indytravl

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OK, this has got to be totally simple question but could anyone help please.

What tissues of the body are not normally seen by your blood, and if they do, they produce antibodies against it?

thanks,
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yellowcat322

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As far as I remember, I think it's brain, eye lens and sertoli cells in the testes. Could be leaving some out though.
 

mojojojo

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cornea
 

felipe5

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yeah, the cornea is a good example.....if you somehow introduce corneal cells into the bloodstream, say by trauma, you can form an immune response and have the other lens attacked by the immune system in a condition called sympathetic ophthalmia. craziness
 

trudub

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Thyroid follicles are also not usually seen by blood. If the blood is exposed to thyroglobulin you can make antibodies against it. That is Hashimoto's Thyroiditis.
 

DrChandy

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indytravl said:
OK, this has got to be totally simple question but could anyone help please.

What tissues of the body are not normally seen by your blood, and if they do, they produce antibodies against it?

thanks,
[email protected]
Articular cartilage is avascular.
 

Rendar5

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blood-brain barrier, blood-testes barrier, blood-retina barrier (and rest of eye), blood-placenta barrier?. one or two more. not sure i ever heard of a blood-thyroid follicle barrier, though.
 

fun8stuff

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yellowcat322 said:
As far as I remember, I think it's brain, eye lens and sertoli cells in the testes. Could be leaving some out though.
heh, i think brains are pretty vascular ;) but i understand- you mean blood-brain barrier... but this doesn't prevent blood from getting to the brain.
 

yellowcat322

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fun8stuff said:
heh, i think brains are pretty vascular ;) but i understand- you mean blood-brain barrier... but this doesn't prevent blood from getting to the brain.
Actually it does. Nutritents from blood filter into CSF which then gets distributed to neural tissue, but brain itself never comes in contact with blood and blood is therefore toxic to brain cells.

Regarding eptithelium and catilage, although they are avascular, I'm not sure that they are antigenic, because there aren't any tight junctions preventing the epithelial antigens from getting into the blood during development (as is the case with the brain for example). I may be wrong on this but i'm pretty sure exposure of epithelium to blood will not result in antibody production.
 

jonb12997

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Rendar5 said:
blood-placenta barrier?.
don't antibodies get into the baby to help protect it till it can make it's own antibodies? which is why babies are not as sick when they're first born, then they start to get sick as the mother's antibodies wear off...
 

OmahaMX80

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jonb12997 said:
don't antibodies get into the baby to help protect it till it can make it's own antibodies? which is why babies are not as sick when they're first born, then they start to get sick as the mother's antibodies wear off...
Yes, Mom's IgG crosses the placenta and resides in baby for about 6 months after birth. That's why kids 6 months - 2 years of age are generally considered at high risk for infections as far as I understand it.
 

Rendar5

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jonb12997 said:
don't antibodies get into the baby to help protect it till it can make it's own antibodies? which is why babies are not as sick when they're first born, then they start to get sick as the mother's antibodies wear off...

Yes, but there's still a blood barrier as far as i remember. The issue isn't whether antibodies can reach the tissues in question. It's whether the tissues get exposed to lymphocytes to induce antibody production or immune reaction. This is why a Rh- mom can carry her first Rh+ fetus without any antibody attack on the fetus. And why after delivery or trauma (exposure to of fetus's antigens to mom's blood), the mom could start producing anti-Rh antibodies.
 

jonb12997

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Rendar5 said:
Yes, but there's still a blood barrier as far as i remember. The issue isn't whether antibodies can reach the tissues in question. It's whether the tissues get exposed to lymphocytes to induce antibody production or immune reaction. This is why a Rh- mom can carry her first Rh+ fetus without any antibody attack on the fetus. And why after delivery or trauma (exposure to of fetus's antigens to mom's blood), the mom could start producing anti-Rh antibodies.
forgot about the whole Rh thing... makes sense :)
 

dinesh

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During the final stage of delivery, when the placenta is being delivered, that is when the Rh antibodies may enter the mother's circulation..I think :)
 

Rendar5

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anytime there's blood exchange, yeah, since bleeding can occur during delivery. also during miscarriages or amniocentesis or any such procedure that'll induce bleeding. so u give rhogam to deal with the mom being exposed to Rh antigen.
 

Rendar5

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but is this pretty much automatic? Haven't covered that area yet, so i'm actually asking, but i was under the assumption the OP was looking for blood-X barriers, not avascular parts of anatomy.
 

TucsonDDS

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yellowcat322 said:
Actually it does. Nutritents from blood filter into CSF which then gets distributed to neural tissue, but brain itself never comes in contact with blood and blood is therefore toxic to brain cells.

