Patho- Neoplasia and Immunology- HIV- PP

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1

Hallmark of HIV/AIDS

Defective cell-mediated immunity

-CD4 T-helper/inducer lymphocytes

2

CD4 T-helper/inducer lymphocytes normally mediate between

antigen presenting cells, B-cells and other T-cells

3

Primary immunodeficiency is caused by

HIV type 1 and 2

4

Most people living with aids are in

Sub-Saharan Africa, but it is spreading through Asia and eastern Europe

5

AIDS is a

The first case identified was in

Lentivirus

1981

6

HIV 1 has at least ___________

Thought to have appeared in __________-

10 subtypes

Central africa

7

Most cases of HIV in central Africa, the US, Europe and Australia are

Type 1

8

thought to have originated in West africa

Characterized by a longer latency period and lower mortality rates

Type 2

9

Modes of AIDS transmission

Sexual

Parenteral

Perinatal

10

Highest risk of HIV transmission, Unites states

men to men

women sleeping with men in high risk groups

mother to infant

sharing needles

11

HIV transmission in africa and southeast asia

Highest risk

heterosexual intercourse

blood contact

pre/perinatal transmission

No gender discrepancies

12

Major routes of transmission of HIV in developing countries

-multiple sexual partners

-sex with prostitutes

-hx of other STDs

-Genital lesions/abrasions

13

Can mosquitos pass along HIV?

No

14

What determines whether exposure will lead to infection?

-virulence

-host t-cells and cytokine response

15

Gene CCR5 Delta 42 provides

A natural resistance to HIV

16

Polymorphism 24-59 (A/G)

Slows the progression of HIV

17

Globally, ___________ is the most common mode of transmission for HIV

Sex

18

In a retrovirus, RNA must

be converted to DNA before gene can be expressed to make copies

19

HIV structure

Core

Nucleocapsid that contains two RNA strands, protein and enzymes surrounded by a lipid bilayer/viral envelope

20

HIV structure

Enzymes

reverse transcriptase (Polymerase and ribonuclease)

integrase

protease

21

HIV structure

Viral envelope

Made from host cell

Viral glycoprotein studs protrude from cell membrane

22

HIV is attracted to CD4 receptors, found on many cells, it starts with

Macrophages, but then moves to T cells or both

(Macrophages and Helper T cells most often implicated

23

When HIV is only attracted to T cells, it is

T tropic

24

What must be present for HIV to gain entry to the cells via binding?

Chemokine coreceptors

25

When early HIV is bound to both CD4 receptor and chemokine receptor...

(KEY CORECEPTOR IS CCR5)

it implants in the cell membrane

26

Once infected, with every cell division,

the virus is replicated and the DNA becomes a permanent part of the cell's DNA

27

Eosinophils phagocytize invading pathogens, allowing them to

present antigens to other cells

28

Hypersensitivity T2 and 3 are ________________ mediated

IgG and IgM

29

Hypersensitivity T1 is _________- mediated

IgE

30

Eosinophils modulate t1 hypersensitivity by degrading

histamine and leukotrienes released by mast cells

31

Neutrophils produce

enzyme that produces histamine

32

High levels of eosinophils can cause

inflammation of the airway

33

H4 receptors (Found of eosinophils) are highly attracted to histamine and

are involved in chemotaxis and the inflammatory process

34

Eosinophils and neutrophils are often

Effector cells

35

A key element in the success of HIV is that it

replicates prolifically from the onset and overwhelms the body's defenses

36

HIV is primarily a

Mucosal disease

37

The major site of HIV replication is the

GI tract

38

HIV is characterized by ______________ and _______________

a high level of virion turnover

a high level of CD4 turnover (host cell death)

39

___________- HIV particles are produced and destroyed each day

at least 10 billion

40

_____________ decline in acute HIV

TOTAL T-cell numbers

41

Children effected by HIV

The virus is more aggressive and immune dysfunction is more rapid

42

HIV can lie dormant in ____________ but not in ________

T-cells

Macrophages and monocytes

43

Long term survivors of HIV tend to have

More CD8 Killer T-cell activity

(Suppresses viral replication)

44

In HIV, _________ is the major reason for CD4 T-cell depletion

Apoptosis

45

A syncytium in HIV results when

A large number of uninfected CD4 cells become fused together by viral particles

Causes mass apoptosis

More common during T trophic phase

46

Why can gp120 and gp41 hide from the immune system?

