Pathogenesis of AIDS

Question 0

HIV infection stage is based on

Answer 0

age specifc CD4+ T cell count

CD4 T cell % of total Lymphocytes

Question 1

Stage 0

Answer 1

early infection
recognized by HIV-test within 180 days of the first HIV+ test
meaning test positive within 180 days of the last negative test

Question 2

stage 1

Answer 2

No AIDS-defining condition and a CD4 cell count at or above the cells/ul indicated per age

Question 3

stage 2

Answer 3

No AIDS defining condition and a CD4 cell count at or above the cells/ul indicated per age

Question 4

stage 3

Answer 4

AIDS

documented AIDS defining condition or CD4 cell count less than 200, 500 or 750 cells/ul indicated per age

Question 5

Stage unknown

Answer 5

lab confirmation of HIv infection but no information on Cd4 cell count, CD4 cell percentage, or the presence of an AIDS-defining condition

Question 6

Staging can be bidirectional given ….

Answer 6

no AIDS defining condition is present

Question 7

AIDS defining illness in children under 6

Answer 7

Bacterial infections, multiple or recurrent

Question 8

AIDS defining illnesses in adults, adolescents or children over 6yo

Answer 8

cervical cancer, invasive
Mycobacterium TB of any site, pulmonary
Pneumonia, recurrent

Question 9

Phases of HIV infection

Answer 9

1. Acute retroviral syndrome - weeks
2. Chronic HIV - years to decades
3. AIDS - Months to years

Question 10

Acute retroviral syndrome

Answer 10

primary infection of cells in blood and mucosa
infection is then established in lymphoid tissues leading to viremia
Acute HIV syndrome when spread of infection throughout body
seroconversion - Anti HIV antibodies and HIV specific CTLs
Immune response

Question 11

Chronic HIV

Answer 11

Clinical latency
establishment of chronic infection
virus trapped in lymphoid tissues by follicular DCs, low level of viral production
other microbial infections or cytokines can lead to increased viral replication

Question 12

AIDS - phase

Answer 12

destruction of lymphoid tissue

depletion of CD4 T cells

Question 13

Constitutional symptoms of ARS

Answer 13

fever*
chills*
fatigue*
Night sweats, anorexia and wt loss

Question 14

Lymphatic symptoms of ARS

Answer 14

*Swollen lymph nodes especially in groin, head and neck

Question 15

Nose and throat symptoms of ARS

Answer 15

*Sore throat, with or without ulcers or thrush

Question 16

GI symptoms of ARS

Answer 16

Nausea
emesis
diarrhea

Question 17

Musculoskeletal symptoms of ARS

Answer 17

Asymmetric joint swelling and tenderness

*myalgias

Question 18

Neurologic symptoms of ARS

Answer 18

personality changes, headache, and painful, stiff neck

Question 19

Rash characteristics of ARS

Answer 19

Maculopapular and primarily on trunk and/or proximal extremities

Question 20

characteristics of oral lesions in ARS

Answer 20

thrush develops commonly on soft palate

early lesions also seen along gingival border

Question 21

Reactivation in ARS

Answer 21

can reactivate HSV - cold sores

or VSZ - shingles

Question 22

How can HIV enter the body?

Answer 22

blood
colon-rectum
vagina

Question 23

What happens when HIV initially enters?

Answer 23

infects macrophages

Question 24

How does HIV affect macrophages?

Answer 24

creates virus reservoir infects the microglial cells of the brain, Pulmonary alveolar macs and Dendritic cells in skin Causes macrophage dysfunction, virus release and cytokine release and dysregulation of immune function

Question 25

Where do HIV travel for its latent period?

Answer 25

Lymph nodes

Question 26

What happens upon increased viral load in the blood with regards to immunopathogenesis?

Answer 26

by this time, HIV has been able to infect CD4 T cells if crosses the BBB leads to AIDS dementia through CD4 ctyloysis causes -immunodeficiency -loss of B cell control - lymphadenopathy, hypergammaglobulinemia -Loss of DTH (delayed type hypersensitivity) function - cutaneous infection and intracellular pathogens

Question 27

what happens as a result of loss of T cell function?

Answer 27

severe systemic opportunistic infections Kaposi's sarcoma Lymphoma

Question 28

HIV causes ??? and what are the outcomes

Answer 28

-Lytic and latent infection of CD4 T cells -Persistent infection of cells of macrophage family -Disrupts neuron function Outcomes are: Immunodeficiency, AIDS dementia (crosses the BBB)

Question 29

Briefly describe progression of untreated HIV

Answer 29

About 6 weeks after primary infection, CD4 T cell count falls drastically. At this same time, viral load peaks. This is acute HIV syndrome and there is wide dissemination of virus and seeding of lymphoid organs small T cell count recovery around 12 weeks as viral load drop while virus enters latent period over next 10-11 years, viral load slowly increases as CD4 count continues to slowly decrease Constitutional symptoms appear 7-8 years opportunistic infections occur as viral load increases exponentially Death by year 10 -11

Question 30

what happens due to loss of CD4 T cells during Chronic HIV?

