n The inflammatory cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha
(TNF-α), IL-6 and interferon-gamma (IFN-γ) mediate an inflammatory response.
n Chemical signals derived from PAMPs (pathogen associated molecular patterns) initi-
ate the activation of a series of membrane-bound molecules known as costimulators.
These molecules assist in the activation of T lymphocyte cells (see section 5.6.2). The
costimulators on the T cells are CD28 and on the antigen-presenting cells they are B7
molecules.
n The effector functions of specified cytokines (eg IL-4, IL-5, IL-10, IL-12, IFN-γ) and
transitional growth factor beta (TGF-β) are controlled by signals derived from the
PAMPs.
n Parasites can induce the secretion of inflammatory cytokines that lead to the stimula-
tion of the cytotoxic cells of the innate immune system.
n IL-1 and TNF-α(inflammatory cytokines) activate adhesion molecules on endothelial
cells and/or stimulate chemotaxis and hence induce the migration of antigen-
stimulated lymphocytes to the site of infection.
n IL-6 (an inflammatory cytokine) acts on activated B cells, converting them into
immunoglobulin secreting plasma cells (this becomes a part of the adaptive immune
response).If the parasite is destroyed by a combination of inflammatory products such as react-
ive nitrogen or oxygen (radicals) and a cellular attack, the innate immune system has
completed its function. However, if the parasite survives or is only partially destroyed,
the process of the innate immune system continues.n 5.4 THE ONSET OF THE SPECIFIC IMMUNE RESPONSE
If the neutrophils are not effective at killing the pathogen they are replaced by
eosinophils, monocytes, lymphocytes, fibroblasts and variety of other phagocytic cells and
generally have no role in the specific immune response.
The monocytes that migrate from the blood into the tissues are now known as tissue
histiocytes. These cells, together with resident macrophages and phagocytic cells, ini-
tiate the specific immune response. The phagocytic macrophages that can identify the
infectious agent, such as a parasite, then attempt to engulf it in an ‘amoeboid’ manner.
Many parasites have the ability to resist phagocytosis. There are protozoans such as
Leishmaniathat actually invade macrophages and survive within them.
However, phagocytes appear to ingest secretions or fragments of most parasites, par-
ticularly helminths. Once the parasitic material is absorbed into the cytoplasm of the
macrophage, it is digested by lysosomes into peptide fragments (see Fig. 5.3). These pep-
tide fragments (antigen peptides) are ‘moved’ through the cell cytoplasm to the surface
membrane where they become associated with the major histocompatibility complex
(MHC) molecules attached to the surface membrane. There are three classes of MHC
molecules, the most important of which are the class I and class II protein molecules.
The macrophages that express the antigen peptides associated with the MHC
molecules are referred to as antigen-presenting cells (APCs). These antigen primed cells
migrate to the nearest lymph node or the spleen (see Fig. 5.4).
The APCs end up in the cortex and paracortex regions of the lymph nodes or spleen.
The role of the APC is now to present the antigen peptide fragment to the lymphocytes,
in particular the T lymphocytes (T cells).
After the first contact with a pathogen the now stimulated macrophages secrete a
range of cytokines and likewise the T cells release cytokines when in contact with thePARASITOLOGY