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Test 4 Immunology AIDS
Test 4 Immunology AIDS
84
Medical
Graduate
05/03/2015

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Term
The absence or failure of the immune system function is called
Definition
immunodeficiency
Term
autosomal dominant, autosomal recessive and X linked are all ____ immnodeificiencies
Definition
primary
Term
lack of T cells in immunodefiency makes patinet at more risk for
Definition
intracellular pathogens like virus, fungi and parasites
Term
what is severe combined immunodeifiency SCID
Definition
Most likely a lack of funct thymus; so now cell mediated immune responses, no T cell dependent Ab responses. AT risk to intracellular pathogens
Term
What is Digeorge syndrome
Definition
deletions on chromosome 22 and results in lack of T box transcription factor. Very lock T cell numbers. Associated with congeital problems
Term
Chediak-Higashi syndrome is?
Definition
mutation of protein that lets phagoctosed material be transported to lysosomes. Can't do a good job with engulfing bacteria. Also less phagocytes in general
Term
leukocyte adhesion deficiency (LAD) Is?
Definition
Problem with beta chain in adhesion molecules resulting in a decreased ablity for leukocytes to bind to the endothelium and migrate to invasion. Person susceptible to bacterial and fungal infections
Term
5x things that contribute to secondary immunodeficiencies
Definition
1. acquired
2. drugs
3. naturitional defi
4. virus or bacterial causes
5. young and old
Term
is AIDS a primary or secondary immunodeficiency
Definition
secondary
Term
most common spread of HIV infection is via what cells
Definition
T cells, macrophages and dendritic cells.
Term
HIV more spread by free virus or infected cells
Definition
INFECTED CELLS not free virus in blood or other fluids.
Term
causative agent identified as aids is called
Definition
causative agent identified as human retrovirus
Term
Is HIV-1 or HIV-2 more pathogenic? Which one is human version and which one primate version
Definition
HIV-1 > HIV-2.
HIV-1: humans
HIV-2: Primates
Term
is HIV closely related to HTLV I
Definition
NO. They are both retroviruses but not closely related.
Term
retroviruses use what as their genetic material
Definition
RNA
Term
The core of the HIV virus is
Definition
2 strands of single stranded RNA (ssRNA)
Term
what enzymes makes double stranded DNA from single stranded RNA
Definition
reverse transcriptase enzyme
Term
Reverse transcriptase enzyme makes DNA that contains no
Definition
introns
Term
Other internal proteins include
Definition
1. p10(Protease)
2. P32 (Integrase)
3. P9
4. P7
Term
what is the purpose of integrase with DNA/RNA/HIV
Definition
integrase helps with the isnertion of viral DNA into the host cell DNA. When the host now infected divides it makes copies of this virus DNA
Term
Once the HIV virus is turned into VIRAL DNA and it invades a cell as a double stranded DNA it is now called
Definition
a provirus.(B/c its origins was a double stranded RNA virus that had to become activated first through reverse transcriptase enzyme activity to be turned into a double stranded DNA) Now this active double stranded DNA is a provirus infecting other cells)
Term
purpose of proteases during virus replications
Definition
cleaves large viurs polypeptides into smaller peptides and for final virus formation and budding from host cell
Term
the hiv virus is enveloped by what
Definition
lipid bilayer which was from the original host cell it previously infected. So the lipid bilayer that is taken may have MHCI and MHCII on its surface dpeending on what kind of cell it infected.
Term
once the enveloped virus is out on its own it begins to put more things on its stolen lipid bilayer such as these two viral glycoproteins
Definition
1. GP 41
2. GP 120
Term
Which viral glycoprotein spans the entire lipid bilayer?
Definition
GP 41
Term
GP120 interacts with 2x
Definition
1. CD4
2. chemokine receptors on host cells
Term
Describe the HIV mutation rate
Definition
HIV mutations are at a greater rate than other viruses such as influenza, and a million times greater rate than human DNA
Term
Is the HIV virus from one person then infected into the next the same?
