Flashcards in Ch4: Skin, Musculoskeletal, Blood, and Lymph Part II Deck (289):
Infections of joint and bone include? 4
1. Parovirus B19: Developed countries (Slapped cheek)
2. Rubella: Nonvaccinated adults
3. Hep B: HIV-1 and HTLV-1
5 classic childhood viral rashes?
1. Measles: Rubeola
2. German measles: Rubella
4. Fifth disease
5. Chickenpox: Varicella zoster
5 herpes virus of skin?
1. Herpes simplexes 1 and 2
2. Varicella zoster
3. Human herpes virus 6, 7, 8
4 families of viruses of skin?
3 subfamilies of herpesvirus?
Which has short growth cycle?
Which has long?
Members of alpha herpes family? 3
Members of gamma herpes family? 2
Kaposi' sarcoma: HHV-8
Members of beta herpes family? 3
In terms of herpes
Shape of capsule?
Since herpes have a capsule, they have a tegument which contains what?
Enzymes for replication
What determines what cell/tissue, the herpes virus attacks?
What are the viral adhesins of herpesvirus?
What is the primary manifestation of herpesvirus in humans?
Common infections but benign in children
What is the immune response of herpesvirus?
What is the primary treatment of herpesvirus?
Targeting viral DNA polymerase
What main feature do all herpesviruses have?
How do viruses do latency? (2)
1. Make non-encoding transcripts that prevent apoptosis
2. Express proteins during latency
What is state of herpesvirus genomes during latency?
Circular, episomal form separate from host genome
How are herpesviruses spread? 3
What herpesviruses can be be spread without symptoms?
When is VZV transmitted?
Only when patient has varicella or zoster
What is required for HSV spreading?
Most herpesviruses are diagnosed how?
What is used in confirming acute or previous herpesvirus infection?
PCR is used to test what herpesvirus?
How to detect VZV in ski nlesions?
What herpesviruses cause both intranuclear and cytoplasmic inclusions?
What herpesviruses result in only intranuclear inclusions?
HSV 1-2 infection
Can infect what cell types?
Where is it lytic? (2)
Where is it latent?
Most cell types
Mucoepithelial and fibroblasts
Where does HSV-1,2
What gives it a tight binding? (2)
What does gC do?
What does gE and GI do?
Heparin sulfate proteoglycans
Nectin-1alpha and HVEM
Binds to and depletes C3 from seru
Complex with Fc on IgG
Which is worse for HSV, 1-2
Primary eruption or recurrence?
What happens in primary eruption of HSV?
Vesicle that erupts into a wet ulcer with pain and itching an dmalaise and fever.
What happens in recurrence of HSV?
Lesions with some local symptoms
Where does the HSV remain latent?
Trigeminal or sacral nerve
First episode of HSV-1 has what two features?
How do primary lesions look in HSV?
Dewdrop on rose petal
First episode primary genital herpes lasts how long?
Longer: 10-12 days
First episodes of genital herpes caused by HSV-2 in patients who already had HSV-1 are different how? 2
1. Less frequent systemic symptoms
2. Faster healing
Herpetic Whitlow signs include what? (3)
Localized tenderness at finger
Herpes gladiatorum is seen in who?
Where do they have herpes lesions?
Trauma to skin transmission
Thorax, ears, face, hands
In patients with eczema, how does HSV present?
Reactivation triggers of HSV? (5)
2. Nerve injury
5. Hormone changes
HSV Reactivation sees what changes in immune response?
Shift from HSV-specific T cells to Th2 cells
What is different about location of lesions in recurrence of HSV?
Only one one side of body
Innate response to HSV?
CMI response to HSV?
How does HSV counteract? 2
IFN and NK cells limit progression
CMI kills infected cells
1. Blocks IFN
2. Blocks TAP proteins --> No MHC Class I
Incubation period of HSV 1-2?
1-26 but usually 6-8
How to stain for HSV? (3)
2. Giemsa (Tzanck preparation)
Things seen upon HSV staining? 3
1. Cowdry type A acidophilic intranuclear inclusions
3. Giant cells
What can you not separate HSV from upon staining?
