Gerardus Kelleger GERARDUS PRESS
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Notifications URGENT information
to read first, urgent
32495 converted by the media
The bible stories
32496 Aut Nihil
Aut Ceasar
32497 or just a simple flooding
Noah's ark
32498 The artificial created anti-Semitism
32499 proof later
Believing first
32500 or just faith.....
An addiction
32501 Bestowed upon us by God
The manner of love
32502 of all.....
The saviour
32503 Who is fooling who
The main question
32504 But who is doubtingh the creation
Some doubt
32505 will He return to us.....
2000 years ago
32506 The story of the Ukraine
Bandera the so admired killer in WW2 by the EU.
32507 With the devil on your side
Who can fail.....
32508 It grows.
Belief is like a tree
32509 I will presch........
Being the least of all saints
32510 The bibles answers
Who can.......
32511 Antique books.
Killing off a market
32512 A path for us.....
God has laid out
32513 You can move mountains.
If you belief
32514 without a church
Spreading the word
32515 On heaven and Earth
Praising the Lord
32516 or are they not?
Are they?
32517 Let us pray.....
When we say.....
32518 wrote those words?
Did Mordecai
32519 Without Jesus?
Would the Hebrew be known
32520 Any real proof of Jesus?
But is there any?
32521 a belief?
32522 Immunity
A system
32523 Revive thy work
Oh Lord
32524 What to do with him
A masn called Christ
32525 Spirits, deities and gods
first three pages
32526 Are the churches getting the hungry
To the table...
32527 Called Jesus.
What tyo do with a man
32528 The mediator
32529 Spirits, Deities, Gods
second part
32530 I should do.
What is it....
32531 It rules religion
32532 full of self control
See a man
32533 Spirits, Deitie, Gods
part four
32534 In the hand of God
We are sinners
32535 Are you?
Iam a Christian
32536 The microben
Human health
32537 Where is my strenght
Heavenly father
32538 Spirits, Deities, Gods
Part four
32539 He shall help us
Do not hesitate
32541 Microbal inflamation
Maladaption of the body
32542 of the feet
The washing.....
32543 Spitits, Deities, Gods
Part five
32544 from gopfor wood
Make yourself an ark
32545 What is life to you,
Our life,
32546 Use it well
Time is short,
32547 When old passes away
All becomes new
32548 Spirits, Deities, Gods
part Six
32549 His love will remove it.
32550 It stirs up your love
His love
32551 The holy spit works.
Through providence
32552 Hell for you.
Hell will be.....
32553 Spirits, Deities, Gods
part seven
32554 Rejoice.......
All the people......
32555 The killing of Floyd
The previous history of
32556 Language
streken Frysk
32557 Karaites
The story
32558 God
The concurend
32559 Atheist
Part two
32560 McCarthyism
A look in the past
32561 a view of God
The Western countries
32562 It's burning
The Negev....
32563 Anti-Semitism
The misuse
32564 The Karaites
Part 2
32565 Is Britian changing
Is it really?
32566 Part 3
The Karaites
32567 Britain
Slowly changing
32568 Sliding back?
The 30tier years
32569 Part 4
The Karaites
32570 non-Jews included
32571 in the past.
Back to the future
32572 Part 5
The karaites
32573 Or hit him with the sword
Shall I beat him with a whip
32574 Follow the first reason
To follow the rest

32522 Immunity

With the Corona virus all around us and the talk by government that we will have mass immunisatio, let us look at the reality.

Immunologic dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. Here we discuss findings which indicate that developmental aspects of the adaptive immune system are influenced by intestinal bacterial colonization. We also highlight the molecular pathways that mediate host–symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support an emerging concept whereby disturbances in the bacterial micro biota result in immunological dysregulation that may underlie disorders such as inflammatory bowel disease. Perhaps the mammalian immune system which appears designed to control microbes is, in fact, controlled by the microbes themselves.

Humans represent a scaffold upon which diverse microbial ecosystems are established. Immediately after birth, all mammals are initiated into a life-long process of colonization by foreign microorganisms that inhabit most environmentally exposed surfaces (such as the skin, mouth, gut and vagina). Shaped by millennia of evolution, some host–bacterial associations have developed into beneficial relationships creating an environment for mutualism. A key example of such an environment is provided by the vast numbers and diversity of bacteria that are harboured by the lower gastrointestinal tract of mammals.

By young adulthood, both humans and other mammals support one of the most complex microbial ecosystems on the planet, with over 100 trillion bacteria comprised of potentially many thousands of microbial species in the distal gut. Symbiotic bacteria of the mammalian gut have long been appreciated for the benefits they provide to the host: through provision of essential nutrients, metabolism of indigestible compounds, defence against colonization by opportunistic pathogens and even contribution to the development of the intestinal architecture.

Moreover, it seems that certain basic developmental features and functions of the mammalian immune system depend on interactions with the human micro biome. Unlike opportunistic pathogens, which elicit immune responses that result in tissue damage during infection, some symbiotic bacterial species have been shown to prevent inflammatory disease during colonization (see below). Surprisingly, the ‘normal’ micro biota also contains microorganisms that have been shown to induce inflammation under particular conditions. Therefore, the micro biota has the potential to exert both pro- and anti-inflammatory responses, and balances in the community structure of gut bacteria may be intimately linked to the proper function of the immune system.

By virtue of its responsibility to recognize, respond and adapt to countless foreign and self molecules, the immune system is central to the processes of health and disease. While the classical view of the immune system is that it evolved to protect organisms from infection by microbial pathogens, we peacefully co-exist with our vast and complex micro biota. In fact, the magnitude of the molecular interactions between the micro biota and the host immune system appear to be extensive. Here, we discuss recent evidence that suggests a beneficial partnership has evolved between symbiotic bacteria and the immune system.

