80% of close contacts)

affects children and adolescents mostly

vax preventable: the “P” in the DPT vax

• booster recommended

bordetella pertussis pathogenesis

adheres to cilia microbilli

• mediated by protein adhesins: pertactin, filamentous hemaglutinin, fimbriae

causes ciliostasis and cilionecrosis

• mediated by tracheal cytotoxin

causes local ischemia (lack of oxygen) and tissue dmg

• mediated by dermonecrotic toxin

causes systemic effects

• mediated by pertussis toxin

increase in respiratory secretions and mucus prod = paroxysmal coughing (repetitive coughing)

bordetella 3 stages

1. catarrhal

   1. nasal discharge, sneezing, lacrimation, mild cough (10-14 days)

2. paroxysmal

   1. cough increases freq and severity

   2. ciliated cells shed, accumulation of mucus, honking cough to try to expel, vomiting, exhaustion

   3. cough bouts during expiration, “whoop” sound during deep inspiration

3. convalescent:

   1. cough improves but may recur

   2. secondary complications

corynebacterium diphtheriae

gram + rod

4 biotypes: mitis most common associated w/ disease

maintained in population by asymptomatic human carriers

transmitted by respiratory droplets

rare in the US

vax preventable disease: the “D” in the DTP vax

corynebacterium diphtheriae pathogenesis

toxigenic strains produce potent exotoxin: diphtheria toxin

• A-B exotoxin:

  • B subunit binds to epithelial cells

  • A subunit: terminates cellular protein synthesis → epithelial cell death → inflammation and necrosis of local tissues

diphtheriae clinical signs and symptoms

• respiratory (nasopharyngeal) diphtheria (most common)

  • multiples locally on epithelial cells in pharynx/larynx, tonsils, uvula, palate

  • causes exudative pharyngitis and pseudomembrane formation

  • cardiac and neurologic complications may occur

• cutaneous diphtheria

  • through skin contact, goes subcutaenous

  • scaling rash to non-healing ulcers

mycobacterium tuberculosis

slow-growing, acid-fast bacilli

transmission (respiratory): inhalation of droplets with bacilli

bovine tuberculosis (M. bovis) transmissible to humans (raw milk)

BCG vax used in high-burden countries, 50% efficacy

tuberculosis pathogenesis

inhibits degradation inside macrophages

Th1 repsonse with IFN-y production

granuloma formation and tissue dmg

primary tuberculosis

previously unexposed individuals

• focal granuloma (“primary complex”) that becomes latent

• clinical disease in 5% of newly infected ppl

• may rarely progress to pneumonia or even disseminated disease

seondary tuberculosis

previously exposed individuals

• months to years after primary infexn

• reactivation and formation of cavitary lesions in lungs

• may progress to disseminated disease

tuberculosis signs and symptoms

pulmonary tuberculosis

• pain in chest and cough (>3 wks)

• hemoptysis

• weight loss

• fever and chills

• sweating in the night

influenza viruses (flu)

enveloped, RNA viruses in family orthomyxoviridae

influenza A, B, C, D

transmission: airborne droplets, close contact, contaminated items

influenza A: diff combo of 2 surface glycoproteins (antigens)

• hemagglutinin (H)

• neuraminidase (N)

by which 2 mechs is influenza prone to evolution

1. antigenic drift: progressive geentic mutations in preexisting HxNx combos, seasonal epidemics

2. antigenic shift: new combos of HxNx due to genetic reassortment

   1. punctual pandemics

influenza pathogenesis

cell entry and release:

• hemagglutinin: binding with sialic acid and fuse with host cell membrane

• neuraminidase: removes sialic acid, promoting viral release from infected host cell

evasion of antbd response: antigenic shift and drift

inhibits sodium channels in pneumocytes: fluid in alveolar lumen

epithelial cell death: caspases activation

danger signals: resident macrophage activation

influenza clinical signs and symptoms

fever, cough, and pain

mild upper respiratory symptoms at first

may evolve to more severe lower respiratory disease

occassionally GI disease

complications:

• pneumonia: viral or superimposed bacterial pneumonia

• myocarditism encephalitis, myoglobinuria

high pathogenic avian influenza H5N1

bird-adapted influenza A virus → wild birds and commercial poultry

zoonotic, but cases in humans are rare

closely monitored due to pandemic potential (antigenic shift)

infects cells in mammary gland in dairy cattle and is shed in milk

• pasteurization kills the virus

SARS-CoV-2

enveloped RNA virus

with spike proteins

zoonotic

airborne droplets, close contact, contaminated items

COVID-19 pathogenesis

cell entry: spike proteins binds to its receptor: angiotensin-converting enzyme 2 (ACE2) — ciliated cells

diffuse alveolar dmg → acute respiratory distress syndrome (ARDS)

• dmg to type 1 and 2 pneumocytes

• activation of alveolar macs

• proinflammatory cytokine prod

• endothelial dmg and procoagulant responses

covid signs and symps

mild upper respiratory disease in most cases

severe pneumonia with hypoxia in some cases

complications:

• disseminated intravascular coagulation

• cardiomyopathies, arrythmias

• GI symps

dimorphic fungi

mold in environment = infectious form

yeast

systemic diseases:

• pneumonia: inhalation of mold forms is the route of infection

• dissemination to other sites from lung

coccidioidomycosis (valley fever)

southwestern US

2 spp.

• C. immitis, C. posadasii

found in soil

late summer/fall exposure - dry, dusty, windy conditions

risk factors: immunosuppression, >65 yo, certain ethnic groups

valley fever pathogenesis

1. inhalation of arthroconidia (mold)

2. development of spherule (yeast) with endospores

   1. spherule outer wall glycoprotein inhibits cell-mediated immunity

   2. endospores resistant to phagocytosis and killing

3. hematogenous dissemination

valley fever signs and symptoms

disease outcomes:

• asymptomatic or sublinical disease

  • self-limited flu-like illness

• progressive pulmonary dz (10%)

• multisys dissemination (1%)

new world camelids and valley fever

llamas and alpacas are very susceptible to coccidioidomycosis

blastomycosis (blastomyces dermatitidis)

ecological niche is decaying organic matter (wet environment)

outbreaks associated with occupation or recreational contact w/ soil

blastomycosis pathogenesis

1. inhalation of aerosolized spores (mold)

2. broad-based budding yeast in tissue

   1. yeast form is resistant to phagocytosis and killing alpha-1,3-glucan and melanin in wall

3. hematogenous dissemination

blastomycosis clinical signs and symps

disease outcomes

• asymptomatic or self-limited acute lung disease

• progressive chronic pulmonary dz rare

• disseminated form rare

• rare primary cutaenous form

histoplasmosis

histoplasma capsulatum

thrives in nitrogen-rich, moist organic matter

outbreaks associated with exposure to

• bird roosts

• bat droppings

• caves

• decaying buildings

• recent excavations

histoplasmosis pathogenesis

1. infection is by inhalation of microconidia (mold)

2. germination into budding yeasts within macrophages

   1. induces TNF (proinflammatory cytokine) secretion by macropahges

3. hematogenous or lymphatic dissemination

histoplasmosis clinical signs and symptoms

diseases outcomes

• 90% of infecxns are asymptomatic

• flu-like illness in localized lung infection

• rare disseminated disease (immunosuppression)

• increased severity depending on exposure dose