Epithelia form a physical barrier that allows the body to main-tain internal homeostasis while protecting the  organism from harmful pathogenic agents from the external environment. The easiest way for many viruses, bacteria, and parasites to suc-cessfully compromise the protective functions of the epithelial layer is to destroy the junctional complexes between epithelial cells. Several proteins found in junctional specializations of the cell membrane are affected by molecules produced or ex-pressed by these pathogenic agents. Bacteria. A common bacterium that causes food poi-soning, Clostridium perfringens, attacks the zonula occlu-dens junction. This microorganism is widely distributed in the external environment and is found within the intestinal flora of humans and many domestic animals. Food poison-ing symptoms are characterized by intense abdominal pain and diarrhea that begins 8 to 22 hours after eating foods contaminated by these bacteria. Symptoms usually abate within 24 hours. The enterotoxin produced by C. perfrin-gens is a small 35-kilodalton protein whose carboxy termi-nus binds specifically to the claudin molecules of the zonula occludens. Its amino terminus forms pores within the apical domain of the plasma membrane. Binding to claudins prevents their incorporation into the zonula occlu-dens strands and leads to malfunction and breakdown of the junction. Dehydration that occurs with this type of food poisoning is a result of a massive movement of fluids via paracellular pathways into the lumen of the intestines. Helicobacter pylori, another bacterium, resides within the stomach and binds to the extracellular  domains of zonula occludens proteins. During this process, the CagA surface-exposed 128-kilodalton protein produced by the bacteria is translocated from the microorganism into the cy-toplasm, where it targets both ZO-1 and JAM proteins. As a result, the zonula occludens barrier becomes disrupted, and its capacity for tyrosine kinase signaling diminishes, causing cytoskeletal rearrangements. H. pylori cause injury to the protective barrier of the stomach that may lead to the development of gastric ulcers and gastric carcinomas. Viruses. The one specific group of RNA viruses responsible for infant enteritis (inflammation of the intestines) uses the intracellular JAM signaling pathway. The attachment and endocytosis of the reovirus is initiated by the interaction of its viral attachment protein with a JAM molecule. This interaction activates nuclear  factor-B pro-tein (NF B), which migrates into the nucleus and triggers a cascade of cellular events leading to apoptosis. This is ev-idence that JAMs are being used as signal transduction molecules to convey impulses from the external environ-ment to the cell nucleus. Zonula occludens–associated proteins that contain the PDZ-expressed sequence are targets of oncogenic aden-ovirus and papillomavirus. The viral oncoproteins produced by these viruses bind via their PDZ binding domains to ZO-2 and multi-PDZ–containing protein-1 (MUPP-1). The oncogenic effect of these interactions is attributed, in part, to the sequestration and degradation of the zonula occludens and the tumor-suppressor proteins associated with the viruses. Parasites. The common house dust mite, Der-matophagoides pteronyssinus, also destroys zonula occludens junctions. It belongs to the arachnid family, which includes spiders, scorpions, and ticks. When its fecal pellets are inhaled with dust particles, serine and cysteine peptidases present in the pellets cleave occluding and ZO-1 protein, resulting in the breakdown of zonula occludens junctions in the respiratory epithelium. The loss of the pro-tective epithelial barrier in the lung exposes the lung to in-haled allergens and initiates an immune response that can lead to severe asthma attacks.