This document discusses HLA transplantation and the complement system. It begins by explaining that the success of organ transplants depends on donor and recipient HLA proteins matching. It then describes that HLA proteins are encoded by genes in the MHC located on chromosome 6, and are classified as class I or II proteins. The document provides details on MHC protein structure and expression, as well as the biological importance of MHC in antigen presentation and T cell recognition. It defines types of transplants and explains transplant rejection processes. Finally, it gives an overview of the complement system, describing its activation pathways and roles in immune responses like opsonization, chemotaxis, and cytolysis.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
Direct
Passive
Reverse Passive
Agglutination Inhibition
Coagglutination
Agglutination tests can be done :
On slides
In tubes
In microtritation plates
-Difference between precipitation and agglutination reaction.
Direct
Passive
Reverse Passive
Agglutination Inhibition
Coagglutination
Agglutination tests can be done :
On slides
In tubes
In microtritation plates
-Difference between precipitation and agglutination reaction.
Beton santralleri ve Beton Pompaları kataloğu pi makina. Sabit ve mobil beton santrallerinden skreyperli beton santrallerine tüm modellerin anlatıldığı katalogda kamyon üstü beton pompası ve çekilebilir beton pompaları da yer almaktadır
3D aanzichten van De Noordhave, afstudeeropdracht, Examenjaar 2014 MBO Bouwku...Fred den Boer
Korte impressie van hoe het pand er in Revit uitziet. Dit is bovendien een geheel vernieuwde indeling van het pand wat als ontwerp dient en nooit daadwerkelijk is en zal worden uitgevoerd.
introduction, history, classification of grafts, transplantation antigens, role of MHC in transplantation, immunology of allogenic transplantation, types of graft rejection, immunology of xenogeneic transplatation, organ trannsplantation.
Immunology of Transplantation and Rejection A. Rakha
This file gives info about transplantation and the immunological problem like tissue rejection. MHC role in transplantation, laws, and types of tissue transplantation. Explains all kinds of tissue rejection and source of tissue. Some immunological terms plus transplantation history, it also includes the genetic basis of Transplantation. Hope it's helpful
TRANSPLANTATION IMMUNOLOGY- MLR, HLA TYPING.pptxBharath S R
PURPOSE OF HLA TYPING, CONDITIONS THAT REQUIRING TRANSPLANTATION, THE PROCESS OF HLA TYPING, HLA TYPING IMPORTANT ROLE, SEROLOGICAL TEST, Microlymphocytotoxic test, MIXED LYMPHOCYTE REACTION, Molecular HLA typing, PCR BASED METHODS/ THREE CATEGORIES, STEPS OF MOLECULAR CLONING, Sequence specific priming, Hybridization with sequence specific oligonucleotide probes (SSOP), SEQUENCE BASED HLA TYPING, CLINICAL SIGNIFICANCE OF HLA TYPING,
2. HLA human leukocyte antigens:
Alloantigen – differ among members of same species
present on surface of cells, encoded on HLA genes
Genes clustered on MHC, located on short arm of chromosome6.
HLA Genes
HLA-A, HLA-B, HLA-C → Class I MHC proteins
HLA-D → DP, DQ, DR → Class II MHC proteins
Class III Genes for → C2, C4, TNF, Lymphotoxin LT
2 haplotypes, maternal and paternal sets
Polymorphic (many alleles) HLA-A – 47, HLA-B – 88, HLA-C – 29, HLA-D - 300
3. Every person has single allele at each locus. So inherit
two haplotypes – 1 maternal on chromosome 6, 1 paternal set.
Each allele can make 2 class I & 2 class II proteins. Co- dominant. Proteins by both are expressed.
Each person can make 12 HLA proteins 3 each at class I and II loci, from both chromosomes
Minor antigens by genes at other sites. Body proteins with 1 or more different amino acid → weak immune response → slow rejection of graft.
