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Apakah sistem kekebalan ditekan saat tidur?

Apakah sistem kekebalan ditekan saat tidur?


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Tentu kita pernah mendengar bahwa selama stres sistem kekebalan tubuh kita ditekan. Ini membuat saya bertanya-tanya, apakah sistem kekebalan tubuh ditekan saat kita tidur dan mengapa? Selama kedua kondisi ini, tubuh mungkin perlu menghemat energi untuk proses biokimia lainnya, jadi saya tidak akan terkejut bahwa sistem kekebalan ditekan saat seseorang tidur.


Selama stres, glukokortikoid, yang merupakan hormon steroid yang diproduksi oleh kelenjar adrenal (seperti kortisol dan kortikosteron), dilepaskan ke dalam aliran darah. Hormon-hormon ini memiliki efek anti-inflamasi. Anda mungkin mengatakan bahwa mereka menekan sistem kekebalan tubuh.

Ritme sirkadian, yang mengontrol siklus tidur-bangun, juga mengontrol sekresi glukokortikoid, sehingga memperkuat respons tidur-bangun. [1]. Kurang tidur adalah bentuk stres dan menyebabkan peningkatan kadar glukokortikoid. Efek kurang tidur dapat direplikasi dengan adrenektomi (operasi pengangkatan kelenjar adrenal); ada downregulation transkripsi dari beberapa gen neuroprotektif [2]. Melalui pensinyalan yang dimediasi glukokortikoid, kurang tidur juga menghasilkan penghambatan neurogenesis dewasa di hipokampus [3].

Studi lain mengatakan bahwa sekresi sitokin (TNFα dan IL6) oleh sel sistem kekebalan, secara inheren dipengaruhi oleh ritme sirkadian melalui mekanisme independen glukokortikoid. [4].

Secara keseluruhan, tidur berkorelasi terbalik dengan berkurangnya peradangan karena kedua proses tersebut berada di bawah kendali jam sirkadian. Kurang tidur, sebagai bentuk stres, juga berkorelasi dengan sekresi glukokortikoid. Harus dipahami bahwa tidur tidak serta merta menghambat sekresi glukokortikoid dan tidak benar jika dikatakan bahwa penurunan efek inflamasi disebabkan oleh tidur.


Studi menunjukkan kurang tidur menekan sistem kekebalan tubuh

27 Januari (UPI) -- Para peneliti dari University of Washington Medical School mempelajari 11 pasang kembar identik untuk mempelajari efek kurang tidur pada sistem kekebalan tubuh.

Sampel darah diambil dari pasangan kembar identik dengan pola tidur yang berbeda dan menunjukkan bahwa kembar yang kurang tidur memiliki sistem kekebalan yang tertekan dibandingkan dengan saudara mereka.

"Apa yang kami tunjukkan adalah bahwa sistem kekebalan berfungsi paling baik ketika cukup tidur," kata Dr. Nathaniel Watson, co-director UW Medicine Sleep Center di Harborview Medical Center dan penulis utama studi tersebut, dalam siaran pers. "Tujuh jam atau lebih tidur direkomendasikan untuk kesehatan yang optimal."

Para peneliti menggunakan anak kembar dalam penelitian ini karena genetika membentuk 31 hingga 55 persen dari durasi tidur, dengan perilaku dan lingkungan membentuk sisanya.

Studi tersebut meneliti efek dari durasi tidur pendek jangka panjang di bawah normal, kondisi "dunia nyata" yang bertentangan dengan laboratorium tidur, dan menemukan bahwa kurang tidur kronis mematikan respon imun dari sel darah putih yang bersirkulasi.

"Hasilnya konsisten dengan penelitian yang menunjukkan ketika orang yang kurang tidur diberi vaksin, ada respons antibodi yang lebih rendah dan jika Anda mengekspos orang yang kurang tidur ke rhinovirus, mereka lebih mungkin terkena virus," kata Watson. "Studi ini memberikan bukti lebih lanjut tentang tidur untuk kesehatan secara keseluruhan dan kesejahteraan terutama untuk kesehatan kekebalan tubuh."

Watson berkolaborasi dengan Dr. Sina Gharib, direktur Computational Medicine Core UW Medicine di Center for Lung Biology, dalam penelitian ini.


Tidur kurang dari enam jam semalam merusak aktivitas ratusan gen

Terlalu sedikit tidur selama beberapa malam berturut-turut mengganggu ratusan gen yang penting untuk kesehatan yang baik, termasuk yang terkait dengan stres dan melawan penyakit.

Tes pada orang yang tidur kurang dari enam jam semalam selama seminggu mengungkapkan perubahan substansial dalam aktivitas gen yang mengatur sistem kekebalan tubuh, metabolisme, siklus tidur dan bangun, dan respons tubuh terhadap stres. berdampak pada kesejahteraan jangka panjang.