Is this why you die if you take a shotgun to the head and you have a mix of blood and brain :D
 

skiz knot

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TucsonDDS said:
Is this why you die if you take a shotgun to the head and you have a mix of blood and brain :D
Tru dat!
 

yellowcat322

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TucsonDDS said:
Is this why you die if you take a shotgun to the head and you have a mix of blood and brain :D
Actually this is why a lot of people USED to die from gun shots before the advance of modern weaponry, in which the bullet is fired so fast that is actually sears the edges of the wound as it passes through the brain and so you don't have leakage of blood into the neural tissue. That's actually why there was so much progress made in neural sci in the 40's and 50's. The scientists studied soldiers from WWII who survived bullets and shrapnel lodged in their brain and had various defects depending on what the bullet destroyed. You'd be surprised at how many parts of your brain you could live without.
 

humuhumu

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I think the OP is talking about "immune privilege," which is nicely defined in the following abstract:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12424841&query_hl=5

"The host response to pathogens involves complex inflammatory responses and immune reactions. While these are central to host defense and vital to clearing infections, they are often accompanied by injury to surrounding tissue. Most organ systems can tolerate these responses without permanent consequences. However, there are sites that limit the spread of inflammation because it can threaten organ function. The most prominent examples of these are the eye, brain, and reproductive organs (testis, ovary), where even minor bouts of inflammation can have long-term consequences for the survival of the organism. In these organs immune responses either do not proceed, or proceed in a manner different from other areas; thus, they are called 'immunologically privileged.' Here a functioning immune response can be the culprit that leads to disease."
 

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yellowcat322 said:
Actually it does. Nutritents from blood filter into CSF which then gets distributed to neural tissue, but brain itself never comes in contact with blood and blood is therefore toxic to brain cells.
By this definition, there is no tissue in the body that gets "touched" by blood - in all tissues nutrients, O2 etc diffuse out of the blood into the tissue and then into the cells of the tissue - the blood stays in the capillaries, etc and never "touches" the tissue if we use this definition. The brain is only different because the blood-brain barrier restricts the things that can get out of and into blood vessels to a greater extent than other tissues.
 
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indytravl

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Thanks everyone for your helpful answers.

Just thought I'd post what your answers have led me to...



Immune privilege = Part of the body not attacked by the immune system
Medawar’s (1948) original explanation for this phenomenon– that immune privilege was just immune ignorance, with privileged sites isolated behind blood-tissue barriers lacking lymphatic drainage, and with antigenic material (trapped within these isolated sites) remaining invisible to the immune system – is now known to be incorrect. It has since been found that foreign tissues in privileged sites could eventually evoke antigen-specific systemic immunity and that certain privileged sites (such as the testis) had extensive efferent lymphatic pathways. Rather than immune ignorance, the systemic immune apparatus recognizes antigens in privileged sites and cooperates to create and sustain a graft-friendly environment. Infectious organisms or tumor cells inserted into immune-privileged sites do not elicit destructive or protective immunity.

Within such immune privileged organs immune responses are suppressed:
(1) MHC-mismatched (the half-paternal placenta)
(2) harbor germ-line cells (ovary and testis)
(3) contain bradytrophic tissues with poor regenerative capacity (lens and cornea in the anterior chamber of the eye)
(4) their function crucially depends on highly specialized, interconnected, postmitotic cells (the CNS)

One might speculate that for all these reasons, inflammation-induced cell loss must be limited to a minimum, and as a consequence, many antigens that elicit strong immune responses elsewhere in the body are tolerated in immune privileged sites. For example, certain viruses are removed at those sites of the body where neighboring cells can divide and replace lost cells, but persist within the CNS. From an evolutionary point of view, it is obviously less detrimental for an individual to live with such viruses in the brain than losing all infected neurons as a result of an adaptive immune response.

At least four pathways are known by which immune privilege can lead to T-cell tolerance:
(1) clonal deletion
(2) clonal anergy
(3) immune deviation
(4) T-cell suppression

Privileged tissues also are often characterized by:
(1) intratissue structural barriers such as extensive tight junctions among parenchymal cells (Sertoli cells, retinal pigment epithelium)
(2) elaborate surface _expression of hyaluronic acid (placenta, trabecular meshwork of the eye)
(3) reduced or absent _expression of MHC class I and class II molecules (brain, eye, placenta)
(4) _expression of class Ib molecules (placenta)
(5) release of class I molecules (liver)
(6) secretion of immunosuppressive cytokines (eye) and corticosteroids (gonads)
(7) fetal-like fibroblasts (gingival oral mucosa)

