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Oleh : syukria 100101053
dosen : ns. Nurleny, s. kep
prodi s1 keperawatan stikes piala sakti pariaman 2013
because every society or nation has . because it involves the engineering of in-utero. because once IgE response has been initiated. S-IgA. sinusitis and otitis media. Ariyanto Harsono Division of Allergy Immunology Part / SMF Pediatrics FK-Unair/RSU Dr.Soetomo Surabaya Abstract Allergy prevention in the first trimester of infant age is very important especially to cow’s milk. and down-regulate the over activity of Th1.Prospects of Probiotics in allergy prevention through active induction of immunological tolerance Anang Endaryanto. Key words: Probiotic. For effective prevention it is necessary. not easily applied in the wider community. IgE. the cost of treatment and the occurrence of co-morbidities such as asthma. such as elimination diets. prevention of allergy. In the systemic immune response. Probiotic has a unique role in the prevention of allergic disease. Th1 Preliminary Adverse effects allergy is decreased quality of life. While secondary prevention. instead of inhibitory to other patogen growth. it progresses throughout the infant life. Primary prevention is very effective but it is still difficult to implement. probiotic also enhances the development of mucosal S-IgA response. and sensitization to other food allergen and aero-allergen may develop. Th2. its influence even to the disruption of the learning ability and decreased quality of life of their parents. T-regulatory. probiotic enhances the development of regulatory T-cell which in turn will down-regulate the over-activity of Th2. In children.
and GM-CSF. Control specialized pattern recognition receptors (PRRS) is a Toll-like receptors (TLRs) on dendritic cells (DCs) of the innate immune response determines Th1 adaptive immune response. IL-10. norepinephrine. Interaction between allergens. Lymphocytes generated when TH2 cytokines interact with B lymphocytes. IL-5. Allergen peptides presented by APC induces the activation of T lymphocytes APC activation of T lymphocytes by allergen processing activates lymphocytes to produce Th2 cytokines-sitokinnya. activation of structural cells. basophils and eosinophils. eosinophils and basophils. activation and recruitment of mast cells. especially TNF- will suppress TH2 development. Imunopatologi Allergies Allergic reactions occur through activation stages of immunocompetent cells. Allergens that made it into the body will be processed by the APC. such whereas as H3-histamine receptors increases the release and of 5- neurotransmitters hydroxytryptamine. TH2 cytokine production.had strong beliefs about what is fair about the type of food. IL-9. Degranulation of mast cell mediators histamine release. acetylcholine. IFN- and TNF-. B lymphocytes will then differentiate into plasma cells that produce IgE. whereas Th2 lymphocytes produce IL-4. The new TH lymphocytes activated TH2 allergen will berfenotip. especially IL-4 suppresses Th1 development and production of TH1 cytokines. IL-6. mediator reaction with the target organ and stage of onset of symptoms. the allergic reaction will occur. Th1 lymphocytes produce IL2. mast cells and mast cell degranulation IgE produced. Treg or Th2. H2-histamine receptors have a role in the occurrence of itching and pain on the skin as well as peripheral vasodilation and increased permeability. H1-histamine receptors have a wider role in the inflammatory process rather than mediators that cause allergies. Mast cell histamine release histamine receptor arrested in a target organ. The resulting TH2 cytokines stimulate the production of mast cells. When the interaction of histamine with its receptors on the target organ. histamine. IL-13. peptide . Development of science and technology enables a paradigm shift from the paradigm of prevention of allergy avoidance of risk factors become active induction paradigm immunologic tolerance.