Perubahan, yang mempengaruhi lebih dari 700 gen, dapat menjelaskan mekanisme biologis yang meningkatkan risiko sejumlah penyakit, termasuk penyakit jantung, diabetes, obesitas, stres dan depresi, pada orang yang kurang tidur.

"Kejutan bagi kami adalah perbedaan yang relatif sederhana dalam durasi tidur menyebabkan perubahan semacam ini," kata Profesor Derk-Jan Dijk, direktur Pusat Penelitian Tidur Surrey di Universitas Surrey, yang memimpin penelitian. "Ini merupakan indikasi bahwa gangguan tidur atau pembatasan tidur tidak hanya membuat Anda lelah."

Penelitian sebelumnya telah menunjukkan bahwa orang yang tidur kurang dari lima jam semalam memiliki risiko kematian 15% lebih besar dari semua penyebab dibandingkan orang pada usia yang sama yang mendapatkan tidur malam yang baik. Dalam satu survei terhadap pekerja di Inggris lebih dari 5% mengaku tidur tidak lebih dari lima jam semalam. Survei lain yang diterbitkan di AS pada 2010 menemukan bahwa hampir 30% orang mengaku tidur tidak lebih dari enam jam semalam.

Tim Profesor Dijk meminta 14 pria dan 12 wanita, semuanya sehat dan berusia antara 23 dan 31 tahun, untuk hidup dalam kondisi laboratorium di pusat tidur selama 12 hari. Setiap sukarelawan mengunjungi pusat tersebut pada dua kesempatan terpisah. Selama satu kunjungan, mereka menghabiskan 10 jam semalam di tempat tidur selama seminggu. Di sisi lain, mereka hanya diizinkan tidur enam jam setiap malam. Pada akhir setiap minggu, mereka tetap terjaga selama sehari semalam, atau sekitar 39 hingga 41 jam.

Menggunakan sensor EEG (electroencephalography), para ilmuwan menemukan bahwa mereka yang tidur 10 jam per malam dalam seminggu tidur sekitar 8,5 jam semalam, sedangkan mereka yang dibatasi enam jam di tempat tidur setiap malam rata-rata tidur 5 jam 42 menit.

Waktu yang dihabiskan untuk tidur memiliki efek besar pada aktivitas gen, diambil dari tes darah pada para sukarelawan, menurut sebuah laporan di jurnal AS Proceedings of the National Academy of Sciences. Di antara mereka yang kurang tidur, aktivitas 444 gen ditekan, sementara 267 gen lebih aktif daripada mereka yang tidur lebih lama.

Perubahan pada gen yang mengontrol metabolisme dapat memicu atau memperburuk kondisi seperti diabetes atau obesitas, sementara gangguan pada gen lain, seperti gen yang mengatur respons peradangan tubuh, mungkin berdampak pada penyakit jantung. Gen lebih lanjut yang terpengaruh telah dikaitkan dengan stres dan penuaan.

Kurang tidur juga memiliki efek dramatis pada gen yang mengatur jam biologis tubuh, menunjukkan bahwa kurang tidur dapat memicu lingkaran setan memburuknya gangguan tidur. Tes menunjukkan bahwa orang yang tidur selama 8,5 jam semalam memiliki sekitar 1.855 gen yang aktivitasnya naik dan turun selama siklus 24 jam. Namun dalam kondisi kurang tidur, hampir 400 di antaranya berhenti bersepeda sama sekali. Sisanya naik dan turun sesuai dengan jam biologis, tetapi dalam rentang yang jauh lebih kecil.

"Ada umpan balik antara apa yang Anda lakukan terhadap tidur Anda dan bagaimana hal itu memengaruhi jam sirkadian Anda, dan itu akan menjadi sangat penting dalam penyelidikan di masa depan," kata Dijk.

Para peneliti tidak memeriksa berapa lama waktu yang dibutuhkan gen untuk kembali ke tingkat aktivitas normal pada sukarelawan yang kurang tidur, tetapi mereka berharap dalam studi lebih lanjut. Meskipun sejumlah gen terganggu pada orang yang kurang tidur, para ilmuwan tidak dapat mengatakan apakah perubahan itu merupakan respons jangka pendek yang tidak berbahaya terhadap kurang tidur, tanda tubuh beradaptasi dengan kurang tidur, atau berpotensi berbahaya bagi kesehatan.

Jim Horne, profesor psikofisiologi di Pusat Penelitian Tidur Universitas Loughborough, mengatakan: "Potensi bahaya 'utang tidur' di masyarakat saat ini dan kebutuhan 'delapan jam tidur semalam' sering dilebih-lebihkan dan dapat menyebabkan kekhawatiran yang tidak semestinya. Meskipun ini studi penting tampaknya mendukung kekhawatiran ini, para peserta tiba-tiba tidur mereka terbatas pada tingkat yang sangat rendah, yang pasti agak membuat stres.

