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Immunological Role of Cytokines

Secretes Type 1 cytokines IL-2, IFNy, TNF

Support immune responses in which macrophages, natural killer cells, and CTL are effector cells.

Responsible for DTH responses Support isotype switching to lgG2a (mouse)

Required for immunity against viruses, parasites, fungi, and intracellular bacteria

" 'jTh2 cell

Secretes Type 2 cytokines IL-4, IL-10, IL-13.TGFP

Support B cell induced activation

Support antigen induced differentiation of B cells to plasma cells

Support isotype switching to lgG1 and IgE

Required for immunity against extracellular bacteria and parasites.

Fig. 9.6. Immunological relevance of Type 1 and Type 2 cytokines. Whether a Type 1 or a Type 2 cytokine profile predominates in response to antigenic stimulation has profound consequences since the cytokines produced by Th cells preferentially activate distinct branches of adaptive immunity.

Fig. 9.6. Immunological relevance of Type 1 and Type 2 cytokines. Whether a Type 1 or a Type 2 cytokine profile predominates in response to antigenic stimulation has profound consequences since the cytokines produced by Th cells preferentially activate distinct branches of adaptive immunity.

Autoimmune disorders

In many patients with a variety of autoimmune disorders (multiple sclerosis, insulin-dependent diabetes, Hashimoto's thyroiditis), pathology is associated with the existence of a Th1 response to the relevant autoantigen. This underlies the scientific rationale for attempting to identify the factors that skew the Th profile in these scenarios, in order to develop immunotherapeutic strategies that would alter the relative balance of antigen specific Th 1 versus Th2 subsets. As one example of such a strategy, it has been found that oral administration of antigen preferentially induces Th2 subsets, perhaps by stimulating TGFß production (a cytokine believed to promote Th2 development). Thus, patients with multiple sclerosis have been fed myelin extracts with the expectation that this might favor Th2 development at the expense of Type 1 cytokine production, with a concomitant beneficial effect on their disease status. While the results were not as dramatic as had been hoped, there were some clinical benefits observed, more apparent in men than in women. These sex-related differences may be taken to imply that endogenous hormones contribute to the microenvironment that regulates the cytokine profile induced in response to antigenic stimulation.

Transplantation

There has been interest within the field of transplantation in the possible role for manipulation of Type 1 vs Type 2 cytokine production as a means to regulate graft rejection (Chapter 17). There seems to be a consensus that T cells isolated

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