Immune response must recognize threat by distinguishing wellness from un-
wellness. Recognition of pathogen-generated antigens is an adaptive response.
Generic pathogen identifiers such as bacterial surface polysaccharides or
viral capsid proteins are recognized by cells of the innate immune system.
However, cellular debris and dysfunctional whole cells such as tumor cells or
cells marked for apoptosis must also be recognized for autophagy ("self-
devouring") by the innate immune system.
A. Describe the characteristics of a model of innate immunity that
distinguishes wellness from un wellness without the specificity of antigen
receptors. Autoimmunity is the breakdown in the immune system鈥檚 ability to
distinguish self from non-self. The list of diseases categorized as autoimmune
diseases grows, as does the intensity of research into the causes. One
criterion for classification as an autoimmune disease is the presence
of high antibody concentrations in the blood. An autoinflammatory disease is
defined by chronic inflammation,
unprovoked by an infection, when antibody concentrations
are not high. Consider the following:
\(\bullet\)Macrophages and phagocytes share information with the adaptive immune
system by displaying protein fragments of their targets on their surfaces to
communicate with T cells.
\(\bullet\) The onset of autoimmune disease often follows an infection.
\(\bullet\) After an infection has passed, tissue must be repaired, and
macrophages and phagocytes remain active in the affected tissue, often leading
to chronic inflammation.
\(\bullet\) Type 2 diabetes, traditionally categorized as a metabolic disease,
begins as chronic inflammation
and is now classified as an autoimmune disease by many scientists.
\(\bullet\) Autophagy is induced by stresses such as starvation.
B. Evaluate the strength of the question, do cell fragments produced by the
innate immune response during inflammation communicate self as non-self to T
cells leading to autoimmunity?
In the "fight or flight" response, neural signals are sent to the adrenal
gland activating the release of epinephrine. Epinephrine increases metabolic
activity, heart rate and alertness. The activation of the endocrine system by
the nervous system has been positively selected by survival in response to
threat.
C. Describe a model for the evolution of the activation of immune system by
the nervous system in an environment in which wounds are frequent and
potentially lethal. Include the selection process in your description. In the
famous experiment of Pavlov, a reward (unconditioned stimulus) received
synchronously with a bell (conditioned stimulus) became associated in the mind
of the dog. After a few repetitions, the response of the dog to the bell was
to drool. The digestive system had been
activated by the nervous system through a conditioned stimulus.
An emerging area of research is psychoneuroimmunology, the study of the
relationship between the immune system and the nervous system. Exton and co-
workers (Brain Behavioral Research, 110, 2000) have shown that a reward (an
injection of epinephrine) received synchronously with candy (conditioned
stimulus) become associated through repetition. The response of the patient to
a shot of epinephrine is the proliferation of natural killer, NK, cells (a
cell type of the innate immune system). After conditioning, the patient
displayed an increase in NK cells in response to the candy.
The drug cyclosporine is used to suppress immune rejection of organ
transplants by inhibiting production of interleukin, a cytokine messenger that
increases expression in T cells.
D. Design an experiment to test the use of conditioning using the
administration of cyclosporine as the unconditioned stimulus and sugar water
as the conditioned stimulus by measuring the blood concentration of
interleukin. Assume that interleukin is flushed from the blood in a single
day. In your design include a vehicle control where conditions are identical
to the treatment and a "do-nothing" or na茂ve control.
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