"Kita harus berhati-hati untuk tidak menggeneralisasi temuan tersebut, katakanlah, kebiasaan tidur enam jam yang senang dengan tidur mereka. Selain itu, tidur dapat beradaptasi dengan beberapa perubahan, dan juga harus dinilai berdasarkan kualitasnya, bukan hanya pada jumlah totalnya. ."


Tahap 3

Tidur malam yang paling dalam dan paling menyegarkan terjadi pada tahap ini. Selama siklus tidur pertama Anda di malam hari, Anda menghabiskan 20–40 menit di tahap 3. Ini menjadi lebih pendek atau menghilang dalam siklus setelah itu.

Detak jantung dan pernapasan turun ke level terendah.

Jaringan tumbuh dan memperbaiki diri. Sistem kekebalan Anda mendapat dorongan.

Gelombang otak menjadi lebih lambat daripada di tahap 1 dan 2. Itu sebabnya tahap ini juga disebut tidur gelombang lambat.

Dalam cerita rakyat Jerman, mara atau mart adalah roh jahat yang duduk di dada Anda saat Anda tidur, menghalangi napas dan mengubah mimpi Anda menjadi mimpi buruk.


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Khateb, A., Fort, P., Alonso, A., Jones, B. E. & amp Muhlethaler, M. Bukti farmakologis dan imunohistokimia untuk modulasi serotonergik neuron nukleus basalis kolinergik. Eur. J. Neurosci. 5, 541–547 (1993).

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Imeri, L., Mancia, M. & Opp, M. R. Blokade reseptor 5-HT2 mengubah perubahan yang diinduksi interleukin-1 dalam tidur tikus. ilmu saraf 92, 745–749 (1999).

Gemma, C., Imeri, L. & Opp, M. R. Aktivasi serotonergik merangsang sumbu hipofisis-adrenal dan mengubah ekspresi mRNA interleukin-1 di otak tikus. Psikoneuroendokrinologi 28, 875–884 (2003). Ini adalah makalah pertama yang melaporkan bahwa aktivasi sistem serotonergik mengubah ekspresi mRNA IL-1 di otak.

Dinarello, C.A. dkk. Interleukin 1 menginduksi interleukin 1. I. Induksi sirkulasi interleukin 1 pada kelinci in vivo dan dalam sel mononuklear manusia in vitro. J. Imun. 139, 1902–1910 (1987).

Taishi, P., Churchill, L., De, A., Obal, F. Jr & amp Krueger, J. M. Induksi mRNA sitokin oleh interleukin-1β atau faktor nekrosis tumor in vitro dan in vivo. Otak Res. 1226, 89–98 (2008).

Turnbull, A. V. & Rivier, C. Regulasi sumbu hipotalamus-hipofisis-adrenal oleh sitokin: aksi dan mekanisme aksi. Fisiol. putaran. 79, 1–71 (1999).

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Toth, L. A., Tolley, E. A. & Krueger, J. M. Tidur sebagai indikator prognostik selama penyakit menular pada kelinci. Prok. Soc. Eks. Biol. Med. 203, 179–192 (1993). Analisis retrospektif data yang berasal dari hampir 100 kelinci ini mengungkapkan hubungan antara kualitas tidur dan gejala klinis, morbiditas dan mortalitas. Kelangsungan hidup dari patogen menular dikaitkan dengan kualitas tidur yang lebih baik.

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Obál, F. Jr, Rubicsek, G., Sary, G. & Obál, F. Perubahan suhu otak dan inti dalam kaitannya dengan berbagai keadaan gairah pada tikus dalam periode terang dan gelap hari itu. Pflügers Arch. 404, 73–79 (1985).

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Haack, M., Schuld, A., Kraus, T. & amp Pollmacher, T. Efek tidur pada respon host yang diinduksi endotoksin pada pria sehat. Psikosom. Med. 63, 568–578 (2001). Bersama dengan referensi 101 dan 102, makalah ini menunjukkan efek pada tidur sukarelawan manusia yang sehat dari aktivasi pertahanan inang dengan injeksi endotoksin.

Friess, E., Wiedemann, K., Steiger, A. & Holsboer, F. Sistem hipotalamus-hipofisis-adrenokortikal dan tidur pada manusia. Adv. Neuroimunol. 5, 111–125 (1995).

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Krueger, J. M., Walter, J., Dinarello, C. A., Wolff, S. M. & amp Chedid, L. efek mempromosikan tidur pirogen endogen (interleukin-1). NS. J. Fisiol. 246, R994–R999 (1984). Ini dan referensi 134 adalah artikel penelitian pertama yang menunjukkan efek IL-1 pada tidur dan elektroensefalogram.

