INTRODUCTION TO HOST RESPONSEcompounds, most notably histamine. The products of the degranulated mast cells,
mainly histamine, heparin, bradykinin, 5-HT (5-hydroxytryptamine) etc, affect the per-
meability of cell membranes particularly the endothelial cells and also ‘loosen’ the bind-
ing of these cells to one another. This enables the leukocytes that have congregated
at the site where the adhesion molecules have been activated to migrate into the tissues
where the tissue damage or pathogen invasion has occurred. Once the cells have passed
out of the lumen of the blood vessel, they interact with collagen, laminin, fibronectin,
the extracellular matrix and tissue cells.
This has two effects, firstly fluid leaks out from the capillary lumen through the
endothelial cells into the damaged tissues and secondly the end-on walls between the
endothelial cells loosen, which permits leukocytes to migrate into the tissues. The local
infected tissue becomes swollen with the increase in fluid.
n Neutrophils — granulocyte leukocytes — are the first cells to migrate from the cap-
illary lumen to the damaged tissues and will attempt to phagocytose any invading
pathogens, assisting the local resident phagocytic cells. The neutrophils release neuro-
toxins into the infected area which cause the sensation of local pain.
n The mast cells also release serotonin and bradykinin and slow release substances
which add to general swelling and pain.
n The local area becomes swollen and red with the increase of fluid, in particular blood,
and there is also pain all of which are symptoms of inflammation (see section 7.2).n 5. 3THE HOST’S RESPONSE TO THE PATHOGEN
The majority of helminth and protozoan parasites are able to resist being phagocytosed
by neutrophils. However neutrophils are relatively short-lived and are replaced by
eosinophils and blood monocytes. If the parasite is first damaged and then destroyed, fibrob-
lasts invade the damaged area and the deposited fibrocytes bind together and secrete col-
lagen and fibrinogen to form scar tissue. During the healing process dead cells and
cellular debris are discarded in the form of a cellular exudate (pus).
If the parasite is not destroyed and does not develop into a life-threatening disease,
the infection then changes from the acute to the chronic phase during which the para-
site can either migrate and/or multiply or remain. If the parasite migrates it could
move to a preferred site or become systemic. The parasites migrate by moving through
the ground substance matrix in the connective tissues or via the body fluids, mainly the
bloodstream.
Once the resident phagocytic cells (the surveillance cells) have identified an invad-
ing pathogen by the methods just described, their function is to destroy it. Once the
pathogen associated molecular patterns (PAMPs) on the surface membrane of the para-
site are recognised by the pathogen receptors regions (PRRs) on the surveillance cells,
this induces the secretion of cytokines (inflammatory cytokines) by the surveillance
cells.
Cytokines are proteins secreted by cells prominent in the immune response eg T cells
and macrophages that act like hormones affecting the behaviour of similar or different
cell phenotypes. If the cytokine stimulates self cells it is referred to as being autocrine
but if the cytokine stimulates different cells it is known as paracrine. The cytokines act
on specific cell receptors.
On a cell surface membrane there are cell surface molecules which are identified
by specific monoclonal antibodies and referred to as CD (Cluster of Differentiation)
molecules or markers.