As summarized by Streilein (1997), privileged sites incorporate multiple additional features allowing them to accept foreign grafts:
(1) blood-tissue barriers (for eye, brain)
(2) absence of efferent lymphatics (eye)
(3) direct tissue fluid drainage into the blood (eye, brain)
(4) functional integrity of the spleen (eye)
(5) establishment of a potent immunosuppressive microenvironment containing growth factors such as TGF-beta (eye, brain, placenta, testis) and neuropeptides (eye)
(6) soluble and membrane-bound inhibitors of complement activation and fixation (anterior chamber of eye)

There are two distinct loci of immune privilege:
privileged sites (the best example being the fetus)
privileged tissues....
(1) EYE (anterior chamber, cornea, and retina) (blood-retina barrier) critical to avoidance of stromal keratitis, blinding disease of cornea accompanying ocular infection with HSV-1. Existence of ocular immune privilege is believed to serve the purpose of limiting the extent to which innate and adaptive immunity can cause intraocular inflammation. By limiting intraocular inflammation, immune privilege preserves the integrity of the visual axis and thereby prevents blindness. Ocular inflammation, whether expressed within the cornea or within the uveal tract, is a frequent cause of visual impairment. The eye is relatively protected from the vision-damaging effects of intraocular inflammation.
Orthotopic corneal allografts are the most successful of all solid-organ transplants in humans because the eye is a privileged site and the cornea is a privileged tissue (acute rejection if immune privilege lost)
(2) BRAIN (blood-brain barrier)
Endothelial cells are packed much tighter together in the brain, due to the existence of zonula occludentes (tight junctions) between them, blocking the passage of most molecules. The blood-brain barrier blocks all molecules except those that cross cell membranes by means of lipid solubility (such as oxygen, carbon dioxide, and ethanol) and those which are allowed in by specific transport systems (such as sugars and some amino acids). It is generally accepted that substances with a molecular weight higher than 500 Daltons can not cross the blood-brain barrier, while the lighter ones can.
(3) GRAVID UTERUS & PLACENTA & EMBRYO & AMNIOTIC MEMBRANE (blood-placenta barrier) biologically necessary for success of pregnancy so normal immune function does not occur. In order that the fetus is not attacked by the mother's immune system, the uterus/ uterine endometrium is an immune-privileged site during pregnancy. That makes sense; what is the implanting conceptus but something chimerically foreign (xenograft)?
The Rh factor marker is a protein, so there is no incidental preexposure. One either has the factor, Rh+, or one doesn’t, Rh-. (Yes,oversimplifying.) For transfusions, it is important to get it right. But there is another case where it can be a problem, and that concerns maternity. Suppose mother is Rh-, and father is Rh+. If he is homozygous Rh+/Rh+, then all conception will be phenotypically Rh+; if he is heterozygous Rh+/Rh-, then half the conceptions will be of Rh+ phenotype. The first pregnancy with an Rh+ conceptus is generally not a problem. At parturition, however, there is no way to avoid fetal blood mixing with maternal blood, and so mother will be exposed to the Rh-antigen, and generate circulating anti-Rh IgG molecules. If the next pregnancy is an Rh+ conceptus, these anti-Rh IgG molecules will cross the placenta, destroying the fetal erythrocytes, resulting in erythroblastosis fetalis or hemolytic disease of the newborn. The drug RhoGam® is essentially an anti-(anti-Rh IgG) IgG.
(4) TESTES / SERTOLI CELLS (blood-testes barrier)
The junctions of Sertoli cells form the blood-testis barrier (between the blood vessels & the seminiferous tubules of the testes), a structure that partitions the interstitial blood compartment of the testis from the adluminal compartment of the seminiferous tubules. Sertoli cells control the entry and exit of nutrients, hormones and other chemicals into the tubules of the testis.
The seminiferous tubules have a basement membrane that, together with Sertoli cells, forms a blood-testis barrier. Because blood does not penetrate the seminiferous tubules:
1. The developing spermatozoa receive nutrients indirectly, from Sertoli cells, rather than from capillaries.
2. The interior of the tubules are 'immunologically privileged' - no immune reactions. This is important because sperm become haploid (by meiosis) beginning at puberty— long after the immune system develops — so haploid sperm are considered nonself by the immune system.
A male will produce antibodies that attack his own sperm, if the sperm are exposed to circulation (lymphocytes).
(5) OVARY
(6) PROSTATE
(7) TUMORS
(8) HAIR FOLLICLES
(9) CARTILAGES
(10) LIVER
(11) ADRENAL CORTEX
 
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indytravl

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Antigenic materials placed in privileged sites evoke a state of deviant systemic immunity in which the usual mediators of immunogenic inflammation (e.g., delayed hypersensitivity T cells, complement-fixing antibodies) are curtailed, and other mediators (e.g., cytotoxic T cells, noncomplement-fixing IgG antibodies) are enhanced. For example, antigen injected into the eye is picked up locally by intraocular dendritic cells, which then migrate via the blood to the splenic white pulp where antigen-specific regulatory and effector T cells are activated.

