PARASITOLOGY

PARASITOLOGY

n The major requirement is that the operative cells of the innate immune system can dis-

tinguish between self and non-self.

n The most important aspects of the innate immune system are that it is the first line of

defence against any infectious agent and that it is non-specific.

n 5.2 ENTRY OF A PATHOGEN

Skin consists of two basic layers: the outer epidermis and the inner dermis. The dermis

is composed mainly of connective tissue — a reticulum of fibroblasts embedded in a semi-

fluid ground substance — with blood vessels, nerve endings and various cells including

mast cells. The composition of the dermis is normally stable. The equilibrium is chem-

ical as well as physical and any change is first detected locally. Damage to the skin such

as a cut or abrasion provides rapid access to the dermal layers for pathogens.

Alterations to the local skin environment can result in changes to the local temper-

ature, pH and oxygen concentration. All, or any of these changes can affect the stability

of the local cells, especially the mast cells.

The endothelial cells that line the walls of capillary blood vessels have membrane-bound

proteins which allow one cell to react with another and these are known as intercellular

adhesion molecules (IAM). These molecules bind to a specific group of molecules — the

ligand located on a cell membrane such as a neutrophil. Each adhesion molecule is cap-

able of binding to more than one ligand using different binding sites.

In general the binding affinity to individual adhesion molecules is low but due to the

abundance of these molecules and ligands there is a high interaction. The interaction

between the endothelium and circulating leukocytes involves a number of different pairs

of these molecules. The function of the adhesion molecules is to control the aggregation

and migration of leukocytes into sites of infection.

Most of the leukocytes (neutrophils, monocytes, eosinophils, lymphocytes etc,)

express ligands on their membranes and these then bind to matching adhesion molecules.

Soon after any skin or tissue damage, the adhesion molecules and their ligands are

activated. This leads to the binding of circulating leukocytes to the endothelium.

Destabilisation of the local equilibrium can lead to mast cell degranulation. Mast

cells are granular cells which contain the precursors to numerous pharmacological

n BOX 5.1

The different types of adhesion molecules are:

nSelectins— transmembrane molecules such as endothelial adhesion molecules (ELAM-1)

which have extracellular domains that bind to the carbohydrate residues present on the

appropriate ligands.

nThe immunoglobulinsuper gene family is expressed on the vascular endothelium and

includes intercellular adhesion molecules (ICAM-1, ICAM-2) and vascular cellular adhe-

sion molecule (VCAM).

nIntegrins, involved in the interactions of platelets and neutrophils at inflammatory sites or

sites of vascular damage, leukocyte adhesion to immune cells and binding of cells to the

extracellular matrix.

nVascular addressinsexpressed on endothelial venules and on the endothelium at sites

of chronic inflammation. These molecules modulate lymphocyte traffic into secondary

lymphoid tissue and inflammatory sites.