Definition
NO. Different in each infected individual and then it even mutates further in that same person
Term
what contributes to the extremely high mutation rate of the HIV virus
Definition
reverse transcriptase makes errors in the sequencing of the Double stranded DNA From single stranded RNA of the HIV virus thereofore making additions, deletions and substitutions of bases leading to different varieties of the HIV and its amino acids
Term
whats the differences between reverse transcriptase and DNA Polymerase
Definition
DNA polymerase makes more accurate replications and has "proof-reading" ability unlike reverse transcriptase which makes many mistakes when it converts virus RNA to DNA
Term
Why HIV surface glycoprotein is associated with more protein mutations
Definition
GP 120 > GP 41
Term
What cells does HIV have a high affinity to and why? Give 3 x examples of these type of cells
Definition
CD4 T cells because its GP 120 wants to bind to the CD4 on the TCR of T cells. So cells with high # of CD4 on their surface are
1. Monocytes
2. macrophages
3. APC (Dendritic cells) in the lymph nodes and skin.
Term
What is the sequence for HIV binding to cells
Definition
1. First GP 120 binds to CD4 on host cell
-GP 120 which previously was covering GP41 binds to CD4 on host cell. This then means GP 41 now open to bind too.
2. GP 120 next need to aslo bind to chemokine receptors on host cell.
3. Now GP41 will fuse to host cell membrane via hydrophobic fusion and invade it
Term
first receptor needed for HIV fusion is?
Second receptor needed for HIV fusion is?
Definition
1. first is GP120 to CD4
then CD41 available
2. CD120 binds to Chemokinreceptor
3. now the available CD41 can fuse to host cell and bomb it with enveloped virus
Term
Chemokine receptors are classified as
Definition
7-membrane G protein-coupled receptor
Term
what does GP41 do in the invasion of a host cell
Definition
once GP120 gets off of it (from CR and CD4 binding) then GP41 can cause fusion of virus to host cell and inject its poision
Term
on ACTIVATED T cells what chemokine receptor is expressed
Definition
CXCR4
Term
T tropic HIV-1 cells bind to what kind of chemokine receptor on host cells
Definition
CXCR4
Term
The CCR5 receptor is in vivo or in vitro? What chemokines can bind to it
Definition
In Vivo
1. RANTES: Regulated on Activation, Normal T Expressed & Secreted
2. MIP-1 alpha and MIP-1 Beta Macrophage inflammatory protein.
Term
CCR5 chemokine receptors used by? CXCR4 Chemokine receptor used by?
Definition

CCR5 chemokine receptors used by M Tropic HIV-1 virus to enter macrophages and dendritic cells

 

CXCR4 Chemokine receptor used by T cell-tropic HIV-1 for entry into T cells and dendritic cells in vitro

Term
how can chemokines block HIV-1 into cells
Definition
by competitively binding to the same receptors.
Term
if cytokines were to induce expression of more chemokine receptors would HIV be worse or less
Definition
WORSE! B/c more chemokine receptors then more chance for HIV-1 to bind to those chemokine receptors.
Term
which WBC has both CCR5 and CXCR4 co-receptors? What's the importance of this cell?
Definition
TH17 cells. They get knocked out and no longer can block pathogens from crossing gut. SO gut diseases!
Term
after the provirus of HIV made from replication of ssRNA to dsDNA, then it is spread by what mechanisms
Definition
HIV is picked up by dendritic cells and hten spread HIV to more TH cells.
Term
IS M tropic HIV or T-Tropic HIV more common in early HIV infected people compared to Late HIV infected
Definition
Early HIV Infected > M-tropic HIV using CCR5.
Late HIV Infected > T-Tropic HIV using CXCR4
Term
is T tropic HIV or M-tropic HIV associated with hte faster decrease in CD4 T cells and progression to AIDS
Definition
T-tropic HIV which we know are more predominant in late HIV infection.
