genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
As T cells have a central position in the immune defense as cytotoxic effectors or potent
activators of other immune cells, MHC-molecule binding alone does not lead to their activation,
but co-stimulatory signals are necessary. These signals originate from co-stimulatory surface
receptors like the B7-family of proteins expressed by antigen-presenting cells (APC), e. g. the
dendritic cells. Only when both signals initiate signal transduction at the same time, the T cell
activation takes place (Fig. I.2 B).
Modulation of Immune Reactions
The immune system is not only influenced by its own regulatory mechanisms and by the
pathogens’ factors, but also by additional elements like physical efforts (Gleeson et al. 1995) or
the psychological state of the organism (Glaser et al. 1999). While short stressful episodes might
even enhance the immune response, the immune response can be suppressed when the stress is
lasting too long. Immune suppression is mainly mediated by glucocorticoids (Dallman 2007).
Thus, different stressors might affect the demands of time for fighting an infection or even the
success of immune defense mechanisms (Fig. I.3, Peterson PK et al. 1991, West et al. 2006). But
not only the immune system, but also metabolic processes might underlie modification by such
stressors. Increasing demands and overwhelming environmental stimuli in the modern society
continuously heighten the stress level of humans and escalate the pathogenesis of stressassociated
illness such as the metabolic syndrome or depression and increase the risk of
infections (Bartolomucci 2007, Leonard 2006, Lundberg 2005).
STRESSOR
type
intensity
timing
duration
PATHOGEN
species, strain (virulence)
inoculum size
HOST
species (genetics)
age
sex
concomitant disease
nutritional status
previous experience
with pathogen (immunity)
with stressor (tolerance)
INFECTIOUS DISEASE
Fig. I.3: Various factors can modify the impact of a stressor on the
pathogenesis of an infectious disease.
From: Peterson et al. 1991.
symptomatic
infection
DEATH
asymptomatic
infection
HEALTH
A physiological stress response is short lasting and physiologically important for survival to
cope with a changing environment or to deal with potentially life-threatening situations.
Adaptive processes are very rapidly mounted to reconstitute a balanced allostatic system in the
stressed body which primarily include the neuroendocrine and immune system. Stress-induced
neuroendocrine alterations include activation of the sympathetic nervous system with increased
secretion of catecholamines, and stimulation of the hypothalamus-pituitary-adrenal (HPA) axis
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