Delayed type hypersensitivity and TH1 function in TB skin test

[MudPhud20XX]

So Kaplan immuno says:

"When TH1 cytokines activate macrophages and cause tissue damage, the result is delayed-type hypersensitivity (DTH). Assay of DTH by skin testing is often used as a measure of the patient's ability to mount a cell mediated response."

So my questions are:
1. So when you do TB test, how is the size of the inundation and one's TH1 function related to each other?

Bigger the inundation means more TH1 respond, thus is positive for TB? How come?

Does it have to do with the T cell's memory to recall the protein they inject during the TB skin test?

2. Why does it take time for the body to react toward TH1 cytokines?

Many thanks in advance.

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[alicealicealice]

Its all about the memory.
Upon initial TB exposure, Mphages carry the engulfed TB around the blood stream until it finds a novice Th1 that recognizes the antigen its presenting on its MHCII. The Mphages secrete IL12, prompting Th1 to form memory cells as well as secrete IFN back onto Mphages allowing them to form granulomas and contain the infection. Th1 in teh granuloma also secrete Macrophage Inhibiting Factor to make sure the granulomatous reaction stays localized. The importance of IL12 is seen in IL12 receptor deficiency, which may present as disseminated infection after BCG vaccine. The treatment for that disease is supplemental IFN.
Upon PPD placement, langerhan cells engulf the proteins and then migrate to lymph nodes in order to eventually present to the memory Th1. This is why its delayed type sensitivity, as it takes time for this to occur and for the memory Th1 to generate the cytokines to coordinate a robust local response, creating induration. Induration is what is measured, not the size of the local red spot, which in a patient never exposed is just the innate non specific reaction to a foreign (never seen before) antigen.
Why aren't memory Th1 cells generated in response to a PPD? My guess would be that because there is no macrophage providing that second signal (IL12) because there is no genuine infection going on.

 

[alicealicealice]

. dp

 

[surgok]

Excellent answer by alice. Person exposed to TB -> memory TH1-> TB test-> large induration.