Many of the outcomes of the innate immune response are mediated by three major interacting cascades. Answer the following questions:
a) For each of these 3 cascades, briefly outline the trigger (or stimulus) of the cascade, and the outcomes of the cascade in terms of products and their actions. AND
b) How do these cascades interact? AND
c) Briefly explain the significance of the fact that these are cascades, rather
than a one-step reaction. AND
d) What morphological changes result from these cascades?

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During infection, there are 3 major processes occurring to destroy the invading microorganisms. First, phagocytes, a type of white blood cell, recognize and engulf bacteria and viruses. Neutrophils, the most abundant white blood cell, and macrophages have specific receptors that detect foreign particles and phagocytose them to clear them from the bloodstream. These foreign particles are taken up by the white blood cells and digested into their macromolecular components.

Second, inflammation is a coordinated response to innate immunity. When infection occurs, molecules specific to bacteria trigger an inflammatory response. This leads to the dilation of blood vessels, an increase in vessel permeability, and ultimately an influx of immune cells to the site of infection or injury.

Lastly, infection also activates the complement system. The complement system is a cascade of serum proteins which eventually form a membrane attack complex to make holes in the plasma membranes of the invading microorganisms. These holes cause the microorganisms to lyse, killing the bacteria or virus. The presence of complement proteins on microorganisms also signal to neutrophils and macrophages to phagocytose them, linking the complement system to the immune cell response. Activation of the complement system further increases the inflammatory response, allowing for the efficient removal of infectious microorganisms from the body.

The fact that these responses are cascades offers two major advantages. First, the cascades allow for an amplified response, where a few triggers can lead to the response of many immune cells to increase the efficiency of fighting infections. For example, if these were one step reactions, each bacteria would have to be detected by one immune cell, whereas a cascade allows for one immune cell to start the immune response of several other immune cells after the detection of one bacteria. Secondly, having several steps in the cascade allows for positive and negative regulation, or checkpoints in various steps of the cascades. This is important for localizing the effects of the immune system to where infections are occurring, and allows for the immune response to be shut off in case a false trigger was detected.

Morphologically, the initiation of an inflammatory response often leads to swelling (due to increased vessel dilation and permeability). Infections may also lead to fever, which is a response of the brain to increased cytokines released from immune cells. Fever is important in host defense as it may speed up body defenses, while making the temperature too high for pathogens to grow and replicate.

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