Autoimmunity Flashcards
(21 cards)
What are the subdivisions of adaptive immune system?
- Cell mediated (T cells)
- Humoral (B cells)
What are the three different types of T cells and their roles?
- Cytotoxic T cells: break shiz down
- T regulartory cells: keep the cytotoxic/helper cells in check
- T helper cells: activate b cells and cytotoxic t cells
What is tolerance?
“A state of unresponsiveness of the Immune system to self”
Explain the central control of tolerance:
- Inactivation of cells required for initiation of an immune response
- “Negative Selection” ensures only those that work make it out of the thymus
- Tolerance sensitive stage of maturation CD4+ and CD8+ thymocytes
Explain the role of peripheral tolerance:
- Inhibition of expression of the immune response
- Key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.)
- Treg cells carry out this tolerance
- Th17 cells
What is HLA?
Human leukocyte antigen
aka
MHC
What is the difference between autoimmunity and autoimmune disease?
- AUTOIMMUNITY
- Physiological autorecognition with secondary epiphenomena
- AUTOIMMUNE DISEASE
- Immune response contributing directly to tissue / organ damage
- Often exist as a mix of different autoimmune reactions
- Environment and Genetics play a key role
What are some notable features of autoimmune disease?
- In identical twin studies, only 10-50% develop the disease - meaning that the causation is more than just genetics
- Some HLA alleles occur in certain populations and people more often
What are some causes of autoimmunity?
- Immune regulation
- Hormonal (women 4x more likely)
- Environmental (people more northern get MS)
- Genetic factors
- Unknown
What are the different types of autoimmunity?
- Cell mediated
- Antibody mediated
- Antibody and complement
- Immune complex mediated
- Environmental
- Genetic
Cell mediated autoimmunity
Basic process?
- T cells destroy intracellular pathogens by killing infected cells and by activating macrophages but they also have a central role in the destruction of extracellular pathogens by activating B cells.
Cell mediated autoimmunity
How does it go wrong in DM?
- Autoreactive T cells against Pancreatic Islet cell Antigens, leading to destruction and non-production of insulin
Cell mediated autoimmunity
How does it go wrong in crohn’s?
- Triggered by a foreign pathogen leading to APC presentation to TH
- Autoreactive T cells against intestinal Flora antigens leading to lymphocyte infiltration of exocrine glands
- Cytokine reaction from T-Helper cells is dysfunctional and exaggerated, leading to lots of Macrophages creating proteases and platelet activating factors, which causes inflammation
- Can be familial (NOD2 gene)
Cell mediated autoimmunity
How does it go wrong in psoriasis?
Autoreactive T-cells against Skin associated antigens
Cell mediated autoimmunity
How does it go wrong in coeliac?
- In coeliac disease B cells for transglutamine are helped by T cells recognising gliadin (an amino acid sequence in Gluten).
- Secretory IgA in mucosal membrane (normally a marker of immune cell destruction, crosses to lamina proprieta.
- Macrophages uptake these TTG antibodies, express MHCII antibodies (HLA-DQ2)
- CD4+ TH Cells release IFNγ and TNF – destroying villi, CD8+ TC destroy damaged endomysial cells
Antibody mediated autoimmunity
- Antibody binds to targets leading to damage by Fc receptor macrophage with or without complement lysis
- Type II Hypersensitivity Reaction
Immune complex autoimmunity?
- Antigen-antibody/Immune complex formation and deposition, activating phagocytes and causing damage
- Type III Hypersensitivity reaction
- A failure of self-tolerance allows a B-cell to react to leaked DNA auto-antigen from a damaged cell
- If a T-cell that is also specific to this, it begins to secrete anti-dsDNA antibodies to be produced
- Complexes form from DNA fragments, but are too small for Macrophages to sweep uo
- They deposit in tissues, wherein Complement is activated – causing inflammation
Innate recruitment autoimmunity?
- Antibody binds to targets leading to damage by FC receptor macrophage and or complement lysis (AIHA, ITP, Anti-GBM)
- Can also lead to immune complex formation and deposition, activating phagocytes and causing damage (SLE)
- You can also have a direct effect of the autoantibodies on the autoantigen affecting its function (Pemphigis, Myaesthenia)
What is molecular mimicry?
- The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self.
- The cross reactive immune response is responsible for the autoimmune disease state.[14] Cross-reactive immune responses to self were first described for antibodies
- Rhematic fever
What is a disease in which all 4 types of autoimmunity are expressed?
Multiple sclerosis
How do we treat autoimmune disease?
- Immunosuppressive therapy
- Anti-inflammatory therapy
- Plasmapheresis
- Stem Cell/Bone Marrow Transplant (?)
- Replacement of lost physiological factor
- Organ / tissue / mechanical graft