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Ada variasi sirkadian dalam fungsi kekebalan tubuh

Sistem kekebalan memiliki fungsi utama untuk melindungi terhadap benda asing dan penyakit yang berpotensi berbahaya. Komponen bawaan dari sistem kekebalan terdiri dari kulit, semua membran mukosa, sel fagosit (monosit, neutrofil, eosinofil, makrofag dan basofil) dan sel T pembunuh alami (NK). It is considered a first line of defence against foreign bodies and it also has a critical role in the activation and regulation of adaptive immunity (Iwasaki and Medzhitov 2015). This component is semi-specific, non-adaptable, non-plastic and has no ‘memory’. In contrast, the adaptive component of immunity comprising B and T lymphocytes are adaptable, plastic and have ‘memory’. Immune cells of both innate and adaptive immunity become activated and are recruited to sites of infection or injury in the process of inflammation (Riera Romo et al. 2016 Bennett et al. 2017 Ward and Rosenthal 2014). Although beneficial, this inflammatory response can become over expressed leading to diseases and autoimmune disorders (Barnes 2008 Lien et al. 2012 Rose 2016).

Many cells and tissues of the immune system have been shown to have clocks that regulate many of their functions. In mammals, circadian clock genes oscillate in the spleen, lymph nodes, thymus, jejunum, macrophages, NK cells and CD4+ T cells (Keller et al. 2009 Bollinger et al. 2011 Alvarez and Sehgal 2005 Froy and Chapnik 2007 Arjona and Sarkar 2005 Arjona and Sarkar 2006). In fact, about 8% of the expressed genes in mice peritoneal macrophages show circadian variation, including genes involved in the regulation of pathogen recognition and cytokine secretion (Keller et al. 2009). A recent microarray study on the human blood transcriptome from sampled around the clock shows that the number of oscillating transcripts decreases and other genes are either up-, or down-regulated when subjects are sleep deprived, and genes associated with immune system amongst the most affected genes (Möller-Levet et al. 2013b). Whilst this suggests variations throughout the day in immune function, acute responses to infection or response to allergen exposure, future work is still needed to confirm a causal link between underlying rhythms in immunity and the clock mechanism and functional outcomes.

It has been known since the 1960s-70s that the mortality rate of mice exposed to the bacterial endotoxin lipopolysaccharide (LPS) greatly varies depending on time of exposure (Halberg et al. 1960 Shackelford and Feigin 1973 Feigin et al. 1969 Feigin et al. 1972). In mice, a LPS challenge given at the end of the rest time results in a mortality rate of 80%. When the challenge is given in the middle of the active time the mortality rate is only 20%(Halberg et al. 1960). Similarly, bacterial infection has been shown to lead to higher mortality when initiated during the rest period (Shackelford and Feigin 1973). More recently, these results were confirmed and extended showing that exposing mice to LPS at the end of their rest period or beginning of the active period resulted in a stronger cytokine response and NF-κB activation compared with LPS exposure starting during the active period or beginning of the rest period (Marpegan et al. 2009 Gibbs et al. 2012 Nguyen et al. 2013 Spengler et al. 2012). Similar results have been obtained in humans using the LPS challenge both in vivo injecting LPS to healthy volunteers (Alamili et al. 2014) and in vitro exposing blood samples obtained at different times of the day from volunteers to LPS (Petrovsky et al. 1998 Rahman et al. 2015). The greatest response of the immune system in terms of cytokine release occurs during the rest and early active periods. However, this also implies that the risk of immune-related illnesses, such as, sepsis, allergies and uncontrolled immune reactions are more likely to occur during the late rest period and early active period.

Allergic reactions are initiated with antigen specific IgE production and fixation of IgE to FcεRI receptors on mast cells and basophils (Stone et al. 2010). Importantly mast cells, eosinophils and basophils display circadian oscillations of clock gene expression as well as circadian gene expression and release of their mediators following IgE-mediated activation (Baumann et al. 2013 Wang et al. 2011 Ando et al. 2015 Baumann et al. 2015). Several recent studies have shown that the circadian clock regulated the daily rhythms in IgE/mast cell-mediated allergic reactions. For example, Per2 mutant mice have a decreased sensitivity to the corticosteroid dexamethasone inhibition of the IgE-mediated degranulation in bone marrow-derived mast cells (Nakamura et al. 2011). Furthermore, anaphylactic reactions to an allergen challenge display a time of day dependent variation in wild-type mice which disappears in Per2 mutant mice exhibiting a strong reaction at all times throughout the cycle (Nakamura et al. 2011). This could be due to the disrupted circadian clock that specifically results from the Per2 mutation (Spoelstra et al. 2014 Albrecht et al. 2001 Chong et al. 2012 Xu et al. 2007) compromising the mice’s response to dexamethasone as well as to an allergen challenge and its consequent anaphylactic reaction. Another possibility is that PER2 protein has a clock-independent role in allergic reactions as most clock proteins have in different processes and pathways (Yu and Weaver 2011). The authors hypothesized that Per2 could be regulating the rhythmic secretion of glucocorticoids or gating the glucocorticoid responses of mast cells to specific times of the day. It could also be a combination of clock-dependent and, −independent roles. Loss of clock function due to other factors also leads to disrupted responses to allergic reactions. For example, Clock gene mutation in mast cells leads to disruption of temporal variations in IgE mediated degranulation in mast cells associated with loss of temporal regulation of FcεRI expression and signalling (Nakamura et al. 2014). Collectively, these studies suggest that not only proper functioning of the immune system is regulated by circadian clocks but also allergies have a strong circadian component.