Treatment of HSV?
VZV is broken into what two parts?
Varicella = Primary
Zoster = Recurrence
What keeps VZV in latency?
T cell response
What allows zoster to reoccur?
T cells aging leading to shingles
How does VZV infect and remain latent in body?
Droplets inhaled --> Gets in lymphatics (Primary viremeia) --> Goes to secondary lymph organs --> Gets in blood (Secondary viremia) --> Goes to skin --> Goes into latency in neurons
Rash is described how in VZV?
Cropping rash that are at one location for one stage in disease
How is VZV described?
How long does the dermal rash last?
Where does the rash occur most? 2
3-5 days of cropping
Trunk and SCALP
How is VZV infection different in adults for first time?
More serious: Pneumonia and encephalitis
How long does VSV incubation last?
Reactivation of VZV results in what?
Zoster or Shingles
Where does Zoster/Shingles occur?
Entire dermotome due to virus at that nerve root spreading down it.
What dermatomes are most involved in zoster/shingles?
Thoracic and lumbar
Herpes zoster goes where if 1st or 2nd branch of 5th cranial nerve is affected?
How does someone know a shingles attack is coming?
What happens after?
Pain in dermotome 2-3 days before
Chronic debilitating pain
Zoster/shingles last how long?
Zoster/shingles is seen in what % of population?
Over 45 years old
Immune response to VSV? 2
2. TLR-2 of innate
1. FcRgammaII receptor
2. Inhibition of MHC-I
3. Decreased IFN-gamma
Route of transmission of VZV?
Latency of VZV?
Sensory neuronal cells (trigeminal, dorsal root, cranial ganglia)
How is VZV different during latency from other herpes?
Expresses different RNA transcripts during latency
How do you diagnose VZV?
Same as you would HSV 1-2
How do you treat adult zoster infections? (3)
1. Acyclovir (DNA Poly inhibitors)
2. Pain killers
How do you treat someone with chickenpox? 2
1. Good hygiene
The vaccine for VSV is in what form?
Live attenuated Oka strain
The VSV vaccine has what immune reaction?
T cell immunity
Zoster vaccine is different from VSV vaccine how?
High titer version of Oka
What is common side effect of VSV vaccine?
What is the risk factor for it?
HHV-6 and HHV-7 infect what type of cells?
What do they cause?
What patients do they reactivate in?
Exanthema subitum/roseola infantum
Two types of HHV-6?
HHV-6A and HHV-6B
HHV-6 lives where?
Infects what type of T Cells?
HHV-6A likes what type of cells?
HHV-6B likes what type of cells
Peripheral Blood Mononuclear cells
HHV-6 is in what type of form in WBC's?
Infection in these cells appears how?
ballooning cells with intranuclear inclusions
What percentage of adults are seropositive for HHV-6?
Why do moms pass on HHV-6 to their kids so easily?
Mom's antibodies decline and allow kids to get infected
HHV-7 infects what cells?
CD4 T cells
Salivary gland cells
Lung and skin cells
Where is HHV-7 shed the most?
How does HHV-7 combat immune response?
Induces degradation of MHC I
What is the main cause of roseola?
Subset of roseola cause?
Primary manifestation of HHV6 and HHV7?
High fever (several days) followed by a rash (1-3) days
How to diagnose HHV6 and 7?
Culture, PCR, serology
How to detect acute HHV6 in children?
Compare acute and latent serum
HHV-6 is sensitive to what in vitro?
Ganciclovir, foscarnet, cidofovir
HHV6, HHV7 and CMV are not sensitive to what famous anti-viral?
Kaposi's sarcoma is a tumor arising where?
Multiple locations in blood an dlymph
What virus is Kaposi's sarcoma?
What cells are infected?
Two main changes that will cause tumor?
1. Spindle shaped proliferating cells
Nuclecapsid contains what two things in measles/Rubeola?
Envelope contains what two things in measles/Rubeola?
Fusion Protein F
Attachment Protein Hemagglutinin H
What enzyme is NOT found in measles virus?
