Impact of Metabolism on Immune Response:

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Impact of Metabolism on Immune Response Implicati
ons for Neurological Repair
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• Authors
• Biology Department
• M. Karen Newell
• E.Villalobos-Menuey
•  
• Physics Department
• R. E. Camley, Z. Celinski and T. M. Christensen
• University of Colorado at Colorado Springs,
• Colorado Springs, CO

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Key Idea   Energy metabolism, the efficient use
of fuels for energy, and the consequent levels of
intracellular reactive oxygen species, directly
impacts the expression of molecules recognized by
the immune system.   Consequences   If we
understand how to manipulate metabolism, we can
facilitate effective repair and regeneration of
defective tissues.
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How does immune recognition work?
T-cells (white blood cells) travel through the
body checking to see if you are okay.  Several
things can happen If your cells are okay
T-cells leave you alone.   If your cells are not
okay, T-cells can either 1) destroy damaged
cells 2) fix damaged cells by promoting
regeneration 3) attract other cells to promote
repair
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Metabolism and Cancer

• Protection from Reactive Oxygen

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How do T Cells Work?
The outside of T-cells have two types of
receptors that must be engaged to activate the
cell. Each receptor "looks for" a different
structure on the cell being recognized. These
structures are 1) Peptides in association
with MHC 2) B7 or Fas providing
costimulation and thought to be the
result of damage or danger (see
picture)
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Response of Breast Cancer Cells to Microwaves
When breast cancer cells are exposed to 10 GHz
microwave radiation (2 mWatts) both metabolic and
immune recognition levels increase.   The effect
persists at least 21 hours after microwave
treatment.
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Can we cause changes in immune recognition?
We saw that microwaves produce changes in
reactive oxygen (measure of metabolic change) and
immune recognition. Can the addition of reactive
oxygen (H2O2) by itself cause differences in
immune recognition? The data below shows the
answer is yes!
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Can we cause changes in immune recognition by
other methods?
We saw that adding reactive oxygen (H2O2) changes
immune recognition. We can ask if other
substances that also alter the metabolism can
change immune recognition. We investigate 1)
Glucose -- yes 2) Insulin -- yes 3)
Drugs -- yes
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Can we cause changes in immune recognition in
neurons?
YES! Our very recent experiments show the
addition of reactive oxygen (H2O2) to neurons
induces significant increases in expression of
B7.
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Neurons and T Cells
Sometimes T cells attack the myelin sheath, as in
multiple sclerosis. If we can prevent T cell
attack, we can reduce the severity of the
disease. T cells can also facilitate repair of
neurons! If we can promote T cell repair, we can
help repair spinal cord injuries. (see
picture)
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Metabolism and Cancer

• Protection from Reactive Oxygen

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Implications for Neural Systems
We have seen that changes in cellular metabolism
dramatically impact immune recognition. Why is
this important?   The answer is that if we can
change how the immune system recognizes a cell,
we may be able to direct the immune system to
repair, regenerate, or destroy the recognized
cell.
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This could help all of the following
Neural repair -- helping stroke victims Neural
regeneration -- helping people with spinal
cord injuries Destruction of tumor cells --
helping those with brain
tumors Immune system attacks of healthy tissue --
helping those with MS or preventing graft
rejection.
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Leishmania Lysosomal pH In Susceptible and
Resistant Strains of Mice
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Levels of Reactive Oxygen In Resistant versus
Susceptible Strains of Mice
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