HIV IMMUNOLOGY Flashcards
First Case was reported to the CDC in _____
The etiologic agent of AIDS is a human ______ –
___________
1981
retrovirus
Human immunodeficiency virus (HIV).
Retroviruses are (DNA or RNA?) viruses that contain ___________, an enzyme that makes _____ from viral ______.
RNA viruses
reverse transcriptase
DNA ; RNA.
Two types of HIV have been identified.
– HIV-1- causes AIDS in ________ and ______
– HIV-2 – causes AIDS in _____
America and Europe
Africa
HIV is closely related to a group of (transforming or non transforming?) , ________ retroviruses called _____viruses which cause chronic neurodegerative and wasting disease in animals.
non transforming ; cytopathic
HIV is also related to the __________________________ virus type ____ which causes a form of AIDS in _________
simian T-cell lymphotrophic virus type III
African green monkeys.
Epidemiology of HIV/AIDS
The global pandemic of HIV/AIDS began in _____, and is an on going world wide public health issue.
1981
Epidemiology of HIV/AIDS
According to WHO, as of 2021, HIV/AIDS has killed approx. _______ people, and approx. _______ people are infected with HIV globally
40.1 million people
38.4 million people
The HIV virus particles, or virion, is approximately _____nm in diameter.
100
The HIV virus particles, or virion
It consists of 3 parts
___________
____________
___________ that contains the viral RNA.
The HIV virus particles, or virion
an outer envelop
a core shell of protein
a cone shaped inner core
The HIV virus particles
_____________ combine to give it a spherical shape.
Small viral surface proteins
The HIV virus particles, or virion
These proteins are embedded in a lipid bilayer from which the surface glycoproteins protrude as _____ like structures.
knob
HIV
The glycoprotein (gp) has two components: gp ___ transverses the membrane and gp _____ extends beyond the surface as a knob.
41; 120
The glycoprotein (gp)
gp41 is a ______ D glycoprotein while gp120 is a highly immunogenic protein of m/w ________D.
41,000
120,000
The HIV outer envelope also contains _________ antigens.
These antigens are derived from ________ when ____________________ during the process of viral particle formation.
human leucocyte antigens
human cell membranes
new HIV virions bud from human cells
HIV
Beneath the outer envelope lies a protein core composed of viral proteins _______ and ______
p24 and p17.
HIV
Inside the protein core shell lies a ____-shaped central core containing the ______ and ______
cone
viral RNA and reverse transcriptase.
The complete nucleotide sequence of the HIV genome have been determined, making it possible to _______,_________, and ________
identify viral genes, viral gene products and the clinical course of AIDS.
The HIV genome has ____ regulatory genes
List them
five
tat, art/trs, sor, 3’ orf, and R.
The HIV genome
It also has the usual structural genes – ____ ,________, and ________.
gag, pol and env
The HIV genome
The _____ gene codes for the core proteins from which the three core structural proteins, ____,______ ,_____ are formed.
gag
P18, P24 and P15
The HIV genome
The gag gene codes for the ______ from which the __________ proteins ____,_____,_____ are formed.
core proteins
three core structural
P18, P24 and P15
HIV
The pol (polymerase) gene codes for ___ enzymes:
List them
4 enzymes
reverse transcriptase, RNase, protease, and integrase.
Reverse transcriptase transcribes _______________ into _____________
It is an _________ protein designated p__/___.
single stranded RNA
double stranded DNA.
immunogenic protein
p66/51.
RNase is an enzyme that ______ the _____ in RNA- DNA hybrids that form an intermediate in the creation of _______.
digests the RNA
viral DNA.
Protease (p___) ________ from ______ and cleaves _______ from their _________.
31
cleaves itself from an initial polyprotein
other proteins; polyproteins
Integrase is responsible for _______ the ________ into the _______
inserting the viral DNA
host DNA.
The env (envelope) gene codes for the glycoprotein gp____, which is found in infected cells.
It is cleaved to form the two envelope glyco proteins gp___, found on the outside of the viral envelope and gp ___, which is embedded in the viral membrane.
160
120
41
The sor (_______________) gene is related to viral infectivity.
It produces a protein, p___ which is present in the _____ of virus infected cultures and against which _______ form in the ______ of HIV infected persons.
short open reading frame
p23
filtrate ; antibodies; serum
The tat (_________) gene accelerates ____________ and is required for viral replication.
trans-activation translation
viral protein production
The tat gene
Without tat ______________ and __________ are formed.
