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For instance, say a host is infected with salmonella where the pathogen can enter into a macrophage without the macrophage destroying it. How does the body then fight off an infection that is capable of surviving the mechanism by which pathogens are destroyed?

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  • $\begingroup$ what do you mean by: pathogen can enter into a macrophage without the macrophage destroying it. $\endgroup$ – user 33690 Apr 16 '18 at 7:29
  • $\begingroup$ You're asking for an entire course on immunology. Googling for "immunity to salmonella" turns of hundreds of answers, from detailed peer-reviewed articles to Reddit and Quora summaries. $\endgroup$ – iayork Apr 16 '18 at 13:06
  • $\begingroup$ Basically read this article and understand that an answer to this questions can boil down to Figure 1 in the paper, but comprehending Figure 1 is an entire college course. frontiersin.org/articles/10.3389/fimmu.2014.00516/full $\endgroup$ – CKM Apr 16 '18 at 14:16
  • $\begingroup$ You can also try this review for an overview of what happens when you can't clear viruses. $\endgroup$ – CKM Apr 16 '18 at 14:28
  • $\begingroup$ It definitely 100% does not take an entire course to generally explain this one single phenomena, I can guarantee that having graduated from a program in which I studied human anatomy and microbiology, so I 100% absolutely expect it to be generally answerable within the stackexchange platform. The problem is no one went into detail about this interaction with salmonella since it is less commonly studied compared to microbes like e-coli, and many sources on the internet are commercially based, but I remember a related topic being briefly covered and not at all overly complicated by any means. $\endgroup$ – John Joe Apr 16 '18 at 15:20
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There are two broad types of infection classified by their persistence: acute and chronic infections.

I find that most courses on immunology nicely cover acute infections and their detection, and resolution. In the case of S. typhi, which has the ability to invade host cells such as phagocytes and inhibit their ability to properly function, the case isn't so pretty (1). The same can be said for some viruses like HepC and HIV, or other bacteria like Mycobacterium.

Salmonella spp. have a number of virulence factors. The flagellum of the bacteria actually acts as a TLR agonist that activates phagocytes like monocytes/macrophages and neutrophils, which are often first-responders. Then, the bacteria can facilitate the injection of some of its own proteins into the host cell which does a number of things like modulate vessicle trafficking, suppress cellular functions, induce apoptosis and promote overall survival of the bacterium inside the phagocytes (2).

So normally, and referring to the below figure, the overall reponse to a Salmonella infection is adaptive in nature, presumably because your innate effectors have been stunted:

enter image description here

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You can see in healthy phagocytes that through one of two pathways, protein antigens end up displayed on HLA molecules for cellular immunity to take over. Option B is that another cell like a macrophage detects distress signals from the infected cell and induces cell death in it through receptors or oxidative burst. In the case of Salmonella, HLA expression is down-regulated and oxidative burst can be inhibited so localized, infected antigen-presenting cells cant mount an effective response.

That's not to say everything is de-regulated early on. If you succeed in antigen presentation or innate killing (perhaps a non-pathogenic strain), you will resolve the infection as seen in the above figure: a combination of T-mediated killing, B-mediated killing, NK-mediated killing, and generalized inflammation.

In the chronic case, the pathogen will have escaped the primary immune response, but the system will attempt to continue to resolve the infection. This can lead to a number of things: cellular anergy, cellular hyperactivity, sequestration (see granuloma), chronic inflammation & tissue damage, and so forth. The following diagram is predicated upon viral infections but the immunology is largely similar:

enter image description here

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There are changes to the system that are a result of over-exposure to antigen, and an inability to clear that stimulation. The best way to explain it is that chronic stimulation leads to both hyperactivity and suppression. The constant presence of effector molecules like TNF-a leads to a persistent state of tissue inflammation, which is bad for the tissue, but taken together with the persistent presence of antigen, this may lead to dysfunctional responses by lymphocytes (3).

A particularly virulent infection may be impossible for your immune system to clear without assistance, then, requiring the intervention of gram-negative antibiotics, for example.

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