Mediators include histamine. and they are a source of interleukin-3 (IL-3). IgE sensitized mast cells undergo degranulation. smooth muscle contraction and mucus production. mediator release pre-formed and newly synthesized mediators in sensitive individuals. 2005. 5 Nature Reviews Immunology. In individuals who have a predisposition to allergies. The release of eosinophils cause the release of pro-inflammatory mediators. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. which is known as allergic sensitization. Neuropeptides also contribute to the pathophysiology of allergic symptoms. eosinophil peroxidase. within a few minutes contact with an allergen. major basic protein and eosinophil-derived neurotoxin). 271-83) . Allergic mechanism.Figure 1. leukotrienes and cytokines that increase vascular permeability. including leukotrienes and leukotriene-basic proteins (cationic proteins. which can cause early (acute) allergic responses (EARS) and late allergic responses (Lars). At EAR. IL -5. which is characterized by the influx of eosinophils and TH2 cells. IL-13 and granulocyte / macrophage colony-stimulating factor. Chemokines released mast cells and other cells recruit inflammatory cells that cause the LAR. Subsequent allergen exposure will lead to the withdrawal of inflammatory cells and activation and release of mediators. (Quoted from Hawrylowicz CM and O'Garra A. the first exposure to allergens cause activation of the cells of allergen-specific T helper 2 (TH2) and IgE synthesis.
Allergens are affecting the immune system since the time of the fetus. In addition to the pregnancy itself is "allergic phenomenon" (with the domination of Th2 immune system) in order to avoid rejection of the fetus by the maternal immune system. Some approach it as a precautionary measure that is currently being evaluated is the provision of microbial products through oral or intranasal administration of allergens via the mucosal (eg. Hypoallergenic elimination diet regimen effective for the benefit of avoidance of risk factors vary depending on the racial. Development of science and technology enables a paradigm shift of allergy prevention in the form of avoidance of risk factors to the active induction of immunologic tolerance.Development of allergy prevention and the problem in the present. the development of therapies aimed at improving current homoestasis biological systems aimed at allergy sufferers immunomodulating the immune response by balancing Th1 and Th2 immune response. provision of allergen with microbial products and the provision of anti-IgE allergen together. having to undergo allergen avoidance is quite difficult. Prevention of problem solving. Elimination of allergens in pregnant women who do not have a consistent effect on the manifestation of allergic children in the future. sublingual immunotherapy). so that allergic reactions can be repaired. Children who suffer from allergies are not severe enough to live safely and comfortably. 2. 4. To cope with various problems on allergy prevention. Primary prevention in this period is still difficult to implement and controversial because it involves the engineering of in-utero. Cause of this discomfort is due to allergy management is still focused on the concept of risk aversion factor. Prevention programs in the form of immunotherapy that is known to improve the natural course of allergic disease as a whole still faces constraints on the "acceptability" of patients and only effective on aeroallergens. Prevention program still faces many obstacles of various factors. . 3. geographic. such as : 1. eating habits and so on.
PAMPs existing one on probiotics is lipoteichoic acid (LTA). What is the role of probiotics in the prevention of problem solving? Giving probiotics in allergy prevention is also an improvement efforts homoestasis patient biological systems aimed at balancing the immunomodulating an immune response with Th1 and Th2 immune responses. specifically the molecules are known as pathogen-associated molecular patterns (PAMPs). Allergy is a form of "Th2-disease" that requires improvement efforts host returns to a state of "Th1-Th2" are balanced. Immunotherapy has been used in allergic diseases over a century. currently being developed allergen extracts that are more directed immune modulator with a more general purpose approach for patients who are sensitive to multiple allergens. Better future immunotherapy with standardized extracts development and use of recombinant extracts. Immunotherapy is an effort to seek redress homoestasis that biological systems are aimed at allergy sufferers immunomodulating the immune response by balancing Th1 and Th2 immune responses. food allergens and for allergy sufferers still have to undergo an elimination diet to avoid recurrence. In asthma and allergic rhinitis whose symptoms were clearly triggered by exposure to aeroallergens showed good results. Specific molecules (PAMPs) recognized by specific receptors (specific pattern recognition receptors. PRRS). early treatment with a dust allergy immunotherapy program is known to improve the natural course of allergic disease as a whole. Capture mechanism dotted immunotherapy on T cells by lowering the formation of IgE response to allergen stimulation. Along with it. immunotherapy is very effective and safe. Why is the concept of active induction of immunological tolerance that we lead to probiotics? Because probiotics are the normal flora of the gastrointestinal tract that can control the balance of intestinal microflora and the physiological effects that benefit the health of the host. .The role of allergen vaccination (immunotherapy) in the prevention of problem solving. Both will provide a more complete security patterns. but must consider the side effects. In microbiology. In the secondary prevention programs. Probiotics also have the ability as a strong activator of the innate immune system because it has a specific molecule on the cell wall. If used in the right patients. However. the clinical effectiveness of immunotherapy is still limited to the symptoms caused by inhaled allergens.