What is the diagnostic progression of measles? 3
Cough, Coryza, Conjunctivitis --> Koplik's spots --> Rash
What is the path of measles pathogenesis?
Inhaled --> Replicates in RT --> Spreads by lymph --> Viremia --> Conjunctiva + RT + UT + BV's + lymph + CNS --> Endothelial cells infected --> Rash --> Usually recover
What is a fatal manifestation of measles/rubeola?
What causes it? 2
Subacute sclerosing panencephalitis
1. Host: Defective immunity and Ab's
2. Virus: Defective virus that can't replicate
Immune response to measles?
Route of measles transmission?
When is measles most contagious?
Late prodromal phase: Peak of CCCP peak
Incubation period of measles?
What is historically best test for diagnosing measles?
Hemagglutination inhibition test
What's diagnostic in serum for measles?
Serum titer 4X increase in measles Ab
Vaccine type for measles?
Treatment for measles? 3
1. Treat secondary bacterial infections
German measles/rubella has what main clinical manifestation?
What demographic is it significant in?
Type of virus?
Pathogenesis of Rubella?
URT infection --> Lymph --> Viremia --> Rash
What is the important protein in Rubella for attachment, fusion, hemagglutination and neutralization
How many viremias occur in Measles and german measles?
Rubella/German measles virus is seen in which cells first
What determines severity of Rubella/German measles?
How does Rubella/German measles rash change over 3 days?
Day 1: Starts on forehead then spreads down and back
Day 3: Becomes faint but disappears how it appeared
What is the problem if a fetus gets Rubella/German measles?
High risk for serious sequelae
Immune response to Rubella? 3
1. Ab's limit viremia
2. Type III HS results in rash
3. CMI clean up
Rubella pathogenesis transmission?
When are patients most contagious with Rubella/German measles?
While rash erupts
Incubation of rubella?
Best lab diagnosis for Rubella/German measles?
Vaccine for Rubella/German measles?
Live attenuated MMR
Rubella vaccine may have what side effects
Viremia --> Type III HS --> fever, arthritis
Complications in Rubella/German measles vaccine is seen in who?
Women older than 25
What is the smallest DNA virus?
Does Parovirus have a envelope?
Parovirus B19 replicates where?
Which causes what? (2)
Viremia and spread to bone marrow
What does parovirus B19 depend on for replication?
What seems to be spared?
Is the infection cytotoxic?
Active replicating cells
Bone marrow blood cells
Pluripotent stem cells
What are required for Parovirus B19 to replicate?
Replicating factors of S phase
Cellular DNA polymerase
What acts as primer for parovirus B19?
Where is assembly?
How is the virus released?
Target cell receptor for parovirus B19?
Blood Group P antigen (globoside)
2 phases of Parovirus B 19?
Lytic infection phase
Noninfectious immunologic phase
Things happening during Parovirus B10 lytic phase? 3
1. Hb and RB count drops
2. Virus in throat and blood
3. Flu like symptoms
Things happening during noninfectious immunologic phase of parovirus b19? 3
1. Hb and RB count drops
2. Virus-specific IgG Ab present
3. Rash/arthralgia (Type III HS)
Primary manifestation of Parovirus B19?
Slapped cheek rash
Parovirus B19 can cause what in patients with anemia?
Intrauterine infection with parovirus b19 results in what?
Abortion (anemia + CHF)
Immunodeficient patients develop what with parovirus b19?
Bone marrow suppression
Immune response to parovirus b19?
Ab's stop viremia
Route of transmission for parovirus b19?
Diagnosis for parovirus b19?
ELISA or PCR
In most people how do you treat parovirus b19?
You don't. it's self-limiting
Coxsackie A and B are members of what family?
Type of genome?
Shape of genome? (2)
Linear and nonsegmented
Coxsackie A produces what?
Enters through mouth --> Replicates in oropharynx --> Primary viremiain blood --> Goes to target tissue --> Secondary viremia
What is herpangina?
Who is it seen in?
How many lesions?
Vesicular ulcerated lesions around soft palate and uvula
Children under 10
Hand/foot and mouth disease is caused by what?