Term
what is syncytia formation in regards to HIV spread
Definition
A form of spread via cell-to-cell transmission with fusion. When an infected cell fuses with a healthy cell it is called a syncytium. 50-500 cells can form together in this syncytium.
Term
syncytium formation of HIV cells with other cells can be as large as ____ cells fused together
Definition
50-500 cells fused together.
Term
syncitia formation of HIV occurs with T cells or macrophages
Definition
only between T cells.
Term
silent HIV infected cells are more common in what type of WBC
Definition
1. memory CD4 T cells
2. Dormant macrophages
Term
a dormant HIV infected cell means
Definition
the cell is not replicating
Term
Which cells are hard for HIV to kill? And therefore act as a reservoir for the virus
Definition
1. macrophages
2. dendritic cells
Term
after a cell is infected by HIV why does that kill die and via what mechanism
Definition
Budding of the newly replicated HIV virus as it tries and eject out of the host cell may weaken that host cells membrane since the ejecting cell may release GP120 which puts holes in the host cell.
Term
Which type of cells are more at risk for death when the HIV virus buds
Definition
Cells with more CD4 since the mechanism for which the host cells die is from HIV virus GP120 binding to CD4 and causing holes. Cells with more CD4 (T cells > macrophages) are at more risk
Term
how does GP 120 play a role in CD$ T cell maturation and budding
Definition
GP120 can be left on host cell's membrane of budding HIV virus. This will bind to CD4 if its on that particular cell and cause holes which kill the host cell.
2. GP 120 can also be freely floating around in the body and on its own bind to T cells in lymphoidal tissues and distort them thereby preventing them from further maturation.
Term
are circulating CD4 TH cells or CD4 TH cells in lymphoidal tissues more at risk for HIV Infection
Definition
Lymphoidal TH CD4 cells
Term
name other ways other than budding that INFECTED host CELLS may be killed as a result of infection
Definition
immune system! Will recognize GP120 and GP41 as foreign and kills via
1. Ab and Complement mediated cell lysis
2. compelment mediated opsonization
3. Ab mediated opsonization
4. Tc cells kill infected cells
Term
How can body kill free gp120
Definition
1. Ab and complement mediated lysis or opsonization can kill free gp120 that may bind to CD4 of UNIFECTED cells.
2. The unifected cell ITSELF can commit suicide via apoptosis b/c free GP120 binds to its CD4 it realizes its been hacked when it goes to bind with an Ag and self-destructs
Term
how does syncytia formation of HIV and other cells result in a mechanism of cell death
Definition
those clusters of infected cells can act as a superantigen which has mitogenic effect causing an extreme immune response.
Term
you can have an INCREASE in HIV replication from
Definition
1. infected CD4 cells that stimulated by an Ag and then increase their syntehsis of everything.
2. If a HIV proviurs (ssDNA) is incorporated into a cell and that cell uses its transcription factor such as nuclear factor kB then it makes LOTS of copies.
Term
Transcription of Provirus by a cell is made possible by what transcription factors
Definition
Nuclear factor KB. Remember the proviurs is in a ssDNA form not ssRNA form. That DNA is then trascribed to MRNA/RNA to make LARGE AMTS of viurs copies.
Term
if a provirus is using a host cells apparatus to increase its copies via transcription factors then it goes from a latency state to a lytic state and this is correlated with a conversion of its promoters from a ___ to a ___
Definition
from a weak promoter to a strong promoter signifies the virus is stronger at binding to host cells RNA (higher promoter) Transciptase factors make this possible.
Term
what is NF=kB (Nuclear factor kB)? What cells may increaase it? what does it do
Definition
Nuclear factor kB is important cause it makes the HIV provirus go from being a weak promoter to a strong promoter. The stronger hte promoter of the proviurs than the higher chances it will be read by RNA and replicated with its apparatus. It also increases replication of IL-2. This NF-kB is increased from TH cell-APC interactions.
