Secondary Immunodeficiencies Flashcards

1
Q

what are 2y immunodeficiencies

A

Acquired failure of immunological function as a result of infection or using immunosuppressive drugs, ratherthanasaresultofdefectsingenesencodingcomponentsoftheimmunesystem

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2
Q

3 ways 2y immunodeficiencies can be acquired

A

malnutrition

deliberate immunosuppression (e.g. following organ transplantation or chemotherapy for cancer)

disease (AIDS)

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3
Q

2 theraupeutic agents that can negatively affect immune system

A

x-rays
cytotoxic drugs

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4
Q

2 things B-lymphoproliferative disorders like chronic lymphocytic leukaemia and myeloma are associated with

A

Varying degrees of hypogammaglobulinemia (ow serum immunoglobulin or antibody levels)

impaired antibody responses

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5
Q

are 1y or 2y immunodeficinies more common

A

2y

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6
Q

how many people affected with HIV virus

A

60 million

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7
Q

how many new HIV infections each day

A

14,000

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8
Q

what does AIDS stand for

A

Acquired Immunodeficiency Syndrome

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9
Q

what year was AIDS first seen

A

1980s

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10
Q

how were first Africans infected by AIDS

A

by jumping from chimpanzee (HIV-1) and sooty mangabey (HIV-2)

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11
Q

why can chimps not be infected by AIDS

A

as HIV uses CD4 as its cellular receptor-and it cannot bind in chimps

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12
Q

2 clinical features of AIDS when first discovered

A

Massive reduction in circulating CD4+ T cells

Severe recurrent infections (Pneumocystis carinii)

high incidence of aggressive forms of cancers (Kaposi sarcoma, B-cell lymphoma)

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13
Q

what infection causes AIDS

A

RNA retroviruses Human Immunodeficiency Virus number 1 (HIV-1) and HIV-2

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14
Q

what type of virus is Human Immunodeficiency Virus

A

RNA retrovirus

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15
Q

what type of the virus is main cause of AIDS in most countries

A

HIV-1

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16
Q

How many human proteins does HIV recruit for its benefit to prevent the immune system terminating HIV infections

A

273

17
Q

what cells have a progressive decrease due to AIDS

A

CD4 cells (t helper cells)

18
Q

what is an individual susceptible to once the CD4 cell count falls below 200 cells/cu mm

A

opportunistic infections

(most commonly pneumocystis carinii, cytomegalovirus, herpes simplex virus and fungi such as candida, aspergillus and cryptococcus, and the protozoan toxoplasma)

19
Q

what is HIV transmitted inside as it is spread sexually or through blood or blood products

A

infected CD4+ cells and macrophages

20
Q

what glycoprotein of HIV binds to cell-surface CD4 molecules on helper T-cells, macrophages, DCs and microglia to cause infection

A

glycoprotein gp120 of HIV

21
Q

what do Dendritic cells do in HIV infection so that they are directly exposed on the mucosal surface

A

populate the human mucosa and project their dendrites through the epithelial cells

22
Q

what have been found in 1% of caucasians, associated with increased resistance to infection

A

Mutations or complete absence of the CCR5 receptor

23
Q

first few steps of HIV cycle in human cells

A

gp120envelopeproteinofthevirusbindstoCD4,sogp120alsobindsa
coreceptor(eitherCCR5orCXCR4).

Thisbindingreleasesgp41,causing fusionoftheviralenvelopewiththe plasmamembraneandthe releaseofviralcoreintothe cytoplasm.

TheRNAgenomeisreleasedand
reverse-transcribedintodouble-strandedcDNA.

DNAmigratestothenucleusin associationwiththeviralintegraseandbecomesintegratedintothe
cellgenomeasaprovirus

24
Q

last few steps of HIV cycle in human cells

A

T cell activation causeslow-leveltranscriptionoftheprovirusintomRNA.ThatdirectsthesynthesisoftheearlyproteinsTatandRev.

Theseproteinschangethepatternofprovirustranscriptiontoproduce mRNAencodingtheprotein
constituentsofthevirionandRNAmoleculescorrespondingtotheHIVgenome.

Envelopeproteinstraveltothe
plasmamembrane,whereasother
viralproteinsandviralgenomicRNAassembleintonucleocapsids.

Newvirusparticlesbudfromthe
cell,acquiringtheirlipidenvelope
andenvelopeglycoproteinsinthe
process.

25
Q

how long after AIDS infection does it take for the adaptive system to be mobilized and virus-specific b cells, helper t cells and CTLs to be activated, proliferate and start to work

A

after 1 week or so

26
Q

what is there a dramatic rise of during the early acute phase of HIV infection, before it then decreases

A

A dramatic rise in the number of viruses in the body (the viral load) as the virus multiplies in infected cells.

27
Q

what phase, unlike other viruses, does a full-blown HIV-1 infection always lead to

A

a chronic phase that lasts for 10 or more years

28
Q

in the chronic progressive stage of AIDS, what cells are present at very low levels

A

CD4+ cells

29
Q

what does CCR5 co-receptor mutation cause in AIDS

A

increased resistance (protection)

30
Q

what type of CCR5-Δ32 variant mutation is the only one that protects against AIDS (only 1% European origin have this)

A

homozygous CCR5-Δ32 (2 identical alleles)

31
Q

3 ways How HIV-1 can defeat the immune system and resist antiviral drugs

A

forms latent infection which cannot be detected by CTLs

reverse transcriptase is highly error prone, producing mutations that result in HIV-1 “being one step ahead” of CTLs or Abs directed against it

specifically targets helper T cells, macrophages & dendritic cells

Uses immune cells to spread infection

32
Q

what drugs can rapidly clearthe virusfromthebloodandincrease
thenumberofcirculatingCD4T
cells

A

Anti-retroviraldrugs

33
Q

why does the maintenance of HIV levels in the blood depend on continual infection of newly produced CD4 t cells

A

as cells only live for a few days once infected

34
Q

what are the effects of administering that blocks HIV viral life cycle

A

existing virions in the blood are rapidly cleared by neutralising antibody, complement and phagocytes

New CD4 T cells are not infected and so live longer and accumulate

35
Q

2 main things HIV causes

A

immunodeficiency
death

36
Q

2 cancers those with HIV tend to get due to immunodeficiency

A

non-hodgkins lymphoma
primary lymphoma of brain
kaposi’s sarcoma

37
Q

3 HIV laboratory diagnosis

A

Reversal of CD4:CD8 ratio (less than 1)

Quantitative-PCR of HIV-RNA (measures viral load)

Delayed hypersensitivity skin response (due to decreased CD4)

38
Q

2 issues with treating HIV

A

drug resistance
long-term toxicity of antiretroviral agents

39
Q

4 things needed for long term survival with HIV

A

antiretroviral agents (drugs stop virus replicating)

immunisation (HPV, Flu)

Chemoprophylaxis

Aggressive treatment of infections

Aggressive treatment of malignancies

Triple therapy-HAART in symptomatic patients, CD4 below 500mm/cm3 or viral load >50,000 copies/ml (several antiretroviral drugs)