Because of the large amount of carbohydrate on the surface

47

Antibody dependent cellular cytotoxicity

Complement system

48

Why does the body sometimes attack healthy cells in HIV?

the binding and glycosylation of gp120 and gp41 make them appear similar to MHC class 1 "self" antigens

49

what is gp120 and gp41?

The components of the viral envelope glycoprotein, gp160

coded by the env gene

50

During acute and chronic, untreated HIV, the immune system is in a

Hyperactive state

high t-cell death

nonspecific T-cell activation

elevated proinflammatory cytokines

polyclonal B-cell activation

51

Why does the immune system suck in HIV

CD4 helper T-cells don't adequately activate and help B-cells

52

Why does HIV hand out in macrophages?

The have CD4 receptors

act as both reservoirs and targets

53

Humoral =

antibody mediated

54

Macrophages infected w/ HIV have

defective chemotaxis and phagocytosis

abnormal antigen presentation

abnormal cytokine production

Cause T-cell death

55

Cell mediated

Not antibody mediated

56

In HIV B-cells

have decreased differentiation and response

Exhausted cell population

57

In children with early HIV

salivary IgA was found to be low

58

Autoantibodies associated w/ HIV attack

Spermatozoa

erythrocytes

myelin

thrombocytes

lymphocytes

nuclear proteins

neutrophils

59

HIV antibodies are produced by the body, but

they are not effective

60

Pts wit HIV, ant antiretroviral therapy respond to

old, but not new infections

increase in memory T-cells, but low numbers of naïve T-cells

Indicative of deteriorating immune function

61

What must be present for the HIV particle to bind to the CD4+ cells during the M-tropic phase?

CCR5- Chemokine

62

In later infection, during the T-trophic phase, what must be present?

CXCR4-Chemokine

63

WHat helps untwist HIVs RNA to fit it into the pores of the nucleus?

DDX3

64

How do macrophages contribute to T-call decline?

Increasing CD4 death

65

HIV's effect on B-cells

-overproduction of nonessential and/or ineffective antibodies

-Increased Apoptosis

66

Other than the carb thing, how does HIV hide in the body?

Noncovalent bonds between gp120/gp41 that make it so early antibodies cannot bind to it

once they can, its too late

67

Infected cells (HIV) undergo ___________ leading to production of more virion

Viral budding

68

What mutation can inhibit HIV?

Delta 32 in the CCR5 gene

69

What components of the immune system can inhibit HIV?

-Interferon type 1

-Natural killer cells

70

In the acute infection with HIV, what is present?

-Widespread virus

-viremia (If lymph tissue destroyed)

-viral seeding in lymph nodes

71

in the asymptomatic phase of HIV,

-Viral seeding in lymph nodes leads to HIV replication and destruction of lymph tissues

Chronic lymphadenopathy with lowered numbers of CD4 T-cells

72

How do most CD4 cell deaths occur?

Due to gp120 or immune processes

MAY be due to accumulation of viral particles, or loss of cellular protein synthesis

73

Cross linking of gp120 and CD4 results in

-apoptosis

-halted dividing

-rips holes in cell membrane

-anergy

74

Cell death can be sedondary to

Type 3 hypersensitivity reaction

75

AIDS is a syndrome, therefore

it may express itself in multiple ways

76

When does HIV seroconvert to AIDS

3wks to 6 months

Comes w/ flulike symptoms- acute retroviral syndrome symptoms

77

CD4 T-cell count to be HIV, not AIDS

400 cells/ul

(Decrease in all WBC except CD8 t-cells)