In turn, inflammation can also affect the circadian clock and the pathways it regulates such as metabolism and sleep-wake cycle (Bellet et al. 2013 Jewett and Krueger 2012 Lundkvist et al. 2002 Lundkvist et al. 2010). The circadian firing rhythms of the SCN neurons as well clock gene expression in the SCN is differentially affected by various cytokines, i.e. IFN-γ, TNF-α, IFN-α as well as the LPS challenge (Lundkvist et al. 2002 Kwak et al. 2008 Nygård et al. 2009 Okada et al. 2008). Furthermore, the effect of cytokines or LPS on clock gene expression in the SCN and peripheral clocks of rodents such as liver, heart or spleen, temperature or locomotor activity will vary depending on the time of day at which cytokines are administered (Duhart et al. 2013 Ohdo et al. 2001 Koyanagi and Ohdo 2002 Yamamura et al. 2010 Westfall et al. 2013 Marpegán et al. 2005 Leone et al. 2012 Boggio et al. 2003). Similarly in humans, LPS injection causes a suppression of clock genes e.g. Clock, Cry1,2, Per1,2,3, Csnk1ε, Ror-α dan Rev.-erb-α in peripheral blood lymphocytes, neutrophils and monocytes (Haimovich et al. 2010).

Marpegan and colleagues suggested that immune responses may be acting as a synchronizing signal for the clock in a similar way to light that advances and delays circadian rhythms depending on time of day at which they administered (Marpegán et al. 2005). Immune responses could be acting as disrupting circadian clock signals instead. Chronic inflammation achieved by weekly injecting LPS to mice for 2 months leads to a decreased response of the SCN to light 7 days after the last LPS injection however, the SCN response to light was restored 30 days after the last LPS injection (Palomba and Bentivoglio 2008).

As for potential mechanisms by which the immune system interacts with the molecular clock there are a few of studies so far. Cavadini and colleagues showed that TNF-α inhibits CLOCK-BMAL1 function by interfering with E-box mediated transcription leading to downregulation of expression of clock-controlled genes with E-boxes in their promotor (Cavadini et al. 2007). Petrzilka and colleagues extended this work and showed that TNF-α requires p38 mitogen-activated protein kinases (MAPK) and/or calcium signalling to upregulate expression of several core clock genes but it can downregulate Dbp (clock controlled gene) expression independently from p38 but requires calcium signalling (Petrzilka et al. 2009). And Bellet and co-workers showed that the RelB subunit of NF-kB interacts with BMAL1 protein and represses the circadian expression of Dbp (Bellet et al. 2012 ). Overall, these studies provide clues to understand the cross-talk between the circadian and immune systems in inflammatory diseases. Further research should be directed at understanding the potential mechanisms by which the immune system gives time cues to the circadian system, both in health and in acute and in chronic inflammation.


Isi

Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. [14] Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory.

The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into a more primitive innate immune system and, in vertebrates, an acquired or adaptive immune system. The latter is further divided into humoral (or antibody) and cell-mediated components.

The immune system has the capability of self and non-self-recognition. [15] An antigen is a substance that ignites the immune response. The cells involved in recognizing the antigen are Lymphocytes. Once they recognize, they secrete antibodies. Antibodies are proteins that neutralize the disease-causing microorganisms. Antibodies do not directly kill pathogens, but instead, identify antigens as targets for destruction by other immune cells such as phagocytes or NK cells.

The humoral (antibody) response is defined as the interaction between antibodies and antigens. [16] Antibodies are specific proteins released from a certain class of immune cells known as B lymphocytes, while antigens are defined as anything that elicits the generation of antibodies (antibody generators). Immunology rests on an understanding of the properties of these two biological entities and the cellular response to both.

It is now getting clear that the immune responses contribute to the development of many common disorders not traditionally viewed as immunologic, [17] including metabolic, cardiovascular, cancer, and neurodegenerative conditions like Alzheimer’s disease. Besides, there are direct implications of the immune system in the infectious diseases (tuberculosis, malaria, hepatitis, pneumonia, dysentery, and helminth infestations) as well. Hence, research in the field of immunology is of prime importance for the advancements in the fields of modern medicine, biomedical research, and biotechnology.

Immunological research continues to become more specialized, pursuing non-classical models of immunity and functions of cells, organs and systems not previously associated with the immune system (Yemeserach 2010).

Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features.

The diseases caused by disorders of the immune system fall into two broad categories:

    , in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease and primary immune diseases) , in which the immune system attacks its own host's body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis).