Answer 30

through infection and loss of CD4 cells - loss control of nonlymphoid cells - loss of growth and control of B cells - Growth and control of CD4 and CD8 T cells and NK cells - this leads to tumors and HIV progression - loss of DTH which leaves vulnerable to intracellular organisms

Question 31

what are some immunologic events affecting Macrophages and DCs during an HIV infection?

Answer 31

``` Macrophages carry HIV into CNS Excess secretion of cytokines in lymph nodes Decreased antigen presentation Decreased MHC II expression Decreased chemotaxis Decreased phagocytic ability Decreased cytotoxic ability ```

Question 32

AIDS-dementia complex

Answer 32

``` (HIV/AIDS encephalopathy) results of HIV entering brain via microglial transport leads to: -memory loss -impaired cognition -impaired motor function -behavioral changes -Apathy -depression occurs as CD4 count falls to <200 cell/microliter ```

Question 33

Due to Highly active anti retroviral therapy, ADC has

Answer 33

declined to <20% of those HIV+ | may also improve mental function in those with ADC already

Question 34

How does HIV evade the immune system?

Answer 34

- Antigenic drift of gp120 - evades antibody detection - Heavy glycosylation of gp120 - evades antibody detection - Infection of lymphocytes and Macrophages - inactivation of key element of immune defense - Inactivation of CD4 helper cells - loss of activator of immune system and delayed type hypersensitivity

Question 35

what are the possible outcomes of HIV infections?

Answer 35

rapid progression - AIDS in 2-3 yrs typical progressors - AIDS in 10 yrs Long-term nonprogressors - low HIV levels, normal CD4 T cells >10 yrs after HIV positive - BM transplant case (usually HIV-2 or HIV-1 ??) Highly exposed persistently seronegative patients - infected but no HIV antibodies or HIV-RNA detected

Question 36

Describe M-Tropic (R5)

Answer 36

Initial stages of infection mediated by R5 Macs and DCs are persistently infected and major reservoirs and means of distribution (Trojan Horses) Targeting of CCR5 expressing T cells depletes GALT of CD4 T cells - lyse Deficient CCR5 receptor pts more resistant to HIV infection and CCR5 in binding target for antiviral drugs

Question 37

Describe T-Tropic (X4)

Answer 37

change in receptor preference to CXCR4 occurs late and correlates with progression of disease Mutation of ENV gene for gp120 shifts tropism from R5 to X4 some viruses use both R5X4 receptors Development of symptoms of AIDS

Question 38

what is occuring pathology wise during development of symptoms of AIDS?

Answer 38

correlates with increased release of virus into the blood increase in X4 virus decrease in CD4 T cells subsequent decrease in total T cell numbers (CD3 bearing cells) due to the lack of helper function

Question 39

CD4 expressed

Answer 39

on surface of CD4 T lymphocytes (helper) and macrophages (including dendritic cells)

Question 40

CCR5 expressed

Answer 40

on CD4+ T lymphocytes and macrophages

Question 41

CXCR4 expressed on

Answer 41

CD4+ T lymphocytes and T cell lines

Question 42

HIV-2 is less _____ than HIV-1

Answer 42

pathogenic most HIV-2 pts are long term non progressors longer asymptomatic stage, slower decline in CD4 T cell count lower mortality rate due to AIDS pts with HIV-2 are less infectious in early stages but trasmission rate increases as disease progresses

Question 43

HIV-2 was more difficult to monitor but

Answer 43

in 2014, first FDA licensed viral load assay to detect HIV-2 nucleic acid was approved

Question 44

Treatment of HIV-1 vs. HIV-2

Answer 44

some drugs for HIV-1 are not effective for HIV-2 | HIV-2 is intrinsically resistant to Fusion inhibitors and non-nucleoside reverse transcriptase inhibitor based regimens

Question 45

List some Antiviral therapies

Answer 45

Nucleoside Analogue reverse transcriptase inhibitors Non nucleoside reverse transcriptase inhibitors Protease inhibitors Binding and Fusion inhibitors Integrase inhibitors

Question 46

A small number of ppl are resistant to infection because

Answer 46

have mutations in genes encoding CCR5 and/or CXCR4 co receptors CCR5delta32 mutation - leads to a truncated protein with loss of extracellular component -Homozygous mutation - immune -Heterozygous mutation - decreases chances of infection, slows disease progression

Question 47

Out of ppl who are naturally HIV immune, they were found to carry

Answer 47

gene called HLA B57 leads to larger production of CD8/killer cells CTLs are cross reactive - attack more than one epitope associated with HIV including mutants that arise contributes to strong response towards viruses that rapidly evolve increase susceptibility to autoimmune diseases, in which T cells attack the body's own cells

Question 48

Mucosal immunity generated by frequent ______

Answer 48

sexual exposure to HIV | meaning immunity generated by cells lining the genital membranes prevented infection

Question 49

Cells of macrophage lineage include

Answer 49

``` monocytes macrophages alveolar macs of the lung dendritic cells of skin microglial cells of brain ```