SNAREing immunity: the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.

The role of the innate immune system in the clearance of apoptotic cells

Rapid clearance of dying cells is a vital feature of apoptosis throughout development, tissue homeostasis and resolution of inflammation. The phagocytic removal of apoptotic cells is mediated by both professional and amateur phagocytes, armed with a series of pattern recognition receptors that participate in host defence and apoptotic cell clearance. CD14 is one such molecule. It is involved in apoptotic cell clearance (known to be immunosuppressive and anti-inflammatory) and binding of the pathogen-associated molecular pattern, lipopolysaccharides (a pro-inflammatory event). Thus CD14 is involved in the assembly of two distinct ligand-dependent macrophage responses. This project sought to characterise the involvement of the innate immune system, particularly CD14, in the removal of apoptotic cells. The role of non-myeloid CD14 was also considered and the data suggests that the expression of CD14 by phagocytes may define their professional status as phagocytes. To assess if differential CD14 ligation causes the ligand-dependent divergence in macrophage responses, a series of CD14 point mutants were used to map the binding of apoptotic cells and lipopolysaccharides. Monoclonal antibodies, 61D3 and MEM18, known to interfere with ligand-binding and responses, were also mapped. Data suggests that residue 11 of CD14, is key for the binding of 61D3 (but not MEM18), LPS and apoptotic cells, indicating lipopolysaccharides and apoptotic cells bind to similar residues. Furthermore using an NF-kB reporter, results show lipopolysaccharides but not apoptotic cells stimulate NF-kB. Taken together these data suggests ligand-dependent CD14 responses occur via a mechanism that occurs downstream of CD14 ligation but upstream of NF-?B activation. Alternatively apoptotic cell ligation of CD14 may not result in any signalling event, possibly by exclusion of TLR-4, suggesting that engulfment receptors, (e.g. TIM-4, BAI1 and Stablin-2) are required to mediate the uptake of apoptotic cells and the associated anti-inflammatory response.

The human immune system: Part 1

The immune system protects the human body against infectious and maligant disease. The concept of an immune system arose because of the observation that an attack of measles or mumps, two common childhood diseases, conferred an immunity on the individual, the immunity being specific to the disease. It was only much later that it was discovered that a system in the body conferred this immunity.

The human immune system Part 2: auto-immune disorders

For the immune system to function effectively, the body must be able to distinguish foreign antigens from self-antigens. However, the mechanisms which maintain this distinction may break down and result in auto-immune disease in which self-reacting antibodies and T-cells are produced. This article discusses first, the evidence for the existence of human auto-immune disease and second, the auto-immune diseases which have characteristic ocular symptoms.

The human immune system: Part 1

The immune system protects the human body against infectious and malignant disease. The concept of an immune system arose because of the observation that an attack of measles or mumps, two common childhood disease, conferred an immunity on the individual, the immunity being specific to the disease. It was only much later that it was discovered that a system in the body conferred this immunity. This article discusses the various components of the immune system, how they develop and their action in conferring immunity.

The human immune system: Part 2

For the immune system to function effectively, the body must be able to distinguish foreign antigens from self antigens. However, the mechanisms which maintain this distinction may break down and result in an auto-immune disease in which self-reacting antibodies and T-cells are produced. This article discusses first, the evidence for the existence of human auto-immune disease and second, the auto-immune diseases which have characteristic ocular symptoms.

'An Artificial Immune System as a Recommender System for Web Sites'

Artificial Immune Systems have been used successfully to build recommender systems for film databases. In this research, an attempt is made to extend this idea to web site recommendation. A collection of more than 1000 individuals' web profiles (alternatively called preferences / favourites / bookmarks file) will be used. URLs will be classified using the DMOZ (Directory Mozilla) database of the Open Directory Project as our ontology. This will then be used as the data for the Artificial Immune Systems rather than the actual addresses. The first attempt will involve using a simple classification code number coupled with the number of pages within that classification code. However, this implementation does not make use of the hierarchical tree-like structure of DMOZ. Consideration will then be given to the construction of a similarity measure for web profiles that makes use of this hierarchical information to build a better-informed Artificial Immune System.

