viral infection of blood cells Flashcards
(49 cards)
1
Q
list Viruses infecting white blood cells
A
- Human Immune deficiency virus (HIV)
- Human Lymphotropic virus (HTLV)
- Cytomegalovirus (CMV)
- Epstein Barr virus (EBV)
2
Q
what’s Human Immune Deficiency Virus (HIV )?
A
- Non oncogenic retrovirus that causes AIDS
- Kills cells with CD4 protein on their surface (T-helper lymphocytes, MQ & monocytes):
1. Loss CMI
2. Develop opportunistic infection
3
Q
illustrate structure of HIV
A
- capsid : cone shape
- genome : 2 identical RNA copies
- internal protein
- surface (envelope) glycoproteins:
GP120 : major Ag on surface
GP41
4
Q
illustrate internal protein of HIV
A
- three enzyme :
integration & replication
- reverse transcriptase
- protease
-integrase - core proteins :
P24
-most abundant core protein
- detect during early infection
- indicate viral replication - other proteins :
- enhance gene transcription
- dec MHC class I expression
5
Q
list steps of pathogenesis
A
- cell tropism
- attachment & entry into CD4
- transcription & translation
- assembly
- release
6
Q
illustrate cell tropism in HIV pathogenesis
A
- CD4 Th cells are the 1ry target of HIV
- certain subsets of monocytes & MQ express CD4 molecules
7
Q
illustrate attachment & entry into CD4 in HIV pathogenesis
A
- GP120 binds to CD4 molecules on target cell
- exposuer for binding site to coreceptor (chemokine) receptor CXCR4 on Th or CCR5 on MQ
- exposure of fusogenic GP41 = fusion of viral envelope with target cell membrane lead to entry of virus content & infection
- Abs against GP120 neutralize the virus cause rapid mutation in env gene lead to GP120 antigenic variant =
- escape from immunity
- difficulty in vaccine development
8
Q
illustrate transcription & translation in HIV pathogenesis
A
- reverse transcriptase converts RNA into Ds DNA which is transported to nucleus
- integrase inserts Ds DNA into host chromosome
(HIV DNA integrated into DNA of the cell is called provirus) - host cell polymerase transcribes viral genes into viral mRNA than translation into viral proteins & replication of viral genome
9
Q
- assembly take place at the ……….. = immature version
- illustrate how the maturation happen
A
- membrane of the host cell
- HIV protease processes capsid polyproteins leading to maturation & production to the infectious virus
10
Q
- release by ………..through the cell membrane leading to …………..
A
- budding
- infection of new target cells
11
Q
illustrate Fate of infected cells
A
- HIV destroys CD4+ TH cells in an HIV infected individual. These include 3 mechanisms :
1. Direct cell killing
2.Apoptosis
3.lysis of Innocent bystanders
12
Q
illustrate Fate of infected cells by
Direct cell killing
A
- budding of large amounts of viruses from cell surface
- accumulation of viral proteins& nucleic acids
- cytotoxic T lymphocytes
13
Q
illustrate Fate of infected cells by Apoptosis
A
distortion of cell regulations by HIV proteins.
14
Q
illustrate Fate of infected cells by
lysis of Innocent bystanders
A
CTLs destroy uninfected cells bound by HIV (have the appearance of the infected cells)
15
Q
illustrate mechanisms of immune system evasion by HIV
A
- Integration of viral DNA into host cell DNA, resulting in a persistent infection
- A high rate of mutation of the genes encoding surface glycoproteins.
- Down regulation of class I MHC proteins required for cytotoxic T cells
to recognize and kill HIV-infected cells.
16
Q
illustrate ttt oh HIV
A
- immunotherapy :
- monoclonal antibodies aganist GP120
- soluble CD4 molecules - antibiotic :
for opportunistic infections - antiretroviral drugs:
*aim : suppress HIV replication not eradication (no cure) + protection of immune system
*Mode of action :
- fusion inhibitor = fuzeon
- reverse transcriptase inhibitor =
nucleoside analog = AZT , DDI
non-nucleoside analog = navirapine
- integrase inhibitor = Raltigravir
- protease inhibitor = inhibit budding &assembly (indinavir)
* combination HAART regimen
(highly active antiretroviral ttt)= 2 nucleoside analog + protease inhibitor
to avoid development of resistance due to high mutation rate of HIV
* monitoring of ttt =
measurement of virus load
CD4+cell count
17
Q
clinical picture of HIV appear in ………….
A
3 stages:
1. early acute stage
(2-4 weeks after infection)
2. middle latent stage
3. late (AIDS) stage
18
Q
virological feature of early acute stage of HIV differ from early than late one . discuss
A
- early : high viremia
a- spread to many regions as lymphoid tissue & brain
b- most infectious stage - later on : low level viremia , dec viral load
19
Q
what’s clinical feature of early acute stage ?
A
- infectious mononucleosis-like symptoms (90%): fever, sore throat , LN enlargement & maculopapular rash
- asymptomatic in 10%
20
Q
what’s immunological feature of acute early stage?
