Wikipedia

User:Immcarle65/sandbox

< User:Immcarle65

Look into discovery of histocompatibility (mixed lymphocyte reactions) The following is my in progress draft for Histocompatibility:

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), the human version of the major histocompatibility complex (MHC).[1] Each individual expresses HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism.[2] T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells.[3] Histocompatibility is relevant in whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant.[4] The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.[4]

Discovery edit

The discovery of the MHC and role of histocompatibility in transplantation was a combined effort of many scientists in the 20th century. A genetic basis for transplantation rejection was proposed in a 1914 Nature paper by C.C. Little and Ernest Tyyzer, which showed that tumors transplanted between genetically identical mice grew normally, but tumors transplanted between non-identical mice were rejected and failed to grow.[5] The role of the immune system in transplant reject was proposed by Peter Medawar, whose skin graft transplants in world war two victims showed that skin transplants between individuals had much higher rejection rates then self-transplants within an individual, and that suppressing the immune system delayed skin transplant rejection.[6] Medawar shared the 1960 Nobel Prize in part for this work.[7]

In the 1930's and 1940's, George Snell and Peter Gorer individually isolated the genetic factors that when similar allowed transplantation between mouse strains, naming them H and antigen II respectively.[8] These factors were in fact one and the same, and the locus was named H-2. Snell coined the term "histocompatibility" to describe the relationship between the H-2 cell-surface proteins and transplant acceptance.[8] The human version of the histocompatibility complex was found by Jean Dausset in the 1950's, when he noticed that recipients of blood transfusions were producing antibodies directed against only the donor cells.[9] The target of these antibodies, or the human leukocyte antigens (HLA), were discovered to be the human homologue of Snell and Gorer's mouse MHC. Snell, Dausset and Baruj Benacerraf shared the 1980 Nobel Prize for the discovery of the MHC and HLA.[10]

Major histocompatibility complex (MHC) edit

Main article: Major histocompatibility complex
 
HLA genes and their location on chromosome 6

HLA, the human form of the major histocompatibility complex (MHC), is located on chromosome 6 at 6p21.3.[11] Individuals inherit two different HLA haplotypes, one from each parent, each containing more than 200 genes relevant to helping the immune system recognize foreign invaders. These genes include MHC class I and class II cell-surface proteins.[12] MHC Class I molecules, HLA-A, HLA-B, HLA-C, are present on all nucleated cells and are responsible for signaling to an immune cell that an antigen is inside the cell.[2] MHC Class II molecules, HLA-DR, and HLA-DQ and HLA-DP, are only present on antigen presenting cells and are responsible for presenting molecules from invading organisms to cells of the immune system.[13]

MHC genes are highly polymorphic, with thousands of versions of the MHC receptors in the population, though any one individual can have no more than two versions for any one loci.[14] MHC receptors are codominantly expressed, meaning all inherited alleles are expressed.[15] The wide variety of potential alleles and multiple loci in the HLA allow for many unique combinations in individuals.

Role in Transplantation edit

After receiving a transplant, the recipient's T cells will become activated by foreign MHC molecules on the donor tissue and trigger the immune system to attack the donated tissue[3] The more similar HLA alleles are between donor and recipient, the fewer foreign targets exist on the donor tissue for the host immune system to recognize and attack.[16] The number and selection of MHC molecules to be considered when determining whether two individuals are histocompatible fluctuates based on application, however matching HLA-A, HLA-B, and HLA-DR has been shown to improve patient outcomes.[17][18] Histocompatibility has a measurable effect on whole organ transplantation, increasing life expectancy of both the patient and organ.[3] HLA similarity is therefore a relevant factor when choosing donors for tissue or organ transplant.

Due to the inherited nature of HLA genes, family members are more likely to be histocompatible. The odds of a sibling having received the same haplotypes from both parents is 25%, while there is a 50% chance that the sibling would share just one haplotype and a 25% chance they would share neither. However, variability due to crossing over, haplotypes may rearrange between generations and siblings may be intermediate matches.[19]

The degree of histocompatibility required is dependent on individual factors, including the the type of tissue or organ and the medical condition of the recipient. While whole organ transplants, can be successful between unmatched individuals, increased histocompatibility lowers rates of rejection, result in longer lifespans, and overall lower associated hospital costs.[20] The impact of HLA matching differs even among whole organ transplants, with some studies reporting less importance in liver transplants as compared to heart, lung, and other organs.[17] In comparison, hematopoietic stem cell transplants are often require higher degrees of matching due to the increased risk of Graft-versus-Host disease, in which the donor's immune system recognizes the recipient's MHC molecules as foreign and mounts an immune response.[21] Some transplanted tissue is not exposed to T cells that could detect foreign MHC molecules, such as corneas, and thus histocompatibility is not a factor in transplantation.[22] Individual factors such as age sometimes factors into matching protocol, as the immune response of older transplant patients towards MHC proteins is slower and therefore less compatibility is necessary for positive results.[23] Post-operative immunosuppressant therapy is often used to lessen the immune response and prevent tissue rejection by dampening the immune system's response to the foreign HLA molecules[24], and can increase the likelihood of successful transplantation in non-identical transplants.[25]

Testing edit

Because of the clinical significance of histocompatibility in tissue transplants, several methods of typing are used to check for HLA allele expression.

