Chapter 6- HIV, AIDS, Amyladosis Flashcards
Candidiasis most commonly presents in AIDs patients as what symptoms
Infection of the oral cavity, vagina, and esophagus
What are the factors of HIV that lead to B cell proliferation
- latent EBV or CMV reactivation
- gp41 activated B cells
- HIV macros produce IL-6
What is the steps in HIV infecting cells
1) gp120 binds to CD4
2) gp120, CD4 bind to CCR5
3) gp41 penetrates the membrane
Familial Mediterranean fever is clinically presented by
Fever and inflammation of serosal surfaces (peritoneum, pleura, synovial membrane)
Why is the T tropic X4 HIV referred to as syncytia inducing (SI) virus
Because it is the form of HIV that can cause the fusion of the infected cells with the non infected
How long after infection will the patient seroconversion
3 to 7 weeks
What are the two major targets of the HIV
Immune cells and CNS
X4 HIV prefer to infect which cells
T-tropic, so T cells
Which protein is associated with secondary amyloidosis and what is the mechanism
AA
-Due to the increased production of SAA protein in response to increased acute inflammation state. So any chronic inflammation can cause this
What is the mechanism of action for AL proteins
quirked mutation that results in the increased production of Plasma cell light chains, which have limited proteolysis and begin to aggregation
What rate do AIDs patients develop lymphomas compared to the general healthy population
10 fold greater
What is the good clinical marker to monitor the severity of the HIV disease
HIV-1 RNA levels
What is the telltale sign of moving from HIV to AIDS
The presence of invasive candiadiasis, as normally this will not occur
What are Bence-Jones proteins and when are they commonly seen
Free/unpaired kappa or lambda light chains that can be seen in the urine. This occurs during primary amyloidosis
Which HIV subgroup is the fastest growing
C
What does Cryptosporidium and Isosporidiosis present as in patients with AIDS
Enteritis, leading to diarrhea
What percentage of HIV patients develop pneumonia
15-30%
What are the typical genes of retroviruses
Gag, pol,env
Acute HIV infection is assocaited with which type of cell
Memory T cell expressing CCR5 in mucosal
Which HIV subgroup is most common in Thailand
E
How is the AB protein formed
Proteolysis from the larger transmembrane glycoprotein known as amyloid precursor protein
Which HIV strain is dominant early in the infection
R5 (M tropic) accounts for 90% in the early stages, then moves to T tropic
Which protein is associated with familial amyloid polyneuropathies
Transthyretin aka TTR
What is primary amyloidosis
Systemic or generalized amyloidosis when associated with plasma cell disorder
What is the pathogen causing atypical mycobacteria
Mycobacterium avium-intracellular
How does having concurrent STIs lead to increased spread of HIV
More immune cells present in the semen, skin lesions or abscesses make transmission easier
Which enzyme is likely involved in B cells that can lead to lymphomas
AID, where the imperfections lead to lymphomas
What is the protein that allow protection from HIV in naive T cells
APOBEC3G
What are the predominant cells in the brain that are the target for HIV
Macrophages and microglia
What does toxoplasma Gondii present as clinically
Invader of CNS, causing encephalitis
How is Familial amyloidosis polyneuropathy inherited
Autosomal dominant
Which form if HIV is most common in the US, Europe, and Central Africa
HIV-1
Histologically, where does amyloid deposition begin
Always extracellular and begins between cells
What is the mutated protein in senile cerebral disease
Assoacited with Alzheimer’s dieases, and the APP protein leads to Beta amylase protein
What is the viral set point
The levels of viral load at the end of the acute phase and is a good indicator of rate of CD4 decline
Which protein is associated with the core if cerebral plaques found in Alzheimer’s
AB
What do patients with salmonella and shigella present with in patients with AIDs
Diarrhea
Primary effusion lymphomas are rare because
Coinfected with EBV and KSHV
What is the protein making up the fibrils in Familial amyloidosis polyneuropathy
Mutant TTR
Which group of people are associated with generalized AA amyloidosis
Heroin abusers who use SubQ, associated with “skin popping”
What is the most common neoplasm in patients with AIDS
Kaposi sarcoma
Which chemokine receptors do HIV X4 bind to
CXCR4
Where does AIDs rank in lethality in men and women
Men- 2nd between ages of 25 to 44
Women-3rd in same age
What are AA fibrils derived from
Proteolysis of larger serum amyloid-associated (SAA) proteins in the liver, which are bound to HDL
What is the major cause of death in patients with untreated AIDS
Opportunistic infections
Which HIV subgroup is most common in the world
M
What is the major fibril protein in secondary amyloidosis, aka reactive systemic amyloidosis
AA
What is the result of syncytia
Giant cell formation, in which infected cells will fuse with non infected cells via gp120 binding to CD4 of uninflected cells
How do high levels of chemokines inhibit the HIV infection
They compete for the chemokine receptors and can block entry/infection
What is the function of the normal TTR
Binds tyrosine and retinol
B2 of MHC1 is seen in which condition and what patients are at risk