What is seen in Hand/foot and mouth disease? 2
1. Tender, papules and vesicles on hands, feet, mouth, and tongue surrounded by erythema
HSV gangiostomatitis occurs where?
Anterior oral cavity: Inner lips, buccal mucosa, tongue
What is seen in HSV and not herpangina?
2. Systemic toxicity
3. Cervical lymphadenitis
Aphthous stomatitis is what?
Recurrent ulcers on lips, tongue, buccal mucosa of older children and adults
3 manifestations of Coxsackie B?
What is Pleurodynia also known as?
What are the symptoms? (2)
How long does it last?
Where is it tender?
Bornhom disease or Devil's grip
2. One sided low thoracic pleuritic chest pain
Involved side muscles
Myocarditis coxsackie B is life threatening when?
HPV has what genome shape?
What genome type?
Does HPV genome integrate into host?
How many regions does HPV genome have?
What are most important proteins in HPV?
E5, E6, E7
E5 in HPV does what? (2)
1. Prevents acidification of endosomes
2. Stimulates EGF-R
E6 in HPV does what?
Binds and destroys P53:
E7 in HPV does what?
Binds and inhibits Rb
How does HPV replication rates differ by location?
In basal epidermis --> Little to no replication
As you move to surface --> More replication
Most of the time what do you get from EPV on skin?
Upregulated E6 and E7 can cause what?
Benign mass or invasive cancer
Does HPV spread?
No, remains local
Plantar warts are found where?
Why is their growth different?
Are they painful?
Are most warts plainful?
Sole of feet
Weight compression forces them to grow inward
How do patients with HPV caused Benign head and neck tumors present?
1. Hoarseness of strange cry
2. Respiratory distress
3. Airway obstruction
What forms of HPV cause laryngeal tumors that can kill children?
6 and 11
HPV manifestations on the cervix?
Warts after sexual contact
Main types that cause cervical growth in HPV?
16, 18, 31, 45
What is special about HPV 16 and 18?
Can get in our genome
Immune response to HPV?
Attack the L1 protein of the virus
Route of transmission of HPV? 4
Direct contact: abrasions, fomites, sex, birth
Incubation of HPV?
Weeks to years
Diagnosis of HPV?
Koilocytes (Enlarged keratinocytes with clear haloes around shrunken nuclei)
Vaccine for HPV?
Inactivated quadrivalent 6, 11, 16, 1
HPV's status in permissive cells?
Chronic latent and transforming
Besides cervical cancer what can HPV 16 and 18 also cause?
Remove clinical manifestations (freeze, burn, chemicals, duct tape)
Smallpox/Variola replicates where?
Family of viruses?
How does poxvirus leave the cell?
Disruption of exocytosis
How does smallpox spread?
Virus is inhaled --> Multiplies in URT --> Gets in lymph --> Nodes --> Goes systemic + hemorrhages in BV's --> Rash
4 main clinical types of variola/smallpox?
Ordinary small pox
Vaccine-modified small pox
Ordinary smallpox is what % of cases?
What does mortality depend on?
Fever and rash
Extent of rash
Vaccine-modified smallpox produces what?
Mild prodrome with a few skin lesions
Flat smallpox sees what?
Slow focal lesions with overall infection and 50% death rate
Hemorrhagic smallpox sees what?
Bleeding into skin and mucous membranes --> Death in a week
Where are smallpox lesions seen most?
Where are chickenpox lesions seen most?
Palms, soles, and Face (EXTREMITIES)
Route of transmission of smallpox? (2)
2. RT mucosa
Incubation period of smallpox?
5 to 17 days
Diagnosis of smallpox by histo?
Rounded and fused cells
Vaccine for smallpox is important why?
1st live vaccine
What are two of 11 pox viruses that are not zoonoses?
Which zoonose can be transferred by humans
Reservoir host of monkeypox?
Most important symptom?
Lymphadenopathy of submandib, cervical and sublingual
Cowpox is acquired how?
Where are lesions? (2)
Skin lesions eventually form what?
Is lesion painful?
