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Pathology > Immunopathology IV: HIV > Flashcards

Immunopathology IV: HIV Flashcards

1
Q

HIV infection causes sickness and death largely by

A

damaging the immune system, leading to opportunistic infections and unusual tumors/ odd cel proliferations

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2
Q

the fully manifest dz of HIV

A

aquired immunodeficiency syndrome

aids

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3
Q

List of dz.’s that define AIDS

A 
cryptospridiosis/isosporidiosis
pneumocystosis
toxoplasmosis
candidiasis (esophagus, trachea, lung(
cryptococcosis (CNS)
coccidioidomycosis (disseminated)
histplasmosis (disseminated)
mycobacteria (MAC or TB)
Nocardiosis
Salmonellosis (disseminated)
CMV
herpes simplex/ herpes zoster
progressive multifocal leukencephalopaty 
Kaposi's sarcoma
primary lymphoma of the brain
invasive cancer of the uterine cervix
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4
Q

Pnemocystis jirovecii

A

is an atypical fungus that will not grow in the lab and is probably a commensal in humans

it grows in the alveoli (PCP, an established acronym now stands for pneumoCystis Pneumonia) and produces the lung infection that led, in combination with Kaposie’s in MSMs to the first identification of AIDS as a new disease

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5
Q

PCP pcoduces

A

consolidation of the lung. The alveoli fill with micro-organisms with a limited or absent inflammatory response.

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6
Q

Pneumocystis morphology

A

Silver stain: they look like crushed ping pong balls

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7
Q

pneumocystis pneumonia morpology

A

the pink frothy looking material in the alveolar spaces contains the pale staining microorganisms

there may be a fair inflammatory response in the interstitial or none at all.

a high resolution CT scan show ground glass opacities, because the alveoli are either packed or empty

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8
Q

The PCP fungi anchor to

A

type I pneumocytes. Thus, very little material is coughed up in PCP - the cough is non productive.

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9
Q

Pneumocystis has always been most strongly linked to the kind of immune defect seen in

A

AIDS - low CD4 counts. It may affect its immunosupressed from other causes, especially hematologic malignancies

PCP historically seen when CD4 counts dropped below 200

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10
Q

pneumocystis as a pathogen was first describes as the cause of

A

a plasma cell rich interstitial pneumonia in malnourished infants in the years after WWI

apart from the abundant plasma cells in the interstitial, the pathology was the same as pcp seen in aids today, with the foamy, organism rich exudate within the alveolar spaces

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11
Q

making the diagnosis of PCP can be tough

A

1-beta-d-glucan is produced by pneumocystis and blood levels above 80pg/mL favor PCP

you may need to induce sputum to send to the lab to search for the organisms. Lavage fluid, endotrachial aspirate or lung biopsy are more likely to show as posititve

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12
Q

mycobacterial infections include both

A

the familiar TB bug and the atypical mycobacterium (avium, intracellular, etc)

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13
Q

many people have been exposed and have confined M tuberculosis with ian

A

Ghon focus of complex.

The caseous necrosis, granuoma formation with giant cells and acid fast bacilli are familiar to you from general pathology

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14
Q

The appearance of advanced TB in the lungs (more severe at the apices with cavities) is similar in HIV

A

positive and negative patients.

macrophages can form granulomas even with few CD4’s

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15
Q

Miliary TB results form

A

invasion of the blood stream. The name comes from a resemblance to millet seed.

