Stanični imunitet

Mnogi prijatelji HCOIE portala postavljaju isto pitanje vezano za imunitet kod onih koji su preboljeli i onih koji su cijepljeni, dosta pitanja vezana su i za memorijske stanice. Postoje dva glavna mehanizma imunosti unutar adaptivnog imunološkog sustava – humoralni i stanični.

Humoralni imunitet se također naziva imunitet posredovan antitijelima. Uz pomoć pomoćnih T stanica, B stanice će se diferencirati u plazma B stanice koje mogu proizvesti antitijela protiv specifičnog antigena. Humoralni imunološki sustav se bavi antigenima iz patogena koji slobodno cirkuliraju ili izvan zaraženih stanica. Protutijela koja proizvode B stanice vezat će se za antigene, neutralizirajući ih ili uzrokujući lizu (otapanje ili uništavanje stanica lizinom) ili fagocitozu.

Stanična imunost javlja se unutar inficiranih stanica i posredovana je T limfocitima. Antigeni patogena su izraženi na površini stanice ili na stanici koja predstavlja antigen. Pomoćne T stanice oslobađaju citokine koji pomažu aktiviranim T stanicama da se vežu na kompleks MHC-antigena zaraženih stanica i diferenciraju T stanicu u citotoksičnu T stanicu. 

Nakon infekcije virusom SARS-CoV-2 ili cijepljenja dolazi do reakcije imunosnog sustava organizma koja dovodi do stvaranja specifičnih stanica zvanih limfociti. Limfociti su stanice koje cirkuliraju putem krvi i obavljaju svoje specifične funkcije u svrhu obrane organizma od virusa. Postoji velik broj limfocita, ali ih dijelimo u dvije osnovne skupine: limfocite T i limfocite B. Limfociti B su stanice koje stvaraju antitijela, a ona specifično prepoznaju virus te se na njega vežu, neutraliziraju ga i sprečavaju ulazak virusa u naše zdrave stanice. Ako virus ipak uspije dospjeti u naše zdrave stanice, u njima započinje replikacija virusne nasljedne upute te virusnih proteina i stvaranje novih virusnih čestica. Takve patološki promijenjene, bolesne stanice (prethodno fagocitirane od strane antigen predočnih stanica) mogu prepoznati naši limfociti T, koji u svojim granulama sadrže brojne citotoksične tvari, a na površini specifične stanične receptore. Stanični receptori limfocita T imaju sposobnost naše bolesne stanice potaknuti na programiranu staničnu smrt, čime stanica u kojoj se virus nalazi odumire te je spriječeno daljnje umnažanje virusa. Limfociti T čine prvu liniju naše stanične imunosti koja je naziv dobila upravo po tome što je posredovana stanicama - limfocitima T, a ne antitijelima.

Dio limfocita T i limfocita B nakon preboljene infekcije ili cijepljenja ima sposobnost pretvorbe u stanicu sa specifičnom funkcijom koju nazivamo memorijska stanica. Memorijske stanice imaju sposobnost pamćenja virusnih dijelova kako bi se aktivirale u trenutku kada organizam dođe u ponovni doticaj s virusom. Takve stanice višestruko ubrzavaju stvaranje aktivnih limfocita T koji će prepoznati bolesne stanice inficirane virusom i uništiti ih. Također, memorijske stanice ubrzavaju stvaranje limfocita B, koji će produkcijom antitijela neutralizirati slobodne virusne čestice u krvi. Tajna dugovječnosti stanične imunosti upravo je u memorijskim stanicama, a istraživanje objavljeno u jednom od najcitiranijih svjetskih časopisa - Nature otkriva da je stanična imunost na virusni antigen N trajala čak 17 godina u pacijenata nakon infekcije SARS-om 2003. godine.