'Immune System Approaches to Intrusion Detection - A Review'

Abstract. The use of artificial immune systems in intrusion detection is an appealing concept for two reasons. Firstly, the human immune system provides the human body with a high level of protection from invading pathogens, in a robust, self-organised and distributed manner. Secondly, current techniques used in computer security are not able to cope with the dynamic and increasingly complex nature of computer systems and their security. It is hoped that biologically inspired approaches in this area, including the use of immune-based systems will be able to meet this challenge. Here we collate the algorithms used, the development of the systems and the outcome of their implementation. It provides an introduction and review of the key developments within this field, in addition to making suggestions for future research.

'Movie Recommendation Systems Using An Artificial Immune System'

We apply the Artificial Immune System (AIS)technology to the collaborative Filtering (CF)technology when we build the movie recommendation system. Two different affinity measure algorithms of AIS, Kendall tau and Weighted Kappa, are used to calculate the correlation coefficients for this movie recommendation system. From the testing we think that Weighted Kappa is more suitable than Kendall tau for movie problems.

'On Affinity Measures for Artificial Immune System Movie Recommenders'

Abstract. We combine Artificial Immune Systems (AIS) technology with Collaborative Filtering (CF) and use it to build a movie recommendation system. We already know that Artificial Immune Systems work well as movie recommenders from previous work by Cayzer and Aickelin ([3], [4], [5]). Here our aim is to investigate the effect of different affinity measure algorithms for the AIS. Two different affinity measures, Kendall's Tau and Weighted Kappa, are used to calculate the correlation coefficients for the movie recommender. We compare the results with those published previously and show that that Weighted Kappa is more suitable than others for movie problems. We also show that AIS are generally robust movie recommenders and that, as long as a suitable affinity measure is chosen, results are good.

Immune System Approaches to Intrusion Detection - A Review

The use of artificial immune systems in intrusion detection is an appealing concept for two reasons. Firstly, the human immune system provides the human body with a high level of protection from invading pathogens, in a robust, self-organised and distributed manner. Secondly, current techniques used in computer security are not able to cope with the dynamic and increasingly complex nature of computer systems and their security. It is hoped that biologically inspired approaches in this area, including the use of immune-based systems will be able to meet this challenge. Here we review the algorithms used, the development of the systems and the outcome of their implementation. We provide an introduction and analysis of the key developments within this field, in addition to making suggestions for future research.

'Immune System Approaches to Intrusion Detection - A Review'

Abstract. The use of artificial immune systems in intrusion detection is an appealing concept for two reasons. Firstly, the human immune system provides the human body with a high level of protection from invading pathogens, in a robust, self-organised and distributed manner. Secondly, current techniques used in computer security are not able to cope with the dynamic and increasingly complex nature of computer systems and their security. It is hoped that biologically inspired approaches in this area, including the use of immune-based systems will be able to meet this challenge. Here we collate the algorithms used, the development of the systems and the outcome of their implementation. It provides an introduction and review of the key developments within this field, in addition to making suggestions for future research.

'On Affinity Measures for Artificial Immune System Movie Recommenders'

Abstract. We combine Artificial Immune Systems (AIS) technology with Collaborative Filtering (CF) and use it to build a movie recommendation system. We already know that Artificial Immune Systems work well as movie recommenders from previous work by Cayzer and Aickelin ([3], [4], [5]). Here our aim is to investigate the effect of different affinity measure algorithms for the AIS. Two different affinity measures, Kendall's Tau and Weighted Kappa, are used to calculate the correlation coefficients for the movie recommender. We compare the results with those published previously and show that that Weighted Kappa is more suitable than others for movie problems. We also show that AIS are generally robust movie recommenders and that, as long as a suitable affinity measure is chosen, results are good.