Immunology Hypersensitivity Quiz

Hypersensitivity Type II

• This type of hypersensitivity involves alloantibodies (atypical antibodies).
• Examples include Haemolytic Disease of the Foetus and New-born (HDFN) and Haemolytic Transfusion Reactions (HTRs).

Learning Aims and Outcomes

• The videos aim to cover the immune response to blood group antigens in HDFN and HTRs, linking this to pregnancy and pathogenesis of HDFN.
• They also focus on prevention, monitoring, and treatment of HDFN.
• By the end, students should be able to explain the immune response to blood group antigens in HDFN and HTRs, how pregnancy impacts the risk, methods of preventing/testing/monitoring for antibodies, and disease progression.

Contents

• Type II hypersensitivity includes alloantibodies (atypical antibodies) and HDFN.
• Normal immunity during pregnancy is covered.
• Patient symptoms of atypical antibodies and HDFN (maternal and foetal symptoms) are included.
• Diagnosis, detection, monitoring, and laboratory tests for HDFN are detailed.
• Prevention and cure strategies are also discussed.

Learning Objectives

• Students will learn about sensitisation leading to type II hypersensitivity reactions.
• They will understand how sensitisation to blood group antigens leads to haemolytic anaemia.
• The information will cover extravascular haemolysis and the body's biochemical processes for coping with it.

Alloantibodies (Atypical antibodies vs Natural antibodies)

• Natural antibodies are IgM anti-A or anti-B.
• No immune challenge is needed directly from foreign blood.
• Atypical alloantibodies require exposure to someone else's red blood cells.
• They are made to antigens not expressed by the patient.
• Clinically significant atypical antibodies are typically IgG.

Routes of Exposure

• Blood transfusions may involve mandatory ABO and RhD grouping, discretionary Rh phenotype, and K antigen grouping.
• Blood matching is done based on mandatory and discretionary grouping.
• Foetal-maternal haemorrhage occurs when maternal and foetal blood streams mix during labour, birth, 3rd trimester, or miscarriage.

What is Type II Hypersensitivity?

• Type II hypersensitivity is an inappropriate IgG response to immunological challenges.
• IgG, rather than IgE, is the immunoglobulin involved.
• Sensitisation involves a large immunological challenge, which leads to a larger IgG response with repeated smaller challenges.

Differences between sensitisation and subsequent immunisation

• Primary immunological challenges involve high volumes of foreign material (~4mL).
• Subsequent immune responses can be low volume.
• ABO incompatibility is the most frequent but not always clinically significant.
• Clinically significant causes of HDFN include RhD (most risky), then Rhc and K antigens, and then Fya, Fyb, Jka, Jkb, S,s.

Extravascular destruction of red cells

• IgG opsonises red cells.
• Red blood cells are slowed through the Reticular Endothelial System (liver and spleen) by macrophages.
• Macrophages digest the marked red blood cells.
• The pathway enzymes and albumin are finite.
• Unconjugated bilirubin and jaundice buildup occur.

Summary

• The process of sensitisation and when it is most likely to occur in HDFN and haemolytic transfusion reactions (HTRs) are covered.
• The immunological response, presentation timeline, extravascular haemolysis, and biochemical coping mechanisms are included.

Normal Immunity During Pregnancy

• Information about normal immunity during pregnancy is covered.

Learning Objectives (different set)

• The role of the placenta in normal maternal/foetal immunity, classes of immunoglobulin involved in passive immunity, and how maternal immunity changes during pregnancy are described.

Aim of immunity during pregnancy

• Pregnancy immunity aims to protect the mother and baby, destroying any foreign material, and establishing a placenta barrier.
• The barrier breaks down during birth in the 3rd trimester.

Passive immunity during pregnancy

• Pregnancy passive immunity aims to protect the foetus.
• IgG1 and IgG3 are the major subtypes actively transported across the placenta.
• Passive immunity covers the prenatal and birth periods up to the postpartum, with the neonatal immune system not fully developed until 3-6 months after birth.
• Colostrum provides passive immunity to the newborn.

Maternal Immune Timetable

• The maternal immune system experiences changes in inflammatory response across the different phases of pregnancy.
• During the first trimester, an increased inflammatory response occurs.
• The second trimester involves a regulated, anti-inflammatory response.
• The third trimester involves a pro-inflammatory response.
• Susceptibility to infection and miscarriage risks vary among the phases.