These molecular interactions seem to direct the development of immune responses, and in turn, the immune system shapes the composition of the micro biota. We highlight seminal examples of microorganisms that have a role in preventing inflammatory bowel diseases (IBD), and the beneficial immune responses they elicit during protection. Furthermore, technological advances now allow a more detailed understanding of the alterations of the microbial population of the gut during IBD. If some bacteria are actively shaping a healthy immune system, does the absence of these organisms lead to disease?

It has recently been proposed that the mammalian genome does not encode the information (i.e., molecules) capable of carrying out all functions required for health, and that products of our micro biome (the collective genomes of the micro biota) are crucial for protection from various diseases. It is possible that alterations in the development or composition of the micro biota (known as dysbiosis) disturb the partnership between the micro biota and the human immune system, ultimately leading to altered immune responses that may underlie various inflammatory disorders in humans.

Several important effects of the micro biota on the host immune system have been determined by studies of gnoto-biology, which is the selective colonization of germ-free (sterile) animals. Immune responses in germ-free animals can be considered naïve to the ‘education’ provided by molecules of both pathogenic and beneficial microorganisms. Germ-free animals show extensive deficits in the development of the gut-associated lymphoid tissues (GALT). In addition to numerous defects in antibody production (Box 1), germ-free animals have relatively fewer and smaller Peyer's patches and mesenteric lymph nodes (MLNs) compared to animals housed under specific pathogen free (SPF) conditions.

A recent report has shown that germ-free animals display impaired development and maturation of isolated lymphoid follicles (ILFs). These inducible structures seem to form normally following the introduction of gut bacteria, suggesting a dynamic relationship between the immune system and the micro biota. Together with various morphological tissue defects observed in the intestines of germ-free animals, it appears that the entire ultra structural development of the gut is intimately connected to intestinal bacteria. For example, intestinal epithelial cells (IECs), which line the gut and form a physical barrier between luminal contents (including the micro biota) and the underlying cells of the immune system, have altered patterns of microvillus formation and decreased rates of cell turnover in germ-free animals compared with wild-type animals.

Gut bacteria have been shown to direct the glycosylation of lumenally-exposed surface proteins of the epithelium. IECs have many immunological functions: they can secrete and respond to various cytokines and express molecules (such as major histocompatibility molecules) that directly interact with lymphocytes. Expression and localization of pattern-recognition receptors (e.g., Toll-like receptors; TLRs) by the epithelium is influenced by bacterial colonization of the gut, and expression of defensins and other antimicrobial proteins are deficient in germ-free animals. Consistent with this notion, the Gram-negative commensally organism Bacteroides thetaiotaomicron, but not the Gram-positive microbe, Bifidobacterium longum, induces the expression of the antimicrobial peptide, RegIIIγ, by specialized IECs known as Paneth cells. Intriguingly, the specificity of RegIIIγ is directed toward specific Gram-positive bacteria. It is therefore tempting to speculate that symbiotic bacteria direct innate immune responses of the gut in an effort to protect their environment. Collectively, these observations of developmental defects in germ-free mice at the tissue, cellular and molecular levels suggest that ‘normal’ immune function may be impaired in the absence of the micro biota.

Germ-free animals are more susceptible to infection by certain bacterial, viral and parasitic pathogens. When challenged with the Gram-negative enteric pathogen Shigella flexneri, germ-free animals showed decreased immune resistance to infection and increased mortality compared with conventionally colonized animals. Prior colonization with specific commensal bacteria antagonized S. flexneri infections, whereas colonization with control species such as E.coli did not, implying that some members of the micro biota provide protection against intestinal bacterial pathogens. Infection by the Gram-positive intracellular pathogen Listeria monocytogenes results in decreased bacterial clearance in germ-free compared with colonized animals.

The mechanism for this increased susceptibility has been attributed to a T cell trafficking defect in germ-free animals to the site of Listeria infection. L-selectin and CD44 are known to be involved in homing of lymphocytes to sites of inflammation. Listeria infected germ-free mice have decreased accumulation of CD44+L-selectin+ T cells resulting in increased bacterial burden compared to SPF animals. Salmonella typhimurium is known to cause a more severe acute gastroenteritis in germ-free animals; however the reasons for this remain unclear. Establishing an infection requires the initial task of colonizing the host. For intestinal pathogens this can pose a difficult problem as all mammals are stably colonized by a consortium of bacteria that can act as a barrier to infection (“colonization resistance”).

Recent studies suggest that inflammation induced in response to S. typhimurium changes the composition of the micro biota and suppresses its regrowth. Moreover, S. typhimurium exploits this deficiency in “colonization resistance” to establish infection and cause disease. While important for maintaining a barrier to the colonization of potentially pathogenic organisms, it appears that the micro biota may also provide the host immune benefits. Supporting this, germ-free animals show reduced antigen-specific systemic immune responses to S. typhimuirum. These studies support the idea that enteric pathogens such as S. typhimurium may have developed strategies to counter both the immune system and the micro biota during the infectious process.

Although significant work is still required to determine the beneficial immune responses induced by the micro biota, it is exciting to consider the teleological notion that indigenous bacteria actively prevent enteric disease by infectious microorganisms to fortify their niche. If true, then an evolutionary alliance has been forged between mammals and beneficial bacteria that is critical in maintaining the long-term survival of both. In other words, is our wellbeing is depending on the microbes we harbour. And if we take that in account we are more than halfway.


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