Week 6: Blood Transfusion & Transplant Immunology Flashcards
what is The ABO blood System based on?
The ABO system consists of four basic types (A, AB, B, and O) into which human blood may be classified, based on the presence or absence of certain inherited sets of antigenic carbohydrate structures that are present on erythrocyte surfaces and some endothelial cells.
Define Blood type
The blood “type” is determined by the types of oligosaccharides present on the surface of the red blood cells:
if only the antigen A or B is found, the blood is type A or B, respectively,
if both A and B antigens are present, the blood type is AB
if neither the A or B type antigen is present, the blood type is 0 The A and B antigens differ only in a side-chain on the terminal sugar.
The Genetics of ABO Group
The presence of A and B carbohydrates in our tissues is determined by three alleles at a single genetic locus. One allele encodes an enzyme which produces the A substance, another the B substance; and when both of these alleles are present in a heterozygote both carbohydrates are made. The third allele, O, behaves essentially as a “null” allele, producing neither A nor B substance. Thus, while the ABO system yields only four blood types (phenotypes), there are six possible genotypes:
Genotype blood type
A/A. A
A/O A
B/B. B
B/O. B
A/B AB
O O
Only a single genotype can produce the phenotype AB, namely the heterozygous state A/B. Likewise, type O individuals must be homozygous O/O. However, type A or type B individuals can be either homozygous or heterozygous, the O allele being effectively recessive since it does not contribute either of the two antigens.
The inheritance of the ABO blood groups follows simple Mendelian rules. For instance, a homozygous type A mother and a type AB father can yield only two kinds of offspring, type A (genotype A/A) or type AB (genotype A/B). On the other hand, a heterozygous type A and a heterozygous type B, on the other hand can yield four genotypes and four corresponding phenotypes.
Describe the Rhesus System
The Rhesus system is defined by the presence or absence of a single red blood cell antigen, representing the two blood types Rh+ and Rh-.
‘Natural’ antibodies to Rh do not exist in humans, as they do for the AB antigens. However, Rh+ cells infused into a Rh-negative recipient can give rise to a strong antibody response. This exposure stimulates the production of anti Rh IgG immunoglobulins. This is very clinically significant as IgG is the only known immunoglobulin capable of crossing the placenta.
A Rh+ male and a Rh- female can create a Rh+ fetus. Leakage of fetal Rh+ erythrocytes into the maternal blood during pregnancy, labour or delivery can stimulate the formation of anti Rh IgG antibodies. Subsequent Rh+ fetus
are at risk because the IgG antibodies can pass from the maternal blood supply into the fetus and destroy fetal blood cells and cause organ damage (Erythroblastosis Fetalis, also known as Haemolytic Disease of the New born or HDN).
It is important to note that unlike the A and B antigens, the Rh antigens are present only on red blood cells. Therefore, while they are important for blood transfusion, they do not normally play a role in organ transplantation, and Rh typing of organ donors and recipients therefore not a significant consideration.
what is the importance of Blood Typing and Cross-matching?
Typing blood to match donor and recipient with respect to ABO antigens is an important and widely used procedure; however, there are a number of antigenic molecules on erythrocytes and even the same blood group and rhesus status can trigger an immune response in a blood recipient’s system to a donor blood.
The presence of these antigens and antibodies can be readily detected by an agglutination reaction.
Patient’s serum is tested against RBCs of known blood groups and known serum types.
Define Haemolytic Transfusion Reaction
The reaction occurs when the red blood cells that were given during the
transfusion are destroyed by the person’s immune system.
Define Transfusion Induced Acute Lung Injury (TRALI)
TRALI is a form of acute respiratory distress due to donor plasma containing antibodies against the recipient HLA antigens, mediating the characteristic lung damage. It is the number one cause of transfusion related death in Europe and US.
Transfusion is followed within six hours of transfusion by the development of prominent non-productive cough, breathlessness, hypoxia and frothy sputum. Fever and rigors may be present. CXR shows multiple peripheral nodules with infiltration of the lower lung fields.
Define Transfusion Associated Graft Versus Host Disease (TAGVHD)
Acute GVHD is a complication of allogeneic hemopoietic progenitor cell transplantation when viable lymphocytes in the allograft recognise the host HLA antigen type as foreign. TA-GVHD is typically evident from 8-10 days post transfusion. The clinical syndrome includes fever, diarrhoea, abnormal liver function tests and a characteristic rash particularly affecting the palms. It is almost uniformly fatal, with death occurring within 1 month in over 90% of cases. There is no effective treatment of TA-GVHD and the mortality rate is extremely high.
Define Transfusion-related Immunomodulation (TRIM)
Transfusion-related immunomodulation refers to the transient depression of the immune system following transfusion of blood products.
What happens is an Allergic Reaction as a result of blood transfusion?