A
- CD4+count:
a- early: low significantly
b-late: rebound to original level due to high CD8+cells &Ab against HIV - seroconversion: detection of Abs in serum usually 1-4 weeks after infection
** may be delayed up to 6 months :
(window period) NO Abs are detected although the viral load is high & the patient is symptomatic
21
Q
illustrate virological feature of middle latent stage
A
HIV continuous to replicate in lymphoid organs = large amount of virus is produced by LN cells, but remains sequestered in LNs
22
Q
clinical feature of middle latent stage…………….& lasts for ……..
A
- asymptomatic
- (7-11) years
23
Q
discuss immunological feature of middle latent stage
A
- early : immune competence
- generation of new CD4+T cells by bone marrow compensate the destroyed one
- immune surveillance prevents most of infection
24
Q
discuss the three ways for HIV Transmission
A
- sexual route (main route)
virus present in semen or vaginal secretion
- male homosexual (commonest)
- heterosexual - blood or blood products route
- blood transfusion
- sharing needle or syringes - perinatal route
- transplacental
- time of delivery
- breast feeding
25
describe the virological feature of late (AIDS) stage
- collapse of LNs architecture
- inability of immune system to trap HIV or other pathogens
- viral load inc in peripheral circulation
26
discuss immunological feature of late (AIDS) stage
CD4+ count dec to < 200 cells / mm3
lead to loss of immune competence
27
clinical feature of late (AIDS) stage...............after infection (faster in absence of ttt)
10 years
28
illustrate clinical feature of late (AIDS) stage
a. long lasting fever (>1 month) & weight loss
b. inc susceptibility to cancers & opportunistic infections characteristic of AIDS:
- Kaposi sarcoma
-pneumocystis jiroveci pneumonia
- bacterial : listeria, mycobacterium TB
- viral : CMV, HSV&VZV
- fungal : candida, cryptococcus
29
list steps of laboratory diagnosis of HIV
1. initial HIV screening test
2. follow up testing
3. CD4 cell count
30
illustrate initial HIV screening test
1. Ab test
( detect Ab for both HIV1/HIV2 Ags )
2. Ag /Ab test
(detect Ab & P24 Ag )
31
illustrate follow up testing
1. Ab differentiation test:
distinguishes HIV1 from HIV2
2. qualitative & quantitative detection of HIV nucleic acid :
initial baseline viral load for :
-predictor of the time for disease appearance
- prognostic marker after initiation of treatment
32
illustrate CD4 cell count
- lower limit of normal cell count is 500 cells / mm3
- patient needs chemoprophylaxis against opportunistic infection
- When CD4 count falls < 200cells / mm³
opportunistic infections increases
33
what about vaccination of HIV ?
- no available vaccine
- vaccine is under trial & hindered by :
1. rapid mutation in env region
2. spread from cell to cell by fusion, no contact with Abs
3.no animal models for AIDS
34
humanT- Cell Lymphotropic Viru( HTLV )
a- it is an .........
b-causes:
1. ........
2. ............
a- Oncogenic retrovirus
b-
1. T- cell leukemia
2. Tropical spastic paraparesis
35
list Mode Of Transmission of HTLV
1. Breast feeding
2. sexual
3. blood transfusion
4. sharing contaminated needles
(IV drug users)
36
illustrate Pathogenesis of HTLV
1. on mature T cell:
- oncogenic non-cidal
- viral RNA turned to Ds DNA by reverse transcriptase
2. on nervous system :
degeneration lead to spastic paraparesis
37
diagnosis of HTLV :
1......
2......
. Diagnosis :
- Detection of viral RNA by RT- PCR
- Detection of Abs to HTLV by ELISA
38
ttt of HTLV
No treatment or cure for latent infection
39
how to prevent HTLV ?
-Screening of blood for Abs
-infected mother refrain breast feeding
-condom to prevent sexual transmission
40
- EBV infects ..........
- lead to latent infection in..........
- B lymphocytes & RES (liver, spleen)
- B lymphocytes & pharyngeal epithelial cell
41
- CMV infect & become latent in ...........
- reactivated in ........
- mononuclear cells
- immunocompromised pts
42
EBV cause .........
1. infectious mononucleosis
2. Burkitt's lymphoma
43
CMV cause............
1. infectious mononucleosis
2. serious disease e.g. pneumonia in IC pts
44
list structure of parvovirus B19
- ss DNA
- non enveloped
45
MOT of parvovirus B19
1. droplet
2. transplacental (vertical)
3. blood transfusion
46
illustrate pathogen of parvovirus B19
infects 2 types of cells
- RBCs precursors(erythroblasts) =Aplastic anemia
- endothelial cells = rash with erythema infectiosum
47
discuss Clinical manifestations in parvovirus B19.
1. transiant aplastic crisis(TAC):
- temporary arrest of RBCs production
apparent only in patients with chronic hemolytic anemia
2. Pure Red Cell Aplasia :
A persistent infection in IC pts =
chronic aplastic anemia ,
need blood transfusion
48
illustrate Laboratory diagnosis of parvovirus B19.
- specimen: serum / blood cell
1. Direct detection:
- ELISA for viral antigen
- PCR for viral DNA (most sensitive)
2. Serology; ELISA
to detect B19 IgM (recent infection)
49
discuss treatment & prevention of parvovirus B19.
- Treatment : symptomatic
- Prevention and control
1. Screening of blood donors
2. Infection control to health workers from :
- the patient with TAC
- immunodeficient pts with chronic infection (PRCA)
3. NO Vaccine against human parvovirus B19