Contact with cows and other animals
Hands and face
Molluscum contagiosum causes what type of lesion?
How is it transmitted?
What do the lesions become?
Where are they seen?
Umbilicated nodules with central caseous plug
Trunk and genitalia
Molluscum contagiosum incubation period?
Curettage or liquid nitrogen
target tissue? (2)
Target cell? (2)
Target cell receptor? (2)
Oropharynx + salivary gland
B cells + Epithelial cells
C3d receptor + MHC II
At peak of infection, how many B cells have EBV?
Why is good immune response needed for EBV?
What is the consequence?
Have to shutdown proliferation of B cells
Cause infectious mononucleosis
Why is there an increase in EBV infection with age of seroconversion?
Differences in immune response of different age groups (Young better than old)
EBV in saliva --> B cells --> B cells proliferate --> T cells activated -
How is EBV mono spread?
How does the imune system respond to EBV?
CD8 and CD4 T cells and NK cells attack B cells
The killing of lymphocytes by the immune system is done by who?
CD8 T cells
CD8 t cells also are responsible for the symptoms of mono why?
What is the humoral response to EBV?
Ab's against EBV antigens VCA and EA
When does the Ab response to latency EBV antigens occur?
What are these?
Diagnosis of EBV? (7)
1. Clinical symptoms
2. Palatal petechiae
3. Atypical lymphocytes
4. Heterophile Ab
5. Anti-EBV Ab's
6. IgM to VCA
7. IgG to VCA and EBNA
Primary treatment of EBV?
What cells are seen in EBV in histo?
When do you see all but the Anti-EBNA Ab together?
When do you see Anti-EBNA?
CMV is of what family of viruses?
Shape of genome?
Largest herpes virus
Target tissue of CMV? (5)
1. Salivary gland
2. Kidney tubules
How does CMV mess with immune response?
1. Interfere with MHC-1
2. Induce FC receptors
Target cell type of CMV?
Target cell receptor of CMV?
Heparan sulfate proteoglycans
CMV appears how clinically in most people?
Primary infection with CMV In young adult can produce what?
Mono with fever, lymphadenopathy
What % of mono is EBV?
What % is CMV?
How do you determine EBV vs. CMV?
EBV = Heterophile ab
CMV result in normal person?
Seronegative mother's baby?
1. Silent or mono
Cytomegalic inclusion disease
Multisite symptomatic disease
When is CMV DNA monitored in whole blood?
Infected specimens with CMV show what on histo?
Large cells with basophilic intranuclear inclusions called Owl's Eye
Immune response to CMV?
Since CMV goes latent in blood cells, CMI takes forever to get rid of it
Route of transmission for CMV?
Saliva, sex, blood, transplant
Latency of CMV is in what cells? (3)
Primary treatment of CMV?
HIV has what adherence infusion proteins? 2
1. TM gp41
2. SU gp120
HIV-1 has what 4 groups?
M, N, O, P
M group of HIV-1 contains what subtypes?
Which are in North America?
Which are in Africa?
A and C
HIV-2 has what subtypes?
How does it compare to HIV-1?
How does HIV attach?
Gp120 and Gp41 binds to Primary CD4 receptor but also needs either CCR5 co-receptor on monocytes or CXCR4 on T cells
Penetration of HIV is done how?
Bind to chemokine receptor --> gp41 has change
Early phase of genome replication for HIV involves what?
Reverse transcriptase synthesizes complementary -cDNA copye of genome
What else does RT do for HIV?
Serves as ribonuclease H --> Degrades RNA + Finishes dsDNA
What happens after HIV's dsDNA is made?
Put into genome of cell
Late phase of HIV expression sees what?
What does this require?
Transcription by host RNA Polymerase II
Activation of cell and ability of host TF's
Products of gag, gag-pol and env are what?
How is HIV assembled?
Gag and gag-pol proteins are acetylated and bind to PM glycoproteins --> 2 RNA molecules with tRNA then complex --> Budding
After envelopment, what happens to HIV?
Protease cleaves gag and gag-pol --> Release RT
Major determinant of where HIV goes in tissues is what?
HIV-1 will stick to what in epithelium?