4. Class I MHC: glycoprotein. Present on All nucleated cells
20 proteins encoded by A, 40 by B, 8 by C gene locus
45,000 Mol. wt. Heavy chain non covalently bound to β2 microglobulin. Similar to Ig molecule. Highly polymorphic. Importance is recognition of self & non self. Hypervariable region at N terminal region. constant region binds to CD 8 of cytotoxic T cell
5. Class II MHC: glycoprotein. Highly polymorphic
Present on Macrophages, B cell, Dendritic cell Spleen, Langerhans cell (skin)
Made up of 2 polypeptides (mol wt. 33000, 28000) non covalently bound. Constant region for CD4 protein of helper T cell
Functions of Major Histocompatibility Complex MHC
1. Positive selection of T cells in thymus
2. Antigen presentation
6. Present antigens to T cells which recognize antigen only if associated to self class I or II MHC → immune response - MHC restriction.
Success of organ or tissue transplant - compatibility of donor & recipient MHC genes. If HLA proteins differ → immune response → rejection of graft. Minor antigens → slow rejection.
Autoimmune diseases: occur in individuals who carry
certain MHC genes
7. Auto graft: Transfer of individuals own tissue to another site in the body. Permanently accepted
Syngeneic graft: Transfer of tissues between genetically identical individuals e.g identical twins
Xenograft: Transfer between different species.
Allograft: Transfer between members of same species. Usually rejected unless immunosuppressive drugs given e.g from one human to another.
8. Allografts are rejected by a process known as allograft reaction.
In an acute allograft reaction;
vascularization of the graft is normal initially, but in 11-14 days, marked reduction in circulation and mononuclear cell infiltration occurs, with eventual necrosis.
This is called a primary (first-set) reaction
A T-cell-mediated reaction is the main cause of rejection of many types of grafts, e.g., skin, but antibodies contribute to the rejection of certain transplants, especially bone marrow
9. If a second allograft from the same donor is applied to a sensi
Description of various immunological mechanisms involved in the rejection of transplants. Lecture notes for medical, dental and allied health sciences undergraduate medical students.
Transplantation : Introduction to immunology part of Major Histocompatability complex(MHC) that facilitates you to understand the basic principles or issues of graft rejection and How it occurs.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
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The Importance of Community Nursing Care.pdfAD Healthcare
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The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
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Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
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Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
2. Human Leukocyte Antigen
• The success of tissue and organ transplants
depends on the donor's and recipient's human
leukocyte antigens (HLA) encoded by the HLA
genes.
• These proteins are alloantigens
(They differ among members of the same species)
• If the HLA proteins on the donor's cells differ
from those on the recipient's cells, an immune
response occurs in the recipient.
Based upon Warren Levinson 2
3. Major Histocompatibility Complex
• The genes for the HLA proteins are
clustered in the major
histocompatibility complex (MHC),
located on the short arm of
chromosome 6
– Three of these genes (HLA-A, HLA-B,
and HLA-C) code for the class I MHC
proteins.
– Several HLA-D loci determine the
class II MHC proteins, i.e., DP, DQ,
and DR
– Class I MHC proteins are found on
the surface of all nucleated cells,
including those that have class II
MHC proteins.
Based upon Warren Levinson 3
4. MHC Proteins
Class I MHC Proteins
• These are glycoproteins found on the surface of virtually all nucleated
cells.
• The complete class I protein is composed of a 45,000-molecular weight
heavy chain non-covalently bound to a Beta 2-microglobulin.
• The polymorphism of these molecules is important in the recognition of
self and non-self.
CLASS II MHC PROTEINS
• These are glycoproteins found on the surface of certain cells, including
macrophages, B cells, dendritic cells of the spleen, and Langerhans' cells of
the skin.
• They are highly polymorphic glycoproteins composed of two polypeptides
(MW 33,000 and 28,000) that are non-covalently bound.
• Like class I proteins, they have hypervariable regions that provide much of
the polymorphism. Based upon Warren Levinson 4
6. Mode of HLA Expression
• Each person has two haplotypes
– one on the paternal chromosome
– Other on the maternal chromosome
• These genes are polymorphic
– For example, there are at least 47 HLA-A genes, 88 HLA-B genes, 29 HLA-C genes, and
more than 300 HLA-D genes, but any individual inherits only a single allele at each locus
from each parent and thus can make no more than 2 class I and II proteins
at each gene locus.
