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Immunology

The Moredun Immunology Theme, led by Professor Gary Entrican, encompasses researchers from across the Institute that are interested in identifying immunological relationships that lead to the development of new vaccines, diagnostic tests and management systems for controlling disease in farmed ruminants.     

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Function of the Immune System

The immune system has evolved to protect the host against disease. Infectious disease can be caused by many different types of pathogens. These include viruses, bacteria, protozoa and parasitic worms. Some of these pathogens live and grow inside cells within the body (e.g. viruses, bacteria, protozoa) while others live and grow outside cells but within body fluids and tissues (e.g. bacteria, protozoa, parasitic worms). Many pathogens infect their hosts through mucosal surfaces such as the lung, gut and reproductive tract. They may cause disease at these initial sites of infection or they may spread and cause disease in other tissues and organs. The immune system therefore needs to be both flexible and highly specific if it is to combat different infections, while at the same time avoiding collateral damage to host tissues (immunopathology). It does this through a combination of sensory mechanisms that detect invading pathogens and effector mechanisms that combat the pathogens. 

Components of the Immune System

Detection of infection is mediated by the innate immune system, triggering a series of events designed to limit the spread of infection while at the same time activating the adaptive immune system. The innate immune system can discriminate different types of infection, but does not provide immunological memory, namely prior exposure to an infection will not alter future innate immune responses to the same infection. In contrast, activation of the adaptive immune system does generate immunological memory. The effector arms of the adaptive immune system are humoral immunity (namely antibody, produced by B cells) and cell mediated immunity (production of cytokines and cell killing by T cells). Both of humoral and cell mediated immunity are highly specific and tightly regulated by cytokines. Immunological memory is a result of selective expansion of subpopulations of B cells and T cells, providing rapid protection against future infection. It is this process that can be exploited by vaccination to generate protection without disease.   

Immunological Reagents

Moredun Research Institute has a long history of producing immunological reagents that underpin research into prevention and control of infectious diseases of livestock. Gary Entrican, Colin McInnes and Sean Wattegedera (in collaboration with others at Moredun and elsewhere) have developed a panel of Chinese Hamster Ovary (CHO) cells transfected with genes or cDNAs encoding ovine and bovine cytokines and other immunomodulatory molecules. These CHO transfectants have been used to develop monoclonal antibodies (Mabs), to evaluate Mabs for intracellular staining (see below) and to definitively assess Mabs for species-cross reactivity.

A list of ELISAs currently available for detecting ovine cytokines.

Further information on these and other veterinary immunological reagents can be found at The Immunological Toolbox  and the USDA Veterinary Immune Reagent Network. Further links to other reagent and technology resources can be found within those websites.

Mucosal Immunology

The mucosal immune system is the part of the immune system which provides protection to an animal’s various mucosal surfaces (e.g. respiratory tract mucosa, gastro-intestinal tract mucosa) from invasion or colonisation by pathogens. It provides three main functions (i) to protect the mucosa from infection; (ii) to prevent the uptake of pathogens which may subsequently infect other parts of the body; (iii) to regulate the immune response to non-harmful micro-organisms or innocuous foreign material present at the mucosal surface.  

As the majority of infectious agents affect or initiate the infectious process at mucosal surfaces, mucosal immune responses play a crucial role in determining the outcome of infection.  This is particularly true of pathogens such as gastro-intestinal nematodes or bacteria such as Escherichia coli O157:H7 which reside at the mucosal surfaces.  

Due to the recognised importance of mucosal immunity, there is increasing interest in the development of vaccines which generate robust mucosal immunity. A major hurdle in developing such vaccines is that conventionally injected vaccines are generally poor inducers of mucosal immunity. Hence there is a pressing need for the development of novel vaccines which are capable of inducing strong mucosal immune responses.

Mucosal immunology research at Moredun is focused on two main areas: firstly, to study host-pathogen interactions at the mucosal surface in order to identify the mechanism(s) by which the host is able to combat pathogens; secondly, to develop vaccines which are capable of generating robust mucosal immune responses. This will hopefully lead to the development of improved methods of control for a number of important diseases of livestock.

MHC defined flock

The major histocompatibility complex (MHC) is the most gene dense region of the mammalian genome and plays an important role in the immune system and autoimmunity. 

The diversity of MHC is important in understanding the immunology diveristy within a population.  With this in mind, Moredun developed, and now maintains, a major histocompatibility complex (MHC) defined sheep flock.  This resource allows for significant advantages in the areas of T cell immunology, analysis of cellular immune mechanisms and vaccine development research in sheep.

The strategy is to utilise this resource and associated cellular and molecular tools to unravel the natural mechanisms of protective immunity to parasitic, bacterial and viral pathogens of sheep.  Such information will allow more informed decisions to be made regarding the approach to vaccine development as well as providing the tools to identify the protective antigens involved in stimulating protective immunity.

 

Immunopolymorphism Database

Moredun's MHC defined flock comprises animals homozygous for one of four common MHC haplotypes along with a large number of matched MHC heterozygous animals.  Each of the MHC haplotypes has been extensively characterised at the genetic level with the important MHC class I and class II genes cloned, sequenced and expressed. 

These sequences have provided the reference sequences for populating the sheep section of the immunopolymorphism database.  This public database provides a source of information on MHC genetic diversity in domestic sheep. Its purpose is to collate data on allelic diversity and provide a forum for the analysis, verification and nomenclature of diversity in the genes and proteins of the ovine MHC.