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16
Q

Overview of immunopathogenesis of TB

A

perforin and granulysin from the CD8 T cells kill bacteria and ones own cells

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17
Q

When you suspect TB (history , physical, imaging) in an HIV positive pt, the lab can help you

A

look for acid fast microbes in sputum
culture the microbe from sputum/ bronchoscopy specimens/ pleural biopsies (2-8 weeks to grow)
see/cultrue the microbe on lymph nod aspirates
search for TB using nucleic acid assays
determine susceptibility to anti TB medicines

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18
Q

Mycobacterium avium complex (MAC; includes the species mycobacterium avium and mycobacterium intracellular) is probably the most treacherous of the

A

aids oppotunists

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19
Q

MAC microbe can produce

A

a trivial infection in helthy pts and diarrhea in pts who have advancing HIV (GI involvement)

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20
Q

MAC - when cd4 counts drop below around 50, patients are at risk for

A

sudden development of a systemic illness with fever, sweats, weight loss, and perhaps lung (pneumonia) GI (diarrhea, malabsorption) and/or marrow problems

The microbe grows from the blood, but it takes 1-2 weeks. If MAC isn’t diagnosed and treated it is rapidly fatal. SOme treatment protocols give prophylaxis for its at risk

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21
Q

Mycobacterium avium organisms (like real TB and other non TB mycobacteria) occasionally produce infection of

A

the cervical lymph nodes in health people, especially children

(you may have heard this cervical lymphadenitis called scrofula, superstition had tit that it could be cured by the touch of a king)

curiously this has reappeared in the HAART era, during immune recontitituion MAC can preset as single-site lymphadenitis

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22
Q

Cytomegalovirus (herpes 5) is a common virus that infects

A

a majority of humankind. it is generally acquired early in life through kissing (saliva) or less often by blood transfusion

most often transmission produces no symptoms, but in teens and adults, it may produce fever, lymphadenopaty, and/or sore throat, and a blood picture with atypical lymphocytes

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23
Q

The diagnosis of acute CMV infection is made clinically by

A

a rise in complement fixing antibodies (4-fold titer over 2-4 weeks) or finding IgM 30% or more of IgG

like the more common and more familiar Epstein Barr infectious mononucleosis, CMV travels by kissing

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24
Q

If mom has her first CMV infection while pregnant , it can do

A

major harm to the child, even if she has normal immunity. Hearing loss or extensive brain damage are common.

CMV is one of the dread neonate infections

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25
Q

CMV produces enormous cells because

A

the emerging viruses destroy the cytoskeleton

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26
Q

CMV, like all herpes viruses, remains

A

latent following initial infection.

as immunity disappears in advancing HIV infection or from one other cause, CMV is prone to reactivate

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27
Q

When the AIDS epidemic struck, we were already familiar with CMV as an

A

opportunistic infection in immunosupressed transplant recipients

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28
Q

CMV cells are easy to spot by

A

their huge size, and big, single intranuclear inclusion

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29
Q

CMV pneumonia in advanced HIV infection could be

A

fatal

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30
Q

CMV retinitis

A

was a common, dread illness in full blow aids

histopathology shows hemorrhage, necrosis, and big CMV cells

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31
Q

Glanciclovir implant

A

used in the eye to control CMV chorioretinitis in the era before effective antiretroviral therapy

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32
Q

CMV in the colon was a common problem in

A

classic AIDS

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33
Q

CMV encephalitis is less common than toxoplasmosis as a cause of

A

focal brain lesions, and less common than eye, GI tract or liver involvement, but devistating

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34
Q

Making the diagnosis of CMV

A

most often it presents as chorioretinitis or colitis. Usually the pt has a CD4 count below 50

in serious CMV p65 (lower matrix protein) antigenemia will usually be detectably by the lab, and PCR may help show the virus to be present

CMV can be grown on fibroblast cultures, or a shell via culture

ask your lab about testing using PCR for resistance genes against the common antivirals. This still takes about a week

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35
Q

more extensive oral candidiasis is more worrisome. Before effective treatment, oral candidiasis tended to paper when

A

the CD4 count dropped below 500 or so

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36
Q

______ defines AIDS

A

candida

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37
Q

esophageal candidiasis was well known as a sign that

A

HIV infection was progressing to the late stage (AIDS)

usually the CD4 count will be below100

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38
Q

Candida looks like

A

balloon animals

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39
Q

______ help fight candida, and it is seldom the ______ infection in aids

A

neutrophils

fatal

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40
Q

Toxoplasmosis is infection with the protozoan ______, which completes its life cycle in_____

