Transcript Immunology For The Uninitiated - Dr Dawn

Immunology for
the uninitiated
Alternative title: Immunology: it
only hurts a bit.
[email protected] Twitter: @MsMacrophage, G+: +Dawn Bowdish, www.bowdish.ca
Immunology for the
non-immunologists
Infection control/
Inflammation
Wound healing/
repair
We all have our own set-point influenced by our age, gender,
immune experience, genetics, lifestyle & chronic conditions
What shifts the balance?
Innate immunity:
Monocytes, neutrophils, macrophages
Adaptive immunity:
B cells, T cells
Kyle
Novakowski
Unstimulated
Macrophages are exquisitely tuned
to their microenvironment
TNF
Infection control/
Inflammation
IFNγ
Wound healing/
repair
IL4
You give me fever……
Anorexia
Changes in food sources
(glutamine, lipids)
Lethargy, sleepiness
Conservation of energy
Cold
Conservation of energy
Irritable, apathetic,
depressed
Social exclusion
You give me fever…(and tissue
damage)
The good:
Antibacterial/viral immunity
The bad:
Tissue damage (ARDS)
Metabolic drain (muscle
wasting, weakness)
Everything in moderation……
The good:
Tissue repair
The bad
Fibrosis/scarring
Immune suppression
“Beware the rally”
What causes the shift?
Infection control/
Inflammation
Wound healing/
repair
Metabolic factors: glucose, arginine, lipids
Examples from PROSPECT
Plots of serum TNF (Red, left) and Endotoxin activity EAA (Blue, right) over time in 3
representative patients in ICU for >2 weeks
Dr. Chris
Verschoor
Aging is the ultimate
inflammatory condition
Aging is the ultimate
inflammatory condition
Dr. Chris
Verschoor
Cytokines
Total
IL-10
IL-1β
IL-6
TNF
CRP
Sick
19.7
0.93
42.5
11.9
51.2
Young
5.5
1.1
1.5
5.0
9.7
*”sick” data from the PROSPECT trial
Erythrocyte Sedimentation Rates
Old
9.2
1.4
5.0
8.7
54.6
Older adults are skewed towards
inflammation…does this affect outcome?
Metabolic limitations?
Nutrient limitations?
Do immunological parameters
correlate with APACHE scores?
p-value
0.006
Age
adjusted for false
discovery rate
0.04
Leukocytes
0.015
0.064
Serum proteins IL-6 (pg/ml)
0.007
0.04
IL-10 (pg/ml)
0.005
0.04
TNF (pg/ml)
0.03
0.102
Older adults have abnormal
fever responses
Holmes et al. Neurology 77 July 19, 2011
Low levels of TNF
High levels of TNF
Immunological checks on
longevity.
Nature Reviews Molecular Cell Biology 8, 703-713 (September 2007)
An immunological check on
longevity
The bone marrow is the primary
source of immune cells
Cellular immunophenotyping
to characterize inflammation
Myeloid cells change with age & chronic
disease
CD14++CD16+
Inflammatory
CD14+CD16+
Non-Classical
CD14++ Classical
Monocytes
Diabetes
Anemia
Dementia
CD141+ mDC
CD15- MDSC
CD15+ MDSC
Myeloid Derived
Suppressor Cells
Age
Cancer
(previous)
CD141- mDC
pDC
Dendritic
Cells
No link to
chronic
inflammatory
disease
BB
Dr. Deborah
Cook
Dr. Jennie
Johnstone
Dr. Mark Loeb
Central
Animal
Facility
Dr. Kathy
Delaney
April “The mouse
whisperer” Cook
Dr Mike Surette
J.C. Szamosi
Laura Rossi
Michelle Shah
Fiona Whelan
and others!
Dr. Deborah Cook, Dr. Param Nair, Dr. Elyanne Ratcliffe, Dr. Jane Foster, Dr. Elena Verdu, Dr. Premsyl
Bercik, Dr. Maggie Larché, Dr. Jose Moran-Mirabel, Dr. Jon Schertzer & their staff & lab members