1. Immune Responses to HIV
Zoran Galic Ph.D.
Division of Hematology/Oncology
David Geffen School of Medicine UCLA
August 19, 2014

2. Innate vs adaptive immunity
In response to pathogens, vertebrate immune systems use two interconnected systems:
Innate immunity
Adaptive immunity

3. 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.

4. Adaptive immune response

5. HIV induces strong cellular and humoral immune responses
CTL-cytotoxic T lymphocytes (CD8 killer T cells)

6. 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

7. CD4 T cells are depleted in the course of HIV infection

8. Why are CD4 T cells depleted during the course of HIV infection?
HIV-infected CD4 T cells are targeted by the immune response
CD4 T cells are lost due to immune exhaustion

9. 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

10. 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)

11. 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

12. 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:
Insufficient signals to
activate more killer cells
Defective memory
Impaired function

13. 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