78

Symptoms of **HIV**

-High viral count in genital fluids

-highly infectious

-Elevated ESR

-Decreased platelets

79

Latency period AFTER seroconversion from HIV to AIDS

3-12 yrs

80

Latency period symptoms

CD4 over 400 cells/ul

may feel well, may feel kinda lame

virus production maintained

virus extremely active

81

symptomatic, chronic HIV , CD4 drops

to <400 cells/ul

antiviral innate immunity gets shitty

82

Symptoms of chronic symptomatic HIV

seroconversion to AIDS

-PIV

-Flakey/rashy skin

-oral hairy leukoplakia

-oral/genital herpes

-complete anergy- no response to skin testing

83

Chronic, symptomatic HIV in children

-growth delays

-frequent illness

-Opportunistic infections

84

AIDS diagnosis

-CD4 <200 cells/ul

-one or more opportunistic infectons

-one or more tumors/cancer

-SOB/coughing/painful swallowing

-mental symptoms/vision loss/headaches/fatigue

-GI symptoms/weight loss

85

Children with AIDS

Two groups

fast and slow progression

86

Children with aids have the same

opportunistic infections, plus extreme cases of childhood illness

87

Category 1 CD4 T-cell count

>/= 500 cells/ul

88

Category 2 CD4 Tcell count

200-499/ul

89

Category 3 CD4 Tcell count

<200/ul

90

Clinical symptom category A

HIV

Asymptomatic lymphadenopathy

variety of symptoms

Hx HIV w/ accompanying illness

91

Clinical symptom category B

HIV

conditions secondary to impaired cell-mediated immunity

cadnidiasis, PID, shingles, fever, diarrhea, oral hairy, idiopathic thrombocytopenic purpura, peripheral neuropathy, listeriosis

92

Clinical symptom category C

HIV

Qualifies as AIDS

93

CHildren HIV categories

N- Asymptomatic

A-2 or more: hepatomegaly, splenomegaly, lymphadenopathy,dermatitis, parotitis, upper respiratory/otitis media

B-Moderately symptomatic- opportunistic infections due to lack of cell immunity

C- Severely symptomatic AIDS

94

Diagnostic testing- First _______, if positive, then ________ to confirm

In combination, they are _________ effective

ELISA

Western blot (identifies antibodies, uses electrophoresis)

more than 99.9%

95

Rapid HIV testing uses ______________________

Must be confirmed by western blot

Blood, oral secretions, serum

may cause false positive

used on newborns

96

When CD4 Tcells drop below 200/ul,

prophylactic meds are started

97

The strongest predictor of HIV outcome over time

Level of RNA in plasma

(Goal is to reduce viral load)

98

antigen testing indicitave of active HIV replication, confirms HIV diagnosis

p24

99

What does the anergy/delayed hypersensitivity test look for

TB, Mumps, Rubella

(Advanced and early disease will be no response/normal)

100

Unintended, involuntary loss of >10% body weight

Malnutrition/wasting syndrome

(Leading cause of death, worldwide!)

101

TNF is elevated in ____________ because it increases breakdown of fat and causes anorexia

Malnutrition/wasting syndrome

102

TNF inhibitors

Ketofin

Thalidomide

103

Anabolic steroid to increase lean mass, along with human growth hormone

Oxandrolone

104

What can be done to prevent/delay wasting syndrome?

Antioxidants (A, C, E, Bs, zinc, selenium, sulfur amino acids)

(Prevents upregulation of inflammatory cytokines)

105

Major GI complication of HIV

Diarrhea

106

Common cause of diarrhea in HIV?

protozoa cryptosporidium

Acute onset, explosive, stool is HIGHLY infective

107

Oropharyngeal lesions that are an opportunistic infection. May cause white plaques that bleed when removed (Pseudomembranous type)

Candida albicans

(Treated with ANTIFUNGALS)

108

P. Jiroveci (Carinii) (PCP Pneumocystis pneumonia)

CMV

M. Tuberculosis

Histoplasma

Staph

Opportunistic pneumonias

109

Kaposi sarcoma

Lymphoma

Nonspecific pneumonitis

ARDS

Parenchymal lung diseases of HIV

110

Most common opportunistic infection

Pneumocystis pneumonia (PCP)

MAJOR PULMONARY FEATURE-- Severe hypoxemia (PaO2<60 mmHg)

111

Decreased surfactant

Prevented and treated w/ trimethoprim sulfamethoxazole

ARDS symptoms

early dry cough

diagnosed by chest radiography

PCP (Pneumocystis pneumonia)

P. Jiroveci

112

Usually the first symptom of HIV (Mucocutaneous)

HIV viral exanthem

(erythematous, maculopapular rash on trunk, face, and arms)

40-60% self limiting, but comes with other more broad symptoms

Occurs 2-6 wks after exposure AND late in illness

113

Origins of HIV viral exanthem may be

neoplastic

infectious

allergic

114

Viral causes of HIVV viral exanthem

herp simplex

varicella zoster

Epstein barr

HPV

115

Oral hairy leukoplakia may be caused by

Epstein barr

HPV

No specific treatment

MAY PRODUCE PROTEIN THAT ENHANCES HIV REPLICATION

116

Common bacterial skin infection in HIV pts

S. Aureus

folliculitis, furuncles, bullous impetigo, maybe sepsis

117

Fungal skin infections of HIV

Histoplasma

Cryptococcus

Candid (Vaginal frequently the first sign among women)

(Mites that cause scabies)