Serological Typing edit

Serological typing involves incubating lymphocytes from the recipient with serum containing known antibodies against the varying HLA alleles. If the serum contains an antibody specific for a HLA allele that is present on the recipient's lymphocyte, the antibodies will bind to the cell and activate a complement signaling cascade resulting in cell lysis. A lysed cell will take up an added dye such as trypan blue allowing for identification. Comparing which serums triggers cell lysis allows identification of HLA alleles present on the cell surface of the recipients cells.[26]

Serological typing has the benefit of quickly identifying expressed HLA alleles, and ignores any non-expressed alleles that could be of little immunological significance. However, it does not recognize subclasses of alleles, which are sometimes necessary for matching.[26]

Molecular Typing edit

HLA alleles can be determined by directly analyzing the HLA loci on chromosome 6. Sequence specific oligonucleotide probes, sequence specific primer PCR amplification, and direct sequencing can all be used to identify HLA alleles, often providing amino acid level resolution. Molecular methods can more accurately identify rare and unique alleles, but do not provide information about expression levels. [26]

See also edit

References edit

  1. ^ "Histocompatibility". Dorlands Illustrated Medical Dictionary. Philadelphia, PA: Elsevier. 2012.
  2. ^ a b Cite error: The named reference :0 was invoked but never defined (see the help page).
  3. ^ a b c Cite error: The named reference :1 was invoked but never defined (see the help page).
  4. ^ a b Kindt, Thomas J.; Goldsby, Richard A.; Osborne, Barbara Anne; Kuby, Janis (2006). Kurby Immunology. Macmillan.
  5. ^ Auchincloss, Hugh; Winn, Henry J. (2004-02-01). "Clarence Cook Little (1888–1971): The Genetic Basis of Transplant Immunology". American Journal of Transplantation. 4 (2): 155–159. doi:10.1046/j.1600-6143.2003.00324.x. ISSN 1600-6143. PMID 14974934. S2CID 39596314.
  6. ^ Starzl, Thomas E. (March 1995). "Peter Brian Medawar: Father of transplantation". Journal of the American College of Surgeons. 180 (3): 332–336. ISSN 1072-7515. PMC 2681237. PMID 7874344.
  7. ^ "The Nobel Prize in Physiology or Medicine 1960 - Speed Read". www.nobelprize.org. Retrieved 2018-02-13.
  8. ^ a b Elgert, Klaus D. (2009-09-08). Immunology: Understanding The Immune System. John Wiley & Sons. ISBN 9780470081570.
  9. ^ "The Nobel Prize in Physiology or Medicine 1980 - Speed Read". www.nobelprize.org. Retrieved 2018-02-13.
  10. ^ "The Nobel Prize in Physiology or Medicine 1980 - Speed Read". www.nobelprize.org. Retrieved 2018-02-13.
  11. ^ Kasahara, M. (2000). Major Histocompatibility Complex: Evolution, Structure, and Function. New York: Springer. ISBN 978-4-431-70276-4.
  12. ^ Cite error: The named reference :2 was invoked but never defined (see the help page).
  13. ^ Schwartz, R. H. (1985-01-01). "T-Lymphocyte Recognition of Antigen in Association with Gene Products of the Major Histocompatibility Complex". Annual Review of Immunology. 3 (1): 237–261. doi:10.1146/annurev.iy.03.040185.001321. PMID 2415139.
  14. ^ Cite error: The named reference :3 was invoked but never defined (see the help page).
  15. ^ Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001 The Major Histocompatibility Complex and Its Functions
  16. ^ Trowsdale, John, Knight, Julian C (2013). "Major Histocompatibility Complex Genomics and Human Disease". Annual Review of Genomics and Human Genetics. 14: 301–323. doi:10.1146/annurev-genom-091212-153455. PMC 4426292. PMID 23875801.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b Zachary, Andrea A.; Leffell, Mary S. (2016). "HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act". Frontiers in Immunology. 7: 575. doi:10.3389/fimmu.2016.00575. ISSN 1664-3224. PMC 5141243. PMID 28003816.
  18. ^ Petersdorf, Effie W. (2017-05-03). "Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation". F1000Research. 6: 617. doi:10.12688/f1000research.10990.1. PMC 5419254. PMID 28529723.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ Cruz-Tapias, Paola; Castiblanco, John; Anaya, Juan-Manuel (2013-07-18). Major histocompatibility complex: Antigen processing and presentation. El Rosario University Press.
  20. ^ Takemoto, Steve; Port, Friedrich K.; Claas, Frans H.J.; Duquesnoy, Rene J. (2004). "HLA matching for kidney transplantation". Human Immunology. 65 (12): 1489–1505. doi:10.1016/j.humimm.2004.06.008. PMID 15603878.
  21. ^ Apperley, Jane; Niederwieser, Dietger; Huang, Xiao-jun; Nagler, Arnon; Fuchs, Ephraim; Szer, Jeff; Kodera, Yoshihisa (2016). "Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States". Biology of Blood and Marrow Transplantation. 22 (1): 23–26. doi:10.1016/j.bbmt.2015.11.001. PMID 26551633.
  22. ^ Immune response and the eye : in memoriam J. Wayne Streilein. Niederkorn, J. Y. (Jerry Y.), 1946-, Kaplan, Henry J., Streilein, J. Wayne. (2nd, rev. ed.). Basel: Karger. 2007. ISBN 9783805581875. OCLC 85243138.{{cite book}}: CS1 maint: others (link)
  23. ^ Dreyer, G. J.; Hemke, A. C.; Reinders, M. E. J.; de Fijter, J. W. (2015). "Transplanting the Elderly: Balancing Aging with Histocompatibility". Transplantation Reviews. 29 (4): 205–211. doi:10.1016/j.trre.2015.08.003. PMID 26411382.
  24. ^ Sandwijk, Bemelman, ten Berge C, M.S. van, F.J., I.J.M. (2013). "Immunosuppresive drugs after solid organ transplant". The Netherlands Journal of Medicine. 71 (6): 281–289. PMID 23956308.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Petersdorf, Effie W. (2017-05-03). "Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation". F1000Research. 6: 617. doi:10.12688/f1000research.10990.1. PMC 5419254. PMID 28529723.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  26. ^ a b c Core concepts in renal transplantation. Chandraker, Anil., Sayegh, Mohamed H., Singh, Ajay, 1960-. New York: Springer Science+Business Media, LLC. 2012. ISBN 9781461400073. OCLC 768245800.{{cite book}}: CS1 maint: others (link)

