What are granulomas?
Based upon our work we have come to
define granulomas as innate sequestration responses of mononuclear leukocytes
i.e. macrophages that can be amplified and or modified in cellular composition
by superimposed signals arising from innate and adaptive immune recognition
mechanisms.
This response is phyllogenetically
ancient since it occurs among invertebrates and Ilya Metchnikov's observation of
this response in starfish larva in the late 19th century launched the field of
cellular immunology. Click
here to see his Nobel prize winning experiment and diary notes
Granulomas are likely defensive reactions
as they develop in response to many infectious agents (Table 1). However,
they likely represent a suboptimal response since sometimes the sequestered
agent is not incompletely destroyed and there is often collateral damage to the
normal tissues with associated fibrotic reactions. Tuberculosis
is the classic granulomatous disease
(click
here for image of M. tuberculosis
granuloma) which is sometimes associated with incomplete destruction of the
causative bacteria.
Immunologic investigation has revealed
that granulomas are in two major classes. 1) Foreign-body or innate type i.e.
those that form in an antigen independent manner and 2) Hypersensitivity-type
which are T cell-mediated responses to specific antigens associated with
granulomagenic agents. Work by our laboratory and others has shown that
the latter can be further subdivided into type-1 (amplified by interferon-g
and tumor necrosis factor) and type-2 (associated with interleukins 4, 5 and
13). The former are generally observed with intracellular infections whereas the
latter are seen in helminthic diseases such as schistosomiasis (click here for
image of S. mansoni egg granuloma)
and usually contain a significant
component of eosinophils.
Our laboratory has developed and
characterized experimental models of innate, as well as hypersensitivity-type
granulomas in order to study the molecular mechanisms which govern the
development and function of these lesions.