Browsing by Author "Malago, J. J."

Now showing 1 - 11 of 11

Contribution of microbiota to innate and acquired gut immunity during health and disease
(Nova Science Publishers, Inc, 2014) Malago, J. J.
The contribution of intestinal epithelium to the innate immune system includes detecting luminal microbes, transducing signals, and activating inflammatory mediator release by epithelial and other cells of the immune system like the antigen presenting cells. Microbial antigens are detected by cells of the innate immune system through their pattern recognition receptors (PRRs). The PRRs recognize microbe-associated molecular patterns and generate signals that activate transcription pathways like nuclear factor kappa B and mitogen activated protein kinases. This activation leads to production of inflammatory and growth mediators that drive the immune system to elicit tolerance or immune response designated at maintaining immune homeostasis. Key to this signaling is the gut microbiota. Intestinal epithelial cell sensing of optimally balanced microbiota favors immune homeostasis whereas sensing under disrupted microbiota impairs immune function and predisposes to disease. Understanding the PRR-microbiota signaling would be useful in designing therapeutics for various immune-mediated disorders caused by imbalances of microbiota.
Contribution of microbiota to innate and acquired gut immunity during health and disease
(Nova Science Publishers, Inc, 2014) Malago, J. J.
The contribution of intestinal epithelium to the innate immune system includes detecting luminal microbes, transducing signals, and activating inflammatory mediator release by epithelial and other cells of the immune system like the antigen presenting cells. Microbial antigens are detected by cells of the innate immune system through their pattern recognition receptors (PRRs). The PRRs recognize microbe-associated molecular patterns and generate signals that activate transcription pathways like nuclear factor kappa B and mitogen activated protein kinases. This activation leads to production of inflammatory and growth mediators that drive the immune system to elicit tolerance or immune response designated at maintaining immune homeostasis. Key to this signaling is the gut microbiota. Intestinal epithelial cell sensing of optimally balanced microbiota favors immune homeostasis whereas sensing under disrupted microbiota impairs immune function and predisposes to disease. Understanding the PRR-microbiota signaling would be useful in designing therapeutics for various immune-mediated disorders caused by imbalances of microbiota.
Contribution of microbiota to the innate and acquired gut immunity during health and disease
(Nova Science Publishers, Inc., 2015) Malago, J. J.
The large number of microbials in the intestine that overrides the total human cells by ten folds alludes to significant contribution of the microbiota to human health. This is vivid in enteric and some systemic diseases emanating from disruption of the microbiota. The microbiota influences the development and functioning of both, innate and acquired immune systems for gut health. The effect of microbiota spills throughout the various components of the gut immune systems from “primitive” non specific pattern recognition receptors (PRR) to most specific adaptive T cell responses. To induce immune responses, commensal microbes are recognized by PRRs, which in turn regulate mucosal innate immunity and inflammatory responses. PRRs detect microbe-associated molecular patterns (MAMPs or "infectious non-self") or endogenous "danger signals" derived from stressed, damaged or infected tissue to stimulate the intestinal innate immunity that initiates adaptive immune responses. MAMPs include peptidoglycans, lipoproteins, lipopolysaccharides, teichoic acids, CpG DNA motif, double strand RNA and flagellin. In a balanced microbiota profile, PRR signaling ensures immune homeostasis and protects the host against enteral pathogens. Chapter one of this book will discuss the influence of the microbiota to PRR signaling during health and disease for intestinal immunity. Chapter two of the book focuses on a second level of innate immune system. This involves cells of the innate immune system that are responsible for driving non-specific innate immunity. They include natural killer cells, mast cells, eosinophils, basophils and the phagocytic cells including macrophages, neutrophils and dendritic cells. However, owing to the great commitment of macrophages and dendritic cells, a separate chapter for these two phagocytic cell types is allocated. Thus chapter two discusses the influence of microbiota on innate cells engendering intestinal immunity under health and disease. It concludes the innate immune system of the intestine. Macrophages and dendritic cells are professional antigen presenting cells. They sample antigens from the intestinal lumen, process, and present them to cells of the adaptive immune system. Despite of enormous types of enteral antigens ranging from harmful to beneficial, the antigen