mechanisms of pathogenesis in E. histolytica

By: Akram A. Ismael yüzüncü yıl üniversitesi

Introduction

E. histolytica is a protozoan parasite that infects humans and causes the disease amebiasis. The spectrum of intestinal amebiasis varies from colonization without symptoms to fulminating diarrhea and intestinal hemorrhage. The dissemination of the parasite via invasion of the intestinal epithelium allows the trophozoites to invade extra-intestinal sites, most usually the liver.If no treated cause death

Introduction

The host-parasite interaction in human amebiasis is very complicated,Different aspects of innate immunity of the human host against the parasite still are unknown. new molecular and genetic approaches,that both innate and acquired immunity response to  E. histolytica pathogenesis,

Innate immune system of the host

Intestinal mucins act as (FLDM) are highly glycosylated molecules and consist of a core protein joined to oligosaccharides.Mucin glycoproteins line the surface epithelium of respiratory, urogenital, and digestive tracts from the nasal cavity/oropharynx to rectum. Mucin may differ in size Some are small, whereas others are among the largest known.Mucins consist of a peptide backbone containing glycosylated and nonglycosylated domains, with O-linked glycosylated regions comprising 70–80% of the polymer.

Mucin oligosaccharides consist of 4 primares:1-N-Acetylglucosamine,2-Nacetylgalactosamine, 3-fucose, and 4-galactose.

Gastrointestinal mucins are the first line of host defense against enteric pathogens, including E. histolytica. Binding sites of mucins compete with those of underlying epithelium, preventing attachment of pathogens to the intestinal wall.

Mechanisms of pathogenesis

Once the Trophozoites colonise the large bowel and feed on bacteria and food particles.

Trophozoites move through the mucus layer where they come in contact with the epithelial cell layer and start the pathological process.

E. histolytica has a lectin that binds to galactose and N-acetylgalactosamine sugars on the surface of the epithelial cells.The lectin normally is used to bind bacteria for ingestion.

Several factors contribute to the pathogenicity of E. histolytica, at molecular levels three pathogenic factors of the parasite have been investigated extensively and characterized. These three virulence factors are:1. Gal/GalNAc2. amoebapores3. cysteine proteinases.

1- Gal/GalNAc ( adherence phase)

The Gal/GalNAc lectin is multifunctional virulence factor of E. histolytica.participating in adherence, cytolysis, invasion, resistance to human complement and also perhaps encystation.  Adhesion occurs mainly through the Gal/GalNAc lectin, which binds to exposed terminal Gal/GalNAc residues of target cell glycoproteins

This image showGal/GalNAc

Along with Gal/GalNAc lectin, Other molecules thought to be involved in part in adhesion of the parasite are:1- 220-kDa lectin,2- 112-kDa adhesin,3-surface lipophosphoglycan.

The Gal/GalNAc adhesin is composed of :a. heavy (170-kDa)b. light (35/31 kDa)c. a non-covalently-linked intermediate (150-kDa)

subunit

 The 170-kDa heavy subunit is a type I transmembrane protein with a small intracellular domain and a carbohydrate recognition domain (CRD) contained in its extracellular domain.The 30-kDa light subunit (lgl) is covalently attached to the heavy subunit through disulfide linkages and have several isoforms, the significance of the different isoforms is not clear yet. The intermediate subunit of the Gal/GalNAc has been cloned and characterized recently, and it has been shown that it lacks a carbohydrate recognition domain (CRD).

To establish colonization, E. histolytica needs to bind to colonic mucin oligosaccharides via the 170kDa heavy subunit of the parasite’s Gal/GalNAc lectin.

The Gal/GalNAc lectin mediates adherence of trophozoites to human colonic glycoproteins, colonic epithelium, neutrophils, and erythrocytes, and to certain bacteria

2-Amoebapores and cysteine proteinases.Amoeba histolytica secretes a strong proteolytic

enzyme, an enzyme that breaks down the tissue in our intestinal wall, and causes formation of amoebapore in between epithelial cell in the intestine.

Enzymes such as pore forming proteins, lipases, and cysteine proteases, are used to digest bacteria and cause lysis of the epithelial cells by inducing cellular necrosis and apoptosis.

Amoebapore Damage the epithelial cells attracts immune cells which are then also lysed by the trophozoite.

This releases the hydrolytic enzymes which then cause damage to the tissue.

This destruction manifests itself in the form of an 'ulcer' in the tissue.

THE BODY’S SECOND LINE OF DEFENCE:

IF THE PATHOGENS ARE ABLE TO GET PAST THE FIRST LINE

OF DEFENCE, THE SECOND LINE OF DEFENCE BECOMES ACTIVE.

The second line of defence is a group of cells (leukocytes), tissues and organs that work together to protect the body. This is the immune system.The cells involved are:1. Neutrophils2. T helper cells3. Cytotoxic (killer) T cells4. Macrophages 5. Dendritic cells6. B cells7. Suppressor T cells8. The tissues and organs

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