A

toxoplasma gondii

cats

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41
Q

If you avoid eating undercooked meant and change the cat litter box dilly, you are u

A

unlikely to contract toxoplasmosis.

only about 10% of folks in th eUS have antibodies

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42
Q

Primary infection of toxoplasmosis is usually

A

asymptomatic or may mimic infectious mononucleosis,

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43
Q

if toxoplasmosis mimics mononucleosis, the diagnosis will not be made unless

A

the physician finds anti-toxoplasmosis IgM without IgG in the serum or the tacyzoites are found on fine nee dal aspiration of the enlarged lymph nodes

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44
Q

Toxoplasmosis remains

A

latent in the body after infection, and HIV patients who have antibodies as well as CD4 counts below 100 are prone to develop opportunistic toxoplasmosis

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45
Q

most common and most feared of toxoplasmosis

A

are areas of necrosis in the brain. These are often multiple and appear as ring-enhanging lesions, often in the basal ganglia.

brain biopsy may be required, unless the presentation is classic

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46
Q

Toxoplasmosis involving the retina.

A

this can happen to healthy people for unknown reasons, but is fairly common in AIDS

more white fluff, less hemorrhage than CMV retinitis, you’ll get a consult

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47
Q

Cryptococcus

A

a single narrow based bud, and a capsule

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48
Q

cryptococcosis is a deep fungal infection caused by

A

cryptococcus fungus (usually C. neoformans) found in the environment. A link to pigeons remain anecdotal

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49
Q

cyrptococcal meningoencephalitis may occur in

A

anyone
some people with apparent normal immunity get this infection and mount a fair immune response. In the immunocompromised, there is little or no inflammatory response, and headache, mental changes, and perhaps CN problems (from the increased ICP - the fungus makes CSF gooey and hard to reabsorb)

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50
Q

pulmonary cryptococcosis occurs only when

A

immunity is very poor. The yeasts fill the alveoli with little or no inflammation

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51
Q

If cyrptococcosis is suspect, perform

A

neuroimaging first, and if no other cause of symptoms is found and lumbar puncture is safe, send CSF for culture, antigen assay, and india in prep (you will miss the organisms on frame stain)

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52
Q

what defines infection of cryptococcus

A

growth of cryptococcus on culture

they usually grow by 3 days, at the max, 7. Blood culture may also be positive, but its lower yield.

around 75% of patients will have a positive India ink preparation on the CSF, and the antigen assays are very sensitive and specific (there may be cross-reaction with other deep fungi)

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53
Q

Worldwide, there are around ______ cases of cryptococccal meningoencephalitis

A

a million yearly with around 600,000 deaths. Most are in aids patients

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54
Q

cryptococcus in the lung

A

yeasts with big invisible capsules, and single, narrow based buds

capsular goo separates the yeasts (aids its can drown in the organisms)

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55
Q

Progressive multifocal leukoencephalopathy

CD4 count usually below

A

200

JC papovavirus damages the brain

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56
Q

PML’s anatomic pathology in Aids is similar to

A

other immune compromised conditions, with loss of myelin in patches of grey and white matter, and the glial changes you learned in Neuro

PML was the major cause of seizures/ status epileptics in AIDS

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57
Q

Cryptosporidiosis is infection by ____ or _____ , 3-4 m protozoan that life in _____

A

C. hominis or C. parvum

live in the brush border of the small intestine

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58
Q

The life cycle of cryptosporidiosis is

A

complex and completed in a single host. C hominis is generally passed human to human, C parvum infections often follow contact with farm animals, especially cattle

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59
Q

Cryptosproidiosis organisms fill the

A

brush border of the gut. This accounts for much of the diarrhea in developing AIDS

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60
Q

How cryptosporidiosis causes illness

A

remains unknown
probably its mostly due to damage to the microvilli of the brush border

There’re no know cytokine activity, little or no inflammation, and no cell necrosis. The microbes may make their way into the bile ducts, but never go systemic

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61
Q

Healthy folks with crypto may h ave

A

diarrhea for up to two weeks, usually without blood or white cells in the stool

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62
Q

outbreaks of crypto are generally

A

water-borne, including swimming pools and ponds, and are more common where there’s poor sanitation, and during the rainy season in the tropics.