presenting cells are capable of efficiently discriminating them and driving respective responses to effector cells of the adaptive immune system. While dendritic cells are capable of priming T cell responses, macrophages do polarize the responses. As to how the microbiota influences the functioning of these cells, chapter three is devoted to discuss that phenomenon. The chapter links innate and adaptive intestinal immune systems since macrophages and dendritic cells lie in the interface between innate and adaptive immune systems. The acquired or adaptive immunity of the gut is split in humoral and cellular components. The humoral immune system is mainly geared by gut-associated lymphoid tissue (GALT) whose components include effector (i.e. epithelial lymphocytes and lamina propria) and inductive (i.e. mesenteric lymph nodes, Peyer’s patches, isolated lymphoid follicles, and cryptopatches) sites. It is interesting to note that microbiota influences GALT development and functioning during health and diseases. In germ free animals and those with disrupted microbita, GALT functioning is heavily compromised leading to diseases. Restoration of normal microbiotal profile to such individuals cures the disorders. Chapter four of this book will describe how the microbiota interacts with GALT and other components of the humoral immune system to maintain intestinal immunity under health and disease. The last chapter, chapter 5, focuses on the second part of the adaptive immune system which is cellular immune system. This system is dominated by several CD4 and CD8 lymphocytes that drive the cellular adaptive immune system. The main components are CD4+ cells which include T helper and regulatory T cells. Other T cells include cytotoxic T, memory, natural killer, and mucosa associated invariant T cells. While T helper cells drive most of the inflammatory responses, regulatory T cells downregulate these responses. As such, they are considered potential therapeutic agents of the future. Current knowledge indicates that the functioning of most, if not all, T cells is influenced by the microbiota. Chapter 5 is therefore devoted to discuss how the microbiota interacts with T cells during health and disease to foster intestinal immunity. In the past few years we have encountered mounting evidence showing that the microbiota plays essential role in regulating and maintaining host’s intestinal immunity. This is done through various ways including; regulation of mucin gene expression by goblet cells, modification of glycosylation of mucus to interfere with bacterial adhesion, colonization and invasion, induction of secretion of antimicrobial peptides by intestinal Paneth cells, regulation of alterations of intestinal permeability caused by infection, stress, and inflammation, and influences on development of mucosal and systemic immunity. It is becoming well comprehended that microbiota is pivotal to the intestinal immunity through crosstalk with the epithelium, immune cells and the immune system in general. Disruption of microbiota balance often leads to disease. This book explores recent findings on how microbiota influences the intestinal immune responses, both innate and adaptive, to foster the intestinal mucosal immunity. The insight gained could contribute to designing approaches suitable for treating gastrointestinal diseases caused by disruption of the microbiota.
Detection of Contagious bovine pleuropneumonia in condemned cattle lungs at Morogoro municipal abattoir in Tanzania
(Tanzania Veterinary Journal, 2013) Malago, J. J.; Mlay, J. D.
Control of re-emerged Contagious bovine pleuropneumonia (CBPP) in Tanzania in 1990s left spots of unvaccinated animals in various areas. Some of these animals were carriers of CBPP and have presumably continued to be sources of infection to other animals. We made an abattoir follow-up of slaughtered animals to understand whether the disease is still present in Tanzania. A total of 13 condemned lungs due to CBPP-like lesions at Morogoro municipal abattoir were collected from November 2011 to April 2012 and examined grossly, histologically and bacteriologically. Typical gross lesions of CBPP including expanded interlobular septa, sequestration, coalescing lungs, and fibrinonecrotic exudation were observed. Histologically, we observed fibrinonecrotic exudates filling and expanding the alveoli, desquamation of alveolar epithelial cells, lymphoplasmacytic infiltration in the interalveolar septa and around bronchi, bronchioles, and blood vessels, and vasculitis with subsequent vascular rupture and hemorrhage. Mycoplama cultures in two samples isolated Mycoplasma organisms with “fried egg appearance”, typical of Mycoplasma mycoides mycoides small colony type, the causative agent of CBPP. We conclude that CBPP is still prevalent in Tanzania and continues to pose a potential impending epidemic in the future.
Detection of Contagious bovine pleuropneumonia in condemned cattle lungs at Morogoro municipal abattoir in Tanzania
(Tanzania Veterinary Journal, 2013) Malago, J. J.; Mlay, J. D.
