Describe the difference between the mammalian cell-mediated and humoral responses to a pathogen. Include in your description the roles of antigens and antibodies, T-cells, B-cells, inoculation with vaccines, and the relative response times.

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.

1. 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’s 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 auto-inflammatory disease is defined by chronic inflammation, unprovoked by an infection, when antibody concentrations are not high. Consider the following:
   
    
   • 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.
   • The onset of autoimmune disease often follows an infection.
   • After an infection has passed, tissue must be repaired, and macrophages and phagocytes remain active in the affected tissue, often leading to chronic inflammation.
   • Type 2 diabetes, traditionally categorized as a metabolic disease, begins as chronic inflammation and is now classified as an autoimmune disease by many scientists.
   • Autophagy is induced by stresses such as starvation.
2. 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.
3. 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.
4. 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 naïve control.