Week 5 Flashcards
(115 cards)
1
Q
What is a primary infection?
A
First experience with virus
Typically presents much worse than a secondary infection
2
Q
What is secondary infection?
A
Reactivated infection; renewal of viral replication
3
Q
What is a latent infection?
A
Persistence of virus in a non-replicating state
4
Q
What is a symptomatic infection?
A
infection with clinical signs and symptoms
5
Q
What is an asymptomatic infection?
A
viral shedding without symptoms
6
Q
What are the three subfamilies of Herpesviridae?
A
Alpha, Beta, Gamma
7
Q
What are the alpha viruses?
A
HSV-1, HSV-2, VZV
8
Q
What are the beta viruses?
A
CMV, HHV-6, HHV-7
9
Q
What are the gamma viruses?
A
EBV, KSV (HHV-8)
10
Q
What are the characteristics of the alpha family?
A
short replication cycle then destroys host cells and spreads rapidly.
They become latent in sensory ganglia
11
Q
What are the characteristics of the beta family?
A
Long reproductive cycle
enlargement of infected cells
slow cell-to-cell spread
multiple non-ganglionic latency sites
12
Q
What are the characteristics of the gamma family?
A
Replicate in lymphoblastoid vells
latency in lymphoid tissue (EBV), monocytes and lymphocytes (HHV-8)
13
Q
Describe the lipid envelope of the HSV virus
A
The lipid envelope contains multiple surface glycoproteins
Glycoprotein G
14
Q
How does HSV infect a host?
A
enters via skin-to-skin contact, mucous membrane contact, or openings in the skin (wound, burn, diaper rash)
15
Q
What happens after HSV enters the host?
A
It replicates at the site of entry, destroys the cell, spreads rapidly, then becomes latent in sensory ganglia
16
Q
Where is HSV-1’s latent site? HSV-2?
A
HSV-1: trigeminal ganglia
HSV-2: S2-S5 ganglia
17
Q
What are the clinical hallmarks of HSV?
A
fluid filled vesicles
18
Q
What type of cells are found in HSV lesions?
A
multinucleated giant cells and intranuclear inclusions
19
Q
describe characteristics of HSV latency.
A
- mediated by viral genes
- maintained by T cell mediated immunity
- viral genome is circular during activity
20
Q
Are antivirals effective against latent viruses?
A
no
21
Q
What happens when HSV comes out of latency?
A
The DNA becomes linear and the virus travels back to the site of entry
Replication causes the cell to lyse
22
Q
What is the reservoir for HSV?
A
humans
23
Q
Are HSV clinical presentations typically more sever in the primary infection? How so?
A
Yes
illness severity anatomic distribution amount of virus in secretion duration of shedding no antibodies present
24
Q
Can HSV-2 be found above the belt? HSV-1 below the belt?
A
Yes and yes. However, they are generally associated as HSV-1 above the belt and HSV-2 below the belt
25
What are the common HSV-1 infections?
gingivostomatitis
cutaneous lesions
ocular infections
encephalitis
26
What are the characteristics of herpes gingivostomatitis?
```
Typically caused by HSV-1
more common at age 1-3
extensive oral +/- cutaneous lesions
Fever, irritability, tender adenopathy
Poor oral intake leading to dehydration
```
27
What are characteristics of HSV cutaneous infections?
```
Usually caused by HSV-1
Herpetic whitlow (lesions on fingers)
Herpes gladiatorum (wrestlers)
Scrum pox (rugby players)
Eczema herpeticum
```
28
What are characteristics of HSV ocular infections?
Usually caused by HSV-1
Follicular conjunctivitis
Corneal involvement with dendritic ulcers
Recurrence may be sight threatening
29
What are characteristics of HSV encephalitis?
Usually caused by HSV-1
Most common, sporadic form of encephalitis
Fever, headache, altered sensorium (state of consciousness)
Focal signs within the temporal lobe
Lumbar puncture will show CSF with RBCs, WBC, protein
- PCR CSF to diagnose
30
What are characteristics of HSV genitalis?
Usually caused by HSV-2
Sexually transmitted
Genital, rectal, perirectal, proctitis
31
What are the clinical presentations of HSV infections in immunocompromised hosts?
```
More recurrent infections
More prolonged
More progressive and destructive
More widespread
- Liver, lungs, esophagus, brain
```
32
Name 5 methods that can be used to diagnose HSV infections
1) Biopsy may indicate histological features of infection
2) DFA (direct fluorescent antibody) test that labels antibodies specific to HSV with dye
3) PCR
4) Viral culture
5) Serology (Look for HSV antibody in the serum)
33
What is the typical antiviral therapy used for HSV infections?
acyclovir
34
What are some strategies to prevent HSV infections?