Control of re-emerged Contagious bovine pleuropneumonia (CBPP) in Tanzania in 1990s left spots of unvaccinated animals in various areas. Some of these animals were carriers of CBPP and have presumably continued to be sources of infection to other animals. We made an abattoir follow-up of slaughtered animals to understand whether the disease is still present in Tanzania. A total of 13 condemned lungs due to CBPP-like lesions at Morogoro municipal abattoir were collected from November 2011 to April 2012 and examined grossly, histologically and bacteriologically. Typical gross lesions of CBPP including expanded interlobular septa, sequestration, coalescing lungs, and fibrinonecrotic exudation were observed. Histologically, we observed fibrinonecrotic exudates filling and expanding the alveoli, desquamation of alveolar epithelial cells, lymphoplasmacytic infiltration in the interalveolar septa and around bronchi, bronchioles, and blood vessels, and vasculitis with subsequent vascular rupture and hemorrhage. Mycoplama cultures in two samples isolated Mycoplasma organisms with “fried egg appearance”, typical of Mycoplasma mycoides mycoides small colony type, the causative agent of CBPP. We conclude that CBPP is still prevalent in Tanzania and continues to pose a potential impending epidemic in the future.
Gastrointestinal disorders: symptoms, treatment and prevention
(Nova Science Publishers, Inc, 2012) Malago, J. J.
The digestive system, which extends from the mouth to the anus, is responsible for receiving food, breaking it down into nutrients (digestion), absorbing the nutrients into the bloodstream, and eliminating the undigestible parts of food from the body. It consists of the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and the anus. In addition, the digestive system consists of accessory digestive glands namely the liver, exocrine pancreas, and the biliary system consisting of the gallbladder and the bile duct. Disorders of the gastrointestinal system can be divided into: 1. Upper gastrointestinal disorders which involve diseases of the oral cavity, esophagus, and the stomach. Disorders of the oral cavity include those in the mouth, parotid and other salivary glands, and the pharynx. 2. Intestinal disorders which include disorders of the small intestine, large intestine, those involving both small and large intestine, rectum, and the anus. Conditions affecting the small intestine include conditions like enteritis (duodenitis, jejunitis, ileitis), duodenal (peptic) ulcer, and malabsorption. Those affecting the large intestine include appendicitis, colitis, functional colonic disease (e.g. irritable bowel syndrome, intestinal pseudoobstruction), megacolon, and diverticular disease. Examples of conditions occurring in both large and small intestines are enterocolitis and Crohn’s disease. Conditions affecting the rectum and the anus include proctitis, rectal prolapsed, anorectal fistula/fissure, and hemorrhoids. 3. Accessory digestive gland disorders are disorders of the liver, exocrine pancreas, gallbladder and bile duct. Examples of conditions affecting the liver include disorders of the liver parenchyma such as acute viral hepatitis (hepatitis A,B,C,D,E), yellow fever, cirrhosis, haemochromatosis and tumors like hepatocellular carcinoma. The biliary system could suffer from cholecystitis, gallstones, and cholesterolosis whereas the exocrine pancreas may have developmental abnormalities, pancreatitis, and pancreatic insufficiency. Owing to the nature and location of the condition, symptoms and subsequent treatment and prevention vary significantly. In general terms, congenital disorders may need surgical correction while infectious cases need antimicrobial therapy following identification of specific causative agents. Most of the gastrointestinal disorders are treated symptomatically. In this case, therapy is instituted to correct effects of symptoms such as vomiting and diarrhea (antiemetics, oral rehydration salts, intravenous fluid infusion) or muscular disorders like esophageal spasms where long acting anticholinergics or calcium blockers such as nifedipine relief the symptoms. Thus use of antimicrobials, surgery, and symptomatic therapy are major approaches to treatment of gastrointestinal disorders. Apart from congenital and inherited disorders, many gastrointestinal conditions can be prevented by proper and safe nutrition as well as drinking of safe water. Some specific conditions, such as gastritis, gastric and duodenal ulcers, inflammatory bowel diseases, cirrhosis, liver failure, and pancreatitis may need very special attention for treatment. In this book chapter, current findings on research and medical practice on symptoms, treatment and prevention of specific gastrointestinal disorders will be described in detail.
Immunohistochemical detection of Mycoplasma mucoid mucoid small colony type in lungs of slaughtered cattle at Morogoro slaughterhouse, Tanzania
(Tanzania Veterinary Journal, 2015) Malago, J. J.; Mlay, J. D.
