HIV infection mechanism Flashcards
AIDS is caused by
HIV
HIV infects and destroys
CD4 T cells
- important for antibody response
AIDS was originally called
GRID
when first reconised
1980s in the US in intravenous drug users and gay men with no apparent cause for impaired immunity but who showed symptoms of Pneumocytstics carniii pneumonia (PCP)
how many people infected per year in us
50,000
how many deaths globally since 8s
39+ mill
2 mill new cases in
2014
how many people infected in sub-saharan africa
2/3
how many infected in asia
1/5th
most aids is caused by
HIV-1
HLR-DR stands for
Human Leukocyte Antigen - antigen D Related
HLR-DR acts as
ligands for TCRs
where did HIV originate
southern cameroon from a simian immunodeficiency virus
SIV
simian immunodeficiency virus
- a retrovirus that infects non-human primates
how was SIVcpz intruded into human
through bushmeat activities with subsequent mutation into HIV- required one or more high risk transmission channels for human to human spread
why were these transmission channels absent in africa prior to 20th century
growth of large Colonial African cities led to societal changes such as prostitution (increasing frequency of STDs- e.g. syphilis) that allowed sexually transmitted infection.
earliest documented case of HIV in the congo
1959
origin of AIDS pandemic traced back to
1920 in city of Kinshasa in Congo
Pneumocystis pneumonia
a form of pneumoniaa caused by yeast like fungus - Pneumocystis jiroveciii
Pneumocystis jiroveciii
commonly found in lungs of healthy, but source of opportunistic infection in immunocompromised patents
Pneumocystis jiroveciii especially seen in
those undergoing chemotherapy, HIV/AIDS and the use of medication that affects the immune system
cryptococcal meningitis is caused by
Crypotococcus gattii and neoformans
Cryptococcal meningitis prevalence
- Around 950,000 cases worldwide
- 600,000 deaths
- 70% in sub-Saharan Africa
usually just effects the immunocompromosied patients, however can affect the healthy
Aids and microbial infections: brain
Toxoplasmosis
Cryptocooccal meningitis
Aids and microbial infections: Eyes
Cytomegalovirus
Aids and microbial infections:mouth and throat
Candidiasis (yeast)
Aids and microbial infections: lungs
Pneumocytist carinii pneumonia
TB
Histoplasmosis
Aids and microbial infections: gut
Cytomegalovirus
Cryptosporidiosis
Mycobacterium avid complex
Aids and microbial infections: skin
herpex simplex
shingles
Aids and microbial infections: genitals
Genital Herpes
Human papillomavirus
Vaginal Candidiasis
HIV- epithelia entry
- crosses through M cells- prevalent in tonsils and rectal epithelial
- can gain access via epithelia damage and ulcerative infection by trauma or injection
vaginal epithelial lack
M cells- the way HIV usually gain access
- instead HIV gains access via interdigitating processes on Langerhans cells
pithelial cells in the small intestine express
CCR5 chemokine receptors
HIV-1 binds to which receptor
CCR5 bia the trial envelope glycoprotein GP120 and the virus is trancytosies
HIV epithelia entry summary example
o HIV-1 bind to CCR5 (once tethered by galactosylceramide) via the viral envelope glycoprotein gp120 and he virus is transcytosed
o Once across mucosal barriers, HIV-1 encounter sub-epithelial dendritic cells
o C-type lectin (CLRs) on dendritic cells bind high mannose N-linked oligosaccharides on viral envelope glycoprotein gp120
o Interaction with CLRs initiates dendritic cell migration to regional lymph nodes
o Once in lymph nodes, intact virus, internalised with CLRs , is re- exposed at the surface and displayed to T cells
regardless of route of infection
o predominant site of virus replication early in disease is in the s.intestine- this reflects the large number of activated T cells, that express CCR5 in that organ
entry of HIV into cells is mediated by
viral envelope glycoprotein gp120.
- Binds to CD4 and chemokine receptors (CCR5 or CXCR4) on host surfaces.
- Binding with receptor leas to a conformational change in gp120 that exposes the transmembrane components of the envelope protein gp41.
-Gp41 mediates fusion of the virus envelope with the host cell membrane
HIV-1 infection cycle
1) HIV-virion binds via chemokie receptor
2) fusion occurs
3) reverse transcription of viral RNA genome occurs
4) integration into hosts chromosomal DNA
5) expression and translation
6) synthesis of viral core proteins and reverse transcriptase in the cytoplasm
7) synthesis of gp12 and gp41 in the ER and membrane budding
7) assembly
8) budding
9) maturation
10) new HIV virion
dendritic cells translocate HIV from mucosa within
30 mins of infection
immunological consequence of HIV infection
- o A wave of viral proliferation in lymph nodes peaks at 4-7 days after infection
o Viremia peaks at 14 days and all lymphoid tissues are infected by 3 weeks
o HIV is quiescent in resting CD4 T cells, but on T cell activation, virus production is also activated and the host cell dies
> 99% of virus is produced by
newly infected CD4 T cells
around how many CD4 T cell ar producing virus at any time
10^7- 10^8 CD4 T cells
consequence of CD4 T cells being affected
o loss of helper activities (mainly through cytokine stimulation) means that maintenance of cytotoxic CD8 T Cells is lost as is the antibody response of B cells
progression of untreated HIV infection
- flu like illness from days to weeks after exposure
- CD4- dependent antiviral cytotoxic CD9 T cell response develops and is responsible for prolonged period of stable viremia- viral set point
- patients ar normally asymptomatic until the CD4 T cell counts define further- infection of developing lymphocytes in the bone marrow and thymus results in failure to replace lost Tcells
- opportunist infections begin when CD4 T cell count reaches below 200/ul
flu like symptoms are a result of
drop of CD4 T cells
viral set point
CD4- dependent antiviral cytotoxic CD9 T cell response develops and is responsible for prolonged period of stable viremia
when do opportunistic infections arise
- when CD4 T cell count reaches levels below 200/ul
death typically ensues around
2 years later without treatment