storage. focusing on the innate immune system activation of NFhas the ability to induce the transcription of several proinflammatory cytokines in response to stimulation by microbes. IRAQ-related adapter molecule TNF receptor-associated factor (TRAF6). Degradation of NF-kB inhibitor I-kB releasing NF-kB is translocated to the nucleus immediately to induce the expression of the corresponding genes. and MAP kinases. TRAF6 subsequently activate MAP3K family member NIK (NF-kB-inducing kinase). TLRs was PRRS (pattern recognition receptors) of mammals that functions as a signal transducer associated with the CD-14 to help the host cells to recognize pathogens and initiate a signaling cascade. In its role to help bridge the innate immune system to TLR adaptive system. Probiotics are microbes useful (useful) Lactic Acid Bacteria from a class that has a long history in biotech. MyD88 is an adapter protein that interacts with the receptor transmembrane domain through the C-terminal TIR. All TLRs have the same structure and have the character to channel the signal through the NF-1. a merger in . especially in the production. MyD88 recruits Ser / Thr kinase IRAQ (IL1R associated kinase) to form receptor complexes. Downstream effector of several TLRs. is a characteristic of gram-positive bacteria and has a biological impact (eg in the induction of cytokine production) similar to LPS.LTA is a biologically active molecule. Is it safe to use probiotics in humans? Probiotics are microbes of Lactic Acid Bacteria group that works to maintain health of the host. At the molecular level. There are more than 100 species and more than 10 billion bacteria in the human gut. Bacteria in the human gastrointestinal tract can be divided into 2 groups: the good bacteria (useful) and dangerous (Harmful). such as TLR2 and TLR4. So the concept of probiotics on allergy prevention based on the active induction of immunologic response that starts from the innate immune system and lead to a host of return on the condition of "Th1-Th2" are balanced. TLRs also help bridge the innate immune system to the adaptive system by inducing a variety of effector molecules and kostimulator. which activates NF-kB inhibitors of kinases (IKKS). TLR-2 and TLR-4 are known to have an important role in the polarization of the immune response to microbial exposure. able to induce a good immune response towards Th1 or Treg.
which helps cells to recognize pathogens and initiate a signaling cascade. Some effects are often reported to increase in human health. TLRs was PRRS (pattern recognition receptors) mammals that serves as the cluster of differentiation (CD) -14 associated signal transducers. IRAQ-related adapter molecule TNF receptor-associated factor (TRAF6). Figure 2: Signal TLR 2 and TLR 4.the food and fermentation processes. further activating the . bacteria that work to maintain the health of the host. TRAF6. more broadly defines probiotics. MyD88 recruits Ser / Thr kinase IRAQ (IL-1R associated kinase) to form receptor complexes. Expanded the definition of probiotics in its development into live bacteria or bacteria mixture has beneficial effects on the gastrointestinal tract and respiratory tract host through its ability to improve the balance of intestinal microflora. TLRs also help bridge the innate immune system to the adaptive system by inducing a variety of effector molecules and kostimulator. Toll-like receptors (TLRs) to help bridge the innate immune system to the adaptive system. and Salminen et al. Downstream effectors of TLR2 and TLR4 is an adapter protein MyD88 transmembrane receptors that interact with the C-terminal domain through TIR. Lee et al.
which activates NF-kB inhibitors of kinases (IKKS). survive able to tolerate acid and bile. (Quoted from: Takeda and Akira. hydrogen peroxide. and bacteriocins antagonistic to pathogen growth. eliminating pathogens. was not carcinogenic. Degradation of NF-kB inhibitor I-kB releasing NF-kB is translocated to the nucleus immediately to induce the expression of the corresponding genes. produce: acid. as well as improve the intestinal microflora. reduce pathogen adhesion. safe. there are pathogenic. Seminars in Immunology 16: 3-9) Microbes can be regarded as a probiotic if you have: the ability attached to the host epithelial tissues. . 2004.MAP3K family member NIK (NF-kB-inducing kinase).