Sva cjepiva koja su sada na tržištu zasnivaju se na prezentaciji virusnog antigena S našem imunosnom sustavu kako bi naše stanice mogle prepoznati spike (S) protein virusa i pravodobno reagirati tijekom ulaska virusa u naš organizam. S druge strane, tijekom infekcije virusom SARS-CoV-2 dolazi do razgradnje cijele virusne čestice, obrade većeg broja različitih virusnih antigena uključujući i antigen S te naš imunosni sustav stvara zaštitu protiv svih virusnih komponenti. Istraživanja koja su u tijeku pokazuju da je razina imunosne reakcije na S protein virusa podjednaka u cijepljenih i onih koji su preboljeli covid-19.

Humoralni imunitet i imunitet posredovan stanicama dvije su vrste adaptivnog imunološkog odgovora koji omogućavaju ljudskom tijelu da se ciljano brani od štetnih agenasa kao što su bakterije, virusi i toksini. Iako postoji određeno preklapanje između ovih krakova imunološkog odgovora - oba se oslanjaju na funkcije limfoidnih stanica - postoje i neke važne razlike. Može se steći humoralni imunitet na određenu infekciju ili bolest ako se daje s protutijelima od nekoga tko je prethodno bio izložen istoj infekciji, zaobilazeći humoralni odgovor. Međutim, imunost posredovana antitijelima uključuje skup molekularnih komponenti i procesa koji se razlikuju od imunosti posredovane stanicama. U ovom članku definiramo humoralnu imunost i stanični imunitet, raspravljajući o različitim imunološkim procesima, svrhama i važnim tipovima stanica.

Jačina stanične imunosti je individualna karakteristika koja se zasniva na velikom broju faktora uključujući i genetsku podlogu pojedinca. Trenutno ne možemo predvidjeti kakva će biti reakcija na virus u pojedine osobe niti znamo koja je to razina stanične imunosti koja nas štiti od zaraze ili teškog oblika bolesti. Međutim, recentna znanstvena literatura objavljena u vodećem medicinskom časopisu Lancet navodi izrazito nisku pojavnost reinfekcije u osoba koje su preboljele i stvorile staničnu imunost na virus SARS-CoV-2. Humoralna imunost omogućuje neutralizaciju virusnih čestica u krvi i sprečava njihov ulazak u stanice, dok stanična imunost prepoznaje inficirane stanice, uništava ih i time zaustavlja daljnje širenje virusa. Svaki rezultat testa interpretira se individualno u kontekstu kliničke slike pacijenta, njegovih komorbiditeta, razine stanične i humoralne imunosti te prema potrebi i genetske analize. 

Ova tablica nije vezana uz temu ali je dobro da je proučite. 

Trajanje stanične imunosti još se ne može sa sigurnošću odrediti, ali istraživanja bazirana na ljudima koji su preboljeli SARS 2003. ukazuju da stanični imunosni odgovor, zahvaljujući memorijskim stanicama, može potrajati i do dva desetljeća. Trenutna pandemija traje prekratko da bismo mogli odrediti koliko će točno trajati stanična imunost na SARS-CoV-2, no Shrestha i kolege iz američke Klinike Cleveland u radu koji je retrospektivno analizirao populaciju SAD-a, i to 52.238 osoba među kojima i njih 1359 koji su preboljeli covid-19 i nisu cijepljeni, potvrđuje da ni jedna od 1359 osoba nije ponovno oboljela od covida-19. S druge strane, prije dva dana Lancet Infect Dis u preglednom članku navodi i studiju objavljenu u Clin Infect Dis, rađenu na 9119 osoba koje su preboljele covid-19 i koja potvrđuje da je samo 0,7 posto osoba imalo ponovnu infekciju SARS-CoV-2 (reinfekcija). Ti su rezultati potpuno u skladu s upravo objavljenom studijom u JAMA Internal Medicine na 1579 osoba u kojoj su analizirani oboljeli od covida-19 tijekom prvog vala bolesti u Italiji, a od kojih je samo pet osoba (0,31 posto) ponovno oboljelo od covida-19, dok je samo jedna ponovno oboljela osoba hospitalizirana. O zaštićenosti od zaraze ovisi nekoliko čimbenika, a među kojima su i stanična i humoralna imunost koje čine temeljnu obranu našeg imunosnog sustava. Među čimbenike o kojima ovisi hoće li se pojedina osoba zaraziti svakako spadaju i količina virusa unesenog u organizam, trajanje kontakta s inficiranom osobom, kao i sposobnost naše prirodne mehaničke zaštite - mukozne barijere koja oblaže nos, usnu šupljinu i unutrašnjost dišnih puteva.