Seen in amyloid fibril subunit in amyloidosis that complicates patients on long term hemodialysis
What conditions are assocaited with a higher rate of transmission from the mother to the child
-High viral load, low CD4 load, and chorioamnionitis
Patients undergoing hemodialysis for renal failure are at a higher risk of developing amyloidosis via which protein
Beta2
Which HIV subgroup is most common in Western Europe and US
B
Familial Mediterranean fever results from a defect in which protein
Pyrin
What components are always present in amyloidosis
Serum amyloid P (SAP), proteoglycans, highly sultanate glycosaminoglycans
Which HIV is most common in West Africa and India
HIV-2
Amyloid appears in which location first in the liver
Space of Disse
In amyloidosis, what are some of the substrates that the fibrillation proteins will bind to
Proteoglycans and glycosaminoglycans aka heparin sulfate and dermatan sulfate, plasma proteins (especially Serum amyloid P (SAP))
What percentage of AIDs patients present with neuro findings at autopsy and what percentage show as clinical presentations
90% at autopsy, 40-60% in clinical
What does herpes simplex virus present as in patients with AIDs
Mucocutaneous ulcerations involving the mouth, esophagus, external genitalia, and paraanal regions
What are the associated diseases in secondary amyloidosis, aka reactive systemic amyloidosis
Chronic inflammatory diseases with increased SAA
Which genes are commonly mistranslated in aggressive lymphomas such as Burkitt lymphoma and large cell lymphoma
Burkitt lymphoma is MYC
Large cell lymphoma is BCL6
What is the function of APOBEC3G
Cytidine deaminase that causes cytosine to uracil mutations in viral DNA
Where does normal TTR deposit in older individual and what does it cause
Deposits in the heart, leading to senile systemic amyloidosis
What are the 4 components in HIV
1) p24 capsid protein
2) p7/9 nucleocapsid
3) Viral RNA genome (2 copies)
4) protease, reverse transcriptase, integrase
What are Reed-Sternberg cells
Hodgkin lymphoma cells that are invaded with EBV
How does HIV transmission via blood even when blood is screened
Recently infected pts will not have seroconverted yet and do not have antibodies present
How will a patient with AIDs present clinically
Long lasting fever (>1month), fatigue, weight loss, diarrhea
KSHV infection has been linked to which two neoplasms
1) Rare B cell lymphomas (aka primary effusion lymphoma)
2) Multicentric Castleman disease (B cell lymphoproliferative disorder)
What is the result of binding of CD4 and gp120
Conformation change to expose hydrophobic region known as fusion peptide on gp41
What is the most common and most serious organ involvement for amyloidosis
Kidneys
What is the pathogen causing pneumonia in HIV patients
Pneumocystis jiroveci (reactivation of a latent infection)
What are the major side effects of HAART treatment
-Insulin resistance, lipoatrophy (loss of facial fat), lipoaccumulation (central fat deposits), elevated lipids, peripheral neuropathy, CV kidney, liver disease
What is the effect of amyloidosis on the kidney
Leads to proteinuria and is commonly the cause of death (renal failure)
What is the proteins allow for the staining
Charged sugar groups
What is the most common fungal infection in AIDs patients
Candidiasis
What is the most abundant HIV protein
P24
What percent of AIDs patients present with cryptococcosis
10%
What is the clinical presentation of cryptococcosis
Meningitis
What types of lymphomas are common in patients with AIDS
Kaposi syndrome, B cell lymphoma, cervical cancer, anal cancer
When does TB usually present in patients with AIDs
Early in course of infection, compared to late with other mycobacterium
What is the role of gag and pol
Cleaved by viral proteases to yield mature proteins
What can amyloidosis bind to in the blood and what is the result
Binds to factor X, which is crucial in clotting. Can lead to bleeding disorders
Medullary carcinoma of the thyroid is the result of which major fibril protein and what is the precursor protein
A Cal is the major fibril protein from the precursor calcitonin
Which week are viral levels dropped and what is the cause
Week 12, the viral levels will drop due to CTL activation
What is the alternative name for the virus causing karposi sarcoma
HSV-8
What is the mechanism of action for the formation of fibrils
Native protein folding is disrupted, causing the formation into Beta sheet structures
Which type of T cells are immune to HIV infection
Naive T cell
What is the mechanism of action for AA proteins
Chronic inflammation leads to IL1/6 production, increased SAA production, limited proteolysis and aggregation begins
What is the most common form of amyloidosis
AL protein as a result of B cell lymphomas
Which tumors is secondary amyloidosis, aka reactive systemic amyloidosis associated with
Renal cell carcinoma and Hodgkin lymphoma
What is the role of the HIV vapor gene
Allows infection of terminally differentiated macrophage via a nuclear pore
What is the primary clinical measurement used to determine when to start antiretroviral therapy
CD4 counts, not viral load
Which chorionic inflammation disease is associated with secondary amyloidosis, aka reactive systemic amyloidosis
RA (3% or all pts)