– Expression of these genes is codominant
– Each person can make as many as 12 different HLA proteins
– 3 at class I loci and 3 at class II loci, from both chromosomes.
– There are an unknown number of minor antigens encoded by genes at sites other than
the HLA locus that can lead to slow graft rejection.
Based upon Warren Levinson 6
7. Biological Importance of MHC
• The ability of T cells to recognize antigen is dependent
on association of the antigen with either class I or class
II proteins.
• For example, cytotoxic T cells respond to antigen in
association with class I MHC proteins.
• Helper cell activity depends on both the recognition of
the antigen on antigen-presenting cells and the
presence on these cells of "self" class II MHC proteins.
• This requirement to recognize antigen in association
with a "self" MHC protein is called MHC restriction.
Based upon Warren Levinson 7
8. Transplant
Terminology
Autograft:
Transfer of an individual's own tissue to another site in the
body is always permanently accepted
Syngeneic graft:
A transfer of tissue between genetically identical individuals
Xenograft
A transfer of tissue between different species, is always
rejected by an immunocompetent recipient.
Allograft
A graft between genetically different members of the same
species
Based upon Warren Levinson 8
9. Transplant Rejection
• Unless immunosuppressive measures are taken, allografts
are rejected by a process called the allograft reaction.
• In an acute allograft reaction, vascularization of the graft is
normal initially, but in 11 to 14 days, marked reduction in
circulation and mononuclear cell infiltration occurs, with
eventual necrosis.
• This is called a primary (first-set) reaction.
• A T-cell–mediated reaction is the main cause of rejection
of many types of grafts, e.g., skin
• Antibodies contribute to the rejection of certain
transplants, especially bone marrow
Based upon Warren Levinson 9
10. Graft Versus Host Reaction
• Well-matched transplants of bone marrow may establish themselves
initially in 85% of recipients, but subsequently a graft versus-host (GVH)
reaction develops in about two-thirds of them.
• This reaction occurs because grafted immunocompetent T cells proliferate
in the irradiated, immunocompromised host and reject cells with "foreign"
proteins, resulting in severe organ dysfunction.
• The donor's cytotoxic T cells play a major role in destroying the recipient's
cells. Among the main symptoms are maculopapular rash, jaundice,
hepatosplenomegaly, and diarrhea .
• Many GVH reactions end in overwhelming infections and death.
• There are three requirements for a GVH reaction to occur:
– The graft must contain immunocompetent T cells
– The host must be immunocompromised
– The recipient must express antigens (e.g., MHC proteins) foreign to the donor
Based upon Warren Levinson 10
11. Complement
• The complement system consists of approximately 20 proteins that
are present in normal human (and other animal) serum.
• The term "complement" refers to the ability of these proteins to
complement, i.e., augment, the effects of other components of
the immune system, e.g., antibody.
• Complement is an important component of our innate host
defenses.
• There are three main effects of complement:
– Lysis of cells such a s bacteria , allografts, and tumor cells
– Generation of mediators that participate in inflammation and attract
neutrophils
– Opsonization, i.e., enha ncement of pha gocytosis.
Complement proteins a re synthesized ma inly by the liver.
Based upon Warren Levinson 11
13. Regulation of Complement
Opsonization
Microbes are phagocytized much better in the presence of C3b.
Chemotaxis
5a and the C5,6,7 complex attract neutrophils.
Anaphylatoxin
C3a , C4a , and C5a cause degranulation of mast cells. Ana phyla toxins can also bind directly to smooth
muscle cells of the bronchioles
Cytolysis
Insertion of the C5b,6,7,8,9 complex into the cell membrane leads to killing or lysis of many types of
cells
Enhancement of Antibody ProductioN
The binding of C3b to its receptors on the surface of activated B cells greatly enhances antibody
production
Based upon Warren Levinson 13