Nakon preboljenja infekcije SARS-CoV-2 razvija se stanična imunost na različite virusne antigene, što znači da se naš imunosni sustav može boriti prepoznajući različite dijelove virusa. Ako s vremenom dođe do promjena u virusnim antigenima, stanična imunost može prepoznati druge komponente i tako aktivirati obranu protiv virusa. Zanimljivo je da su istraživanja pokazala da na pojedine virusne antigene postoji križna reaktivnost te tako stanična imunost protiv virusnog proteina N u osoba koje su 2003. preboljele SARS može križno reagirati i prepoznati protein N virusa SARS-CoV-2.

Stanična imunost nastaje kao reakcija na gotovo sve infektivne bolesti te se razvija i prilikom infekcije drugim virusima i mikroorganizmima. S obzirom na dugotrajnost stanične imunosne memorije te s obzirom na mogućnost križne reaktivnosti, stanična imunost izuzetno je značajna komponenta našeg imunosnog sustava. Nedavno objavljena znanstvena studija u američkom medicinskom časopisu JAMA navodi zabrinutost zbog pojave probojnih infekcija nakon cijepljenja protiv SARS-CoV-2 virusa te ističu nepouzdanost razine titra antitijela kao zaštite od zaraze virusom SARS-CoV-2. Za razliku od antitijela čiji titar ubrzano pada s vremenom, trenutna saznanja ukazuju na dugotrajnost stanične imunosti i njezinu važnu ulogu u održavanju imunosne zaštite. 

Reference:

F.S. Dhabhar, in Encyclopedia of Stress (Second Edition), 2007

J. Descotes, in Encyclopedia of Toxicology (Third Edition), 2014

E. Diane Williamson, in Vaccines for Biodefense and Emerging and Neglected Diseases, 2009

Linda Kidd, Edward B. Breitschwerdt, in Canine and Feline Infectious Diseases, 2014

A.J. Zajac, L.E. Harrington, in Reference Module in Biomedical Sciences, 2014

GUSTAVO PACHECO-LÓPEZ, ... MANFRED SCHEDLOWSKI, in Psychoneuroimmunology (Fourth Edition), 2007

N.V. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry, 2011

Tom R. Phillips, in Encyclopedia of Immunology (Second Edition), 1998

Global Future

A terrifying coalition of big business and big tech is so confident and brazen they are promising the public “you will own nothing, and you will be happy” in an advertising campaign for a global reset.

The Great Reset is a proposal set out by the World Economic Forum for a new globalized fiscal system that would allow the world to effectively tackle the so-called climate crisis.

Zeljko Serdar from CCRES said the plan intends to use the “tools of oppression” implemented during the pandemic, such as lockdowns and forced business closures as well as other measures destroying private property rights, to combat the coronavirus to achieve climate outcomes.

“I've spoken before about the insidious phrases which sound like common sense but is in fact just one of several slogans for the Great reset, another being the Orwellian phrase the fourth industrial revolution. This is as serious and as dangerous a threat to our prosperity and freedom as we have faced in decades”.

Welcome to the year 2030. Welcome to my city - or should I say, "our city." I don't own anything. I don't own a car. I don't own a house. I don't own any appliances or any clothes.

It might seem odd to you, but it makes perfect sense for us in this city. Everything you considered a product, has now become a service. We have access to transportation, accommodation, food and all the things we need in our daily lives. One by one all these things became free, so it ended up not making sense for us to own much.

First communication became digitized and free to everyone. Then, when clean energy became free, things started to move quickly. Transportation dropped dramatically in price. It made no sense for us to own cars anymore because we could call a driverless vehicle or a flying car for longer journeys within minutes. We started transporting ourselves in a much more organized and coordinated way when public transport became easier, quicker, and more convenient than the car. Now I can hardly believe that we accepted congestion and traffic jams, not to mention the air pollution from combustion engines. What were we thinking?