1) Avoid contact
- Horizontal (person-to-person)
- Condoms, antivirals
- Vertical (mother-to-child)
- C-section, antivirals
2) Prophylactic therapy
3) vaccination is the holy grail but one does not exist
35
What are the 3 classical clinical presentations of neonatal HSV infections?
1) Skin, eye, mucosal (SEM) disease
- important to rapidly diagnose via DFA to prevent progression
2) Disseminated disease
- Presents with sepsis, liver dysfunction, coagulopathy resulting in hemorrhage, respiratory distress, encephalitis
3) CNS disease
- Lethargy, irritability, fever, SEIZURES
- Culture CSF and perform PCR
- Be sure to look at temporal lobe!!!
36
What are some strategies to prevent infections in the fetus and newborn?
- vaccinate before pregnancy
- treatment during pregnancy
- avoidance during or after delivery
37
What are some strategies to prevent infections in the fetus and newborn?
- vaccinate before pregnancy (BEST)
- treatment during pregnancy
- avoidance during or after delivery
38
What is the mechanism of fever?
IL-1, IL-6, TNF, and IFN act on the hypothalamus to increase body temperature
Can be caused by a crap ton of things
39
What can cause fever?
Again, a crap ton of things
```
infection
neoplasms
allergies
immune disorders
etc.
```
40
What is FUO?
Fever of undetermined origin
41
What are some microbiologic characteristics of EBV?
- gamma 1 herpesviridae
- dsDNA
- Multiple surface glycoproteins
- virus-specific antigens:
- viral capsid antigen (VCA)
- Early antigens (EA)
- Nuclear antigens (EBNA)
42
How is EBV typically transmitted?
Usually via oral transfer of saliva
43
Describe the pathogenesis of EBV
1) EBV colonizes the epithelium in the oropharynx, including tonsils and salivary glands.
2) There, it replicates and infects B cells by binding to CD21R and enters the cell
3) If it enters the lytic phase,, EBV produces a homologue to IL-10, which inhibits Th1 cells. Inhibition of Th1 cells inhibits IFN secretion and activation of macrophages
44
What are clinical presentations of EBV?
non-specific symptoms with atypical lymphocytes (lots of cytosol including some granulation)
45
What two cells does EBV infect?
epithelial in the oropharynx and B cells
46
When does EBV proceed to the lytic phase? Latent phase? Does the cell lyse?
Typically, when EBV infects epithelial cells, it proceeds directly into the lytic phase and lyses the cell
Typically, when EBV infects B cells, it proceeds directly into the latent phase and enters lytic phase at a later time, which may or may not lyse the cell
47
What are the symptom of mononucleosis?
MONO
fever, pharyngitis, and adenopathy
Known as the "kissing disease" and it typically makes you tired.
48
What occurs when EBV infects a B cell and enters the latent phase?
The DNA becomes circular and attaches to the host DNA with the help of EBNA-1. This allows for the virus DNA to be replicated during cell proliferation
49
What occurs when EBV leaves the latent phase and enters the lytic phase?
The circular DNA becomes linear, which transforms the cell and causes mass proliferation
50
What are some diseases of reactivated EBV infections?
* Burkitt lymphoma
* Nasopharyngeal carcinoma
* Hodgkin’s lymphoma
* CNS lymphoma
* Oral hairy leukoplakia
* Post-transplant lymphoproliferative disease
51
Are lytic genes expressed in EBV-associated cancers?
NO LYTIC GENES ARE EXPRESSED IN EBV-ASSOCIATED CANCERS, ONLY LATENT GENES WITH DIFFERENT PATTERNS
52
What are the clinical presentations of Burkitt lymphoma? Describe endemic and sporadic
The ENDEMIC (African) VARIANT is an 8:14/8:22 translocation involving the c-myc oncogene (just one of the few variants, but all involve the c-myc gene).
can involve the jaw/facial bones, GI, and/or GU
SPORADIC VARIANT is typically not associated with EBV and is seen in the ileocecal region
53
What do Burkitt's lymphoma cells look like on slides?
"Starry sky" lipid droplets inside of the cell
54
What are the clinical presentations of nasopharyngeal carcinoma?
Common in Southern China and native North Americans
Genome expresses EBNA-1 and LMP-1 latent gene products
55
What are the clinical presentations of Hodgkin's lymphoma?
Patients have EBV antibody
nodular sclerosis (scarring of lymph nodes)
56
What are the clinical presentations of CNS lymphoma?
Typically occurs in patients with advanced T cell immunosuppression, particularly in patients with HIV/AIDS
- headache
- focal neurological symptoms
- neuropsychiatric symptoms
- seizures
57
What can bee seen on MRI in patients with CNS lymphoma?
lesion(s) on in the periventricular white matter
58
What does CSF analysis show in CNS lymphoma?
elevated intracranial pressure
elevated protein
lymphocytic pleocytosis
59
What are the clinical presentations of Post-transplant lymphoproliferative disease?