Allergic reactions occur when patients have antibodies that react with proteins in transfused blood components. Anaphylaxis occurs where an individual has previously been sensitised to an allergen present in the blood and, on re-exposure, releases immunoglobulin E (IgE) or IgG antibodies. Patients with anaphylaxis become acutely dyspnoeic due to bronchospasm and laryngeal oedema and may complain of chest pain, abdominal pain and nausea. Urticaria and itching are common within minutes of starting a transfusion. Symptoms are usually controlled by slowing the transfusion and giving antihistamine and the transfusion may be continued if there is no progression at 30 minutes.
Pre-treatment with chlorphenamine should be given when a patient has experienced repeated allergic reactions to transfusion.
Define Febrile Non-Haemolytic Transfusion Reactions
Febrile non-haemolytic transfusion reaction is a type of transfusion reaction that is associated with fever but not directly with haemolysis. Fevers (>1°C above baseline) and rigors may develop during red cell or platelet transfusion due to patient antibodies to transfused white cells. This type of reaction affects 1-2% of patients especially multiparous women and those who have received multiple previous transfusions are most at risk. Reactions are unpleasant but not life-threatening.
Session Six: Blood Transfusion & Transplant Immunology
What was the major breakthrough in transplantation?
The major breakthrough came when it was recognised that the body not only recognises antigens from foreign bodies but also molecules encoded within the body. It was suggested that these histo-compatible antigens were encoded by histocompatible genes. When tissues are transplanted from a recipient to a donor with compatible histo-compatible antigens there is a greater chance of success.
The Major Histocompatibility Complex (MHC) was the first histo-compatible gene to be discovered. These multiple gene loci encode proteins that are responsible for causing rejection of grafts. The human analogue form is called Human Leukocyte Antigen (HLA)
Types of Graft
Grafts can be classified in a number of ways including:
The genetic relationship between donor and host.
The location
The type of tissue involved.
Define Autograft:
A transplantation from one part of an individual to another part of the same individual
Define Syngeneic graft:
A transplantation from one individual to a genetically identical individual.
Define Allogenic graft:
A transplant from one individual to a genetically different member of the same species.
Define Xenograft:
A transplant between members of different species.
Define Orthotopic graft:
placed into its normal anatomical location
Define Heterotopic graft:
A graft placed somewhere other than its normal
anatomical location.
Graft rejection is an immunological phenomenon with the following characteristics:
It shows specificity.
It displays immunological memory.
It is systemic. While rejection occurs in a particular location the
ability to reject a graft is not localized.
Once a MHC molecule from a donor graft has been detected the body will mediate an immune response. Graft rejection is a manifestation of Cell Mediated Immunity (CMI). The response to MHC antigens on another individual’s cell is one of the strongest immune responses.
Define Chronic Rejection
Chronic rejection is often associated with differences at minor histo- compatible genes and is T cell-mediated. The graft appears to heal normally but over a long period (months/years) there is fibrosis of the graft and reduced blood supply. This leads to slow rejection of the graft.
Define Acute Rejection
Acute rejection is associated with the major histocompatibility genes. Acute rejection can occur within days/weeks. It is mediated by T cells and antibodies to the graft which activate the complement pathway.
Define Hyper-acute Rejection
Hyper-acute rejection of the graft starts within minutes. Antibodies specific for antigens on the graft endothelial cells create an immune response that prevents establishment of the graft vasculature. The rejection results in thrombosis and ischemic necrosis of the graft leading to the loss of the graft within days.
Define Mixed Lymphocyte Reaction (MLR)
If lymphoid cells from two different strains of mouse are mixed and allowed to incubate in culture for a few days, each population will be triggered by the foreign antigens of the other and the responses of the T cells assayed.
The magnitude of the reaction is proportional the difference in the MHC molecules; however, the MLR differs from the transplantation reaction in that the antigens responsible for MLR are primarily Class II antigens of the MHC.
T cells can be activated against histocompatibility antigens either directly or indirectly. Describe these two mechanisms.
Direct Induction of Rejection
The donor dendritic cells are transported into the recipient’s body within the transplant tissue. When T cells in the recipient recognise donor allogenic MHC molecules on graft dendritic cells it may activate T cells.
Indirect Induction of Rejection
Indirect stimulation occurs when graft cells are ingested by dendritic cells. The dendritic cells process the antigen and present it on the MHC or APC as a foreign peptide fragment.
An increased risk of rejection can be due to:
Prior exposure to foreign graft antigens
The degree of genetic difference between host and donor
Type of tissue being transplanted
List the Components of blood
Plasma
Packed red blood cells Cryoprecipitate
Platelets
What is meant by rhesus negative and positive?
Rhesus system looks at the presence or absence of D antigen on the RBC surface
