MHC and Transplant Rejection Flashcards
What is an isograft?
A graft between two individuals that are genetically identical (monozygotic twins)
What is an allograft?
Transplant of organ/tissue from one individual to another of the same species with a different genotype (i.e. not identical twins)
What is a xenograft?
a tissue graft or organ transplant between different species
What is HLA?
The human leukocyte antigen (HLA) system or complex is a group of related proteins that are encoded by the major histocompatibility complex (MHC) gene complex in humans.
How does the adaptive immune system become activate after the first few foreign cells have been phagocytosed?
Lymphocytes mount a specific immune response by recognising antigens on the surface on antigen-presenting cells such as macrophages:
- Pathogen is phagocytosed
- The macrophage or dendritic cell digests the pathogen and presents a small peptide (the antigen) on its surface
- The antigen is presented as part of a receptor that is located on the surface of antigen-presenting cells (MHC)
In humans, what are MHCs called?
Human Leukocyte Antigens (HLAs).
What are the 2 classes of antigens found on cell surfaces?
Class I and class II
On which cells are Class I antigens found?
All nucleated cells (except RBC’s)
Describe type I antigens (MHC class I molecules)
- Heterodimers
- Heavy chain
- β2-microglobulin (β2M)
On which cells are Class II antigens found?
APCs
Cytosolic pathogens:
- Where are they degraded?
- What MHC class do the peptides bind to?
- What cells are they presented to?
- What is the effect on presenting cells?
- Degraded in the cytosol
- Peptides bind to MHC Class I
- Presented to effector CD8 T cells (cytotoxic T cells)
- Causes cell death of presenting cell
Intravesicular pathogens:
- Where are they degraded?
- What MHC class do the peptides bind to?
- What cells are they presented to?
- What is the effect on presenting cells?
- Degraded in endocytic vesicles (low pH)
- Peptides bind to MHC class II
- Presented to CD4 T cells
- Activate presenting cell to kill intravesicular bacteria and parasites
Extracellular pathogens and toxins:
- Where are they degraded?
- What MHC class do the peptides bind to?
- What cells are they presented to?
- What is the effect on presenting cells?
- Degraded in endocytic vesicles (low pH)
- Peptides bind to MHC class II
- Presented to CD4 T cells
- Activate B cells to secrete Ig to eliminate extracellular bacteria/toxins
On which chromosome does the MHC region occur on?
Chromosome 6
HLA genes are highly polymorphic. What does this mean?
HLA genes are highly polymorphic, which means that they have many different alleles –> allowing them to fine-tune the adaptive immune system and bind different peptides
Where do T cells originate from?
from haematopoietic stem cells which are produced in the bone marrow
After leaving the bone marrow, where do progenitor T cells travel?
travel to the thymus via the blood
Where do T cells mature?
Thymus
How are T cells positively/negatively selected in the thymus?
- Thymocytes (immature T cells) that recognise self-MHC molecules receive positive signals for survival
- Thymocytes that have receptors to self-antigen molecules receive negative signals and are removed
How can HLA variability be linked to disease?
People with certain HLA antigens are more likely to develop certain autoimmune diseases, such as type I diabetes, rheumatoid arthritis, celiac disease, SLE
E.g. DR3 confers susceptibility to SLE
What is the immunological synapse?
The interface between an antigen-presenting cell or target cell and a lymphocyte such as a T/B cell or Natural Killer cell.
What is indirect alloantigen recognition? Describe in terms of transplantation
Normal antigen mechanism of T lymphocytes:
- Alloantigens derived from graft are internalised, processed and presented in form of peptides by recipient’s APCs on their MHC II molecules
- Presented to T lymphocytes –> rejection of transplant
What is direct alloantigen recognition? Describe in terms of transplantation
- Population of APCs is localised inside donor’s tissues and is co-transferred from donor to recipient via transplant procedure –> ‘passenger cells’
- Shortly after transplantation, these cells migrate through lymphatic system to regional lymphatic nodes.
- Inside the lymphatic nodes, these cells are confronted with recipient’s naïve T lymphocytes and their contact culminate in recognition of allogenic MHC displayed on the surface of the passenger cells.
- This phenomenon is called direct recognition and leads to acute rejection of allografts
In this case, alloreactive T cells are stimulated by donor APCs
Once the CD4+ T cell have recognised a foreign antigen, they can generate many types of responses.
- Antibody production (B cells)
- Cytotoxicity (CD8+ cells)
- DTH (delayed-type hypersensitivity response)
What is a haplotype?
A haplotype is a group of genes within an organism that was inherited together from a single parent.
Example of two children inheriting the very same HLA from their parents, they are an HLA “identical match”. While another child in the same family can inherit a different combination of HLA:
What type of a mismatch is this?
1,1,1 mismatch as 1 mismatch per HLA
Renal transplant pathway
How is flow cytometry used for antibody detection?
Flow Cytometry uses fluorescent markers on antibodies or other proteins in order to quantifiably detect changes in protein expression via excitation of the various fluorescent markers. Flow cytometry can be used for detecting numerous targets either on the surface or within cells in the same sample.
Detection of antibodies methods comparison