Immune-privileged tissues resist immune rejection when grafted into conventional (nonprivileged) sites.
(1) Constitutive _expression of CD95L on the Sertoli cells of a testis graft triggers apoptosis in the recipient’s CD95+ antigen-activated T cells that are challenging the graft.
(2) Myoblasts (muscle cells) genetically engineered to express FasL can protect neighboring transplanted islet cells by inducing apoptosis in visiting T cells for more than 80 days in mice, although the altered myoblasts evidently stimulate an inflammatory response that eventually destroys them.
(3) CD95L-coated tissues (eye, testis, tumor cells) generally stay free of patrolling immune cells. However, Chen et al have noted that while surface-expressed CD95L triggers apoptosis in T lymphocytes, it also stimulates neutrophils and other polymorphonuclear leukocytes. This stimulation may then be inhibited by the local presence of TGF-beta – together, CD95L and TGF-beta promote lymphocyte clonal deletion and suppress inflammation.

Another instance of immune-privileged cells is the embryo, whose developing cells in the placenta manufacture an enzyme known as indoleamine 2,3-dioxygenase (IDO). IDO destroys tryptophan, an amino acid needed by maternal T cells (human cells cannot make their own tryptophan). This localized cell-induced nutrient depletion is believed to suppress the activity of maternal T cells that would otherwise make their way through the placenta and attack the fetal blood supply. Other studies have shown that certain macrophages, induced to express IDO in response to interferon-gamma from activating T cells, inhibit T cell proliferation in vitro by rapidly consuming tryptophan. Amniotic membrane, a related privileged tissue that is fetal in origin and multipotential, lies between mother and baby and reacts with neither. It can be transplanted between species and still survive without the need for immunosuppression. In experimental studies, human amnion has been used to resurface rabbit knee joints and can be useful in ocular and other transplantation procedures. Fibroblasts, which do not constitutively express HLA class II molecules, cannot induce the formation of required helper T cells and thus stimulate no rejection response when transplanted between hosts. Human stem cells were originally believed to provoke no immunogenic reaction because they are not differentiated. However, recent results by Drukker et al found very low but consistent _expression of MHC class I molecules even on undifferentiated human embryonic stem cells. As the cells differentiated, they produced higher levels of the proteins – probably high enough to trigger an immune reaction and to be rejected upon transplantation. (Even though embryonic stem cells aren’t invisible to the immune system, these cells could be genetically engineered so as not to express MHC proteins, or nuclear transfer techniques might be used to create genetically matched stem cells for individual patients.)


Antigen sequestration (or clonal ignorance)
T cells reactive to self-antigen not represented in the thymus will mature and migrate to the periphery, but they may never encounter the appropriate antigen because it is sequestered in inaccessible tissues. Such cells may die out for lack of stimulus. Auto-reactive B cells that escape deletion may not find the antigen or the specific helper T-cells and hence not be activated and die out. A few examples of sequestered antigens: proteins within the lens (If exposed at a later date they will stimulate an immune response. Cataracts of the eye are thought to be such a response.), shielded by the capsule; thyroglobulin within the thyroid follicles; and enzymes forming on the acrosomes of developing spermatozoa on the other side of the blood-testis barrier. (There is evidence that the first two examples may also have granted privilege for there appears to be a specific plasma membrane protein that triggers apoptosis of attacking lymphocytes.)
 

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Right! That's what everybody was trying to say. I'm glad you paid attention.
We were here to help you this time, but don't get in a habit of making SDN a crutch like this.
 

TucsonDDS

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yellowcat322 said:
Actually this is why a lot of people USED to die from gun shots before the advance of modern weaponry, in which the bullet is fired so fast that is actually sears the edges of the wound as it passes through the brain and so you don't have leakage of blood into the neural tissue. That's actually why there was so much progress made in neural sci in the 40's and 50's. The scientists studied soldiers from WWII who survived bullets and shrapnel lodged in their brain and had various defects depending on what the bullet destroyed. You'd be surprised at how many parts of your brain you could live without.

Thanks for the info. It really is amazing how people can adapt to the loss of brain tissue. I have been a nurse for the past 10 years and have taken care of some people with some very devastating traumas who we were all sure they would never feed themselves again. Every now and then one would come back into the hospital to say thanks a year or 2 later after a remarkable recovery. I have also taken care of pediatric patients who have had total hemispherectomies due to seizures and it is amazing how well some of them adapt. If done at an early enough age you may never even know that they ever had surgery.