The protien produced by tat is p___
only minimal RNA is produced
no viral particles
14.
The art/trs (________________) gene regulates the _____ of the viral genome.
anti-repression transactivation
translation
The art/trs
It produces an anti-repression trans activator protein p____, which regulates the expression of viral gene components.
20
The B3’ orf (__________) gene is responsible for the _________, and _____________ by ___ fold in CD4 cells.
3’ open reading frame
latency of the virus
slowing down viral reproduction
ten
The p27 protein produced by B3’ orf raises antibodies that have been found in infected persons.
The B3’ orf gene
The p___rotein produced by B3’ orf raises antibodies that have been found in infected persons.
p27
All the proteins and glycoproteins of HIV may produce an antibody response in an infected person.
T/F
T
HIV
Their antibodies are typically seen in only symptomatic seropositive individuals
Do not act as markers of HIV infection.
T/F
F
F
Their antibodies are typically seen in both symptomatic and asymptomatic seropositive individuals and act as markers of HIV infection.
In one study of 280 specimens from AIDS patients, 96% of patient had antibodies to ___ and 88% had antibodies to _____.
p24
gp41
Declining p24 antibody titres occur in the (early or late?) stages of AIDS when patients clinically ______.
Late
deteriorate
Antibodies to the envelope gene products (gp____, gp ____, gp ___) can be detected in nearly all HIV positive patients and antibodies to the polymerase gene products (p____, p___ and p___) are also commonly detected.
gp 160, gp 120, gp 41
p31, p51 and p66
Immunologic Mechanisms of HIV
Infection
The ____ molecule is a high affinity receptor for HIV, this explains the selective tropism of the virus for ____+ T cells and other CD4+ cells especially the ______,__________, and __________
CD4; CD4
monocytes and macrophages and dendritic cells.
Binding to CD4 is sufficient for infection
T/F
F
Binding to CD4 is not sufficient for infection, HIV gp 120 must also bind to other cell surface molecules (co receptors) for entry into the cell.
Immunologic Mechanisms of HIV
Infection
HIV gp 120 must also bind to other cell surface molecules (co receptors) for entry into the cell.
Two chemokine receptors, _____ and _____ serve this role.
The initial step in infection is the binding of __________ to ________.
This binding leads to a _________ that results in the formation of a new recognition site on ______ for the ———— ——- or ______
CCR5 and CXCR4
the gp 120 envelope glycoprotein to CD4 molecules
conformational change; the gp 120
coreceptors CCR5 or CXCR4.
Immunologic Mechanisms of HIV
Infection
After the conformational change in gp 120
The next step involves _________ in ________; these changes results in the insertion of a __________ at the _______ into the cell membrane of the target cell.
After fusion, the ______ containing the HIV genome enters ______________
conformational changes
gp41; fusion peptide; tip of gp41
virus core; the cytoplasm of the cell.
Immunologic Mechanisms of HIV
Infection
Once internalized, the RNA genome of the virus undergoes ________ leading to formation of _____ (________).
reverse transcription
cDNA; proviral DNA
Immunologic Mechanisms of HIV
Infection
In quiescent T cells, HIV cDNA may remain in the ____ in a ____ form.
In dividing T cells, the cDNA ______, enters the ______ and is then _______________
cytoplasm; linear
circularizes; nucleus
integrated into the host genome.
Immunologic Mechanisms of HIV
Infection
After this integration, the provirus may __________________________ and hence the _______ becomes _______
Alternatively, proviral DNA may be ________, with the formation of complete viral particles that bud from the cell membrane. Such productive infection, when associated with __________ leads to ________.
remain locked into the chromosome for years or months
infection becomes latent.
transcribed; extensive viral budding
cell death
HIV Life Cycle
The HIV _____ carries within it, the genetic information required to reproduce HIV viruses within infected host cells.
genome
HIV Life Cycle
HIV binds to the host cell through a complexing of the _____ molecules on the viral surface and a receptor molecule – the ______ molecule on host cells.
gp 120
CD4
CD4 molecules are found on the surface of some immune cells (_______,_______,__________, and __________).
helper T lymphocytes, B cells, monocytes and macrophages
HIV life cycle
After HIV binds to the CD4 containing cell, it penetrates the host cell and loses its ________ to expose the viral RNA.
