transfusion transmitted diseases Flashcards
What are the differences between viral and protein infectious agents?
Prion=proteinaceous+infection
Virus:
Has filterable infectious agent, presence of nucleic acid, defined morphology, and presence of protein
Prion:
Only has filterable infectious agent and presence of protein. No defined morphology or nucleic acid
What are the symptoms of classic creutzfeldt-jakob disease (CJD) progression?
- Disease progression: long incubation period (up to 30 years), neurocognitive degeneration, rapid progression to death
- Symptomatology: loss of muscle control, myoclonic jerks/tremors, loss of coordination, rapid dementia, ultimately death
Describe variant CJD.
Acquired
- age of onset: earlier
- median age of death: 28 yrs
- Psych/sensory symptoms: frequent in early course of illness
- EEG changes: absent
- Duration of illness: 13 months median
- neuropathologic features: florid prion protein plaques, surrounded by spongiform changes
- immunohistochemistry: abnormal prion protein detectable in lymphoid tissues.
Describe classic CJD.
Spontaneous
- age of onset: later
- median age of death: 68 yrs
- Psych/sensory symptoms: appear later in course of illness
- EEG changes: diagnostic EEG changes commonly seen
- Duration of illness: 4 months
- neuropathologic features: florid prion protein plaques uncommon
- immunohistochemistry: abnormal prion protein NOT detectable in lymphoid tissues.
What is the difference of lymphoreticular system involvement in CJD vs. vCJD?
Classical CJD: brain and spinal cord
vCJD: brain, eyes, tonsil, spinal cord, thymus, spleen, adrenal gland, lymph nodes, appendix, rectum
Explain the structural and behavioral differences between PrP-C and PrP-Sc
Structural:
-normal PrP-C is more alpha helix than beta sheet. Cellular proteins found normally on membranes, endogenous form found in many tissues.
-misfolded PrP-Sc is mainly beta sheet. Scrapie prion proteins, infectious isoform of PrP, induces conversion of PrP-C to PrP-Sc
Behavioral:
-PrP-C: sensitive to proteoytic degradation, sensitive to chemical and physical inactivation
-PrP-Sc: resistant to most proteolytic degradation, resistant to chemical and physical inactivation, can induce conversion of PrP-C to PrP-Sc
Describe the acute stage of Chagas disease caused by T cruzi.
Chagoma: hardened, red small tumor of the skin at the site of parasite entry
-Romana’s Sign: unilateral bipalpebral edema if the port of entry is conjunctiva
Non-specific: Fever, malaise, lymphadenopathy
Describe the intermediate stage of Chagas disease.
- persistently low level of parasite in the blood as well as antibodies
- most persons remain in this phase for life without any progressive change
Describe the chronic stage of Chagas Disease.
- Myocarditis/cardiomyopathy
- CNS: meningoencephalitis (younger patients), Dementia
- Colon and Esophagus: Megacolon, megaesophagus
What is the pathogenesis of Chagas Disease
Direct damage and inflammation:
-intracellular amastigotes kill host cells
-tissue destruction in neurons, heart, intestines
-damage to cardiac muscle frequently cause of death
Autoimmunity
-T Cruzi antigens cross react with host antigens causing autoimmune reactions
-cross reactive T cells or B cells become activated and attach host tissue
Describe primary CMV infection.
- Seroconversion: Ab- to Ab+
- productive viral replication and shedding
- CMV may be shed from bodily fluids: blood, breast milk, saliva, semen, tears, urine
Describe latent CMV infection.
- Viruses establishes latency in T cells, macrophages, epithelial cells, etc.
- no viral proliferaiton
- No cell damage caused during latency and thus no clinical illness
- The disease is controlled by surveillance of CD8+ T cells
Describe recurrent CMV disease.
- Control of viral replication is lost due to suppression of immune response: HIV, transplant, immunodeficient patients
- CMV may be shed intermittently from bodily fluids
Why are immunocompromised individuals more prone to CMV recurrences?
Transplant recipients:
-immune surveillance chemically impaired by suppressive therapy
-seropositive patient receive seronegative graft because graft is still naive/not protected
HIV/AIDS:
-deficient T cell function, inability to mount response
-loss of CD4 cells leads to functional loss of CD8 cells controlling virus
How does CMV affect immunocompetent individuals?
- acquired after birth
- heterophile negative mononucleosis: prolonged fever, mild hepatitis, sore throat
How does CMV affect fetus/neonates?
- most common cause of congenital abnormalities
- primary infection of mother during pregnancy is dangerous: developmental impairment, congenital defects, death
- Diseases: intrauterine growth restriction, prematurity, microcephaly, jaundice, petechiae, hepatosplenomegaly, pneumonia
What diseases does CMV cause in immunocompromised individuals?
- pneumonitis
- GI disease: ulcerative lesions, ab pain, hematemesis, diarrhea
- CMV retinitis: blurred vision, eye pain, photophobia, redness, blindness
How does CMV evade host immunity?
- Decreases viral antigen presentation
- downregulate MHC1 on infected cells and down regulate MHC2 on AP cells - Inhibit cell-mediated immunity
- block NK cell activity by inhibiting synthesis of ligand for NK activating receptors
- inhibit TH1 immune response: CMV encodes Il-10 analogue that inhibits Th1 immune responses
Describe the clinical diseases caused by west nile virus.
-majority are asymptomatic (80%)
WEST NILE FEVER
-incubation period 3-15 days
-symptoms severity increases with age
-headache, chills, fever, weakness
-joint pain, drowsiness, nausea, vomiting
-overall very non specific flu like symptoms
-no permanent health effects
WEST NILE ENCEPHALITIS/MENINGITIS
-<1% cases have CNS infections
-severe headache, neck stiffness, disorientation, convulsions
-40% develop neuroinvasive disease after organ transplantation
-neurological impairment may be permanent
List the methods to test for WNV infection.
Serology:
-WNV IgM antibodies
-WNV IgG neutralizing antibodies
Nucleic Acid:
-Nucleic acid amplification technique (NAAT) detects viral RNA
-useful for immunocompromised patients who can’t mount antibody immunity
List the host mechanisms in limiting WNV infection
- IFN dependent innate immune responses
- Neutralizing antibodies IgG
- Complement mediated lysis
- Cytotoxic T-lymphocytes: patients with suppressed immune status and older patients have worse outcomes