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63
Q

among the immunocompromised, especially those with ______ and _________, cryptosporidium becomes a

A

HIV and depletion of CD4+ cells,

crhonic illness, and was the cause of the diarrhea that made life miserable for its with AIDS related complex during the years before the life threatening infections began.

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64
Q

in advanced HIV immunodeficiency, crypto is blamed for

A

cholangitis and pancreatitis, by invading the ducts

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65
Q

In the lab you can test for cryptosporidium

A

easisest is examining the stool - cryptosporidia are acid fast and can be seen easily on microcopy

immunoflourescence is more sensitive and specific. You can see the internal structure of the cysts

biopsy may reveal the microbes, or it may miss them because infection can be patch. There are ELISA and PCR tests as well

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66
Q

IN HIV patients, crypto can be managed uzing

A

antiprotozoal drugs, but reconstitution of the immune system using antiretroviral drugs is usually required to eradicate the microbe

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67
Q

________ and some of cryptosproridium’s other relative can also produce the same anatomic and clinical lesion

A

isosopora

68
Q

______ is also fairly common in advanced HIV infection, and like cryptosproidiosis is an aids defining illness

A

salmonella

69
Q

Histoplasma capsulatum, the cause of )______ is a _______ fungus - a mold in the soil, a yeast at 37 degrees.

A

histplasmosis

a thermally dimorphic fungus

70
Q

When a healthy person meet the istoplasmosis fungus (by _______), usually the infection is ________

A

by inhaling the microconidia spores from the environment, they ar plentiful especially in bird and bat droppings, starkly roosts are famous

usually the infection is asymptomatic or subclinical

71
Q

HIstoplasmosis yeasts mulitiply in the

A

lungs, and probably some travel in the bloodstream. Before they can do any real damage, they are surrounded and either killed or walled off by macrophages

72
Q

HIV patients who have immigrated from other counties and then developed histoplasmosisi usually have the

A

genetic strains from their former countries, showing that the yeasts live within the body, walled off, probably for a lifetime

73
Q

LIke other fungal diseases ,histoplasmosis is

A

not contagious. It’s estimated that only about 1 in 2000 who meet histoplasmosis in the wild will get seriously sick, but the rid is greater if ter’s a big dose (camping in starling territory, cavers getting into bat guano)

74
Q

The severe acute dz with histoplasmosis

A

may be pneumonia, or a systemic infection with lung involvement (maybe) enlarged liver/spleen (usually) and/or bone marrow replacement (likely)

75
Q

IN KC autopsies, its very common to find a _______ from the person’s long ago meeting with _____

A

Ghon focus or complex
hist.

there’s no telling histoplasmosis from TB on ‘gross’

76
Q

In a histoplasmosis pneumonia and disseminated histoplasmosis, the infiltrate is composed almost entirely of

A

macrophages, laden with the yeast forms

if the immune response is good, granulomas form by the influence of g-interferon. This is probably why anti interferon medications such as the anti TNF agents increase the risk from histoplasmosis

77
Q

Chronic pulmonary histoplasmosis closely resembles

A

TB, with the same caseous necrosis and cavity formation

Sputum culture is likely to be positive,though it takes weeks to grow

78
Q

HIstoplasmosis in bone marrow and in liver. look for

A

two micron yeasts

79
Q

Unusual presentations of histoplasmosis, in immunocompromised individuals or sometimes health folks include

A

fibrosing mediastinitis and eyeball invasion (both as bad as they sound)

80
Q

in people with ________, especially where old histoplasmosis is common, _____________ always needs to be a consideration. Two micron yeasts.

