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Robbins Pathology MOD1 (Chptr 1-6) > Chapter 6- HIV, AIDS, Amyladosis > Flashcards

Chapter 6- HIV, AIDS, Amyladosis Flashcards

1
Q

Candidiasis most commonly presents in AIDs patients as what symptoms

A

Infection of the oral cavity, vagina, and esophagus

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2
Q

What are the factors of HIV that lead to B cell proliferation

A
  • latent EBV or CMV reactivation
  • gp41 activated B cells
  • HIV macros produce IL-6
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3
Q

What is the steps in HIV infecting cells

A

1) gp120 binds to CD4
2) gp120, CD4 bind to CCR5
3) gp41 penetrates the membrane

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4
Q

Familial Mediterranean fever is clinically presented by

A

Fever and inflammation of serosal surfaces (peritoneum, pleura, synovial membrane)

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5
Q

Why is the T tropic X4 HIV referred to as syncytia inducing (SI) virus

A

Because it is the form of HIV that can cause the fusion of the infected cells with the non infected

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6
Q

How long after infection will the patient seroconversion

A

3 to 7 weeks

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7
Q

What are the two major targets of the HIV

A

Immune cells and CNS

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8
Q

X4 HIV prefer to infect which cells

A

T-tropic, so T cells

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9
Q

Which protein is associated with secondary amyloidosis and what is the mechanism

A

AA
-Due to the increased production of SAA protein in response to increased acute inflammation state. So any chronic inflammation can cause this

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10
Q

What is the mechanism of action for AL proteins

A

quirked mutation that results in the increased production of Plasma cell light chains, which have limited proteolysis and begin to aggregation

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11
Q

What rate do AIDs patients develop lymphomas compared to the general healthy population

A

10 fold greater

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12
Q

What is the good clinical marker to monitor the severity of the HIV disease

A

HIV-1 RNA levels

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13
Q

What is the telltale sign of moving from HIV to AIDS

A

The presence of invasive candiadiasis, as normally this will not occur

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14
Q

What are Bence-Jones proteins and when are they commonly seen

A

Free/unpaired kappa or lambda light chains that can be seen in the urine. This occurs during primary amyloidosis

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15
Q

Which HIV subgroup is the fastest growing

A

C

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16
Q

What does Cryptosporidium and Isosporidiosis present as in patients with AIDS

A

Enteritis, leading to diarrhea

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17
Q

What percentage of HIV patients develop pneumonia

A

15-30%

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18
Q

What are the typical genes of retroviruses

A

Gag, pol,env

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19
Q

Acute HIV infection is assocaited with which type of cell

A

Memory T cell expressing CCR5 in mucosal

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20
Q

Which HIV subgroup is most common in Thailand

A

E

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21
Q

How is the AB protein formed

A

Proteolysis from the larger transmembrane glycoprotein known as amyloid precursor protein

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22
Q

Which HIV strain is dominant early in the infection

A

R5 (M tropic) accounts for 90% in the early stages, then moves to T tropic

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23
Q

Which protein is associated with familial amyloid polyneuropathies

A

Transthyretin aka TTR

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24
Q

What is primary amyloidosis

A

Systemic or generalized amyloidosis when associated with plasma cell disorder

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25
Q

What is the pathogen causing atypical mycobacteria

A

Mycobacterium avium-intracellular

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26
Q

How does having concurrent STIs lead to increased spread of HIV

A

More immune cells present in the semen, skin lesions or abscesses make transmission easier

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27
Q

Which enzyme is likely involved in B cells that can lead to lymphomas

A

AID, where the imperfections lead to lymphomas

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28
Q

What is the protein that allow protection from HIV in naive T cells

A

APOBEC3G

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29
Q

What are the predominant cells in the brain that are the target for HIV

A

Macrophages and microglia

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30
Q

What does toxoplasma Gondii present as clinically

A

Invader of CNS, causing encephalitis

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31
Q

How is Familial amyloidosis polyneuropathy inherited

A

Autosomal dominant

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32
Q

Which form if HIV is most common in the US, Europe, and Central Africa

A

HIV-1

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33
Q

Histologically, where does amyloid deposition begin

A

Always extracellular and begins between cells

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34
Q

What is the mutated protein in senile cerebral disease

A

Assoacited with Alzheimer’s dieases, and the APP protein leads to Beta amylase protein