HIV does not allow fo the production of antibodies despite the increase in number of B cells. Which pathogens does this make the patient prone to
Encapsulated bacteria (S.pneumopniae and H. Influenza)
Reverse transcriptase results in the production of which kind of DNA
Double stranded complementary DNA (cDNA, proviral DNA)
What is oral hairy Leukoplakia and what is the cause
White projections on the tongue, and is the result of EBV driven squamous cell proliferation of the oral mucosa
What is the condition of immune reconstitution inflammatory syndrome
When patients in advanced stages of HIV who are given antiretrovirals and experience clinical deterioration during the period of immune system recovery
Which pathogen is responsible for the majority of mass lesions in the CNS
Toxoplasma Gondi
Islets of Langerhans localized amyloidosis is caused by which precursor protein leading to which major fibril protein
Islet amyloid peptide leading the the major fibril protein AIAPP
What is the result of the product tat(transactivator)
1000 fold increase in transcription of viral genes and required for replication
What is the main virus leading to lymphomas
EBV
What is the mechanism of action for ATTR protein
Mutations lead to a mutant form that aggregates
Patients with Beta-2 amyloidosis are clinically presenting with which other symptom
Carpel tunnel syndrome
What is secondary amyloidosis
Systemic or generalized amyloidosis where there is a complication of an underlying chronic inflammation or tissue-destructive problem
Familial Mediterranean fever is characterized by which protein
AA
What are the three routes that HIV infection can spread from mother to child
1) In utero by transplacental route
2) delivery through infected canal
3) ingestion of infected breast milk
During the chronic infection phase , what are the clinical manifestations
There are very few, aka clinical latency period
In the chronic infection stage, where is the primary location of viral replication
LNs and the spleen
What is a rapid and specific test for amyloidosis
Scintigraphy with radiolabed SAP (it binds to the deposits)
Isolated atrial amyloidosis is causes by which precursor protein leading to which fibril protein
ANP leading to the major fibril protein AANF
How are Burkitt lymphoma and large cell lymphoma created
Mislocation of genes during the process of class switching and somatic hypermutation via the enzyme AID
Familial Mediterranean fever is assocaited with what
Overproduction of IL-1 in inflammation responses
What is the majority of amyloid made of and what is the percentage
95% of amyloid consists of fibril proteins
What is the rate of HIV driven cervical dysplasia in AIDs compared to normal
10 times greater
What is the assoacited disease with primary amyloidosis, aka immunocyte dyscrasias with amyloidosis and the major fibril protein
Multiple myeloma and other plasma B cell proliferation disorders, characteristic of the AL protein
Where are the fibril in Familial amyloidosis polyneuropathy depositing
Peripheral and autonomic nerves
What is the amino acid length and molecular weight of AA proteins
76 AA long and 8500 molecular weight
What is the general family of viruses, and the specific ones that lead to neoplasms in AIDs patients
Oncogenes DNA viruses
-EBV, Karposi sarcoma herpes virus, HPV
What commonly makes up the AL protein
Light chains of Ig, in particular, the lambda
Familial Mediterranean fever is common in which group of people
Armenian, Arabic, Sephardic jews
What is the condition of acute retroviral syndrome
Clinical presentation of the initial viral spreading, occuring 3 to 6 weeks after infection. Very similar to the flu
Where are the common locations of the tumors that result of Viral lymphomas
Extranodal sites, such as the CNS, but also the gut, orbit, and lungs
What is the underline cause of all amyloidosis
Extracellular deposits of fibrillarproteins
What type of family is the JC virus and what does it cause
Member of the papilloma virus and causes encephalitis as it invades the CNS
What are the three most common forms of amyloid
1) Amyloid light chain (AL) protein from Igs light chains
2) amyloid associated (AA) proteins from non-Ig liver proteins
3) Beta-amyloid (AB) protein
Which type of T cells do HIV infect
Memory cells, so serve a long time as latent infection
Which chemokine receptors do HIV R5 bind to
CCR5
What is the two mechanism that sexual transmission of HIV occurs
1- Direct inoculation into the blood vessels due to trauma
2- Infection of DCs or CD4 T cells in the mucosa
What are viral mechanisms to counter act APOBEC3G
Production of Vif to bind to complex and degrade it
What is the heritability of familial Mediterranean fever
Autosomal recessive
HIV R5 strains prefer to infect which cells
Monocytes/macrophage aka M-tropic
How does mycobacterium differ in HIV patients
-They will not result in granulomas cause the lack of CD4+ cells
What is the globally most common form of HIV transmission
Heterosexual contact
Which non-T cells can HIV infect
-Macrophages, DCs
What are the three virus assocaited B cell lymphomas
1) EBV+ large cell lymphoma
2) KSHV+ Primary effusion lymphoma
3) EBV+. Hodgkin lymphoma
CMV virus occurs exclusively in patients with a CD4 T cell count less than
50 per microliter
What are the clinical presentations of CMV in patients with AIDS
Pulmonary, eye (retinitis), GI or CNS infections