A

advanced HIV

recurrence of histoplasmosis

81
Q

If you suspect seriou histoplasmosis, your lab can help

A

draw blood and sputum for culture. yield is low
get tissue for culture and microscopy if you can . usu the pathologist can find the microbes
send blood and urine for antigen assays (galactomannan) these are very sensitive nowadays though thers’s cross reactivity with other sep fungi
draw titer for complement fixing antibody. a titer over 1:32 or rising titer suggests active dz. again, cross reactivity with other fungi may be a problem
we can’t recommend skin testing, up to 90% in many areas

82
Q

Coccidioides immitis is a fungus that grows in the

A

US southwest and usually causes a mild lung infection when first encountered. . either or both forms may be seen in tissue during infections (coccidioidomycosis)

83
Q

forms of coccidioides

A

a sphere flu of yeasts, or hyphae with barrel-shaped spores

84
Q

healthy ppl differ in their ability to handle coccidioides fungi. Rarely a severe

A

pnemonia and/or skin involvement develops in people who seem immunocompetent

85
Q

Coccidioides can produce a _____ in aids pts

A

deadly pneumonia or disseminated infection in AIDS patients.

in areas where coccidioides is endemic, HIV positive ppl with low CD4 counts may be given prophylaxis

86
Q

Aspergillosis can produce

A

the familiar fungus balls, invasive pulmonary dz, or disseminated dz. It’s infamous for following pneumocystis pneumonia, which damages the lungs and may requires teroid treatment, making the lungs vulnerable.

87
Q

aspergillus is famillar. mophology

A

septa, 45 degree branching, fruiting bodies

88
Q

spirochetosis of the colon - another cause of

A

diarrhea. The cell will be made on biopsy, and the right antibiotics clear it easily

89
Q

spirochetosis iof the colon is easier to see on

A

silver stain

90
Q

Herpes simplex II in aids. _____ confirms the dx

A

Tzanch touch prep

91
Q

_____ was another famiiarsign that HIV infection was advancing to the later stages, however it could and did occur at any CD4 count. Today the vaccine can be given if the CD4 count is over _____

A

Zoster

200

92
Q

______ has always been rare in AIDS

A

herpes iii pneumonia

93
Q

Erythroviruses (parvo B19 and its kindred) usually produce a

A

mild flu like illness that may be followed with a rash and/or joint pain (fifth dz, erythema infectious)

94
Q

erythrovirus causes episodes of

A

red cell production failure in folks with hemolytic anemias, or severe anemia before birth “hydrops”

95
Q

Erythrovirus morphology

A

nucleated red blood cell precursor with parvo inclusions in the nucleus

96
Q

in HIV pts, parvo may cause

A

a longstanding failure of production of RBCs with severe anemia
These HIV its for some reason fail to make Abs against the virus

97
Q

Bartonella species

A

bacillary angiomatosis. an unusual bacterial infection due to immune compromise

98
Q

Bacillary angiomatosis morphology

A

solid masses of bugs

99
Q

NOcardiosis

A

a filamentous, weakly acid fast bacterium. is a relatively uncommon pathogen in AIDS, it can produce pneumonia, meningitis, or isseminated infection

100
Q

Scabies is

A

even worse in AIDS patients than in other folks

101
Q

penicillium marneffei is a

A

fungal opportunistic seen among immune compromised people in southeast asia and in returned travelers.

local or systemic illness.

102
Q

seborrhea is likely to flare up as Cd4 counts drop below

A

400

and become severe below 200

103
Q

Hairy leukoplakia

A

an EBV effect in which the squamous epithelium on the tongue proliferates

104
Q

______ with _____ led to the identification of AIDS and HIV

A

kaposi’s sarcoma with pneumocystis pneumonia.