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35
Q

What is the viral set point

A

The levels of viral load at the end of the acute phase and is a good indicator of rate of CD4 decline

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36
Q

Which protein is associated with the core if cerebral plaques found in Alzheimer’s

A

AB

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37
Q

What do patients with salmonella and shigella present with in patients with AIDs

A

Diarrhea

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38
Q

Primary effusion lymphomas are rare because

A

Coinfected with EBV and KSHV

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39
Q

What is the protein making up the fibrils in Familial amyloidosis polyneuropathy

A

Mutant TTR

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40
Q

Which group of people are associated with generalized AA amyloidosis

A

Heroin abusers who use SubQ, associated with “skin popping”

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41
Q

What is the most common neoplasm in patients with AIDS

A

Kaposi sarcoma

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42
Q

Which chemokine receptors do HIV X4 bind to

A

CXCR4

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43
Q

Where does AIDs rank in lethality in men and women

A

Men- 2nd between ages of 25 to 44

Women-3rd in same age

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44
Q

What are AA fibrils derived from

A

Proteolysis of larger serum amyloid-associated (SAA) proteins in the liver, which are bound to HDL

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45
Q

What is the major cause of death in patients with untreated AIDS

A

Opportunistic infections

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46
Q

Which HIV subgroup is most common in the world

A

M

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47
Q

What is the major fibril protein in secondary amyloidosis, aka reactive systemic amyloidosis

A

AA

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48
Q

What is the result of syncytia

A

Giant cell formation, in which infected cells will fuse with non infected cells via gp120 binding to CD4 of uninflected cells

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49
Q

How do high levels of chemokines inhibit the HIV infection

A

They compete for the chemokine receptors and can block entry/infection

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50
Q

What is the function of the normal TTR

A

Binds tyrosine and retinol

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51
Q

B2 of MHC1 is seen in which condition and what patients are at risk

A

Seen in amyloid fibril subunit in amyloidosis that complicates patients on long term hemodialysis

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52
Q

What conditions are assocaited with a higher rate of transmission from the mother to the child

A

-High viral load, low CD4 load, and chorioamnionitis

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53
Q

Patients undergoing hemodialysis for renal failure are at a higher risk of developing amyloidosis via which protein

A

Beta2

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54
Q

Which HIV subgroup is most common in Western Europe and US

A

B

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55
Q

Familial Mediterranean fever results from a defect in which protein

A

Pyrin

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56
Q

What components are always present in amyloidosis

A

Serum amyloid P (SAP), proteoglycans, highly sultanate glycosaminoglycans

57
Q

Which HIV is most common in West Africa and India

A

HIV-2

58
Q

Amyloid appears in which location first in the liver

A

Space of Disse

59
Q

In amyloidosis, what are some of the substrates that the fibrillation proteins will bind to

A

Proteoglycans and glycosaminoglycans aka heparin sulfate and dermatan sulfate, plasma proteins (especially Serum amyloid P (SAP))

60
Q

What percentage of AIDs patients present with neuro findings at autopsy and what percentage show as clinical presentations

A

90% at autopsy, 40-60% in clinical

61
Q

What does herpes simplex virus present as in patients with AIDs

A

Mucocutaneous ulcerations involving the mouth, esophagus, external genitalia, and paraanal regions

62
Q

What are the associated diseases in secondary amyloidosis, aka reactive systemic amyloidosis

A

Chronic inflammatory diseases with increased SAA

63
Q

Which genes are commonly mistranslated in aggressive lymphomas such as Burkitt lymphoma and large cell lymphoma

A

Burkitt lymphoma is MYC

Large cell lymphoma is BCL6

64
Q

What is the function of APOBEC3G

A

Cytidine deaminase that causes cytosine to uracil mutations in viral DNA

65
Q

Where does normal TTR deposit in older individual and what does it cause

A

Deposits in the heart, leading to senile systemic amyloidosis

66
Q

What are the 4 components in HIV

A

1) p24 capsid protein
2) p7/9 nucleocapsid
3) Viral RNA genome (2 copies)
4) protease, reverse transcriptase, integrase

67
Q

What are Reed-Sternberg cells

A

Hodgkin lymphoma cells that are invaded with EBV

68
Q

How does HIV transmission via blood even when blood is screened

A

Recently infected pts will not have seroconverted yet and do not have antibodies present

