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How Does the Immune System Tolerate its Host? 1 2 Rapid proliferation generally held to be a survival advantage. Low need for nutrients generally held to be a survival advantage. What about both together? Claim: Rapid proliferation can be contraindicative to low nutritional needs, so that it becomes a liability, [even if nutritional need per reproduction is smaller than for competition] because total need/time increased. Basis for self-tolerance Antigen-provoked growth of immune cells, if too much, yields too much reproduction, and ultimate demise. 3 dNi/dt =piNi – Ksi(t)Ni Ni =concentration of species i, pi= reproductive rate of species i si= strain on species i K = death rate constant Ksi= death rate dsi/dt = (Ti-F), si>0 F = food supply, Ti=nutritional need of species i dF/dt = m –FSaiNipi, m is rate of food input, ai is the food consumed per replication Slowest replication, greatest nutritional need per replication 4 5 Supporting facts: “High –zone” tolerance: Too much antigen causes the immune system to resign itself to the antigen’s presence. All mitogens are toxic beyond some level. Can this principle be the basis for cancer treatment? Cancer cells generally lack checkpoints, cell cycle arrest mechanisms, and reproduction is not slowed by nutritional deficit as for healthy cells. Moreover, cancer cells have a higher nutritional need per reproduction. Should cancer patients eat less protein?