105
Q

Kaposi’s is caused by infection with

A 
herpes 8 (KSHV) 
has varying presentations
106
Q

classi Kaposi’s

A

seen mostly in older men in the developed world. Generally, lesions are confined to the skin and do not shorten life expectancy

107
Q

african kaposis

A

widespread in the subsaharan areas, even before HIV sometimes aggressive

108
Q

transplant asociated kaposi’s

A

seen especially in people suppressed for renal allografts. Could be aggressive

109
Q

HIV associated

A

ranges from minor skin lesions to very aggressive dz with sometimes fatal GI/lung involvement

110
Q

Kaposi’s sarcoma is actually a

A

virally induced polyclonal proliferation of blood vessels

111
Q

kapok’s famous locations

A

on the palate and the nose.

112
Q

one of the most troubling features of kapok’s

A

the emotional impact - people knew what it meant

113
Q

kaposis of the small intestine can produce

A

obstruction or serious bleeding

114
Q

microscopically, kapok’s looks like

A

granulation tissue, because it’s an overgrowth of little blood vessels

at high magnification, look for red cells caught in the cracks

115
Q

KSHV exists as an

A

episome in the host nucleus

116
Q

Several of KSHV proteins (LAMA, vFLIP, and VCyclin) encourage cells to

A

proliferate - the lesions often, but not always regress partly or completely when antiretroviral therapy is instituted

117
Q

Cancers of the lymphocytes that grow as solid masses.

A

malignang lymphoma

much studied, classified and reclassifed, may of them are much more common in HIV patients than in other folks

118
Q

Malignang lymphomas in HIV infected people fall into two categories

A

those that develop early

those that develop later

119
Q

Malignant lymphomas in HIV - that develop early

A

are usually aggressive B cell lymphomas. Probably these are common bc of the greatly increased turnover of B cells during the early years of the infection, providing an opportunity for selection for mutant clones (HIV as cancer promotor)

120
Q

Malignant lymphomas in HIV - that develop later

A

usually related to EBV (less often KSHV) these are often polyclonal and may regress when immunity is restored

121
Q

B cell lymphomas in aids

A

early - Burkitt lymphoma, large B cell lymphoma

later - EBV+ large cell lymphoma, KSHV+ primary effusion lymphoma, EBV+ hodgkin lympoma

122
Q

primary brain lymphomas, usually caused by ____ are___-

A

EBV
common
tend to center around blood vessels

123
Q

the ‘other’ target of HIV (after the immune system) is the

A

nervous system

HIV doesn’t infect neurons, astrocytes, or oligodendroglia
we think the damage is done by chemokines and infected microblia. and gp120 may be a neurotoxin

124
Q

HIV in the nervous system

A

aids encephalopathy /-itis
macrophage “typhus” nodule
giant cell encephalitis
neuronal loss/gliosis

125
Q

The giant cell encephalitis results from

A

macrophages trying to phagocytose one another, as each has HIV gp120 on its surface

126
Q

AIDS peripheral neuropathy includes

A

a variety of lesions, but is seldom studied microscopically. More familiar to pathologists is the late, catastrophic spinal cored vacuolar myelopathy

127
Q

Cachexia in aids has been attributed at least in part to

A

immune mediated apoptosis of skeletal muscle fibers

128
Q

hair loss in advancing HIV infection is

A

poorly understood

129
Q

Thrombocytopenia=

A

low platelets

130
Q

Thrombocytopenia occasionally severe enough to came bleeding problems is a common problem in

A

hiv infection that often precedes damage to the immune and nervous systems.

131
Q

thrombocytopenia

A

megakaryocytic can express CD4 and either coreceptor and are often abnormal and/or unproductive in numbers in HIV infection. Circulating platelets are often coated with gp120 containing immune complexes and destroyed.