Summary (different set)

• How the immune system operates during pregnancy is covered.
• High-risk periods for immune sensitisation are identified.

Patient Symptoms of Atypical Antibodies/Maternal and Foetal Symptoms of HDFN

• Patient symptoms associated with atypical antibodies, and maternal and foetal symptoms of HDFN are discussed.

Learning Objectives (different set)

• Presentation pattern of HDFN and HTRs is described.
• How HDFN represents pathophysiologically and how it relates to detecting active disease.
• The extravascular breakdown of red blood cells, toxic breakdown products, and how the body responds are presented.

Standard Timeline for Transfusion Reaction

• A delayed transfusion reaction, potentially transfusion-dependent, presents 3-4 weeks after the transfusion, and is associated with anemia symptoms (tiredness, shortness of breath, pallor).
• Repeated testing can reveal an atypical antibody.
• The antibody needs identification before crossmatching.
• Blood must be ABO, Rh, and K compatible.

Standard Timeline for HDFN

• Antigen-negative mother, first or new partner pregnancy, issues with future pregnancies (delaying development, miscarriages), risks of kernicterus, and hydrops fetalis are noted.

Maternal and Symptoms of HDFN

• The foetus may show slower developmental issues after the first trimester.
• Faster heart rate and BP.
• Faster flow rate measured using the Medial Cerebral Artery.
• Extravascular hemolysis may lead to an overload of bilirubin metabolic pathways, oedema, hydrops, and brain plaque deposition.

Clinical Manifestations of HDFN

• HDFN may cause subclinical conditions.
• Severe conditions can be fatal, presenting as anemia, hepatosplenomegaly, edema, congestive heart failure, and jaundice.
• High post-natal bilirubin levels increase the risk of kernicterus.

Summary (different set)

• The pathophysiology of HDFN in multiple pregnancies is explained.
• Disease presentation and progression are discussed.
• Active HDFN detection methods, technologies, and foetal monitoring are explored.

Diagnosis of HDFN, Detection and Monitoring

• Laboratory medicine's role in HDFN diagnosis and monitoring is understood.
• Patient's journey through pregnancy is considered.
• Antigen implications for HDFN, relevant ones, and available treatments are covered.

Learning Objectives (different set)

• Laboratory tests used to determine the patient/foetus' genotype/phenotype are described.
• Risks associated with paternal sampling and diagnosing HDFN or foetal blood groups are discussed.
• Detecting foetal maternal haemorrhage to predict sensitisation is included.

New or Existing Patients

• Blood group testing at booking is a preventative measure.
• Tests are done for ABO, RhD, RhC, c, E, e, and K (discretionary).
• Antibody and clinically significant/atypical antibodies are screened.

Identifying and Blood Groups Responsible

• Blood type of the father is analysed.
• Risks are noted.
• Foetal DNA sampling, chorionic villi sampling, amniocentesis, and maternal/foetal blood sampling are presented.

Paternal Blood Samples

• Father's potential blood group and blood type are noted, along with the mother's potential type.
• Relevant child blood groups are given.
• Problems/disparities are identified.

DNA Blood Grouping Analysis

• DNA blood grouping using methods like chorionic villi sampling, ultrasound/foetal blood/maternal blood sampling, and/or foetal DNA is discussed.
• Accuracy of methods for predicting phenotype is acknowledged.
• Potential for predicting phenotypes but not the cause is highlighted.
• Relationship of specific blood types is explained.
• Testing availability and location are included.

Suspected HDFN Cases - Clinical Assessment in the Antenatal Period

• Amniocentesis details are excluded.
• Correlation with spectrophotometric analysis for bilirubin concentration helps determine diagnostic severity and potential for foetal death or maternal immunisation risks.
• Modified Lilley Charts are used to assess zones based on optical density readings.

Phenotyping Blood (Foetal Blood Samples)

• Foetal blood samples show reduced antigen expression.
• Blood type antigen expression is detailed.
• Antigens like Rh, ABO, and Kell groups are discussed in relation to testing.

Laboratory Estimation of Size of FMH

• Acid Elution (Kleihauer-Betke Stain) methodology is described.
• The method involves exposing a maternal blood film to a specific acid buffer and stain.
• The method visually differentiates foetal and adult haemoglobin.
• Visual estimation is done on stained foetal cells vs adult cells.

