Essay: Giardia lamblia

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The pathogen of interest is giardia lamblia, which is ingested as a cyst. In this paper we will consider it to be ingested through contaminated water, as G. lamblia thrives in cold mountain streams and is resilient to chlorine found in tap water (Kucik, et al., 2004).
 
Upon entrance into the oral cavity, G. lamblia encounters the first defense mechanism provided by the human body: saliva. This fluid contains molecules, including lysozyme, lactoferrin, histatins, and salivary IgA, that serve to prevent bacterial growth (Taylor). Lysozyme’s main function is to cleave bacterial cell walls, lactoferrin serves to complex iron ions, and histatins prevent the growth of candida albicans and streptococcus mutans. Salivary IgA is also present in order to prevent the buildup of plaque, a term used to describe the accumulation of oral pathogens (Taylor). Considering G. lamblia is a protozoan, a type of parasite, saliva will not prevent it from moving on through the human body. However, G. lamblia is prevented from establishing residence in the gingiva or gingival sulcus thanks to the gingival epithelium. This tissue comprises the external gums and exhibits constant shedding of its keratinocytes. Due to this high rate of cell turnover, it is difficult for pathogens such as G. lamblia to attach to it (Taylor). In the event that the high rate of cell turnover is not enough to keep away pathogens, there is a secondary defense provided by the streptococcal anaerobes, which reside in the gingival crevice. The presence of this natural flora takes up space so that other pathogens don’t have room to make a home in the gingival sulcus (Davis, 1996).

And thus, G. lamblia must make its way to the back of the oral cavity, where it encounters the natural flora of the pharynx. A variety of anaerobic organisms colonize here, such as C. diphtheria and Bordetella pertussis (Davis, 1996). Similar to the streptococcal anaerobes of the gingival crevice, these anaerobic organisms occupy this space to prevent other foreign microorganisms from attaching. So, G. lamblia must continue its journey down the esophagus to the stomach. Upon reaching the stomach the process of excystation occurs, resulting in two trophozoites produced from the cyst (Kucik et. al, 2004). The trophozoites encounter dendritic cells in the stomach, which are phagocytic cells that connect antigens to T cells, a main component of the adaptive immune system. Another defense the stomach has against pathogens is its low pH, due to a high concentration of gastric acid. This characteristic benefits G. lamblia as the introduction of the cyst to the gastric acid induces the process of excystation (Kucik et. al, 2004). However, the stomach also contains proteases, enzymes that serve to destroy proteins in foreign microorganisms as well as the food we ingest (Wikipedia, Immune system). Fortunately for G. lamblia, if it is strong enough to endure the attack from the dendritic cells and proteases, then it can continue on through the digestive tract.

Next up is the small intestine, specifically the duodenum. G. lamblia prefers to attach to the mucosal wall of the duodenum or jejunum. After it attaches, it can grow though binary fission upon introduction to bile, carbohydrates, and low oxygen tension (Kucik et. al, 2004). However, specialized immunoglobins, termed IgM, present in the small intestine sense the presence of antigens. If found, G. lamblia will be tagged by IgA and IgM to make it more favorable for phagocytosis (Marsh, 1981). A bit farther along in the small intestine, in the ileum, is a population of moderately mixed flora, yet another defense system against the invasion of a foreign microorganism (Davis).

If G. lamblia is unsuccessful in its goal to make a home in the small intestine, it will be brushed along into the large intestine. Here, there is a region of high epithelial cell turnover. Combine this characteristic with the peristaltic activity of the large intestine, and it’s nearly impossible for pathogens to survive. The large intestine is home to a dense population of obligate anaerobes, which provide a variety of functions including the fermentation process of unused energy substrates, prevention of growth of harmful microorganisms, regulation of the development of the gut, production of biotin and vitamin K, and production of hormones that influence the storage of fats (Wikipedia, Gut flora). Additionally, mucus provides a physical barrier to prevent pathogens such as G. lambia from feeding on enterocytes, and IgA again makes an appearance to trap these undesired microorganisms (deSchoolmeester). G. lamblia will also come into contact with innate effector molecules, whose purpose is to produce macrophages, neutrophils, epithelial cells, and goblet cells: a small army poised to attack pathogens through the release of nitrogen radicals and histamines. Defensins are proteins that are also part of the fight against pathogens. Cathelicidin are polypeptides that bind and neutralize lipopolysaccharides (deSchoolmeester). One actor G. lamblia does not have to worry about, however, is RELM-Beta, a goblet cell that is present to kill the parasite Trichuris muris. After traveling through the large intestine, G. lambia may trigger an inflammatory response, brought on by pathogen recognition receptors, which reside in the epithelium and signal for activation of the immune system upon detection of pathogens (deSchoolmeester). If G. lambia successfully passed under the radar of the pathogen recognition receptors in the large intestine it will finish out its journey in the human body by exiting through the anus, usually in fecal matter (Kucik et. al, 2004).

Throughout G. lamblia’s journey through the human body it will encounter two branches of the immune system: the innate and adaptive immune systems. The innate immune system is the general, non-specific response given by the immune system when it is confronted with a foreign organism, or antigen. The innate immune system includes physical barriers such as the skin, gastrointestinal tract, respiratory tract, cilia, and eyelashes, among others. Furthermore, the innate immune system presents a variety of defense mechanisms including secretions, bile, gastric acid, saliva, and tears (Khan Academy, Innate immunity). There are several leukocytes, white blood cells, which are active in the innate immunes system, such as phagocytes, macrophages, mast cells, neutrophils, eosinophils, basophils, natural killer cells, and dendritic cells. The innate immune system attacks through a complement cascade. During this process foreign particles get tagged for phagocytosis (Opsonization), which causes macrophages and neutrophils to move towards the chemical signal, a process referred to as chemotaxis, with the assistance of cytokines and chemokines. The cell membrane is then broken down through lysis, which prevents the infection from spreading. Then, the pathogens are brought together and attacked through agglutination (Khan Academy, Innate immunity).

The adaptive immune system is quite different. The adaptive immune system is more specific than the innate immune system in that it uses certain antibodies, which are specific for presented antigens. Furthermore, the adaptive immune system relies only upon B cells and T cells. B cells have antigen-specific receptors, and will eventually mature into a memory B cell or a plasma cell. Memory B cells express the same antibody as the parent cell, whereas plasma B cells secrete antibodies, which find pathogens circulating throughout the body. B cell receptors bind to antigens in order to initiate a signaling pathway. T cells, on the other hand, express T cell receptors in addition to CD4 or CD8 receptors. These receptors only recognize antigens bound to MHCI and MHCII (Major Histocompatibility Complexes), which are present on the antigen (Khan Academy, Adaptive Immunity). T cell receptors undergo the process of rearrangement, which allows for greater diversity of binding. There is a selection process that T cells must go through in order to take part in the adaptive immune system. The first step is positive selection, eliminating any MHC’s that bind to self-MHC molecules. Negative selection follows with the goal of eliminating any self tolerance. There are three main types of T cells: helper T cells
active cytotoxic T cells and B cells, cytotoxic T cells remove pathogens and infected host cells, and T regulatory cells distinguish between self and nonself molecules (Khan Academy, Adaptive Immunity).

The adaptive immune system can be divided into two different branches: humoral and cell-mediated. Humoral immunity is the immunity provided by serum antibodies, which are derived from plasma cells. Cell-mediated immunity is the immunity provided by acquiring T cells that are capable of fighting the specified disease/infection. Cell-mediated immunity is carried out by cytotoxic cells (Khan Academy, Adaptive Immunity).

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