Transcript Immune Responses to HIV

Immune Responses to HIV
Zoran Galic Ph.D.
Division of Hematology/Oncology
David Geffen School of Medicine UCLA
[email protected]
August 19, 2014
Innate vs adaptive immunity
In response to pathogens, vertebrate immune systems
use two interconnected systems:
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Innate immunity
Adaptive immunity
The major cells of innate immunity
Big eaters/Always hungry
Antigen Presenting Cells (APCs)
Proteins eaten by APCs are broken down to small pieces (peptides),
which are loaded on special receptors (MHCs) and transported to the
cell surface. Peptide+MHC complex can be recognized by a T cell and that
interaction can lead to an adaptive immune response.
Adaptive immune response
HIV induces strong cellular and humoral immune responses
CTL-cytotoxic T lymphocytes (CD8 killer T cells)
Why is HIV not cleared by the immune system?
 High mutation rate of HIV
 HIV latency
 Compromised immune function, primarily through the loss
of CD4 T helper cells
CD4 T cells are depleted in the course of HIV infection
Why are CD4 T cells depleted during the course of HIV infection?
1. HIV-infected CD4 T cells are targeted by the immune response
2. CD4 T cells are lost due to immune exhaustion
Innate immune system vs HIV
Innate responses against HIV
• Rapid and first line of defense
against the virus
• Alert and activate the adaptive
immune response
• Release pro-inflammatory
signals
• Clearance of infected cells
• Internalize and process the
virus to present to T cells to
initiate the adaptive response
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
CD4 T cells vs HIV
CD4 T cells responses against HIV
• Orchestrate adaptive immune
response
• Activated by innate immune
system
• Facilitate CD8 T cell (killer) and
B cell activation
• Provide signals and growth
factors for proper immune
responses
HIV counter-attack
• Infects CD4 T cells
• Causes depletion of the CD4
T cell population and thereby
removes the “brains” of the
immune response
• Uses surviving CD4 T cells
as a reservoir (latent HIV)
B cells vs HIV
B cell responses against HIV
• Directed by CD4 T cell to make
antibodies against HIV
• Antibodies neutralize the virus
to prevent spread
HIV counter-attack
• Virus mutates at a very high rate
• Loss of CD4 T cells results in:
–
–
–
Increase in numbers of
immature B cells
Exhaustion
Decreased memory
CD8 T cells vs HIV
CD8 T cells responses against HIV
• Killer arm of the immune system
• Seek, identify and destroy
infected cells
• Control virus in the initial months
of infection
HIV counter-attack
• Virus mutates and escapes
• Chronic inflammation leads
to exhaustion
• Lack of CD4 T cells:
a. Insufficient signals to
activate more killer cells
a. Defective memory
b. Impaired function
Closing Comments
 APCs, B cells, CD4 and CD8 T cells work together to fight infection
 HIV perturbs APC function, and kills CD4 T cells
 This allows secondary “opportunistic” infections to occur,
leading to disease/death
 Vaccines have the potential to halt HIV infection, but thus far
an efficacious vaccine strategy has proven elusive
 A vaccine approach that takes into account all aspects of the immune
response will likely have the best chance of success