Secondary Immunodeficiencies

Question 1

what are 2y immunodeficiencies

Answer 1

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

Question 2

3 ways 2y immunodeficiencies can be acquired

Answer 2

malnutrition

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

disease (AIDS)

Question 3

2 theraupeutic agents that can negatively affect immune system

Answer 3

x-rays
cytotoxic drugs

Question 4

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

Answer 4

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

impaired antibody responses

Question 5

are 1y or 2y immunodeficinies more common

Answer 5

2y

Question 6

how many people affected with HIV virus

Answer 6

60 million

Question 7

how many new HIV infections each day

Answer 7

14,000

Question 8

what does AIDS stand for

Answer 8

Acquired Immunodeficiency Syndrome

Question 9

what year was AIDS first seen

Answer 9

1980s

Question 10

how were first Africans infected by AIDS

Answer 10

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

Question 11

why can chimps not be infected by AIDS

Answer 11

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

Question 12

2 clinical features of AIDS when first discovered

Answer 12

Massive reduction in circulating CD4+ T cells

Severe recurrent infections (Pneumocystis carinii)

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

Question 13

what infection causes AIDS

Answer 13

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

Question 14

what type of virus is Human Immunodeficiency Virus

Answer 14

RNA retrovirus

Question 15

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

Answer 15

HIV-1

Question 16

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

Answer 16

273

Question 17

what cells have a progressive decrease due to AIDS

Answer 17

CD4 cells (t helper cells)

Question 18

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

Answer 18

opportunistic infections

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

Question 19

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

Answer 19

infected CD4+ cells and macrophages

Question 20

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

Answer 20

glycoprotein gp120 of HIV

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Mutations or complete absence of the CCR5 receptor

Question 23

first few steps of HIV cycle in human cells

Answer 23

gp120envelopeproteinofthevirusbindstoCD4,sogp120alsobindsa
coreceptor(eitherCCR5orCXCR4).

Thisbindingreleasesgp41,causing fusionoftheviralenvelopewiththe plasmamembraneandthe releaseofviralcoreintothe cytoplasm.

TheRNAgenomeisreleasedand
reverse-transcribedintodouble-strandedcDNA.

DNAmigratestothenucleusin associationwiththeviralintegraseandbecomesintegratedintothe
cellgenomeasaprovirus

Question 24

last few steps of HIV cycle in human cells

Answer 24

T cell activation causeslow-leveltranscriptionoftheprovirusintomRNA.ThatdirectsthesynthesisoftheearlyproteinsTatandRev.

Theseproteinschangethepatternofprovirustranscriptiontoproduce mRNAencodingtheprotein
constituentsofthevirionandRNAmoleculescorrespondingtotheHIVgenome.

Envelopeproteinstraveltothe
plasmamembrane,whereasother
viralproteinsandviralgenomicRNAassembleintonucleocapsids.

Newvirusparticlesbudfromthe
cell,acquiringtheirlipidenvelope
andenvelopeglycoproteinsinthe
process.

Question 25

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

Answer 25

after 1 week or so

Question 26

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

Answer 26

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

Question 27

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

Answer 27

a chronic phase that lasts for 10 or more years

Question 28

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

Answer 28

CD4+ cells

Question 29

what does CCR5 co-receptor mutation cause in AIDS

Answer 29

increased resistance (protection)

Question 30

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

Answer 30

homozygous CCR5-Δ32 (2 identical alleles)

Question 31

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

Answer 31

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

Question 32

what drugs can rapidly clear the virus from the blood and increase  the number of circulating CD4 T  cells

Answer 32

Anti-retroviral drugs 

Question 33

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

Answer 33

as cells only live for a few days once infected

Question 34

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

Answer 34

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

Question 35

2 main things HIV causes

Answer 35

immunodeficiency death

Question 36

2 cancers those with HIV tend to get due to immunodeficiency

Answer 36

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

Question 37

3 HIV laboratory diagnosis

Answer 37

Reversal of CD4:CD8 ratio (less than 1) Quantitative-PCR of HIV-RNA (measures viral load) Delayed hypersensitivity skin response (due to decreased CD4)

Question 38

2 issues with treating HIV

Answer 38

drug resistance long-term toxicity of antiretroviral agents

Question 39

4 things needed for long term survival with HIV

Answer 39

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)