B cell proliferation due to immunosuppression following organ transplantation (immunosuppression tells EBV to become active)
60
What are the clinical presentations of oral hairy leukoplakia?
White patches on the margin of the tongue caused by EBV replication
firm, does not scrape off
typically seen in patients with HIV/AIDS
61
What does the varicella zoster virus cause?
chicken pox and shingles
62
What is the classification of VZV?
DNA virus
| alpha herpesviridae
63
What are immune privileged sites?
tissues that are in part protected from the immune system, as inflammation can
(Brain, nerves, eyes, testes, placenta/fetus)
64
Describe VZV pathogenesis
1) VZV infects the respiratory tract and/or conjunctiva
2) Virus replicates in the upper airway and regional lymph nodes
3) Primary viremia results in infection of lymphocytes and nerve cells
4) replication causes secondary viremia leading to clinical symptoms such as fever and malaise
5) infection of skin results in a vesicular rash. Zoster rash occurs in a dermatome pattern
65
Who is at high risk for disseminated disease (VZV)?
Individuals with HIV or who are receiving chemotherapy
66
Who is at high risk for shingles?
older patients who naturally lose memory T cell loss
67
Describe the progression of varicella rash
papules -> vesicles with clear fluid -> vesicles with cloudy fluid (T cells) -> crusting
68
Describe the progression of VZV rash
papules -> vesicles with clear fluid -> vesicles with cloudy fluid (T cells) -> crusting
69
What are the clinical manifestations of Varicella? Zoster?
Varicella
- Itchy vesicular rash that has a central distribution primarily on the trunk
- Because VZV is viremic, it can result in hepatitis, encephalitis, pneumonitis
Zoster
- Painful vesicular rash with a dermatomal distribution
70
How are VZV infections diagnosed?
typically by observing clinical presentations (vesicles). However, these tests can be used:
PCR > Stains/fluorescents > antibody tests > culture (doesn't culture well)
71
How is VZV treated?
symptom control is mainstay of treatment, but anti-viral therapy is indicated in adolescents, adults, and immunocompromised
72
Describe vaccination for varicella. Who should not receive this vaccination?
Live attenuated vaccine that is given alone or with MMR (MMRV)
immunocompromised or pregnant women should not receive this vaccine
73
Describe the zoster vaccination and who gets it. What is given to those who cannot receive the vaccine?
Same live attenuated virus as varicella, but given at a higher concentration to people 60+
immunoglobulins are given to immunocompromised patients who can't receive the vaccine
74
What can cause vesicular rashes?
```
VZV
Herpes
Enterovirus
staph a bullous impetigo
insect bites
contact dermatitis
```
75
define epidemic
rapid spread of infection in a city, state or entire country over a short period of time
76
define pandemic
an epidemic that spreads across boarders, even worldwide, affecting large numbers
77
Describe the structure of the influenza virus
```
orthomyxovirus family
ssRNA (-) sense
segmented genome
enveloped
- Hemagglutin (HA)
- binds sialic acid receptors for viral entry
- agglutinates RBCs
- antigenic (neutralizing)
- Neuraminidase (NA)
- cleaves sialic acid to release virus
- degrades mucin
- antigenic (non-neutralizing)
```
78
What is antigenic drift (relate to influenza)?
small mutations in HA or NA
79
What is antigenic shift (relate to influenza)?
complete mutations in HA or NA
Only occurs in type A
80
Describe the pathogenesis of influenza
1) spreads via large droplets or contaminated surfaces
2) NA degrades protective mucus
3) HA binds to sialic acid receptors and enters cell
4) virus uncoats
5) genome moves to the nucleus
6) mRNAs are created for protein synthesis and for genetic material for new virions
7) Virions are assembled in the cytoplasm
8) Virions are released via budding when NA cleaves saliac acids
9) viral replication results in cell destruction
81
What are the clinical manifestations of influenza (incubation period, type of onset and symptoms, period of infectiousness)
incubation is 1-4 days
abrupt onset of fever, myalgias, headache, pharyngitis, rhinorrhea, cough, fatigue
infectious for 3-5 days after symptom onset
82
What are potential complications of influenza?
- Primary pneumonia leading to respiratory failure
- secondary bacterial pneumonia
- Reye's syndrome
83
What is Reye's syndrome?
Rare potential complication of influenza that occurs in children that is characterized by:
- fever
- rash
- encephalopathy
- liver failure
84
What are the common methods used for diagnosing influenza?
nasopharyngeal aspirate or swab then:
viral culture
- gold standard but takes 10 days
Direct fluorescent antibody
- 1-4 hours
PCR
- most sensitive and specific and takes 1-6 hours
rapid antigen detection
- most rapid (<30 min) but can show false negatives
85
Name two adamantanes. What are their mechanisms and SAEs?
