Diseases of the Immune System 1 Flashcards
What is central tolerance?
What is peripheral tolerance?
CT - During differentiation of lymphocytes we have mechanisms to prevent the generation of mature lymphocytes which may recognise self antigens (e.g. education & selection of T cells in the thymus)
PT - We have additional mechanisms to reduce the chance of mature cells being activated
How do we have soo many TLRs (lymphocyte receptors)?
- The TCR and BCR genes are chopped up into segments and stuck back together to make different receptors
- Receptors are made from the recombination of gene clusters.
Explain B cell receptor development
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How are B cells tested for auto reactivity before leaving the bone marrow?
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Explain T cell development
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How do we teach T cells about ALL the antigens in the body?
- Autoimmune regulator (AIRE) - gene
- AIRE is expressed in the nucleus of thymic medullary stromal cells
- It is a transcriptional regulator which induces the expression of self proteins in the thymus. (problems = autoimmune diseases)
Why is there slow destruction of tissue when there is loss of AIRE gene?
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Draw a Natural T regulatory cell & how it works
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Explain inducible Tregs
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Explain dysregulation of Th17 cells and Tregs in the inflammatory process
- In humans Th17 cells are associated with several diseases including RA, SLE, MS, Psoriasis and IBD
- Chronic inflammation and tissue damage will continue to promote the expansion of Th17 cells (IL-6 &IL-1)
- IL-17 promotes the release of more pro-inflammatory mediators and MMPs. Disruption of this is a target for treatment of inflammatory diseases.
- Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody which disrupts Th17 cells production
- LOSS of Treg function (when mutation in Foxp3 gene) –> IPEX syndrome (Immunodeficiency disorder)
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Types of immunodefiency & define
Immunodeficiency - failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance
- Primary - Inherited mutations
- Secondary - Acquired from diseases or environmental factors (e.g. starvation, HIV)
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What are some problems with lymphocyte generation?
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Severe Combined Immunodeficiency (SCID)
- A defect In T Cell development which mean patients cannot make T-Cell dependent antibody responses.
- Most common is X-linked
3 approaches to treatment of X-linked SCID
- Prophylactic treatment – Sterile environment, antibiotics, immunoglobulins.
- Bone Marrow Transplant – Relies on close HLA match and succesful reconstitution.
- Gene therapy – First trial in 1990s with adenosine deaminase (ADA) SCID replaced the gene in peripheral T cells which survived for a decade.
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Explain AIDS
Acquired Immune deficiency syndrome (AIDS)
- Caused by the human immunodeficiency virus (HIV)
- HIV targets cells which express CD4 and uses CCR5 or CXCR4 as a co-receptor
- Infect mucosal CD4+ cells and spreads in Lymph nodes as T cells enriched with CCR5
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Acute Phase
- Influenza like symptoms in 80% cases ↓ in circulating CD4, activation of CD8. Virus killing and antibody production.
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Clinical Latency
- Get persistent replication of virus and CD4 cell count falls. Virus mutates rapidly to avoid CD8 cells.
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AIDS
- 6-20years after latency
LOW numbers of CD4+ cells
New therapy for AIDS patients
New Therapies – Chimeric antigen receptor T Cells
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