Other immune system disorders include various hypersensitivities (such as in asthma and other allergies) that respond inappropriately to otherwise harmless compounds.

The most well-known disease that affects the immune system itself is AIDS, an immunodeficiency characterized by the suppression of CD4+ ("helper") T cells, dendritic cells and macrophages by the Human Immunodeficiency Virus (HIV).

Clinical immunologists also study ways to prevent the immune system's attempts to destroy allografts (transplant rejection). [18]

The body’s capability to react to antigens depends on a person's age, antigen type, maternal factors and the area where the antigen is presented. [19] Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like Staphylococcus dan Pseudomonas. In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborn's phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early during gestation but are not fully active. [20]

Maternal factors also play a role in the body’s immune response. At birth, most of the immunoglobulin present is maternal IgG. These antibodies are transferred from the placenta to the fetus using the FcRn (neonatal Fc receptor). [21] Because IgM, IgD, IgE and IgA do not cross the placenta, they are almost undetectable at birth. Some IgA is provided by breast milk. These passively-acquired antibodies can protect the newborn for up to 18 months, but their response is usually short-lived and of low affinity. [20] These antibodies can also produce a negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the antigen itself then the child will produce a dampened response. Passively acquired maternal antibodies can suppress the antibody response to active immunization. Similarly, the response of T-cells to vaccination differs in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these same responses in neonates. [20] Between six and nine months after birth, a child’s immune system begins to respond more strongly to glycoproteins, but there is usually no marked improvement in their response to polysaccharides until they are at least one year old. This can be the reason for distinct time frames found in vaccination schedules. [22] [23]

During adolescence, the human body undergoes various physical, physiological and immunological changes triggered and mediated by hormones, of which the most significant in females is 17-β-estradiol (an estrogen) and, in males, is testosterone. Estradiol usually begins to act around the age of 10 and testosterone some months later. [24] There is evidence that these steroids not only act directly on the primary and secondary sexual characteristics but also have an effect on the development and regulation of the immune system, [25] including an increased risk in developing pubescent and post-pubescent autoimmunity. [26] There is also some evidence that cell surface receptors on B cells and macrophages may detect sex hormones in the system. [27]

The female sex hormone 17-β-estradiol has been shown to regulate the level of immunological response, [28] while some male androgens such as testosterone seem to suppress the stress response to infection. Other androgens, however, such as DHEA, increase immune response. [29] As in females, the male sex hormones seem to have more control of the immune system during puberty and post-puberty than during the rest of a male's adult life.

Physical changes during puberty such as thymic involution also affect immunological response. [30]

Ecoimmunology, or ecological immunology, explores the relationship between the immune system of an organism and its social, biotic and abiotic environment.

More recent ecoimmunological research has focused on host pathogen defences traditionally considered "non-immunological", such as pathogen avoidance, self-medication, symbiont-mediated defenses, and fecundity trade-offs. [31] Behavioural immunity, a phrase coined by Mark Schaller, specifically refers to psychological pathogen avoidance drivers, such as disgust aroused by stimuli encountered around pathogen-infected individuals, such as the smell of vomit. [32] More broadly, "behavioural" ecological immunity has been demonstrated in multiple species. For example, the Monarch butterfly often lays its eggs on certain toxic milkweed species when infected with parasites. These toxins reduce parasite growth in the offspring of the infected Monarch. However, when uninfected Monarch butterflies are forced to feed only on these toxic plants, they suffer a fitness cost as reduced lifespan relative to other uninfected Monarch butterflies. [33] This indicates that laying eggs on toxic plants is a costly behaviour in Monarchs which has probably evolved to reduce the severity of parasite infection. [31]

Symbiont-mediated defenses are also heritable across host generations, despite a non-genetic direct basis for the transmission. Aphids, for example, rely on several different symbionts for defense from key parasites, and can vertically transmit their symbionts from parent to offspring. [34] Therefore, a symbiont that successfully confers protection from a parasite is more likely to be passed to the host offspring, allowing coevolution with parasites attacking the host in a way similar to traditional immunity.

The use of immune system components or antigens to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used to treat allergies, autoimmune disorders such as Crohn’s disease and rheumatoid arthritis, and certain cancers. Immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies. This includes regulating factors such as IL-2, IL-10, GM-CSF B, IFN-α.

The specificity of the bond between antibody and antigen has made the antibody an excellent tool for the detection of substances by a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with an isotopic (radio) or fluorescent label or with a color-forming enzyme in order to detect it. However, the similarity between some antigens can lead to false positives and other errors in such tests by antibodies cross-reacting with antigens that are not exact matches. [35]

The study of the interaction of the immune system with cancer cells can lead to diagnostic tests and therapies with which to find and fight cancer. The immunology concerned with physiological reaction characteristic of the immune state.

This area of the immunology is devoted to the study of immunological aspects of the reproductive process including fetus acceptance. The term has also been used by fertility clinics to address fertility problems, recurrent miscarriages, premature deliveries and dangerous complications such as pre-eclampsia.

