Transfusion transmitted diseases Flashcards
1
Q
Prion vs virus
A
- Filterable infectious agent: both
- Presence of nucleic acid: only virus
- Defined morphology: only virus
- Presence of protein: both
2
Q
Prion disease: transmissible spongiform encephalopathy (TSE)
A
- Can be transmitted and non-transmitted
- Transmitted: inoculation, iatrogenic (caused by illness/procedure), ingestion
- Non-transmitted: inherited, spontaneous
3
Q
Classic (non-transmitted) creutzfeldt-jakob disease (CJD) progression
A
- Caused by prion protein (PrP) misfolding (mainly B sheets instead of mainly A helices) that creates a seed, leading to more misfolding of the PrP proteins
- Eventually the proteins aggregate into fibrils, rods and damage normal cell function (become resistant to proteinase K)
- Has a long incubation time (10-30 yrs) and leads to neurocognitive degeneration and rapid progression to death
- Some other symptoms: loss of muscle control (jerks/tremors), loss of coordination, rapid dementia
4
Q
Variant vs classic CJD 1
A
- Variant (acquired) usually onset earlier, w/ median age of death at 28 yrs
- Psychiatric and sensory symptoms are frequent in early course of illness
- Florid prion plaques found, surrounded by spongiform changes
- Abnormal prion protein detectable in lymphoid tissue (usually acquired from digestive system)
5
Q
Variant vs classic CJD 2
A
- Classic CJD onsets later, w/ median age of death at 68 yrs
- Psychiatric and sensory symptoms appear later in course of illness
- Florid plaques uncommon
- Abnormal prion protein not detected in lymphoid tissue (only brain and spinal cord)
6
Q
PrP structure
A
- Normal PrP (PrPc) has more a-helices than B sheets
- Misfolded PrP (PrPsc) is mainly B sheets
- A few misfolded PrPs will form a seed, which then aggregates more misfolded PrPs to form a growing fibril
- PrPc is found normally on membranes, sensitive to proteolytic degradation and inactivation
- PrPsc induces conversion of PrPc to PrPsc (sc= from sheep)
- PrPsc resistant to most proteolytic degradation and inactivation
7
Q
Chagas’ disease 1
A
- Can be asymptomatic, acute, intermediate, or chronic
- Acute: chagoma is the hardened, red small tumor of skin at site of parasite (T cruzi) entry
- Romana’s sign: unilateral bipalpebral edema if the port of entry is conjunctiva (swelling of one eye)
- Have non-specific symptoms: fever, malaise, lymphadenopathy
8
Q
Chagas’ disease 2
A
- Intermediate: persistently low level of parasite and Abs in blood (most people remain in this phase for life w/o any progression)
- Chronic: characterized by hepatosplenomegaly, myocarditis/cardiomyopathy, megacolon and megaesophagus, and severe CNS involvement
- CNS involvement includes granulomas, meningoencephalitis (younger patients), and dementia
- Death due to cardiac arrhythmias and brain damage, or tissue damage to other organs
9
Q
CMV (cytomegalovirus) infection phases 1
A
- Primary infection (seroconversion of Ab- to Ab+) occurs when it is the first time someone is infected w/ CMV
- The pt has productive viral replication and shedding, CMV shed in blood, milk, saliva, tears, semen, urine
- Then the virus establishes latent infection in T cells, macrophages, and epithelium
- There is no viral proliferation (but still viral transcription) or damage caused by virus, and thus no clinical illness
- Disease in latency controlled by CD8 Ts
10
Q
CMV (cytomegalovirus) infection phases 2
A
- Recurrent infection is when the control of virus replication is lost due to suppression of immune system (HIV, transplant, malnutrition, ext)
- CMV is once again shed from bodily fluids
- Since CMV is a member of the herpes family and establishes latency, people have it for life (and shed it even when asymptomatic)
11
Q
People at high risk for CMV
A
- Neonates: mother who experience seroconversion (primary exposure) during term lead to high risk of congenital birth defects
- These include: prematurity, intrauterine growth restriction, microcephaly, jaundice, hepatosplenomegaly, petechiae, pneumonia
- The immunocompromised: Tx recipients on immunosuppressive Rx are unable to control the latent virus, often results in pneumonia and pneumonitis
- Seropositive patient receiving seronegative graft: patients who are receiving a seronegative graft but who have the disease are at high risk of recurrent infection
- In the IC’d CMV causes: pneumonitis, GI disease, and retinitis
12
Q
CMV in normal individuals
A
- Pathogenic hallmark of CMV is an enlarged cell w/ viral inclusion bodies (cytomegaly)
- These look like owl’s or alien’s eyes
- Most people get it soon after birth, usually w/ no or mild clinical symptoms
- Some people get heterophile-negative mononucleosis: prolonged fever, mild hepatitis, sore throat
13
Q
CMV evasion of host immunity
A
- Decreased viral Ab presentation: down-regulates MHC1 on infected cells and MHC2 on APCs
- Inhibit cell-mediated immunity: blocks NKC activity by inhibiting the synthesis of ligand for NK-activating receptors
- It also inhibits the Th1 immune response by producing an IL10 analog to inhibit IL10’s activity
14
Q
West nile virus (WNV) 1
A
- Carried by mosquitos (arbovirus)
- 80% of infected are asymptomatic
- 20% get west nile fever (incubation 3-15 days): headache, chills, fever, weakness, arthralgia, drowsiness, nausea, vomiting (non-specific flu symptoms)
- Symptoms get worse w/ increase in age
- No permanent health effects
- Humans are dead-end carriers
15
Q
West nile virus (WNV) 2
A
- Less than 1% get west nile encephalitis/meningitis
- Distinct neurological symptoms: severe headache, neck stiffness, disorientation, convulsions
- 40% of patients develop neuroinvasive disease after organ transplant
- Neurological impairment effects may be permanent
- Dx using: serology (IgM/IgG), nucleic acid amplification test (NAAT) detecting viral RNA
