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Autoimmune Dis. This is a factor that we as species are not so well adapted for. For example, studying the intestines of wild mice reveals that they are typically full of intestinal parasites, yet interestingly they are otherwise in reasonable health.
Similarly, they are usually also infested with ecto-parasites including lice, fleas, and ticks factors that may markedly affect the immune system by triggering inflammatory cells, thereby affecting the cytokine environment. Although these factors may be of importance for the development of our immune system we do not perceive that anyone of us would like to return to such conditions.
However, the lesson here is that factors such as parasite loads and complexity of the intestinal flora may be of importance for many diseases including allergy, autoimmunity, diabetes, and possibly even certain cancers , , Here studies of wild animals can shed light upon how the immune system reacts to, and handles, all of these parasites and also how a diverse intestinal flora may affect these processes. Respiratory virus infections are most likely also an important factor where respiratory syncytial virus and rhino virus are of prime interest for asthma development There are other, more discrete factors, for example, there is an ever increasing amount of hormone-like substances in our environment, such as estrogens from contraceptives that enter the sewage system.
These may also be other factors to take into account, as it is well known that such substances can markedly affect reproduction of local fish and amphibian species. Wild animals are often more exposed to such pollutants than us, for example, fish and amphibians can live directly within the polluted water and thereby take up the substances more effectively.
Studies of such animals in the wild can provide information on how such pollutants affect their immune functions and thereby give us clues to as to how these substances will also affect us. Such substances may affect us more subtly by shifting the balance of the immune system. The question is very complex, and here by looking at wild populations may present us with a more multifaceted view of the factors involved in shaping immunity and where these factors can go wrong.
Our life style has changed dramatically, and the strong genetic selection acting upon us during early evolution is presently most likely not as efficient, which may be contributing factors to the increase in allergies. However, what factors that dominate this increase are still not known, which may also vary from person to person as both genetic and environmental factors seem to be of importance , In addition to giving us a more detailed view of the regulation and the evolution of our immune system, wild animals may also be a rich source of therapeutic proteins and other potential therapeutic molecules.
As a separate line of research we have also been trying to develop new treatment strategies against atopic allergies. Induction of an immune response against self-molecules, as is the case for all of these targets, is considerably more difficult than inducing an immune response against a foreign molecule. We are generally tolerant to self-molecules, and therefore, we need to use a number of tricks to overcome these tolerance mechanisms in order to induce an immune response strong enough to give a therapeutic effect.
Here, adjuvants are very important and in order to obtain a strong anti-self-immune response potent adjuvants are a necessity , On top of this issue are other factors including having to modify the self-protein by coupling it to a non-self carrier 6 , , This results in the recruitment of non-tolerized T cells to provide help to self-reactive B cells to expand and differentiate The rat variant of this vaccine antigen induced a strong anti-rat IgE response in sensitized rats and resulted in a marked reduction in circulating IgE titers in these animals 7.
Another important factor is the form the self-antigen is being presented Multimeric antigens such as a virus particle or a bacterial surface are very potent antigens, probably due to their potent B cell-activating properties , During the process of optimizing parameters to obtain potent therapeutic vaccines against allergies and different solid cancers, we identified a region of a molecule coming from a wild animal a jawless fish.
The protein and region is the tail-piece of the variable leukocyte receptor B VLR-B that facilitates the pentamerization of the VLRB, which is the functional but not structural Ig equivalent in lamprey and hagfish, similar to pentameric human IgM.
Using the 30 amino acid C-terminal region of lamprey VLR-B, this resulted in very efficient multimerization of the target antigen and in a marked enhancement of the anti-target immune response Figure 10 B In this context, wild animals can not only give us a more detailed view of the function and evolution of our immune system but can also be a rich source of potential therapeutic proteins. Figure Therapeutic vaccine proteins where parts of the vaccine antigen originate from a wild animal.
Panel A shows a vaccine antigen consisting of a fusion protein between the CH2 and CH4 domains of opossum IgE together with the target region for the vaccine: the CH3 domain from the target animal, a human, dog, or rat.
The figure shows the human variant of the vaccine. The rat variant of the vaccine antigen has been shown to induce a strong anti-self-IgE response in rats of several strains and to reduce circulating IgE levels in these animals 7. Panel B shows a multimeric vaccine component generated by the use of the C terminal tail of the lamprey antigen-specific receptor variable leukocyte receptor B VLR-B. VLR-B is the functional but not the structural equivalent of human IgM, a pentameric antigen-binding molecule.
Using the C terminal 30—40 amino acids from VLR-B fused to the C terminal of any soluble vaccine antigen, it is possible to obtain a multimeric vaccine antigen that serves as a very potent antigen due to their similarity to virus particles or bacterial surfaces with multiple identical epitopes. Using three cancer vaccine antigens as test antigens, we have shown that they are soluble when produced in bacteria E.
Wild animals can teach us a lot about our own immune system, including how it is regulated, how it has evolved, and which functions are essential for a potent immune defense. These reasons are but a few to consider, where non-domestic animals may facilitate new solutions to difficult therapeutic challenges.
The patents for the VLR-B sequence used to enhance immunogenicity to therapeutic vaccines targeting self-molecules is owned by a company owned by LH. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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In skin reactions, the immediate phase consists of a pale central area surrounded by redness and swelling. This response reaches its peak at about 15 minutes and goes away after about 90 minutes. However, the immediate response can also merge with the late phase that can last up to 24 hours. In the nose, the immediate response consists of sneezing, itching, and the production of nasal secretions. The late phase response is associated with swelling, constant blockage of the nasal passages, and continuous mucus production.
In the lung, the immediate response begins within minutes or even seconds after exposure to an allergen. This includes shortness of breath, wheezing, and coughing. This disappears after an hour or so. Three to four hours later, the late phase reaction begins. It is also characterized by shortness of breath and coughing, and can last up to 24 hours.
That is why it is so difficult to treat allergies with a single medication.
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