Immunology is strongly experimental in everyday practice but is also characterized by an ongoing theoretical attitude. Many theories have been suggested in immunology from the end of the nineteenth century up to the present time. The end of the 19th century and the beginning of the 20th century saw a battle between "cellular" and "humoral" theories of immunity. According to the cellular theory of immunity, represented in particular by Elie Metchnikoff, it was cells – more precisely, phagocytes – that were responsible for immune responses. In contrast, the humoral theory of immunity, held by Robert Koch [36] and Emil von Behring, [37] among others, stated that the active immune agents were soluble components (molecules) found in the organism's "humors" rather than its cells. [38] [39] [40]

In the mid-1950s, Macfarlane Burnet, inspired by a suggestion made by Niels Jerne, [41] formulated the clonal selection theory (CST) of immunity. [42] On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (e.g., pathogens, an allograft) trigger a destructive immune response. [43] The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells. [44] The self/nonself theory of immunity and the self/nonself vocabulary have been criticized, [40] [45] [46] but remain very influential. [47] [48]

More recently, several theoretical frameworks have been suggested in immunology, including "autopoietic" views, [49] "cognitive immune" views, [50] the "danger model" (or "danger theory"), [45] and the "discontinuity" theory. [51] [52] The danger model, suggested by Polly Matzinger and colleagues, has been very influential, arousing many comments and discussions. [53] [54] [55] [56]


Nerve cells found to suppress immune response during deadly lung infections

Methicillin-resistant Staphylococcus aureus. Credit: NIH/NIAID

When the body is fighting infection, the immune system kicks into high gear. But emerging evidence hints at the involvement of another, rather surprising, player in this process: the nervous system.

New research from Harvard Medical School, conducted in mice, shows just how the interaction between the nervous and the immune systems occurs in deadly lung infections—a tantalizing clue into a complex interplay between two systems traditionally viewed as disconnected.

The findings, published March 5 in Nature Medicine, reveal that neurons carrying nerve signals to and from the lungs suppress immune response during infection with Staphylococcus aureus, a bacterium that is growing increasingly impervious to antibiotics and has emerged as a top killer of hospitalized patients, who are often immunocompromised and weakened overall.

The results, the researchers said, suggest that targeting the nervous system could be one way to boost immunity and can set the stage for the development of nonantibiotic approaches to treat recalcitrant bacterial infections.

"With the rapid emergence of drug-resistant organisms, such as methicillin-resistant Staph aureus, nonantibiotic approaches to treating bacterial infections are sorely needed," said senior study investigator Isaac Chiu, assistant professor in the Department of Microbiology and Immunobiology at Harvard Medical School.

"Targeting the nervous system to modulate immunity and treat or prevent these infections could be one such strategy."

Sensory neurons play a protective role by sensing adverse stimuli and alerting the body that something is awry. In the lungs, the neurons' projections detect mechanical pressure, inflammation, temperature changes and the presence of chemical irritants, then send an alert to the brain—a notification that can come in the form of pain, airway constriction or a cough that expels harmful agents or particles from the airways.

But the new study reveals that when mouse lungs are invaded by staph bacteria, these guardian neurons interfere with the organ's ability to cope with infection. Specifically, they reduce the lungs' ability to summon several types of disease-fighting cells in response to infection. A series of experiments conducted in mice revealed that disabling these neurons promoted immune cell recruitment, increased the lungs' ability to clear bacteria and boosted survival in staph-infected mice.

The results, the researchers said, suggest that different classes of sensory neurons may be involved in restraining or promoting immune response. Another possibility is that certain pathogens may have evolved to hijack and exploit an immunosuppressive pathway to their benefit—a survival mechanism for some classes of infectious bacteria, said study co-author Stephen Liberles, professor of cell biology at Harvard Medical School.

The team's interest in the crosstalk between the immune and nervous systems stems from recent work conducted by Chiu and colleagues. Chiu's earlier research showed that when nerve cells detect bacterial invaders, they produce pain during infection. Other research has revealed nervous system involvement in animal models of allergic asthma.

The team suspected that nerve cells would play a protective role in bacterial infections by boosting immune response to shield the lungs, but the experiments revealed the exact opposite. Much to their surprise, the scientists found that neurons dampened lung immunity and worsened outcomes in mice with bacterial pneumonia.

To determine how nerve cells affect immunity, the scientists genetically or chemically disabled lung neurons and then compared the activity of several types of immune cells involved in infection protection. They also monitored animal survival and took physiological measures such as body temperature and number of bacteria in the lungs.

In an initial set of experiments, researchers injected mice—half with intact neurons and half with chemically disabled neurons—with drug-resistant staph bacteria. Compared with mice with intact nerve receptors, mice with disabled neurons controlled their body temperatures better, harbored 10 times fewer bacteria in their lungs 12 hours after the infection and were markedly more capable of overcoming and surviving the infection. Sixteen of 20 mice with intact neurons succumbed to the infection. By contrast, 17 of 18 mice with disabled neurons survived.