Flow Cytometry

• This method directly measures foetal RhD+ cells.
• Accuracy/reliability in assessing fetomaternal haemorrhage (FMH) above 2 mL is highlighted.
• It involves a direct staining method using fluorescein-labelled monoclonal antibodies to foetal red blood cells.

Summary (different set)

• Role of the blood bank in diagnosing HDFN, use of phenotyping/genotyping for foetal/maternal/paternal samples, and importance of FMH and its detection are covered.

Prevention or Cure

• Prevention/cure methods for HDFN are described.

Learning Objectives (different set)

• Prevention methods for HDFN are examined.
• Prevention vs. cure distinctions in HDFN treatment are explored.
• Antenatal Anti-D Prophylaxis (RAADP) impact is discussed.

Prevention of Rh HDFN

• Suppressing maternal immunisation to the RhD antigen by preventing an immune response to the foetal red blood cells is the key prevention strategy.
• Group O blood types (which lack these antigens) provide some protective effects.

Historical aspects of Rh Prophylaxis

• Historical dates and events related to Rh prophylaxis are listed.
• Key milestones in the development of the prevention techniques are presented.

Prevention of HDFN - Rh Prophylaxis

• Rh prophylaxis, using passive administration of donor anti-D IgG, is discussed as a prevention strategy for HDFN.
• Immunisation of the mother to foetal red cells is prevented.
• Postnatal and antenatal routine prophylaxis introduction dates and NICE recommendations are noted.

Rh Prophylaxis Suppresses Maternal Immunisation - Basic Concepts

• A finite, measured amount of donor anti-D IgG is administered post-potential foetal-maternal haemorrhage.
• It targets and destroys potentially escaped foetal red blood cells to avoid maternal immunisation.
• Clearing within 72 hours is critical.

Mechanisms of immune suppression by Rh Prophylaxis

• How the anti-D-mediated immune suppression works is explained.
• The theories in action, including the immuno-receptor tyrosine-based activation/inhibition motifs, are detailed.

Current Guidelines for Administration of Rh Prophylaxis (Antenatally)

• Routine dosage and timing of antenatal anti-D prophylaxis (RAADP) are outlined.
• Guidelines cover cases with RhD-negative mothers.
• Recommendations for potentially sensitising events, doses based on pregnancy length, and FMH amounts are discussed.

anti-D Ig - Standard Dose

• The standard dose for UK-based postnatal treatments (500 IU) protects against FMH amounts of up to 4 mL of foetal cells.
• The minority 0.7% of clinically relevant haemorrhages beyond that amount require adjustments to avoid complications.
• Calculations involve measuring the FMH size to determine additional doses.

Current Guidelines for Administration of Rh Prophylaxis (Postnatally)

• Postnatal administration to RhD-negative mothers if the baby is RhD-positive or Rh type is unknown is recommended within 72 hours of delivery.
• Doses are measured based on FMH quantities greater than 4 mL.

Rh Prophylaxis - a Success Story

• Rh prophylaxis was a major medical triumph in reducing incidences of perinatal deaths linked to Rhesus disease.
• This reduction corresponds to a major decrease in rates of Rhesus disease over the historical periods.

Rh Prophylaxis - A Success Story?

• Rhesus disease persists despite significant progress in preventing its effects.
• Guidelines and protocols may not be uniformly followed, contributing to continued cases.
• Rhesus disease cases are related to non-adherence to guidelines and missed administration opportunities.

Summary (different set)

• The theory and background of RAADP (route to clinical practice, mechanism, and impact on HDFN cases) are discussed.

Laboratory Tests for HDFN

• Learning objectives address the role of laboratory tests in genotyping and phenotyping patients and foetuses, risks of paternal sampling in diagnosing HDFN/foetal blood groups, and detection of foetal-maternal haemorrhage to predict sensitisation.

Summary (different set)

• Blood bank role in diagnosing HDFN is discussed.
• Methods for phenotyping/genotyping foetal, maternal, and paternal samples are described.
• The clinical significance of fetomaternal haemorrhage (FMH) and its detection are explored.

Prevention or Cure (different set)

• The learning objectives for prevention/cure are explained.

Test your understanding of hypersensitivity, especially Type II hypersensitivity and its relation to atypical alloantibodies. This quiz covers critical concepts such as the immune response in haemolytic disease of the foetus and newborn (HDFN) and essential laboratory tests for its detection. Challenge your knowledge and master the complexities of immunology!