132
Q

once a problem affecting 40% of HIV positive patients at some point in their illness, thrombocytopenia is now uncommon thanks to

A

antiretroviral therapy. When it still requires focused treatment, Rx intravenous immunoglobulin or and anti-RhD (for Rh+ patients - this keeps the spleen busy destroying red cells rather than platelets)

133
Q

structue of the aids virus

A

HIV 1/ HIV2

134
Q

no reasonable person questions that the HIV viruses cause

A

AIDS

135
Q

HIV’s interaction with NFkB may help explain

A

how it reactivates and why transmission is more likely when there’s already another infection

136
Q

HIV contains

A

double stranded RNA, the reverse transcriptase to copi ti to DNA and other enzymes to incorporate it into the host genome.

the mutation rate is 10^6 more than for DNA, with an average of 1-2 mutations per replication cycle, with replication cycles averaging 2.6 days.

hence each HIV infection is a rapidly evolving system, which is why antiretrovirral therapy requires multiple drugs

137
Q

When transmitted, most HIV is ____ binding to the Cd4 receptor and CCR5 coreceptors most abundant on ______ and _____

A

m-tropic (R5)

dendritic macrophages and memory T cells

138
Q

Over the course of the infection, the m tropic strains tend to be replaced by

A

T tropic mutants (X4 binding best to CD4 receptors and CXCR4 co receptors most abundandt on working T helper cells

139
Q

A few percent of folks, mostly of European ancestry have mutant

A

CCR5 receptors. One mutated coply slows progression of the dz; two mutated copies confers resistance to infection

140
Q

Initial infection is followed, in a marjoiry of cases, in around 3-7 weeks by

A

an acute febrile illness (my worst case of the flu ever), often with sore throat, muscle aches, and otherwise resembling infectious mononucleosis.

A rash and long duration may be tip-offs that its “acute retroviral syndrome” At theist ime virus levels are very high in the blood, and patients are extremely infectious
“acute retroviral syndrome” resolves in 2-4 weeks.

141
Q

mucosal ulcers, often at the site of inoculation may alert the physician to

A

acute HIV

142
Q

During the acute infection

A

there is often a high level of virus in the bloodstream and a low cd4 count. ( a few people’s cd4s have dropped well below 100 and they;ve gotten pneumocystis– recovering when the CD4 clls rebounded)
At the peak of the viremia, seroconversion occurs and the virus level drops

143
Q

After the acute infection

A

the CD4 count recovers. After this, the virus lives and multiplies primarily in the deep lymphoid tissue. memory T cells are vulnerable to infection, and other CD4 positive cells can become infected when they are activated

eventually, the cd4 cells are depleted, and the immune system otherwise sufficiently damaged to allow one of the AIDS defining opportunistic infections or tumors to appear.

144
Q

Long before the opportunistic infections appear,

A

the lymph nodes enlarge (big germinal centers, B cell proliferation) and the total blood (immune) globulins increase (polyclonal)

145
Q

In late AIDS, the lymphoid tissues are

A

largely depleted, especially in the areas where there should be T cells

146
Q

HIV destroys T cells through

A

cytopathic lysis from massive virus production

147
Q

HIV in macrophages

A

seldom produces lysis. HIV viruses are sequestered in vacuoles and transported out of the macrophage without damaging it.

148
Q

In additon to lysing CD4 cells and slowing down infected macrophages, HIV has a number of other effects

A

immune cells may die as a result of prolonged activation, or an abortive infection may cause a cell to self-destruct by activating the inflammasomes “pyroptosis”

follicular dendritic cells in the lymphoid tissue become coated with HIV virus and infect CD4 cells as they pass by. Its likely that this reservoir explains why no one is cured of HIV infection

and for some reason, HIV infection causes polyclonal activation of B cells, accounting for the generalized lymph nod enlargement that is often seen before symptoms of AIDS appear, and the polyclonal gammopathy sen in HIV infection

149
Q

What defines retroviruses

A

reverse transcriptase

150
Q

HIV is transmitted when

A

infectious material is injected directly into the bloodstream, or the virus is taken up by dendritic macrophages at the site of inoculation

151
Q

HIV infection was originally recognized in the US as a disease of

A

MSMs. the explanation is that passive anal intercourse is an especially efficient means of transmission. remains the most common route of transmission in the US

152
Q

The other major risk factor for HIV is

A

needle sharing, and female partners of infected male needle sharers are also at high risk.

