**Table 3.**

*Characterization of helper T cell responses in diseases caused by bovine extracellular pathogens. Th1/Th2 cytokines were detected in cultured PBMCs and DLNs; IgG subtype was tested in the serum.*

Immune response against extracellular pathogens may vary at the systemic and local levels, such as in bovine trichomoniasis, where Th0 response is induced in the serum, and Th2 response in the mucosal secretion [220, 221]. More specifically, *Trichomonas foetus* upregulates both IgG1 and IgG2 in the serum but only IgG1 in local secretions from cervix, vagina, and uterus [220, 221]. Furthermore, animals immunized with specific antigen of *Trichomonas foetus* showed resistance to the experimental challenge, which was associated with the upregulation of both antigen-specific IgG1 and IgG2 in the serum [222, 223]. *Trichomonas foetus* seems to induce a Th0 response in the circulation, but a Th2 response in the mucosa. In addition, the systemic Th0 response may be protective against *Trichomonas foetus* rechallange.

Generally, Th2 response is effective in controlling extracellular bacteria [224]. For instance, Th2 response controls *Clostridium difficile* infection *in* humans *and Streptococcus suis* infection in pigs [224, 225]. In cattle, only few reports are available on CD4+ T cell response to extracellular bacteria such as *E. coli.* At this moment, the common understanding is both CD8+ T cell and antibodies seem to be critical to generate protective immunity (consistent with humans) in *E. coli* 0157:H7 infection [193, 194, 226].

Collectively, the results obtained from multiple experiments indicates that extracellular pathogens typically trigger Th2 or Th0 responses in cattle as shown in **Table 3**, and some extracellular pathogens modulate initial Th2 or Th0 responses to ineffective Th1 responses that are associated with the development of chronic infection.
