Immunology IV

common cold (rhinovirus)

• three species → A, B, C

• more than 100 strains

• timeline of infection:

  • incubation period → ~2 days

  • symptomatic course → ~7-14 days

• most common in early fall

• virus in respiratory tract → highest in first two days of symptoms

• detectable from one day before symptoms to 6 days after symptoms

• transmission → airborne (aerosols from coughing/sneezing) or close contact

• 1-3 weeks post-infection → antibodies, T cells

common cold: treatment

• treat symptoms → doesn’t affect duration

• fluids → loosen congestion and prevent dehydration

• for adults and older children…

  • decongestant

  • antihistamine

• do not use antibiotics unless concern for opportunistic bacterial infection

• no specific treatment due to many different viruses and relatively rapid mutation rates

common cold: mechanism

1. mucociliary escalator → cilia on epithelial cells sweep ~90% of inhaled particles out of airway (expelled by cough/sneeze with mucus)

2. remaining virus may enter a subset of airway epithelial cells expressing a specific receptor, ICAM1

3. virus replicates in host cells, inducing release of cytokines, interferons, and bradykinin (vasodilator) → inhibit viral replication and recruitment of leukocytes

4. antigen presentation to helper T cells, amplifying both B cell and killer T cell responses

5. IgM/IgG in blood, IgA secretion into airway mucus, killer T-cell mediated apoptosis

common cold: complications

• reduced mucociliary escalator → mucostasis (mucus accumulates in airway)

  • hypersecretion of mucus (can be caused by too many pro-inflammatory cytokines)

  • environment (ex: smoking or pollution damage cilia)

  • disease (ciliary dyskinesia)

• viral escape from host interferon response or decreased host interferon response

• increased bacterial adherence (susceptible individuals or severe cases) → secondary bacterial infection

• immunodeficiency

cholera (Vibrio cholerae)

• gram negative bacteria

• more than 200 strains

  • only 2 strains are toxigenic

• timeline of infection:

  • incubation period → 0.5-5 days (2-3 days most common)

  • symptomatic course → ~7-14 days

• bacteria shed in stool (water and sewage sanitation)

• 1-3 weeks post-infection → antibodies, T cells

• risk factors → vitamin A deficiency, ABO antigen (O increases disease severity), other genetic factors

• transmission:

  • water

  • contaminated food

  • poor hygiene

  • slow moving, slightly salty waters (ex: raw shellfish)

cholera: treatment

• antibiotic treatment if severe (5-10% of symptomatic cases)

  • shortens disease course and reduces severity

• rehydration therapy is most important

• two oral vaccines, not available in U.S.

cholera: antibiotics

• azithromycin → susceptible

• tetracycline → susceptible

• doxycycline → susceptible

• ciprofloxacin → reduced susceptibility

• sulfisoxazole → resistant

• furazolidone → resistant

• nalidixic acid → resistant

cholera: mechanism

• cholera toxin (exotoxin secreted by live bacteria) is an enterotoxin that causes secretory diarrhea

• some survive stomach pH and attach to small intestine mucosa → release cholera toxin

• toxin B subunit attaches to host intestinal cell → inserts A subunit into cell

• toxin A subunit increases stimulation of adnylyl cyclase → increases cAMP → activates CFTR → increases stimulation of Cl^- secretion into lumen → Na⁺ follows → H₂O follows (pulls water from body)

• bacteria from lumen shed in feces → can contaminate water and food

cholera: immune response

• cholera toxin is extracellular → low-inflammatory infection

• generally no/few fecal leukocytes

• intestinal mucosa and cell integrity remain grossly intact → no bloody stool

cholera: non-specific response

• cytokine release

• neutrophil migration

• alternative complement pathway

• other bactericidal proteins (defensin, lactoferrin)

cholera: specific response

• activation of B cell response

• secretion of IgA

• classic complement pathway

• opsonization to increase phagocytosis

• toxin neutralization

diarrheal diseases

• secretory diarrhea (cholera):

  • toxins in small intestine

  • oversecretion of water

• inflammatory diarhea (salmonella, campylobacter):

  • bacteria infect mucosal cells of small and large intestines

  • intestinal cells damaged by toxins or bacteria

  • often blood and mucus in stool (dysentery)

• hemorrhagic diarrhea:

  • bacterial toxins (ex: Shiga toxins from some E. coli or Shigella strains) directly cause cell death

  • target large intestine

  • may have significant blood loss

• GI tract infections can be caused by bacterial (ex: cholera), viral (ex: norovirus), fungal, and protozoan (ex: giardia) infections

ebola (hemorrhagic fever)

• timeline of infection → ~14-21 days

• 1-3 days after symptoms start → virus detected in blood

• later → IgM and IgG antibodies

• mortality rates:

  • previous outbreaks → 50-90%

  • 2014-2015 outbreak → 28-66%

• not infectious until symptomatic (late stage)

ebola: treatment

• symptomatic:

  • IV fluids/electrolytes

  • monitor PO₂ and blood pressure

  • limit opportunistic infections

• a vaccine is currently under development

ebola: mechanism

• viral glycoprotein prefers to bind to immune cells

  • APC (dendritic cells, monocytes, macrophages) → cytokines → fever, inflammation, malaise

  • endothelial cells → decrease vascular integrity → bleeding (hemorrhagic) → hypotensive shock

  • hepatocytes

• suppresses both non-specific and specific immunity

  • infects APC

  • disrupts recognition of MHC 1 → more difficult to clear viral load → viremia

  • inhibits neutrophil activation