Regulation Of Lymphocytes Flashcards
Why is immune regulation important?
To avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
To prevent inappropriate reactions against self-antigens (“tolerance”)
What is autoimmunity?
Immune response against self antigens
What happens if immune regulation fails? (3 answers)
Autoimmunity
Allergy
Hypercytokinemia and sepsis - excessive immune response triggered by positive feedback loop
What are the 3 signals required to license an immune response?
- Antigen recognition
- Co-stimulation
- Cytokine release
What is self limitation?
Preventing excessive immune response. Primary mechanism is through elimination of antigen removing the first signal for lymphocyte activation.
What are the 5 steps of cell-mediated immunity?
- Dendritic cell collects antigen from infected cells
- MHC peptide TCR interaction
- Naïve T cell becomes effector
- Effector cell performs functions on MHC peptides on infected cell (cytotoxic T cell)
- Effector pool contracts to memory cells
What happens at the end of an immune response?
Resolution - no tissue damage, returns to normal. Phagocytosis of debris by macrophages.
Repair - healing with scar tissue and regeneration. Fibroblasts and collagen synthesis.
Chronic inflammation - active inflammation and attempts to repair damage ongoing.
Responses against pathogens decline as the infection is eliminated. Lymphocytes that lose their survival signals (antigens etc.) undergo apoptosis leaving only memory cells.
Why is immunological tolerance important?
- All individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity.
- Therapeutic potential: Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases.
What is central tolerance?
Central tolerance = destroy self-reactive T or B cells before they enter the circulation.
Lymphocytes that recognise self-antigens before maturation in the generative organs are eliminated (deletion) or made harmless.
What is peripheral tolerance?
Peripheral tolerance = destroy or control any self-reactive T or B cells which do manage to enter the circulation.
Some B cells may change their specificity and some T cells develop into regulatory (suppressive) T lymphocytes.
What is the function of AIRE (autoimmune regulator)?
AIRE is a specialised transcription factor that drives the negative selection of self-reactive T cells.
It does this by allowing the transcription of a wide range of organ-specific genes in the thymus. This produces proteins that are usually only present in other tissues in the thymus. T cells that bind strongly to self antigens are eliminated.
What are the 4 main parts of peripheral tolerance?
Anergy, ignorance, deletion, regulation
What happens to T cells in the thymus that cannot bind to any self-MHC at all?
Undergoes apoptosis by neglect since it no longer receives survival signals.
What happens to T cells that bind to self-MHC too strongly?
Triggers apoptosis (negative selection)
What happens to T cells that bind weakly to self-MHC?
GIven signal to survive (positive selection).
What does it mean for a T cell to become anergic and how does it occur?
A T cell that is anergic is less likely to be stimulated in the future even if co-stimulation is present.
Naive T cells need co-stimulatory molecules from the antigen presenting cell to activate. If a naive T cell sees its MHC without appropriate co-stimulatory protein it becomes anergic.
Role of Th1
Produces interferon gamma. Boosts intracellular immune response.
Role of Th2
Produces il4, il5 and il13. Boosts anti-multicellular orgnaism response.
Role of Tfh
Produces il21, resides in B cell follicles. It is essential for the generation of isotype-switched antibodies.
Role of Th17
Produces il17 in autoimmune diseases such as arthritis. There are also other T helper cells named after the interleukin it produces for example Th9 and Th22 which produces il9 and il22 respectively.
Role of Treg
Expresses transcription factor FoxP3. A mutation in this gene leads to IPEX which is a severe and fatal autoimmune disorder.
What does IPEX stand for?
Immune dysregulation, polyendicrinopathy, enteropathy, X-linked syndrome
What are the 2 types of Treg?
Natural Treg and Inducible Treg
What is the difference between the two types of Treg?
Natural - develops in thymus and resides in peripheral tissues to prevent harmful reactions to self.
Inducible - develops from normal CD4+ T helper cells that are exposed to antigens in the periphery. May be generated in all immune responses to minimise collateral damage.
When is Treg regulation especially critical?
Pregnancy - only mammals have Treg.
Function of il10
Multifunctonal anti-inflammatory cytokine that acts on a range of cells and blocks pro-inflammatory cytokine synthesis including TNF, il6 and il8. It also downregulates macrophages.