Biologically active molecules probiotics peptidoglycan and teichoic acid in the form of a pathogen-associated molecular patterns (PAMPs) are recognized PRRS (pattern recognition receptors) in the case of TLR2 and TLR4. 75: 1-13) Mechanisms of competition and antagonism between gut bacteria are also able to maintain ecological balance by preventing excessive growth of each species occupants. are: organic fatty acids. antibiotics. Competition of adhesion receptors. hydrogen peroxide.Figure 3. lactic acid. and bacteriocins. food competition. (Quoted from: Saito T 2004 Selection of useful probiotic lactic acid bacteria from theLactobacillus acidophilus group and their applications to functional foods Animal Sci J. among others. Relationship between probiotics and stimulation with TLR immune response. . TLR2 and TLR4 to induce transcription of several proinflammatory cytokines in response to stimulation by probiotics. which help bridge the innate immune system to the adaptive system by inducing a variety of effector molecules and costimulators. Lactic acid production by Lactobacillus produces low pH and inhibit the growth of pathogenic bacteria. enzymes. Inhibitor compound (antagonist). and the production of inhibitor compound (antagonist) is also a mechanism that prevents excessive bacterial colonization and growth.
Recent studies in humans on the effects of probiotics on allergic reactions decrease. .Table 1.
IL-10. universal. IL-6. but there is no denying that there is still a lot of credibility alarming epistemology. Gold standard of Evidence-Based Medicine is a randomized controlled clinical trial (RCT) are considered to be correct. including against allergic diseases. modify intestinal mikrobiata atopic children so as to prevent allergic reactions in patients with atopic dermatitis reduce clinical symptoms. In the clinical trials on probiotics (newest shown in Table 1) have been demonstrated that probiotics can reduce allergy symptoms associated with atopic dermatitis and food allergies. satisfactory with adequate blinding. preventing atopic dermatitis in the first 2 years of a child's life. obtained through standard methods of scientific research. reduce symptoms clinic. the therapy is a failure by systematically evaluated using evaluation methods are unbiased. lower levels of IL-12 and IFN- Is the mechanism of probiotics in reducing allergic reactions are clearly known? Approach to allergy therapy benefits through Evidence-Based Medicine has been recognized. in patients with Allergic Rhinitis. and in patients with atopic able to increase the levels of IL-10. and Eselectine fecal IgA levels. It is used for therapeutic approaches through Evidence-Based Medicine (Evidence Based Medicine) in the form of clinical trials.What are the benefits of probiotics in reducing allergic reactions have been supported by the Evidence Base Medicine (Evidence Based Medicine) adequate? Terms of medical treatment. is not contrary to the views of the scientific community and is always open to verifiable. . Cow's Milk Allergy in children increased levels of IFN-. preventing early atopic disease in children with high risk of allergy.
.Table 2. Recent studies in experimental animals about the mechanisms of probiotics in reducing allergic reactions.
much of the research can only be carried out in experimental animals (Table 2).However. reliable and widely used in research klinik. Generally recognized that the RCT has provided correct. the role of RCTs in Evidence-Based Medicine caused controversy in some ways such as RCT (almost everything) is a solution of the methodology to clinical epistemology that does not generate explanatory information and a causal relationship. . So far several biomolecular research on probiotics that seeks to know the mechanism of action of probiotics showed that the ability of probiotics are quite diverse in modulating the immune response. but many clinicians are still not well with its mechanism of action.29 use of probiotics in the treatment of allergies is always accompanied by the question of how it works and where the target organ? Although some clinical trials showed a significant effect on the reduction of allergic reactions. but unfortunately due to problems of ethics.
