Secondary Immunodeficiencies Flashcards
what are 2y immunodeficiencies
Acquired failure of immunological function as a result of infection or using immunosuppressive drugs, ratherthanasaresultofdefectsingenesencodingcomponentsoftheimmunesystem
3 ways 2y immunodeficiencies can be acquired
malnutrition
deliberate immunosuppression (e.g. following organ transplantation or chemotherapy for cancer)
disease (AIDS)
2 theraupeutic agents that can negatively affect immune system
x-rays
cytotoxic drugs
2 things B-lymphoproliferative disorders like chronic lymphocytic leukaemia and myeloma are associated with
Varying degrees of hypogammaglobulinemia (ow serum immunoglobulin or antibody levels)
impaired antibody responses
are 1y or 2y immunodeficinies more common
2y
how many people affected with HIV virus
60 million
how many new HIV infections each day
14,000
what does AIDS stand for
Acquired Immunodeficiency Syndrome
what year was AIDS first seen
1980s
how were first Africans infected by AIDS
by jumping from chimpanzee (HIV-1) and sooty mangabey (HIV-2)
why can chimps not be infected by AIDS
as HIV uses CD4 as its cellular receptor-and it cannot bind in chimps
2 clinical features of AIDS when first discovered
Massive reduction in circulating CD4+ T cells
Severe recurrent infections (Pneumocystis carinii)
high incidence of aggressive forms of cancers (Kaposi sarcoma, B-cell lymphoma)
what infection causes AIDS
RNA retroviruses Human Immunodeficiency Virus number 1 (HIV-1) and HIV-2
what type of virus is Human Immunodeficiency Virus
RNA retrovirus
what type of the virus is main cause of AIDS in most countries
HIV-1
How many human proteins does HIV recruit for its benefit to prevent the immune system terminating HIV infections
273
what cells have a progressive decrease due to AIDS
CD4 cells (t helper cells)
what is an individual susceptible to once the CD4 cell count falls below 200 cells/cu mm
opportunistic infections
(most commonly pneumocystis carinii, cytomegalovirus, herpes simplex virus and fungi such as candida, aspergillus and cryptococcus, and the protozoan toxoplasma)
what is HIV transmitted inside as it is spread sexually or through blood or blood products
infected CD4+ cells and macrophages
what glycoprotein of HIV binds to cell-surface CD4 molecules on helper T-cells, macrophages, DCs and microglia to cause infection
glycoprotein gp120 of HIV
what do Dendritic cells do in HIV infection so that they are directly exposed on the mucosal surface
populate the human mucosa and project their dendrites through the epithelial cells
what have been found in 1% of caucasians, associated with increased resistance to infection
Mutations or complete absence of the CCR5 receptor
first few steps of HIV cycle in human cells
gp120envelopeproteinofthevirusbindstoCD4,sogp120alsobindsa
coreceptor(eitherCCR5orCXCR4).
Thisbindingreleasesgp41,causing fusionoftheviralenvelopewiththe plasmamembraneandthe releaseofviralcoreintothe cytoplasm.
TheRNAgenomeisreleasedand
reverse-transcribedintodouble-strandedcDNA.
DNAmigratestothenucleusin associationwiththeviralintegraseandbecomesintegratedintothe
cellgenomeasaprovirus
last few steps of HIV cycle in human cells
T cell activation causeslow-leveltranscriptionoftheprovirusintomRNA.ThatdirectsthesynthesisoftheearlyproteinsTatandRev.
Theseproteinschangethepatternofprovirustranscriptiontoproduce mRNAencodingtheprotein
constituentsofthevirionandRNAmoleculescorrespondingtotheHIVgenome.
Envelopeproteinstraveltothe
plasmamembrane,whereasother
viralproteinsandviralgenomicRNAassembleintonucleocapsids.
Newvirusparticlesbudfromthe
cell,acquiringtheirlipidenvelope
andenvelopeglycoproteinsinthe
process.
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
after 1 week or so
what is there a dramatic rise of during the early acute phase of HIV infection, before it then decreases
A dramatic rise in the number of viruses in the body (the viral load) as the virus multiplies in infected cells.
what phase, unlike other viruses, does a full-blown HIV-1 infection always lead to
a chronic phase that lasts for 10 or more years
in the chronic progressive stage of AIDS, what cells are present at very low levels
CD4+ cells
what does CCR5 co-receptor mutation cause in AIDS
increased resistance (protection)
what type of CCR5-Δ32 variant mutation is the only one that protects against AIDS (only 1% European origin have this)
homozygous CCR5-Δ32 (2 identical alleles)
3 ways How HIV-1 can defeat the immune system and resist antiviral drugs
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
what drugs can rapidly clearthe virusfromthebloodandincrease
thenumberofcirculatingCD4T
cells
Anti-retroviraldrugs
why does the maintenance of HIV levels in the blood depend on continual infection of newly produced CD4 t cells
as cells only live for a few days once infected
what are the effects of administering that blocks HIV viral life cycle
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
2 main things HIV causes
immunodeficiency
death
2 cancers those with HIV tend to get due to immunodeficiency
non-hodgkins lymphoma
primary lymphoma of brain
kaposi’s sarcoma
3 HIV laboratory diagnosis
Reversal of CD4:CD8 ratio (less than 1)
Quantitative-PCR of HIV-RNA (measures viral load)
Delayed hypersensitivity skin response (due to decreased CD4)
2 issues with treating HIV
drug resistance
long-term toxicity of antiretroviral agents
4 things needed for long term survival with HIV
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)