Sometimes I use my bike when I go to see some of my friends. I enjoy the exercise and the ride. It kind of gets the soul to come along on the journey. Funny how some things seem never seem to lose their excitement: walking, biking, cooking, drawing, and growing plants. It makes perfect sense and reminds us of how our culture emerged out of a close relationship with nature.

In our city, we don't pay any rent, because someone else is using our free space whenever we do not need it. My living room is used for business meetings when I am not there.

Once in a while, I will choose to cook for myself. It is easy - the necessary kitchen equipment is delivered to my door within minutes. Since transport became free, we stopped having all those things stuffed into our homes. Why keep a pasta maker and a crepe cooker crammed into our cupboards? We can just order them when we need them.

This also made the breakthrough of the circular economy easier. When products are turned into services, no one has an interest in things with a short life span. Everything is designed for durability, repairability, and recyclability. The materials are flowing more quickly in our economy and can be transformed into new products pretty easily. Environmental problems seem far away since we only use clean energy and clean production methods. The air is clean, the water is clean and nobody would dare to touch the protected areas of nature because they constitute such value to our well-being. In the cities, we have plenty of green space and plants and trees all over. I still do not understand why in the past we filled all free spots in the city with concrete.

Shopping? I can't really remember what that is. For most of us, it has been turned into choosing things to use. Sometimes I find this fun, and sometimes I just want the algorithm to do it for me. It knows my taste better than I do by now.

When AI and robots took over so much of our work, we suddenly had time to eat well, sleep well and spend time with other people. The concept of rush hour makes no sense any more since the work that we do can be done at any time. I don't really know if I would call it to work anymore. It is more like thinking-time, creation-time, and development-time.

For a while, everything was turned into entertainment and people did not want to bother themselves with difficult issues. It was only at the last minute that we found out how to use all these new technologies for better purposes than just killing time.

My biggest concern is all the people who do not live in our city. Those we lost on the way. Those who decided that it became too much, all this technology. Those who felt obsolete and useless when robots and AI took over big parts of our jobs. Those who got upset with the political system and turned against it. They live different kinds of lives outside of the city. Some have formed little self-supplying communities. Others just stayed in the empty and abandoned houses in small 19th century villages.

Once in a while, I get annoyed about the fact that I have no real privacy. Nowhere I can go and not be registered. I know that, somewhere, everything I do, think and dream of is recorded. I just hope that nobody will use it against me.

All in all, it is a good life. Much better than the path we were on, where it became so clear that we could not continue with the same model of growth. We had all these terrible things happening: lifestyle diseases, climate change, the refugee crisis, environmental degradation, completely congested cities, water pollution, air pollution, social unrest, and unemployment. We lost way too many people before we realized that we could do things differently.

This blog post was written ahead of the World Economic Forum Annual Meeting of the Global Future Councils. Thank you for your interest in the World Economic Forum, the International Organization for Public-Private Cooperation.

Family Farming Platform

 

Family farming is the most common operational farming model in Europe – representing 97 percent of the European Union’s (EU) 12 million farms. Thus it is of great importance in the EU. It covers a diverse range of situations, including farms of all sizes. While there are obvious differences across regions and countries of the world when it comes to family farming, there is also much common ground. Below some of the key challenges and opportunities for family farms across the EU are identified, together with the policy solutions introduced in the EU to address them. The new 2014-2020 Common Agricultural Policy (CAP) that was agreed in 2013 offers a robust policy to maintain the rich diversity of family farms in the European agricultural sector and to ensure sustainability. The CAP continues to provide support to farmers through direct payments and measures to support agricultural, environmental and territorial development under the rural development programs. Some of these measures are of particular relevance for family farming. 