118

Kaposi's sarcoma is a vascular neoplasm which affects

-skin

-mucous membranes

-lymphatic

-other internal organs

119

Kaposis sarcoma is special because

its one of the few neoplasms which indicate immune malfunction

120

HIV related neoplasms

squamous cell carcinoma

basal cell carcinoma

cutaneous lymphomas

Kaposi's sarcoma

121

Gold standard diagnostic for P. Jiroveci (Carinii) (PCP Pneumocystis pneumonia)

bronchioalveolar lavage

122

Kaposi's sarcoma typically starts, _____________ but may end up _________

somewhere on the head/face

in the lungs or intestines

123

Kaposi's sarcoma typically appears as a ______________ and is th emost common tumor found in __________

-Flat, macular subcutaneous patch, start pink,-----> eventually purple or maybe brown, thick large nodules

painless nonblanching, nonpruritic

homosexual men with HIV

124

Gynecologic manifestations of HIV

PID most common, antibiotics manage

persistent monilial vaginitis (C. Albicans)

Cervical dysplasia/neoplasia (Pap every 6 mo)

125

In HIV, the neurologic system is ____________

Invaded early

Glial, endothelial, macrophages

126

Neurologic symptoms of HIV may be caused by HIV itself, or by

Opportunistic meningitis or neoplasm lesions

-Toxoplasma

-Cryptococcus

127

Most common neurologic encephalopathic manifestation of HIV

HIV encephalopathy/HIV associated neurocognitive abnormality (HAND)

128

What causes HIV encephalopathy/HIV associated Neurocognitive abnormality(HAND)

-Directly/indirectly by HIV or viral particles

-cytokine related cellular damage

-competition/interference between gp120 and neuroleukin

129

HIV encephalopathy/ HIV associated neurocognitive abnormality (HAND) manifests as

progressive cognitive impairment

subcortical dementia

-Occurring later in disease w/ other opportunistic infections

130

HIV encephalopathy /HIV associated neurocognitive abnormality (HAND)

Fever, mild metabolic acidosis

Forgetfulness, inattentiveness, confusion, concentration loss

slower verbal response

HA

Apathy

inability to perform/complete complex tasks

May progress to global dementia including muscle weakness

131

Scary shit about HIV encephalopathy

person may be alert, but cognitively impaired mute paraplegic

132

Ocular manifestations of HIV

Infectious (Bacterial, viral, fungal, protazoan)

Noninfectious (HIV retinopathy/malignancy)

133

MOST severe ocular manifestation of HIV

CMV retinitis

infection, necrosis of retina leading to blindness

(Precipitates perivascular hemorrhages, fluffy exudates, vasculitis in retina)

134

HIV associated retinopathy manifests with

cotton wool spots (associated with small hemorrhages)

microvascular changes

not as severe as CMV retinitis

may remit spontaneously

135

In HIV, hypertriglyceridemia and lipidemia are common, meaning

Cardiovascular and renal diseases are more common

136

Liver problems in hiv

Concomitant HEP B and C

HIV drug damage

137

Endocrine dysfunction in HIV

Damage to systems and meds, stress response

-buffalo hump (Visceral adipose tissue hypertrophy)

-insulin resistance

-hypogonadism

-adrenal and thyroid issues

138

HIV in children is quicker than adults, they are usually symptomatic

within the first year of life

-growth retardation/FTT

-impaired intellectual development

-impaired motor functioning/coordination

-lactose intolerant

139

In HIV, children develop normally until

Virus invades nervous system

-Weakness, loss of milestones, hypo/hypertonia

140

In children with HIV, viral/bacterial infections are

Far more severe

-extensive candidiasis

-respiratory and communicable disease

141

Goals of retroviral treatment

-delay progression

-prevent drug resistance

-minimize symptoms

-extend life

142

Recommendations have evolved from monoretroviral therapy to polyretroviral therapy

ART and HAART

better viral suppression

cannot fully remove virus

continuous therapy necessary

143

Antiretrovirals should be used for

anyone with CD4 under 350, even asymptomatic

anyone with nephropathy or HEP B

anyone with AIDS defining illness

144

In children, multidrug therapy should be started, _______, but __________

at birth

some drugs not okay under age 13

145

Controversy surrounding treating children born to HIV + mothers

whether to start intensive therapy immediately

146

HIV drugs

-Nucleoside reverse transcriptase inhibitors/Non-nucleoside

-Protease inhibitors (PIs)

-Fusion inhibitors

-Integrase strand transfer inhibitors

-CCR5 antagonists