What will these cells then do?
Deliver HIV to T cells in lymph nodes
HIV replicates where in the body?
Acute phase of HIV lasts how long?
How much virus made daily?
First 2-4 weeks
What is acute retroviral syndrome during HIV acute phase?
Flu-like symptoms with a rash of the trunk
What does HIV do during latency?
What cells is it latent in?
Replicate in lymph nodes --> Destroys lymph nodes
Macrophages and resting T cells
What is AIDS related complex? (4)
Chronic lymphadenopathy and fever, weight loss, malaise
What is seen in late phase?
At what level do you see symptoms?
At what level do you see opportunistic infections?
Viral levels increase with decrease in CD4
Immune response has what effect on HIV/AIDS?
What cell is in dire need for good immune response against HIV?
What does it need?
Describe the change in virus levels in HIV and AIDS
Initial burst during HIV --.> Drops to almost nothing during latency --> Slowly increases during AIDS phase due to loss of T cells
Describe the change in CD4 and T cell count in HIV and AIDS?
Slow steady decline in both from start to finish
Describe change in Anti-HIV-1 antibody?
Initial big increase due to immune response --> But immune cells start dying --> Don't produce enough Ab
Below what blood level do you see really bad AIDS problems?
Transmission of HIV?
What are sources of infected lymphocytes and monocytes in HIV?
Ulcers and discharge
Why is RT-PCR good in HIV?
Determine viral load (higher it is, poorer the prognosis)
What is the Rule Out test for HIV?
ELISA: Looks for anti-HIV antibodies
What is the Rule IN test for HIV?
How does CD4/8 ratio give prognosis in HIV?
Higher CD8 numbers = better
Treatment for HIV/AIDS?
1. Nucleoside analogues
2. Non-nucleoside analogues
3. Protease and integrase inhibitors
What is HAART?
What does it involve?
High active anti-retroviral therapy
2 NRTI, 1 NNRTI/Protease inhibitor
Side effects of HAART?
Kills mitochondria and alters fat distribution
Arboviruses multiply where?
Arborviruses have what symptoms? 2
What can it lead to?
Silent or Flu-like
Togaviruses and Flaviviruses have an envelope?
Vector-borne togaviruses belong to what genera?
Humoral response to alpha and togaviruses?
AB block prevents secondary viremia
Dengue fever is also known as?
What is the virus?
Where does it replicate? (2)
Monocytes and vascular endothelium
When is dengue fever really serious?
Second time you get it with different antigen
Treatment for dengue fever?
Incubation of dengue fever?
Flu + rash
Serious complication of Dengue Fever?
When does it occur?
Dengue Hemorrhagic fever/Dengue shock syndrome
When someone gets a second version of the dengue fever (different antigens)
Arenaviruses have an envelope?
Appears how on EM?
2 -ssRNA circles
Sandy appearance in ribosomes
Lassa Fever replicates how?
Where is it seen?
Binds to alpha-dystroglycan on mammalian cells
Rodents, some humans
Incubation in lassa fever?
What can it cause?
Hemorrhaging due to capillary damage --> 50% fatality
Pathogenesis of arenaviruses?
Infect macrophages --> Release of mediators --> Vascular damage
Treatment of arenaviruses?
Pathogenesis of filoviruses?
Tissue necrosis of parenchymal cells --> Vascular injury
Manifestation of filoviruses?
Flu like --> Rash --> Fatal hemorrhaging fevers
Diagnosis of filoviruses? (2)
Large eosinophilic cytoplasmic inclusion bodies
Detect viral Ag by immuno or ELISA
Treatment for filoviruses?
Ebola has what 4 subtypes?
Zaire, Sudan, Ivory Coast, Reston
How does Ebola and Marburg enter body?
Mucus membranes of abraded skin
Incubation for Ebola?
Incubation for Marburg?
4 symptoms of Ebola and Marburg?
Fever, hemorrhaging, rash, Disseminated intravascular coagulation
Reservoir for Marburg?
Tropical rainforest fruit bat
Transmission of marburg and ebola? 2
Syringes and semen