Under the new direct payment regime, Member States now have the possibility to establish a simplified scheme for small farmers under which they will be able to receive annual direct support ranging from €500 to €1,250. They will be subject to reduced administrative formalities, and exempted from certain environmental obligations. Member States can also choose to pay a redistributive payment – a top-up to support small and middle-sized farms. Furthermore, a scheme will specifically address the challenge of generation renewal by giving farmers up to the age of 40 an additional top-up payment for up to five years. As part of the market measures, the reform also contains measures to enhance producers’ organizations. Under the rural development elements of the CAP, the modified European Agricultural Fund for Rural Development (EAFRD) also enables spending on a raft of proven measures to strengthen the sustainability of smaller family farms through regional or national rural development programs. These measures include support for training and advice, economic improvements (such as physical investments, business development), cooperation to overcome small-scale disadvantages (such as setting up producer groups, jointly developing short supply chains, new technologies), and compensation for environmental commitments (such as voluntarily improved environmental or organic farming standards).

There is a need to promote innovation within family farms, taking into account their diversity, the different natural conditions under which they operate, and their varying degrees of technological development. There are a number of obstacles to the uptake of innovation that need to be addressed: lack of access to knowledge, insufficient information flow, weak exchange of research results, and too little responsiveness to the needs of farmers. The revised CAP is ready to support innovation, whether it is led by individuals, public sector organizations, or enterprises. A fully-fledged EU innovation package is available for the agrifood sector, comprising the new rural development policy, the Europe 2020 Flagship Initiative on the Innovation Union, Horizon 2020, and the European Innovation Partnership: Agricultural productivity and sustainability. This combination of policy measures aims to encourage researchers, farmers, advisors, and other agricultural sector stakeholders to cooperate more actively. In particular, it is hoped that a more direct and systematic exchange between farming and science will accelerate the speed of technological transfer and innovation.

Agricultural cooperatives can help family farms to overcome the scale constraints inherent to smallholdings while enabling small farmers to respond more effectively to changing market demands. Participating farmers also have more power and control over production than through contract farming, making food security less vulnerable. The increased access cooperatives provide to resources, information tools and services encourages members to increase their levels of food production, while reducing transaction costs, improving quality, and creating jobs. The CAP has supported producer cooperation working through the Common Market Organisation of products, which has enabled improved coordination of specific supply chains. The CAP provides a reinforced framework for producers and other organizations, as well as support for the setting up of producer groups. These should facilitate producer cooperation by granting legal certainty, financial support, and economic advantages to willing farmers. There are also new opportunities through the European Innovation Partnership Operational Groups that can enable new and existing cooperatives to explore and develop their own working practices and penetrate new markets.

Local food supply chains make it easier for customers to identify the origin of their purchases, and they are often willing to pay a premium for fresher and healthier options. By strengthening the relationship between consumers and local farmers, such supply chains promote local family enterprises and boost regional identity. The organization of food chains is a priority in the 2014- 2020 rural development policy. The EAFRD-funded measures aim to help family farmers to sell their products directly to consumers or at least to become involved in short supply chains and to better integrate family farms into distribution channels by providing support for quality schemes, adding value to agricultural products, promotion in local markets and short supply chains,  producer groups, and inter-branch organizations. In addition, the LEADER approach will continue to provide Local Action Groups with the grounds they need to support innovative and experimental approaches to stimulate direct sales and the development of local food markets, where foreseen as part of the Local Development Strategy.

Family farming has survived in Europe over centuries, re-emerging from crises, wars, and natural disasters, adjusting to changing economic fortunes, and, in some countries, to dramatic changes in a political context. This has never been a smooth and painless process, as many small farmers have disappeared over decades to give way to more efficient and competitive farms, able to adopt new inputs and technologies. It is beyond doubt that family farming will survive and will continue to be dominant in EU agriculture as far as the number of farms is concerned and that traditional smaller-scale family farming will continue to be the core of agriculture in many regions. With the majority of the EU’s farms being family farms, discussion about innovative approaches to the promotion and sustainability of the family farming model is certain to continue. The CAP’s role in addressing the challenges set out above and the new ones which will arise, not least as a result of climate change, will be key to assuring the future of the family farming sector, and with it the preservation of the EU’s rural communities and their local economies, traditions and agricultural practices.