153
Q

the most common means of HIV transmission worldwide

A

heterosexual transmission

although a self sustaining HIV epidemic never developed in the straight community in the US

154
Q

transmission of HIV from mother to child may occur

A

across the placenta or from nursing, but it is most common during or just after the birth process

155
Q

HIV infection is a

A

zoonosis
HIV-1 was a chimp virus. HIV2 was a sooty mangabey virus. The infections could only become established as epidemics among humans when social changes greatly increased the likelihood of transmission from human to human

156
Q

The old PGL category “persistent generalized lymphadenopathy” reflected the

A

B cell/germinal center hyperplasia of the lymph nodes throughout the body.
in unRx’s HIV this lasts for years

157
Q

There was a massive die off of america’s hemophiliacs due to

A

contaminated factor VIII

158
Q

The antiretroviral drugs bring their own new anatomic pathology

A

lipodystrophy seen with some protease inhibitors - fat disappears from the face and becomes more abundant on the abdomen. On biopsy, look for fat cells in skeletal muscle itself.

159
Q

IRIS=

A

immune reconstitution inflammatory syndrom

160
Q

IRIS is seen

A

in one form or another in around 10% of patients with very low CD4 counts in the weeks/ months after initiation of anti retroviral therapy.

it’s an aggressive immune response against opportunists that may have been known to be present already (paradoxical IRIS) or maybe not (unmasking IRIS)

161
Q

infections producing IRIS

A

cryptococcal meningitis and CMV involving the eye (immune recovery uveitis) are perhaps the most common;

cryptococcal and JC papovaviurs IRIS can be lethal

most other infections producing IRIS (TB, other mycobacteria, pneumocystis, Kaposi’s, zoster) may require no treatment or may be managed with prednisone

162
Q

Today’s screen for HIV is

A

an elisa, which is sensitive enough to make a good screen. The average person turns positive around day 25, most by 42 and it is rare to remain negative at 6 mo.

a positive elisa is followed up by a nucleic acid assay, which is replacing the classic western blot

163
Q

Nucleic acid testing for HIV remains important for testing, and most people turn positive by days 13-28. No one is certain about the rate of false negatives after a month, but it is low.

You are likely to order nucleic acid testing

A

if you suspect acute HIV infection. It turns positive before any other test, but may be negative (eclipse phase) during the illness

in screening for neonatal HIV infection

after an indeterminate ELISA serology

all blood donor units are screened with a qualitative nucleic acid test

so far FDA approved nucleic acid tests only tsp for HIV 1

164
Q

When diagnosis of HIV infection is established

A

quantitative nucleic acid based assays are used to follow the viral load

genetic studies are performed to test for resistance to current antiretroviral medications. around 20% of new infections are resistant to at least one medication

165
Q

the viral capsid antigen p24, is

A

relatively inexpensive and as a fourth generation assay may turn positive earlier than the elisa

the cdc recommends a p24 and an elisa for screening; if either is positive, follow by an assay for antibodies against HIV1 and HIV2.

others recommend just an elisa unless there’s a suspicion of acute HIV infection, in which case, order nucleic acid testing. The p24 assay tends to turn negative as the person develops antibodies against the protein.

and blood units are of course tested instead using an assay for HIV nucleic acid

166
Q

Seven interventions that work against the spread of AIDS

A
  1. Safe blood/blood components for transfusion
  2. antiretroviral prophylaxis before and during childbirth
  3. condom distribution and use
  4. needle exchange programs for addicts
  5. male circumcision
  6. formula feeding instead of breast feeding for HIV+ moms
  7. early treatment of the infected partner in serodiscordant unions

Pathology (15 decks)

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