.Table 3. Relation theory and empirical facts about the immunological mechanisms of probiotics in reducing allergic reactions.
and the adaptive immune response is activated TLR2 autonomous from regulation Treg. Therefore primary prevention strongly associated with the development of the immune system in-utero. whereas TLR4 is not enabled. suggesting that administration of probiotics can reduce allergic reactions through activation of TLR2 and TLR4 (Figure 4). but it will help in overcoming problems associated with therapeutic effects. The consequences of this protective activity is fetal immune system becomes more dominant to Th2. It should be understood that a pregnancy can take place when the fetus and the placenta is able to overcome the rejection of Th1 activity of the maternal immune system to produce Th2 cytokines. Extrapolation and synthesis of the scientific facts that have been produced by previous studies. in both humans and animals.Questions regarding the mechanisms and causal relationships in terms of allergy therapy with probiotics can partially be answered through extrapolation and synthesis of scientific facts that have been generated by previous research. . and there was priming the immune system that produces fetal gastrointestinal allergic sensitization for the first time. As a consequence swallowed amniotic containing the allergen by the fetus (fetal swallowing). Whether probiotics can play a role in the early prevention? Development of the fetal immune system. Th2 cytokines are in the placenta with the maternal IgE and allergens that have reached amnio fluid through the maternal circulation. Primary prevention is prevention which started since the fetus. This move will certainly not totally satisfying.
This study and previous studies showed that women who received probiotics. 2004. Regarding IgE.Figure 5. As PAMPs molecules. but both groups did not show differences in allergic sensitization as reflected by levels of total IgE and skin test results. (Quoted from Warner JO. A focus on the way the disease evolves in early life. IgE is known that the synthesis can be induced in the fetus through the mother consumed allergens. While the APC. and the ability of the fetus produce IFNresponse from Th2 to Th1-dominated Th2 balance. early primary effect is not the suppression of Th1 but rather leads to the activation of Treg with effects not only as a regulator of Th1 but also Th2 regulator. IgD. Arch Dis Child. and IgE. sCD14 is recognized by TLR4 in DC cells which subsequently activates Th1 lymphocytes and Treg. infants of mothers who received probiotics had fewer allergic dermatitis compared with those receiving placebo. sCD14 (soluble CD14). (A). The early life origins of asthma and related allergic disorders. Early research on probiotics for the prevention of allergies The results showed that the factors that in-utero where maternal IgG. 89:97-102) At the fetal age of 12 weeks. the original antibody product is only a small amount of fetal IgM (10% of adults) as well as a bit of IgA. T cells. (B). The results showed that at the age of 2 and 4 years. . Development of the fetal immune system. As a consequence of fetal swallowing allergens from amniotic fluid. and B cells undergo gastrointestinal maturity at 16 weeks fetal age. and there was priming the immune system that produces fetal gastrointestinal allergic sensitization for the first time. with the results achieved Th1-Th2 homeostasis. Clinical trial of probiotics (Lactobacillus GG versus placebo) was performed on pregnant and lactating mothers. Consequences of fetal face protective activity of immune system rejection mom is fetal immune system becomes dominant Th2 (IL-4 production dominance and 13) and Treg (IL-10 and TGF-?).
. Penelitian probiotik pada ibu hamil menunjukkan bahwa efek dini probiotik pada sistem imun ibu bukanlah pada supresi Th1 tetapi pada aktivasi Tregulator yang berfungsi menjaga homeostasis Th1-Th2. sehingga kelangsungan kehamilan tidak terganggu. Perkembangan ilmu dan teknologi memungkinkan perubahan paradigma pencegahan alergi dari paradigma penghindaran factor resiko menjadi paradigma induksi aktif toleransi imunologik. Konsep probiotik pada pencegahan alergi didasari pada induksi aktif respon imunologik menuju keseimbangan “Th1Th2”. Ekstrapolasi dan sintesis atas fakta-fakta ilmiah yang telah dihasilkan oleh uji klinik dan penelitian mekanisme probiotik pada hewan cobaa menunjukkan bahwa probiotik dapat menurunkan reaksi alergi melalui aktivasi TLR2 dan TLR4. Pada uji klinik.Kesimpulan Alergi merupakan bentuk “Th2-disease” yang upaya perbaikannya memerlukan pengembalian penderita pada kondisi “Th1-Th2” yang seimbang. probiotik dibuktikan dapat menurunkan gejala alergi yang berhubungan dengan dermatitis atopik dan alergi makanan. Kelemahan uji klinik adalah ketidakmampuannya dalam menghasilkan informasi mengenai mekanisme dan hubungan sebab akibat.
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