Professional Documents
Culture Documents
(AIDS)
History
1950s: Blood samples from Africa have HIV
antibodies.
1976: First known AIDS patient died.
1980: First human retrovirus isolated
(HTLV-1).
1981: First reports of Acquired Immunodeficiency Syndrome in Los Angeles.
1983: Virus first isolated in France (LAV).
1984: Virus isolated in the U.S. (called
HTLV-III and AIDS-Related Virus, ARV).
1985: Development and implementation of
antibody test to screen blood donors.
Overview of HIV
-Infect and kills CD4 lymphocytes
- Loss cell mediated immunity opportunistic infect.
- Other (macrofag , monosit) that have protein CD4
on their surface can be infected also
- HIV-1 and HIV-2 cause AID
Viral-host Dynamics
About 1010 (10 billion) virions are produced
daily
Average life-span of an HIV virion in plasma
is ~6 hours
Average life-span of an HIV-infected CD4
lymphocytes is ~1.6 days
HIV can lie dormant within a cell for many
years, especially in resting (memory) CD4
cells, unlike other retroviruses
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Classification of HIV
HIV class: Lentivirus
HIV at Surface
of CD4
Lymphocyte
Courtesy of CDC
Virulogy of HIV
-Is of one the two HTLV
- Two identical ss (+)RNA surrounded by envelop (lipid
bilayer) containing viirus-specifict glycoprotein
(gp 120 and gp 41)
-Genom complex
1. encode structural protein : gag , pol, env
2. tat , rev (replication) ; nef , vif , vpr and vpu
(as accessory gene)
gag
5
LTR
P24,
gag
pol
env
VIF
TAT
VPU
REV
NEF
LTR
pol
PROT
INT
POL
env
H
VIF
gp120
TAT
gp41
VPU
LTR
REV
3
NEF
gene
gag
tat
rev
p24 , p7
p17
riverse trancriptase
protease (PROT)
integrase (INT)
gp 120
gp 41
TAT
REV
nef
Nef
pol
env
Fungtion of protein
nucleocapsid
matrix protein
transcribec RNA DNA
cleaves precursor polipeptide
integrates viral DNA host DNA
attachment to CD4 protein
fussion with host cell
activation of transcription v. gene
transport mRNA from nucleus
to cytplama
decrease CD4 & MHC I protein
on surface infected cellls, induce
death of uninfected CTL, I importand for pathogenesis SIV
gene
vif
Vif
vpr
Vpr
Vpu
Vpu
Fungtion of protein
P17 Matrix
protein
Lipid bilayer
HIV Immunology
Overview of Adaptive
Immune Response
Extracellular
infection
APC
Intracellular
infection
MHC I
presentation of
endogenous
antigen
Nave
cell
Free antigen
MHC II
presentation of
exogenous
antigen
T8
Nave
Cell
B-
Nave T4
helper
cell
Cell-mediated
(CTLs)
22
Th1
Th2
Humoral
(plasma cells /
antibodies)
23
Antibody-dependent cell-mediated
cytotoxicity (ADCC)
Fc portion of antibody binds to NK cell
Stimulates NK cell to destroy infected
cell
25
Pathogenesis of HIV
Indirect injury
Opportunistic infections and tumors as a
consequence of immunosuppression
29
General Principles of
Immune Dysfunction in HIV
All elements of immune system are
affected
Advanced stages of HIV are associated
with substantial disruption of lymphoid
tissue
Impaired ability to mount immune response to
new antigen
Impaired ability to maintain memory responses
Loss of containment of HIV replication
Susceptibility to opportunistic infections
30
Consequence of Cell-mediated
Immune Dysfunction
Inability to respond to intracellular
infections and malignancy
Mycobacteria, Salmonella, Legionella
Leishmania, Toxoplama,
Cryptosporidium, Microsporidium
PCP, Histoplamosis
HSV, VZV, JC virus, pox viruses
EBV-related lymphomas
33
Consequence of Cell-mediated
Immune Dysfunction
Inability to respond to intracellular
infections and malignancy
Mycobacteria, Salmonella, Legionella
Leishmania, Toxoplama,
Cryptosporidium, Microsporidium
PCP, Histoplamosis
HSV, VZV, JC virus, pox viruses
EBV-related lymphomas
34
Consequence of Cell-mediated
Immune Dysfunction
Inability to respond to intracellular
infections and malignancy
Mycobacteria, Salmonella, Legionella
Leishmania, Toxoplama,
Cryptosporidium, Microsporidium
PCP, Histoplamosis
HSV, VZV, JC virus, pox viruses
EBV-related lymphomas
35
Transmission
Modes of infection
Viral tropism
Transmitted viruses is usually macrophage-tropic
Typically utilizes the chemokine receptor CCR5 to
gain cell entry
Patients homozygous for the CCR5 mutation are
relatively resistant to transmission
36
HIV
T-cell
Immature
Dendritic cell
Skin or
mucosa
Via lymphatics or
circulation
24
hours
1.
HIV co-receptors,
CD4 + chemokine
receptor CC5
37
PEP
2.
Burst of HIV
replication
48 hours
Selective of
macrophagetropic HIV
3.
Mature Dendritic
cell in regional LN
undergoes a single
replication, which
transfers HIV to Tcell
CD4 count
Marker of immunologic damage
Number of CD4 T-lymphocytes
cells/mm3 plasma
38
Key Points
HIV is a retrovirus, capable of integrating into
host genome and establishing chronic infection
HIV can be classified into subgroups (clades)
which have characteristic geographic distribution
The important steps in the lifecycle of HIV include
cell entry, reverse transcription, integration, and
maturation/assembly
Cell-mediated immunity is critical for containment
of HIV infection and other intracellular infections
HIV evades host immunity by a variety of
mechanisms
45