The viral RNA is transcribed into DNA and inserted into the host genome during _______ or __________
outer layers
cellular division or activation.
Host cells can be activated by __________ or by _________ stimulation after exposure to _______,_______, or _________
antigenic challenge or by allogeneic
blood, semen or allografts.
HIV cycle
Once host cell is activated, ______________ occurs.
Viral RNA and proteins are then ______ at the host cell’s _______ to produce a _______ that escapes the host cell by ____ from the host cell membrane.
transcription of viral protein
assembled
cytoplasmic surface
mature virion ; budding
HIV life cycle
When HIV replication occurs, the CD4 cell is killed, resulting in ________ of ———— .
It is the ________ that correlates with the progressive severity of ________ and with the increased _______ to _______ seen in the clinical course of AIDS.
severe depletion of helper-inducer T lymphocytes
depletion of these cells ; immune deficiency
susceptibility to opportunistic disease and malignancies
Effect of HIV on Immune
Response
AIDS is so devastating primarily because of the ___________ of __________ cells and the central role of these cells in mediating immune response.
destruction of CD4 containing
__________ lymphocytes have a high concentration of CD4 molecules on their surface and are the major targets of the HIV virions.
Helper T
The depletion of these CD4 cells as a result of HIV infection results in _________________________
severe depression of the immune response.
The increased viral, protozoal and fungal infections found in AIDS patients are as a direct result of _____________________
an impaired cell mediated immune system.
Effect of HIV on T Cells
_______ of CD4 lymphocytes.
_________________ suppressor CD8 lymphocytes.
Increased susceptibility to ___________ and _________ due to decreased T-cell function.
Depletion
Elevated, normal or depressed
opportunistic infections and neoplasms
Effect of HIV on T Cells
_____eased delayed type hypersensitivity.
_____eased production of interleukins 2.
Decr
Decr
Effect of HIV on B Cells
__________ ————
Elevated circulating _________.
Inability to produce a _________ to a new antigen following _______.
Polyclonal hypergammaglobulinaemia.
immune complexes
serologic response
immunization
Effect on Other Immune Cells
Decreased _________ activity.
Defective _______ in monocytes and macrophages.
Enhanced _______________________________________ by monocytes.
natural killer cell
chemotaxis
release of interleukin 1 and cachecxin
Opportunistic Infections and
Neoplasms Seen in AIDS
Bacteria
List 6
– Mycobacterium avian – intracellular
– Mycobacterium kansasii
– Mycobacterium tuberculosis
– Streptococcus penumoniae
– Haemophilus influenzae
– Salmonella species
Opportunistic Infections and
Neoplasms Seen in AIDS
Viruses
___________
_____________
___________
______________
__________
Cytomegalovirus
Herpes simplex
Herpes zoster
Ebstein – Barr virus
Adenovirus
Opportunistic Infections and
Neoplasms Seen in AIDS
Protozoa
________
__________
________
___________
Pneumocystis carinii
Toxoplasma gondii
Cryptosporidium species
Isospora belli
Opportunistic Infections and
Neoplasms Seen in AIDS
Fungi
–___________
–_______________
–_______________
– ____________
–__________ species
Candida albicans
Coccidiodes immitis
Histoplasma capsulatum
Cryptococcus neoformans
Aspergillis
Opportunistic Infections and
Neoplasms Seen in AIDS
Neoplasms
–_________
-______________
–___________
–________
Kaposi’s sarcoma
Hodgkin’s disease
Burkitt-like lymphoma
Undifferentiated Non-hodgkin’s lymphoma
Opportunistic Infections and
Neoplasms Seen in AIDS
Neoplasms
–______ lymphoma
– _________ lymphoma
– __________ sarcoma
–__________ preleukaemia
C.N.S.
Peripheral organ
Immunoblastic
Lymphocytic
Laboratory Diagnosis
The focus of laboratory diagnosis is to ____ HIV, detect ______ and detect ______ in patient’s blood and body fluids.
isolate
HIV antibodies
HIV antigen
Laboratory Diagnosis
We carry out these procedures in order to detect ——— HIV infection, to monitor ________ of ________ and to detect the progression of ___________ to ________
early
effectiveness of antiviral drugs
asymptomatic to symptomatic AIDS.
Laboratory Diagnosis
Detection of HIV antigen in patients specimen indicates _________ whereas detection of antibodies to HIV denotes ___________.
active HIV infection
prior exposure.