69
Q

How will a patient with AIDs present clinically

A

Long lasting fever (>1month), fatigue, weight loss, diarrhea

70
Q

KSHV infection has been linked to which two neoplasms

A

1) Rare B cell lymphomas (aka primary effusion lymphoma)

2) Multicentric Castleman disease (B cell lymphoproliferative disorder)

71
Q

What is the result of binding of CD4 and gp120

A

Conformation change to expose hydrophobic region known as fusion peptide on gp41

72
Q

What is the most common and most serious organ involvement for amyloidosis

A

Kidneys

73
Q

What is the pathogen causing pneumonia in HIV patients

A

Pneumocystis jiroveci (reactivation of a latent infection)

74
Q

What are the major side effects of HAART treatment

A

-Insulin resistance, lipoatrophy (loss of facial fat), lipoaccumulation (central fat deposits), elevated lipids, peripheral neuropathy, CV kidney, liver disease

75
Q

What is the effect of amyloidosis on the kidney

A

Leads to proteinuria and is commonly the cause of death (renal failure)

76
Q

What is the proteins allow for the staining

A

Charged sugar groups

77
Q

What is the most common fungal infection in AIDs patients

A

Candidiasis

78
Q

What is the most abundant HIV protein

A

P24

79
Q

What percent of AIDs patients present with cryptococcosis

A

10%

80
Q

What is the clinical presentation of cryptococcosis

A

Meningitis

81
Q

What types of lymphomas are common in patients with AIDS

A

Kaposi syndrome, B cell lymphoma, cervical cancer, anal cancer

82
Q

When does TB usually present in patients with AIDs

A

Early in course of infection, compared to late with other mycobacterium

83
Q

What is the role of gag and pol

A

Cleaved by viral proteases to yield mature proteins

84
Q

What can amyloidosis bind to in the blood and what is the result

A

Binds to factor X, which is crucial in clotting. Can lead to bleeding disorders

85
Q

Medullary carcinoma of the thyroid is the result of which major fibril protein and what is the precursor protein

A

A Cal is the major fibril protein from the precursor calcitonin

86
Q

Which week are viral levels dropped and what is the cause

A

Week 12, the viral levels will drop due to CTL activation

87
Q

What is the alternative name for the virus causing karposi sarcoma

A

HSV-8

88
Q

What is the mechanism of action for the formation of fibrils

A

Native protein folding is disrupted, causing the formation into Beta sheet structures

89
Q

Which type of T cells are immune to HIV infection

A

Naive T cell

90
Q

What is the mechanism of action for AA proteins

A

Chronic inflammation leads to IL1/6 production, increased SAA production, limited proteolysis and aggregation begins

91
Q

What is the most common form of amyloidosis

A

AL protein as a result of B cell lymphomas

92
Q

Which tumors is secondary amyloidosis, aka reactive systemic amyloidosis associated with

A

Renal cell carcinoma and Hodgkin lymphoma

93
Q

What is the role of the HIV vapor gene

A

Allows infection of terminally differentiated macrophage via a nuclear pore

94
Q

What is the primary clinical measurement used to determine when to start antiretroviral therapy

A

CD4 counts, not viral load

95
Q

Which chorionic inflammation disease is associated with secondary amyloidosis, aka reactive systemic amyloidosis

A

RA (3% or all pts)

96
Q

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

A

Encapsulated bacteria (S.pneumopniae and H. Influenza)

97
Q

Reverse transcriptase results in the production of which kind of DNA

A

Double stranded complementary DNA (cDNA, proviral DNA)

98
Q

What is oral hairy Leukoplakia and what is the cause

A

White projections on the tongue, and is the result of EBV driven squamous cell proliferation of the oral mucosa

99
Q

What is the condition of immune reconstitution inflammatory syndrome

A

When patients in advanced stages of HIV who are given antiretrovirals and experience clinical deterioration during the period of immune system recovery

100
Q

Which pathogen is responsible for the majority of mass lesions in the CNS

A

Toxoplasma Gondi

101
Q

Islets of Langerhans localized amyloidosis is caused by which precursor protein leading to which major fibril protein

A

Islet amyloid peptide leading the the major fibril protein AIAPP

102
Q

What is the result of the product tat(transactivator)

A

1000 fold increase in transcription of viral genes and required for replication

103
Q

What is the main virus leading to lymphomas

A

EBV

104
Q

What is the mechanism of action for ATTR protein

A

Mutations lead to a mutant form that aggregates

105
Q

Patients with Beta-2 amyloidosis are clinically presenting with which other symptom

