Aani Immuno: HIV & Vaccination Flashcards
What is the genetic make up of HIV?
RNA retrovirus
Which cells does HIV target as hosts?
CD4+ T Helper cells
CD4+ monocytes + dendritic cells
How does HIV bind to the CD4 cells?
It binds via gp120
How does HIV get inside the CD4 cells? (receptor)
Binds to gp41 for conformational change
Which receptors of CD4 cells does HIV use?
gp 120 initial bindind
gp41 conformational change
CCR5 and CXCR4 chemokine receptors
What are the stages of the HIV life cycle that can be targeting for anti-HIV drugs?
- Attachment/Fusion
- Reverse Transcription (DNA synthesis)
- Integration of viral DNA
- Viral transcription
- Viral protein replication/synthesis
- Viral assembly + release
What type of immune responses are initiated to an acute HIV-1 infection ?
Innate response: NK/complement/macrophages
Adaptive response:
- Antibody dependent
- Antibody mediated
What happens in the antibody mediated immune response to HIV?
Neutralising Abs (NtAb) block the T cell receptors: Anti-gp120 Ab and Anti-gp 41 Ab
AND Non-neutralising Abs are used too:
Anti-p24 gag IgG
Why is HIV’s target cell bad news for us?
Because CD4 cells (T cells) are needed for orchestration of immune response. They are needed for class recombination to develop Abs and they control B cell response. They also activate monocytes/dendritic cells
What else happens in the adaptive immune response to HIV apart from Abs?
CD8+ T cells release chemokines to target HIV
Which chemokines does CD8+ T cells release to tackle HIV?
MIP-1a, MIP-1b and RANTES
Describe the structure of the HIV virus?
Diploid genome
Icosahedral (20 faces)
How long does it take to develop AIDS once you have HIV?
8-10 years on average
What CD4 count would be considered a shift from HIV to AIDS?
Below 200 cells/microlitre
Which tests can you do to check for HIV?
- ELISA screening- checks for Anti-HIV Abs
- Western blot confirmation test - detects Anti-Abs
- PCR viral load detection (HIV RNA detected)
- Flow cytometry to detect CD4 count
- Genotypic assay testing for resistant strains (looking at mutations in HIV genome)
- Phenotypic assay testing for resistant strains (looking at HIV replication against increasing drug conc)
What is seroconversion?
The period of time during which Anti-HIV antibodies develop and become detectable
When does HIV seroconversion take place?
Approx 10 weeks after infection
When to treat a HIV patient with symptoms?
ASAP
When to treat a HIV patient without symptoms?
<200 CD4 count
Start thinking about it at <350 CD4
Name a common HAART regimen used?
Truvada: ETE
- Emtricitabine
- Tenofovir
- Efavirenz
What types of drugs make up a HAART regime?
Two Nucleoside Reverse Transcription Inhibitors (NRTIs) and One Protease Inhibitor (or a Non-NRTI)
What are the disadvantages of HAART?
- Doesn’t remove latent HIV-1
- Cost
- Threat of drug resistance
- High pill burden
- S/Es e.g. toxicity
Which HIV drug can you give in pregnancy ?
Zidovudine
Side effect of Zidovudine?
Bone Marrow suppression
GI effects
Fever
What kind of drug is Zidovudine?
Nucleoside Reverse Transcriptase Inhibitor
What are the Anti-HIV drug types?
- Fusion Inhibitors
- Attachment Inhibitors
- Nucleoside Reverse Transcriptase Inhibitors
- Non-nucleoside Reverse Transcriptase Inhibitors
- Nucleotide RT Inhibitors
- Integration Inhibitors
- Protease Inhibitors
Name an anti-HIV fusion inhibitor?
Enfuvirtide
Name an anti-HIV attachment inhibitor?
Maraviroc
Name some anti-HIV NRTIs?
Emtricitabine Zidovudine Zalcitabine Abacavir Stavudine
Name the anti-HIV NNRTIs?
Efavirenz
Delavirdine
Nevirapine
Name the anti-HIV anti-Nucleotide RTI?
Tenofovir
Anti-HIV Integration inhibitor?
Raltegravir
Which Anti-HIV drug causes hepatitis and rash?
Nevirapine (neva get a rash and hepatitis)
Which Anti-HIV drug causes CNS effects?
Efavirenz
Which Anti-HIV drug causes mitochondrial toxicity?
Stavudine
Which Anti-HIV drug causes peripheral neuropathy?
Zalcitabine and Stavudine
Which vaccines are given at 2 months?
5 in 1 (DTaP/IPV/HiB)
PCV
Which vaccines are given at 3 months?
5 in 1 (DTaP/IPV/HiB)
Men C
Which vaccines are given at 4 months?
5 in 1 (DTaP/IPV/HiB)
PCV
Men C
Which vaccines are given at 12 months?
MenC
HiB
Which vaccines are given at 13 months?
MMR
PCV
Which vaccines are given at 3-4 years?
DTaP/IPV
MMR
Which vaccines are given at 12-13 years (girls)
HPV
Which vaccines are given at 13-18 years?
DT/IPV
MenACWY
Which cells are T memory Cells?
CD45RO (memory has O in it)
Which cells are T Naive Cells?
CD45RA (Naive has A in it)
Which T cells are more likely to be Central Memory Cells?
CD4
Which T cells are more likely to be Effector Memory Cells?
CD8
What type of memory cells last longest?
B memory cells that turn into plasma cells
What are the T Helper 1 cytokines?
IL2
IFN gamma
TNF
What are the T Helper 2 cytokines?
IL4
IL5
IL6
Which type of vaccine are easier to store?
Inactivated
Give examples of Live Vaccines that are still used?
BCD (TB) Typhoid Varicella Zoster Yellow Fever MMR
Give examples of Inactivated Vaccines?
IPV Hep A Cholera Rabies Pertussis
Give examples of Toxoid vaccines?
Tetanus
Diphtheria
Which LIVE vaccine is it okay to give to HIV patients?
MMR
But NOT BCG or yellow fever
How do ALUM adjuvants work?
Activates Gr1+ cells to produce IL4 and this helps prime naive B Cells
How do CpG adjuvants work?
Activates TLRs on APCs
Which Immunoglobulins are given passively?
HNIG (human normal IG) for Hep A and Measles VZIG (varicella zoster IG) HRIG (human rabies IG) HBIG (Hep B IG) Paviluzimab (RSV IG)
What is the Mantoux test for?
TB protection
What do you do in the Mantoux test?
Inject 0.1 ml of 5 Tuberculin units intradermally
Examine each arm 48-72 hours later
Positive result = red/swollen.
This indicates a potential previous BCG injection