Laboratory Diagnosis
Gene probes for HIV viral RNA for use in ______________ techniques have been developed.
molecular hybridization
Laboratory Methods
________ Methods
__________ Methods
Screening
Confirmatory
Laboratory Methods
Enzyme-linked Immunosorbent Assay
This is a (screening or confirmatory?) test for HIV antibodies.
It is (simple or difficult ?) to perform, relatively (expensive or inexpensive?) and adapted to screening (small or large?) numbers of specimens in a (short or long?) time (________).
screening
Simple
inexpensive
large
short time (<4 hours).
ELISA
HIV antigens derived from either ___________ , _______ antigens, or ___________ are immobilized onto microtiter wells.
Patient _________ is then _____ with the fixed antigen and _____.
______ antibody, conjugated to either _______,________, or _______ , is then added and allowed to incubate.
disrupted virus particles ; recombinant
chemically synthesized peptides
serum or plasma; incubated; washed
Anti-IgG
horseradish peroxidase, glucose oxidase or alkaline phosphatase
HIV antigens derived from either disrupted virus particles ( _____ generation assays), recombinant antigens, or chemically synthesized peptides ( _______ generation assays).
first
second
ELISA
After a washing step, the appropriate _________________ is added and a ______ occurs that is proportional to the amount of ____ present.
Results are read on a _______ by _______ obtained from ______________ to those from ________
This results in an __________ value above which reaction is identified.
chromogenic enzymatic substrate
colour change ; IgG
spectrophotometer; comparing values
positive and negative controls; test specimen.
absorbance cut off
Sources of Error in ELISA testing
for HIV Antibodies
_________ errors.
False positive reactions occur in person’s with _______________, ________ and _______
Technical
autoimmune diseases, some lymphomas and leukaemias.
Sources of Error in ELISA testing
for HIV Antibodies
False negative reactions occur during the ___________ stages of AIDS, in the _____ stages of AIDS, when antibodies typically reduce.
Tests should be run in ________.
incubation
late
duplicate
Slide Agglutination Tests
Rapid slide agglutination tests are for detecting the presence of ____________________________________
They are widely used in field work in Africa.
HIV antibodies or antigens.
Slide Agglutination Tests have some advantages over ELISA.
T/F
T
Slide Agglutination Tests
They are (simple or difficult ?) to perform, takes (lesser or longer?) time (some _________), all the materials are potable.
Results can be read with ________, ___ expensive machinery is needed.
simple
Lesser ; 5 minutes
the naked eye; No
Slide Agglutination test is a screening test
T/F
T
Slide Agglutination test and ELISA are both screening tests.
T/F
T
Western Blot Assay
This is a (screening or confirmatory?) test.
confirmatory
_________ positive screening test is confirmed using this method.
Western Blot Assay
Western Blot Assay
In this assay, ________ is _______ and _________ are separated on the basis of ___________ using _________________
The viral proteins are then transferred onto _________ and cut into ______.
Individual strips are incubated overnight with ___________(_________)
HIV virus is disrupted
HIV proteins ; molecular weight
polyacrylamide gel electrophoresis.
nitrocellulose sheets; strips
patients’ serum (HIV antibodies).
Other Laboratory Methods
___________________ assay.
_______ immunoassay.
_______________ assay.
__________.
Indirect immunofluorescence
Radio
Radioimmunoprecipitation
Gene probes
Prevention of HIV Infection in
Health Care Workers
Each day, health workers are exposed to the blood and body fluids of patients during patient care or in the laboratory.
The healthcare worker should take precaution to minimize the risk of exposure by appropriate use of protective clothing to minimize direct contact; frequent handwashing,
Proper use of equipment to prevent exposure to aerosols and adoption of a policy of universal precaution for all patients.
Okay🚶♂️🚶♂️🚶♂️
AIDS is the most serious infectious disease threatening humans today.
T/F
T
AIDS
To date, there are no effective vaccines and antiretroviral therapies slow progress of the disease.
T/F
T
AIDS
Extensive research has delineated the structure of the virus, its life cycle, its mode of transmission.
T/F
T
AIDS results in __________ of host, with ___ cell and ______ defences being affected.
severe immunodeficiency
T
humoral
Opportunistic infections and cancers are the confounding results of severe immunosuppression of the host.
T/F
T
