Hypersensitivity, Transplantation and Rejection

Question 1

What is an allergen

Answer 1

• Any substance (antigen) that is recognised by the immune system as non-self
• Causes an allergic reaction
• No common structural or biochemical features

Question 2

What is type I hypersensitivity

Answer 2

• IgE mediated hypersensitivity
• Ag induces cross-linking of IgE basophils to mast cells and release of vasoactive mediators
• Hay-fever, asthma, hives, and eczema

Question 3

What is type II hypersensitivity

Answer 3

• IgG mediated cytotoxic hypersensitivity
• Ab directed against cell surface Ags mediates destruction via complement activation or antibody dependent cellular cytotoxicity
• Blood transfusion reactions, autoimmune haemolytic anaemia and erythroblastosis fetalis

Question 4

What is type III hypersensitivity

Answer 4

• Immune complex mediated hypersensitivity
• Ag-Ab complexes deposited in various tissues induce C’ activation and an inflammatory response mediated by infiltration of neutrophils
• Arthus reactions, serum sickness, necrotising vasculitis, glomerulonephritis, rheumatoid arthritis, SLE

Question 5

What is type IV hypersensitivity

Answer 5

• Cell mediated hypersensitivity
• Sensitised Th1 cells secrete cytokines that activate macrophages and Tc cells which mediate direct cellular damage
• Contact dermatitis, tubercular lesions and graft rejection

Question 6

What is solid organ donation vs HSCT

Answer 6

• Solid Organ: Donors are recently deceased, large program of transplanting
• HSCT: HSCs harvested from BM of living donors using peripheral SCs, differentiate cells to repair damaged organs

Question 7

What are immunological issues associated with organ transplants

Answer 7

• Grafted organ or tissue is recognised as foreign
• Degree and type of immune response to a transplant varies
• Tissues that are antigenically dissimilar are histo-incompatible
• Loci most common to cause rejection are MHC genes

Question 8

What are the different types of graft

Answer 8

• Autograft: Self tissue transferred from one body site to another of same individual
• Isograft: Tissue transferred between genetically identical individuals, syngeneic
• Allograft: Tissue transferred between genetically different members of same species
• Xenograft: Tissues transferred between different species

Question 9

What is host vs graft rejection

Answer 9

• Due to immune recognition, system responds and attacks donor tissue
• Synergic animals that are identical at MHC locus accept grafts from one another
• Animals that differ at MHC locus reject graft
• Accepting a graft relies on recipient sharing all donors MHC genes
• Child can receive from parents but parents cannot receive from child

Question 10

What is allorecognition

Answer 10

• Ability of an individual organism to distinguish its own tissues from another
• Occurs through polymorphic MHC presentation to alloreactive T cells
• Direct (APC present to T)
• Indirect (T recognise antigens consumed by APCs)

Question 11

What is graft vs host disease

Answer 11

• If competent immune cells are transplanted into a recipient via graft
• T cells recognise MHC / minor HC antigens as foreign and produce immune response

Question 12

What is the transplant rejection timeline

Answer 12

• Hyper-Acute (minutes to hours)
• Acute (days to weeks)
• Chronic (months to years)
• Second transplantation is often rejected faster due to immunological memory

Question 13

How is compatible matching ensured

Answer 13

• ABO compatibility (blood group)
• MHC compatibility (siblings / parents first choice)
• Anti-rejection drugs (organ transplant between mismatched people)