Diagnosis of contagious bovine pleuropneumonia (CBPP) in carrier animals remains to be a challenge in developing countries partly because of lack of diagnostic tools that can detect asymptomatic animals. As a result many apparently healthy animals pose a potential impending epidemic in periods of stress. We examined condemned lungs with CBPP-like lesions from apparently healthy slaughtered animals to confirm presence of the disease in these animals. A total of 13 lungs collected at abattoir were examined immunohistochemically using 3H12 and 6E3 monoclonal antibodies against Mycoplasma mycoides mycoides (MmmSC), the causative agent of CBPP. Both 3H12 and 6E3 antibodies detected the MmmSC antigens in all the 13 lungs in bronchial, bronchiolar and alveolar epithelia, bronchial glands, bronchial cartilage, and in alveoli. We conclude that CBPP is still present in various places of Tanzania, posing a threat to livestock production and that immunohistochemistry can be an efficient diagnostic method to confirm presence of the disease in asymptomatic healthy animals passed for slaughter.
Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats
(Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2015) Malago, J. J.; Sangu, C. L.
Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate.
Lymphoid leukosis in commercial layers in Morogoro
(Tanzania Veterinary Association, 2010) Mathew, C.; Matondo, R. B.; Malago, J. J.; Maselle, R. M.; Mwamengele, G. L.
A total of 25 commercial layer carcases from seven poultry farms in Morogoro municipality were examined for gross and histopathological changes. Grossly, splenomegally, renomegally and hepatomegally were striking features. Both the liver and spleen were almost twice the size of normal organs. The surfaces of the liver, spleen, kidneys, lungs and the heart had yellowish white to grey multifocal and focally extensive patches of variable sizes. The lungs were consolidated. Histologically, the liver, spleen, kidneys, lungs, and the heart had heavy infiltration of large lymphocytes with abundant cytoplasm and poorly stained eosinophilic cytoplasm. There were also small lymphocytes with scant cytoplasm and deeply stained eccentrically placed nuclei and numerous mitotic figures. The history, clinical signs, and pathologic features were suggestive of avian lymphoid leukosis
Over-expression of heat shock protein 90 reduces the severity of carbon tetrachloride hepatotoxicity in rats
(International Journal of Sciences: Basic and Applied Research, 2018) Malago, J. J.
Cellular response to stress leads to production of heat shock proteins (Hsps) that are protective against various perturbations including stress, infection and inflammation. The liver is a victim to many body disturbances including intoxications and systemic diseases. Stemming on the ability of Hsps to protect an array of perturbations in various body systems, it is justifiable to explore their protective potency to the rat model of carbon tetrachloride (CTC)-induced hepatic toxicity. The current study therefore aimed at testing whether prior induction of Hsp90 could protect the liver against CTC. Rats were exposed to zinc sulphate (ZS) to induce Hsp90 then CTC for 8, 24, 48 or 72 hr. At the end of treatment, rats were sacrificed, autopsied, liver samples taken and fixed in formalin and routinely processed. Sectioned tissues were stained with hematoxylin and eosin or anti-Hsp90 monoclonal antibodies to assess morphological changes and Hsp90 expression respectively. CTC induced damage to the liver that was reduced by ZS. The ZS-mediated reduction of CTC-induced hepatic damage matched with ZS-induced over-expression of Hsp90. It is concluded that over-expression of Hsp90 is beneficial against CTC-induced hepatotoxicity.
The role of probiotics on immune mediated disorders
(Nova Science Publishers, Inc, 2014) Malago, J. J.
According to hygiene hypothesis, diseases of the immune system are increasing with socio-economic and sanitary conditions. This is evidenced by high incidences of allergic and autoimmune diseases in Western countries than in developing countries. The underlying factor is disruption of normal microbiota and their associated beneficial effects on intestinal mucosal immunity. Thus the pathogeneses of these disorders appear to revolve around impaired ability of the intestinal microbiota to effectively modulate and thus balance the body immune responses. As a result the immune system reacts excessively to antigens that would otherwise be tolerated and thus results in allergic reactions. Alternatively, the immune system reacts to self-antigens to cause autoimmune diseases. Some of these disorders are characterized by persistent production of inflammatory mediators leading to chronic inflammation and tissue damage. Several reports have indicated that oral administration of excessive numbers of selected members of microbiota, so called probiotic bacteria, prevents, treats, and improves the conditions of patients with immune-mediated disorders like allergy, inflammatory bowel diseases, and type 1 diabetes mellitus. Current knowledge suggests that probiotic bacteria mediate their beneficial effects via modulation of the immune system to balance its responses and institute protection. Herein the knowledge of new research on the role of probiotic bacteria on the development of some of the immune mediated diseases is reviewed in order to provide an insight in the role of probiotics in health and disease.