Term
what co-infections may increase transciptase factors which means more HIV inadvertantly made
Definition
1. herpes
2. Hep B
3. Cytomegaolovirus
Term
clinical course of HIV infection can be graded based on
Definition
CD4 T cell #s
Term
what clinical phase of HIV infection is there no Ab to HIV
Definition
acute phase
Term
Describe CD4 and HIV levels during acute phase compared to chronic phase
Definition
Acute phase: High HIV, Low CD4
Chronic Phase: Low HIV, Higher CD4 at first, then opposite happens.
Term
Describe characteristics of the AIDS Syndrome
Definition
1. CD4 T cell count <200cells/uL
2. Large #s of HIV cells
3. Impaired or absent Cell-mediated resposne
4. opportunistic infections
Term
In an unifected individual the normal CD4 T cell count is?
Definition
1100 = normal CD4 count
Term
The healthy person CD4 T cell: CD8 Tcell is
Definition
2.0
Term
In HIV infected individual with AIDS what is the:
1. CD4 level
2. CD4-CD8 T cell ratio
Definition
1. CD4 level < 200 cells / ul
2. CD4:CD8 ratio < 1.0
Term
Ab are made against HIV components and this takes how long? what is the name for this
Definition
CAlled sero-conversion; it takes 6 weeks for Ab to be made against HIV
Term
describe the early Ab response to HIV
Definition
There are two types in early Ab attack.
1. Early Ab- envelops glycoproteins around 2-3 weeks, but cant completely prevent
2. Neutralizing Ab: effective in preventing virus from infection and this takes several weeks.
Term
First Ab produced against HIV is? Then followed by more of ___Ab
Definition
First Ab is IgM then IgG replaces it as the main effector.
Term
later Ab responses are less effective and IgG not working why?
Definition
b/c of the loss of TH cells you can't get specific and tailored or even stimulation of Ab.
Term
what can we measure that correlates with the clinical course of HIV infection
Definition
Ab correlates with the clincal course of HIV infection
Term
chronic phase occurs during what period of HIV
Definition
first 8-10 years
Term
TH1 delayed type hypersensitivity responses occur during the progression of the chronic phase which results in?
Definition
Early effects: reduced ability to activate TH1 cells
Later effects: opportunistic infections can help
Term
a decrease in TH1 activity is also associated with an increase in what other immune cells
Definition
increase TH2 activity and Ab response causes decrease TH1 and lack of delayted type hypersensitivity.
Term
The relationship of progression of HIV and cell mediated response is?
Definition
Decrease CD4 TH cells, means less TH1 cells, which means less TH1 cytokines such as IL2 and IFN gamma which means decrease Tc cell activation which means decrease DTH and IFN gamma
Term
what is Tc cell relationship to HIV and its progression
Definition
Tc Cell can kill effectively and decrease viral loads. But to be activated it needs IL2 signalling from CD4 cells and since HIV directly kills CD4 cells then Tc cells stop attacking eventually.
Term
in HIV there is an increase of what cytokines
Definition
1. IL2
2. IL6
3. TNF Alpha
4. GM-CSF = more reverse transciptase
5. TNF Beta - more phag and chemotaxis
Term
what happens to cytokines during HIV progression
Definition
1. the immune response changes resulting in decrease TH1 activity. If you decrease TH1 then you indirectly decrease Tc Cells and delayed type hypersensitivity. Which means decrease levels of IL2, IFN gamma. Also decrease NK cells from decrease levels of those cytokines.

2. increase TH2 cells and the release of their cytokines
Term
what are three tests for HIV detection
Definition
1. ELISA assay detects serum Ab to HIV proteins)
2. Western Blot: confirms
3. Polymerase chain (PCR) confirms, measures viral load in plasma.
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