The lungs of mice with genetically or chemically disabled neurons were also better at recruiting neutrophils—the body's pathogen-fighting troops that provide first responses during infections by devouring disease-causing bacteria. These mice summoned nearly twice as many infection-curbing neutrophils as did mice with intact neurons. But neutrophils in these animals were not simply more numerous. They were also more agile and more efficient in their performance. As a measure of agility, researchers compared how well neutrophils in both groups managed to patrol lung blood capillaries—a key ability that allows these cells to scan for the presence of disease-causing pathogens. Neutrophils in animals with chemically disabled neurons crawled farther, covering greater distances. They were also stickier and thus more capable of adhering to the walls of blood vessels, the site of their pathogen-gobbling action.

"We observed a striking difference in neutrophil presence and behavior between the two groups," said Pankaj Baral, a research fellow in microbiology and immunobiology at Harvard Medical School and first author on the study. "Neutrophils in mice with disabled neurons were simply better at doing their job."

Additionally, mice with disabled neurons marshaled more efficiently several types of cytokines, signaling proteins that regulate inflammation, infection and bacterial clearance. In animals with disabled neurons, the levels of these inflammatory cells ramped up and subsided much faster, indicating that these mice were capable of mounting a more rapid immune response in the early stages of infection.

Conversely, mice with intact neurons showed suppressed function in a class of protective immune cells known as gamma delta T cells, a type of protective white blood cell found mostly in barrier tissues that line a variety of organs, including the lungs.

A final set of experiments revealed just how neurons suppressed immunity. The researchers observed that an immune signaling molecule released locally by neurons—a neuropeptide known as CGRP—was markedly increased in mice with intact neuron receptors during infection but absent in mice with disabled neurons. Researchers observed that the release of this molecule interfered with the lungs' ability to summon immunoprotective neutrophils, cytokines and gamma delta T cells. Experiments in lab dishes revealed that CGRP disrupted immune cells' ability to kill bacteria. When researchers blocked the production of CGRP in live animals infected with staph, these mice showed an enhanced ability to fight infection.

Taken together, these findings show that lung neurons enable the release of CGRP during lung infections and that blocking the activity of CGRP improves survival in bacterial pneumonia.

"The traditional delineation between nervous and immune systems is getting blurry and our findings underscore the idea that these two systems cross-talk to regulate each other's function," Chiu said. "As we move forward, immunologists should think more about the role of the nervous system, and neuroscientists should think more about the immune system."


How much sugar does it take to weaken your immune response

This nutrition study shows that it takes about 75 grams of sugar to weaken the immune system. And once the white blood cells are affected, it's thought that the immune system is lowered for about 5 hours after. This means that even someone who slept 8 hours, takes supplements and exercises can seriously damage their immune system function by drinking a few sodas or having candy or sugary desserts throughout the day.

That study above was published in the 1970s, but another study from 2011 expanded on the previous research and found that sugar, especially fructose (like the sugar in high-fructose corn syrup) negatively affected the immune response to viruses and bacteria.

Just to give you context of how 75 grams of sugar can add up:

  • One can of soda has about 40 grams of sugar
  • A low-fat, sweetened yogurt can have 47 grams of sugar
  • A cupcake has about 46 grams of sugar
  • Sports drinks can contain about 35 grams of sugar

Health authorities say to limit sugar to no more than 6 teaspoons a day.


Are There Certain Conditions That Make You More Susceptible?

From the available data, individuals over 70 and those with any chance of lung disease are at a higher risk, explains Ballow. “We have a lot more patients on biologics for IBD, psoriasis, and autoimmune hemo anemia (this destroys blood cells), which suppress the immune system,” he notes.

The more severe or potentially life- or organ-threatening rheumatic diseases, such as lupus, systemic vasculitis, and severe forms of rheumatoid arthritis, may require stronger or higher doses of medication, Roberts explains.

“These medications suppress the immune system to a greater degree, exposing the individual to greater risks due to infections,” he says. “Sometimes these conditions and medications may make it difficult to detect infections, since patients may not exhibit the normal symptoms of infections, such as high fevers or high white blood cell counts.” Roberts explains that any unusual or unfamiliar symptom in these patients should be viewed with suspicion.


Tonton videonya: как поднять тромбоциты в крови питанием и вылечить тромбоцитопению в домашних условиях? (Juni 2022).


Komentar:

  1. Yozshuzahn

    Rather useful piece

  2. Ewyn

    Ya! terhibur

  3. Calvert

    Tentang ini tidak bisa dan dia berbicara.

  4. Emesto

    Saya pikir Anda tidak benar. Saya menawarkan untuk membahasnya.

  5. Hanley

    tidak mungkin untuk memeriksa tanpa batas

  6. Tygoktilar

    A very useful idea



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