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REVIEWS
IMMUNOLOGY
The immune response to HIV
Nina Bhardwaj, Florian Hladik and Susan Moir
‘Since HIV was discovered the causative agent of
‘AIDS almost 30 years ago, HIV nection has become
‘2 devastating pandemic. with millons of individuals
‘becoming infected and dying from HIV-related
clsease every year. A global research effort over the
past three decades has discovered more about HIV
than perhaps any other pathogen. Immunologists
‘continue to be intrigued by the capacity of HIV to
‘effectively knock out an essentiol component ofthe
adaptive immune systern — CD4*Thelper cells. This
Poster summarizes how HIV establishes infection at
mucosal surfaces, the ensulng immune response to
‘the vrusinvoving DCs, B cells and Teall, and how
HIV subverts this response to establish chronic
Infection Based ona clearer understanding of HIV
Infection andthe response tt the ildhas now
‘entered an eracf renewed optimism forthe
evelopment ofa successful vaccine.Since HIV was dlscovered a the casative agent of
‘ontnue tbe intrigued by the capacity of HIV 10
‘fectvly krack ot an essential component of the
apie stem — CDT hepa als Tis
Foster tumors how HV etablabes nection ot
‘mucosal sirfecesthe ensuing immune response to
{hevirsinalvingDCs Bete and Teel ondhow
iV sbverts narespanetestablsh a cron
‘section und on carer understanding o AVComplexities of HIV infection
HIV primarily infects the CD4+ T-cells.
Establishes Chronic Immune Activation.
Thrives on CD4+ T-cell activation.
Error prone HIV reverse transcription.
Establishment of latent reservoir.Events that happen in an HIV infection
“oo HIV-specific
immune response
’
Massive viremia By
oe { —
ae Wide dissemination
a to lymphoid organs
“—— Establishment of Trapping of virus and
Primary infection in GALT establishment of chronic,
infection persistent infection
Partial immunologic
control of virus replication
t
: a
Destruction of Accelerated virus
Immune System replication eraeecied
a aberrant cell signaling
Rapid CD4+ T cell turnover
Sauce: Longo Ot. Fauc AS, Kasper Ok Mouser St. Jameson i. osc: Hvrsans
Principles of Internal Medicine, 18th Edition: wwn.accessmedicImmune escape
Cellular Immunity
CD8+ Tells
Early
Development of escape
‘mutants
Late:
Apoptosis ~ Expression of PDI
molecule.
Malfunctional CD8+ T cells.
Humoral Immunity
Neutralizing Antibodies
Hypervariability of Primary
sequence of the envelope.
Extensive Glycosylation of the
envelope.
Conformational masking of the
neutralizing epitopes.
Mechanisms of CD4+ T cell depletion
Loss of plasma membrane due to viral budding
Accumulation of unintegrated viral DNA
Apoptosis
Aberrant intracellular signalling events.CD4+ T cells
Extracellular bacteria iniricenaar piatagins
— Autoimmunity
Autoimmunity
Staphylococcus, _ wont
Streptococcus, Gx, be
Pseudomonas, agith Ne Chlamydia,
E.coli "egy ef M. tuberculosis
Salmonelia
T Follicular helper cells
cope homeostasis Humoral Immunity & B cell Extracellular parasites
Regulation of immune responses development ———
:// www. bloodjournal.ora/content/112/5 (adapted)Monocytes & Macrophages Dendritic cells
Normal in Number. But functionally deficient. Crucial role in the establishment of HIV
infection in the host.
HIV is less cytopathic to monocytes.
Main APCs for the HIV infection.
Hence play a role of reservoir of infection.
A target for vaccine.
Increased cellular activation generates a large
pool of monocytes/macrophages
Natural Killer cells (NK)
Normal in number.
Abnormal CD56-/CD 16+ cells predominate.
NK cell — Dendritic cell interaction.Innate responses against HIV
1. Rapid and first line of defense 1.
against the virus
2. Identify and contain the 2.
invader
3. Alert and activate the adaptive 3.
immune response
4. Release pro-inflammatory
signals
5. Clearance of infected cells
6. Internalize and process the
virus to present to cell and T
cells to initiate the adaptive
response
CD4 T cell responses against HIV
1. Orchestrate adaptive immune
response
2. Activated by innate immune
system
3. Facilitates killer T cell (CD8)
and B cell activation
4. Release signals and growth
factors for proper responses
HIV counter-attack
The virus can infect members
of the innate immune system
Innate cells can act as depot
and effectively transmit virus
Inhibition of function via viral
factor release and/or improper
immune signals
B cell responses against HIV
1. Directed by CD4 T cell to make
antibodies against HIV
2. Antibodies neutralize the virus
to prevent spread
HIV counter-attack
1. Infect CD4 T cells
2. Deplete the CD4T cell
population removing the
“brains” of the immune
response
Uses surviving CD4 T cells as
reservoir 5
q
b.
HIV counter-attack
1. Early infection causes too
much activation and
overwhelms B cells:
1. Poor antibody responses
2. Loss of 8 cells,
3. Exhaustion
2. Virus mutates at a very high
rate
3. Loss of CD4 T cells:
41. Increase immature 8 cells
2. Exhaustion
3. Decreased memory
Frmaniy and We Coe
‘Use the immune stmt develop funeiona cue"
‘aes of matraly acer nun agains HN
Development of therapeu vaccines
is the nate lune semTake Home Message
The primary immunopathogenic lesion in HIV infection
involves CD4+ T cells.
The dysregulated immune activation of the host serves to
maintain the HIV persistence.
HIV develops a latent reservoir in the host making the
eradication of the virus difficult.
HIV sets up an evolutionary race with the host B cells and
till today has managed to win it.