A

Carpel tunnel syndrome

106
Q

What is secondary amyloidosis

A

Systemic or generalized amyloidosis where there is a complication of an underlying chronic inflammation or tissue-destructive problem

107
Q

Familial Mediterranean fever is characterized by which protein

A

AA

108
Q

What are the three routes that HIV infection can spread from mother to child

A

1) In utero by transplacental route
2) delivery through infected canal
3) ingestion of infected breast milk

109
Q

During the chronic infection phase , what are the clinical manifestations

A

There are very few, aka clinical latency period

110
Q

In the chronic infection stage, where is the primary location of viral replication

A

LNs and the spleen

111
Q

What is a rapid and specific test for amyloidosis

A

Scintigraphy with radiolabed SAP (it binds to the deposits)

112
Q

Isolated atrial amyloidosis is causes by which precursor protein leading to which fibril protein

A

ANP leading to the major fibril protein AANF

113
Q

How are Burkitt lymphoma and large cell lymphoma created

A

Mislocation of genes during the process of class switching and somatic hypermutation via the enzyme AID

114
Q

Familial Mediterranean fever is assocaited with what

A

Overproduction of IL-1 in inflammation responses

115
Q

What is the majority of amyloid made of and what is the percentage

A

95% of amyloid consists of fibril proteins

116
Q

What is the rate of HIV driven cervical dysplasia in AIDs compared to normal

A

10 times greater

117
Q

What is the assoacited disease with primary amyloidosis, aka immunocyte dyscrasias with amyloidosis and the major fibril protein

A

Multiple myeloma and other plasma B cell proliferation disorders, characteristic of the AL protein

118
Q

Where are the fibril in Familial amyloidosis polyneuropathy depositing

A

Peripheral and autonomic nerves

119
Q

What is the amino acid length and molecular weight of AA proteins

A

76 AA long and 8500 molecular weight

120
Q

What is the general family of viruses, and the specific ones that lead to neoplasms in AIDs patients

A

Oncogenes DNA viruses

-EBV, Karposi sarcoma herpes virus, HPV

121
Q

What commonly makes up the AL protein

A

Light chains of Ig, in particular, the lambda

122
Q

Familial Mediterranean fever is common in which group of people

A

Armenian, Arabic, Sephardic jews

123
Q

What is the condition of acute retroviral syndrome

A

Clinical presentation of the initial viral spreading, occuring 3 to 6 weeks after infection. Very similar to the flu

124
Q

Where are the common locations of the tumors that result of Viral lymphomas

A

Extranodal sites, such as the CNS, but also the gut, orbit, and lungs

125
Q

What is the underline cause of all amyloidosis

A

Extracellular deposits of fibrillarproteins

126
Q

What type of family is the JC virus and what does it cause

A

Member of the papilloma virus and causes encephalitis as it invades the CNS

127
Q

What are the three most common forms of amyloid

A

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

128
Q

Which type of T cells do HIV infect

A

Memory cells, so serve a long time as latent infection

129
Q

Which chemokine receptors do HIV R5 bind to

A

CCR5

130
Q

What is the two mechanism that sexual transmission of HIV occurs

A

1- Direct inoculation into the blood vessels due to trauma

2- Infection of DCs or CD4 T cells in the mucosa

131
Q

What are viral mechanisms to counter act APOBEC3G

A

Production of Vif to bind to complex and degrade it

132
Q

What is the heritability of familial Mediterranean fever

A

Autosomal recessive

133
Q

HIV R5 strains prefer to infect which cells

A

Monocytes/macrophage aka M-tropic

134
Q

How does mycobacterium differ in HIV patients

A

-They will not result in granulomas cause the lack of CD4+ cells

135
Q

What is the globally most common form of HIV transmission

A

Heterosexual contact

136
Q

Which non-T cells can HIV infect

A

-Macrophages, DCs

137
Q

What are the three virus assocaited B cell lymphomas

A

1) EBV+ large cell lymphoma
2) KSHV+ Primary effusion lymphoma
3) EBV+. Hodgkin lymphoma

138
Q

CMV virus occurs exclusively in patients with a CD4 T cell count less than

A

50 per microliter

139
Q

What are the clinical presentations of CMV in patients with AIDS

A

Pulmonary, eye (retinitis), GI or CNS infections

Robbins Pathology MOD1 (Chptr 1-6) (10 decks)

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