External links edit


Editing Plans and Bibliography

One thing I'd like to do is edit the introduction. Currently it is very heavy on inheritance of the MHC. I'd like to move some of this information down and instead include more of the cellular mechanisms the determine whether two tissues are histocompatible. I'd also like to add a section about recognition of self vs. other, which I think would be of interesting and help to people interested in histocompatibility. I'd also like to organize the testing section. I'm not sure how to best go about making a pretty major change to an entire section. I'm also hoping to fill in citations on the whole article as I go.

Bibliography

Histocompatibility Methods[1]

The MHC in Transplantation[2]

HLA[3] [4]

Partial Match Transplants[5]

Mechanisms in tissue rejection[6]

Immcarle65 (talk)

Article Evaluation for Histocompatibility


  • article rated as "stub" by both wikiproject medicine and wikiproject molecular and cell biology. Rated low and mid importance, respectively.
  • the article seems neutral and balanced.
  • talk page is sparse, most comments from immcarle15
  • citations are sparse, many facts are not cited. Citations need to be expanded greatly
  • intro paragraph seems disorganized- Maybe first talk about relevant definitions, then move to inheritance? I think inheritance might need to be its own section and move more of the transplantation info in the intro instead?
  • not sure how info in MHC section meshes with rest of article- will have to research more
  • expand on transplantation section: talk about partial match transplants?
  • break up testing into multiple paragraphs
  • overall seems like info is there, just could be clearer.
  • Need to start researching reveiws, ect!
  1. ^ Tinckam, Kathryn (April 2009). "Histocompatibility methods". Transplantation Reviews (Orlando, Fla.). 23 (2): 80–93. doi:10.1016/j.trre.2009.01.001. ISSN 1557-9816. PMID 19298939.
  2. ^ Ayala García, Marco Antonio; Yebra, Beatriz González; Flores, Andrea Liliana López; Guerra, Eduardo Guaní (2012). "The Major Histocompatibility Complex in Transplantation". Journal of Transplantation. 2012: 842141. doi:10.1155/2012/842141. ISSN 2090-0007. PMC 3388305. PMID 22778908.
  3. ^ Reference, Genetics Home. "Human leukocyte antigens". Genetics Home Reference. Retrieved 2018-01-25.
  4. ^ Delves, Peter J. (January 2017). "Human Leukocyte Antigen (HLA) System". Merck Manual.
  5. ^ "A New Option For Some Patients in Need of Stem Cell Transplant | Norris Cotton Cancer Center". cancer.dartmouth.edu. Retrieved 2018-01-25.
  6. ^ Ingulli, Elizabeth (October 24, 2008). "Mechanism of cellular rejection in transplantation". Pediatric Nephrology (Berlin, Germany). 25 (1): 61–74. doi:10.1007/s00467-008-1020-x. ISSN 0931-041X. PMC 2778785. PMID 21476231.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Immcarle65/sandbox&oldid=1091735118"