Amantadine and Rimantadine
Influenza A M2 ion channel inhibitor that prevents viral uncoating
CNS and anticholinergic effects. teratogenic
86
Name two neuraminidase inhibitors. What are their mechanisms and SAEs?
Oseltamivir and Zanamavir
Influenza A and B NA inhibitor that prevents the release of virions from cell
N/A
87
Describe the population at risk for influenza
infants
- no maternal IgG after 6 months and IgA from milk doesn't protect against influenza
elderly
immunocompromised
obese individuals
pregnant women
- produce more Treg
88
Describe the types of influenza vaccines
trivalent or quadravalent conjugate vaccine
live attenuated nasal spray
- do not give to pregnant women or immunocompromised
89
What are the warnings and contraindications of influenza vaccination?
may cause:
- Guillain Barre syndrome
- allergic reaction
contraindication
- if you've had a sever reaction to the vaccine in the past, don't get it
90
define vaccine antigen
the molecule in the vaccine that an antibody response should be generated against
91
define adjuvant
substance that non-specifically activates the immune system - added to vaccines to enhance the immune response
92
define vaccine titer
a measure of amount of antibody made to a vaccine antigen
93
What are the 5 different types of vaccines?
1) inactivated/killed
2) toxoid (inactivated toxin)
3) subunit
4) conjugate
5) live, attenuated
94
How are inactivated vaccines created? examples?
made by inactivating the whole pathogen by heat or by chemicals
polio vaccine
hepatitis A vaccine
rabies vaccine
95
How are toxoid vaccines created? examples?
inactivate the toxin by heat or chemical
tetanus
diphtheria
96
How are subunit vaccines created? examples?
made by isolating or making a specific component of a pathogen. MUST be mixed with an adjuvant
```
Hep B
HPV
Pertussis
Influenza
Pneumococcal polysaccharide
meningococcal polysaccharide
```
97
How are conjugate vaccines created? examples?
Conjugate a carbohydrate to a protein to enhance immune response
H. influenza
Pneumococcal conjugate
Meningococcal conjugate
98
How are live, attenuated vaccines created? examples?
grow virus in another animal. Over time, the virus becomes worse at growing in humans
```
Measles
Mumps
Rubella
Varicella
Rotavirus
Influenza (nasal spray)
Polio (oral)
Yellow fever
Bacille Calmette Guerin (BCG for TB)
```
99
What are two problems with live, attenuated vaccines?
1) If given to immunocompromised patients, the attenuated virus can be pathogenic
2) The attenuated virus can revert back to wild-type form to become pathogenic
100
Describe T cell dependent antibody production
Small antigens that are recognized by B cells are presented to T cells, which result in activation and potential class switching. This results in B cell memory
101
Describe T cell independent antibody production
Long, repeating carbohydrates cross-link B cell receptor causing activation. No B cell memory
102
Describe how conjugate vaccines help create a T cell dependent response
Conjugate vaccines connect a carbohydrate to a protein, which creates a T cell dependent response, resulting in B cell memory
103
What is meningitis? what are its associated symptoms?
inflammation of the meninges
fever, headache, stiff neck, and potential petechia
104
What is encephalitis? what are its associated symptoms?
inflammation of the brain parenchyma
fever, altered mental status, and seizures
105
What is meningoencephalitis? what are its associated symptoms?
inflammation of both the meninges and the brain parenchyma
fever, headache, stiff neck, altered mental status, and seizures
106
What is myelitis? What are its associated symptoms?
Inflammation of the spinal cord
flaccid paralysis and sensory loss
107
What is a positive Kernig's test?
Pain associated with quadricep flexion (indicates inflamed meninges)
108
What is a positive Brudzinski test?
Pain associated with flexion of the head (indicates inflamed meninges)
109
What indicates bacterial meningitis?
CSF shows:
high PMNs, low glucose, and high protein
110
What is aseptic meningitis?
inflammation of the meninges and a bacterial source is not to blame
111
What are the 3 possible outcomes when collecting CSF for suspicion of meningitis
If no WBC in CSF, consider alternative diagnoses
If WBC present but no bacterial growth = aseptic meningitis
If WBC present and bacterial growth = bacterial meningitis
112
If no bacteria grow in culture, what could be the cause of aseptic meningitis?
1) bacteria that don't grow on standard media
2) virus
3) fungi
4) parasites
5) antibiotics given to patient before lumbar puncture could make it look like aseptic when really septic meningitis
113
How does aseptic meningitis present in CSF analysis?
```
WBC: normal
Glucose: normal/low
Protein: normal/high
gram stain: negative
culture: no growth
```
114
What are Arboviruses? What do they commonly cause?
Arthropod borne viruses
encephalitis
115
What is the most common cause of viral meningitis?
enterovirus
