In hypersensitivity, as I understand it, a normal immune response gets excessive, misdirected or wrongly regulated to cause tissue injury. The various types determine the various ways in which the tissue-causing responses are effected, at all times the ultimate cause being either excessive response (the normal amount being harmless), misdirection or wrong reglation. Hence, the ultimate cause beneath all hypersensitivities is some factor which just unleashes the immune machinery on normal tissues.

With this in mind, as Type IV Hypersensitivity is typically described under the headings of a granulomatous reaction, DTH (Delayed type hypersensitivity) or a contact dermatitis type response, involves the stimulation of $T_{h1}$ and $T_{h17}$ subsets of $T$ cells (along with $\text{CD8+}$ cells). What I fail to understand is that,

What goes wrong along the normal T-cell effector pathway to ultimately cause the injury?

(In type I, it is the IgE arsenal release on parasite mimicking allergen, in type II it is the self-antigen directed or hapten mediated self-tissue direction of Ab, and in type III it is the precipitation of immune complexes owing to the overburdening of the Ag-Ab response due to continued influx of Ag which cause the problem)

The events of stimulation, cytokine release and macrophage proliferation and activation is exactly what you would expect to be, in case the cells are doing what we want them to, to ward off a normal invader. But it ends up damaging the tissues.

Moreover, a lot of books say some variant of

"DTH is necessary to fight some specific pathogens"

Since hypersensitivity, (and hence DTH) by definition is immune-mediated tissue injury, do they mean that this tissue injury is indispensable in the fight against these pathogens (in which case, is worrying about DTH necessary?) or that the normal unaltered form of the pathway of immune response (the altered form of which results in DTH) is necessary for the fight (in which case there is a minor semantic error in the quoted statement)?

  • $\begingroup$ In some cases where your hypersensitivity reaction is due to autoreactivity it's cause for alarm. In other cases, though, nothing is going wrong with the development of the T cell response except for some reason they can't clear the infection in a reasonable amount of time or effort. The situation escalates as more effector cells are recruited, producing more and more cytokines/TNF-α/etc. as a part of their normal response. In fact, you end up with chronic DTH reactions when phagocytes uptake microbes but fail to get rid of them, such as Mycobacterium spp. that prevent lysophagosome formation. $\endgroup$ – CKM Nov 27 '15 at 19:29
  • $\begingroup$ @Kendall So, the tissue injury is just the result of a prolonged activation of the immune mechanisms or of pathogen-mediated misdirection of the system? Thanks. Can you also shed light on the questions following "Moreover, a lot of books....." $\endgroup$ – stochastic13 Dec 17 '15 at 10:13
  • $\begingroup$ It's not 100% misdirection; while the pathogen remains the immune system is getting signalled "We need to clear this infection." So it's the normal response, just over an abnormal period of time and circumstance. I tried to answer that last part w/ the Mycobacterium spp. example. They infiltrate cells and are difficult to clear, so the DHT is actually an attempt to clear out the microbes by scuttling the infected tissue. $\endgroup$ – CKM Dec 17 '15 at 21:37

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