Week 1: Diseases of the Immune system 2 Flashcards
What selection processes to T and B cell undergo whilst maturing?
T cell: positive selection and negative selection
B cell: negative selection
Describe how tolerance in T cells confers tolerance in B cells?
B cell require (normally) a T cell activation signal in order to carry out their function.
If a self recognising B cell survives, it is unlikely that the complimentary self recognising T cell has also survived, therefore the B cell will likely never become activated
Where can negative selection of B cell occur?
Bone marrow
Some negative selection may also occur in the spleen as B cell continue to mature.
What is the co-stimulation reaction between a T reg, Th and an APC?
T reg - CTLA4
T help - CD28
APC - B7
What is the difference between an autoimmune condition and an auto-inflammatory condition?
Autoimmune condition - known specific self antigen that is targeted by the immune system
Autoinflammatory - specific antigen is not know, general inflammatory response causes unnecessary damage.
Is a response to self normal?
Yes, normally there is a small response to self, but this is normally of a lower quality or requires a high concentration of antigen to be activated
The damaging effector response in autoimmunity is not normal - it is pathological
What are some examples of diffuse autoimmune diseases?
Diffuse - spread over a large area.
Rheumatoid arthiritis
Systemic Lupus Erthyematosus
What are some examples of organ specific autoimmune diseases?
Type 1 diabetes
Multiple Sclerosis
Crohns disease
Psoriasis
Graves disease
Hashimoto thyroiditis
How does chronic autoimmune disease develop through a positive feedback loop?
- Insult or injury leads to inflammation
- Macrophage phagocytosed necrotic material (self cells) hence presents cell antigen contained within phagosome onto MHC1
- Self reaction T cell recognises presented antigen and can trigger an immune response
- Immune response attempts to clear the antigen causing more damage, hence creating an endless supply of antigen.
In basic terms, what processes are involved in developing autoimmunity?
Genetic factors - creates hypersensitive immune signalling or turns off tolerance factors. Is a predisposing factor
Combined with an environmental exposure - smoking etc that causes damage releasing self antigen. Acts as the trigger.
This causes an immune regulation by breaching tolerance
Leads to autoimmunity.
How can autoimmune diseases be classified by cause?
Monogenic (mainly genetic - one gene- small interaction with enviro)
Polygenic (require large interaction with environment and many genes)
Is autoimmunity genetic?
Has a genetic componenet - acts as a pre-disposing factor
Autoimmunity (but not always the same autoimmune condition) tends to be familial, shown in monzygotix twins
What do the mutation of genes tend to cause in order to lead to an autoimmune condition?
- disrupt tolerance
- disrupt apoptosis
-promote inflammation - promote cell activation
What is a monogenic autoimmune disease?
Predominant genetic risk factor with minor additional genetic and environmental factors (IPEX and APECED)
What is a complex autoimmune disease?
Multiple genetic and environmental factors influcne the cause
(MS and RA)
How is the mutated AIRE gene involved in an autoimmune condition?
Caused APECED
AIRE gene - allows thymus to express self antigens, expose developing T cell to self antigens, allows for negative selection
When mutated - decreased expression of self antigens in the thymus, results in defective negative selection of self reactive T cells, so enter periphery
How is the mutated CTLA4 gene involved in an autoimmune condition?
Functional CTLA4 used by Treg cells to complete for co-stimulatory molecule B7 from other T cell phenotypes,.
Mutation in CTLA4 decreases T reg function, by reducing the activation threshold of self reacting T cell - hence failure of T cell energy
Associated with type 1 Diabetes and Graves disease
How is the mutated FOXP3 gene involved in an autoimmune condition?
Causes IPEX syndrome
Normal gene acts as a transcription factor for nTreg and iTregs
Mutated T regs are unable to carry out their function.
How is the mutated Fas gene involved in an autoimmune condition?
Results in Autoimmune lymphoproliferative syndrome
When mutated - Failure to induce apoptosis in self reactive T and B cells
How is the mutated C1q gene involed in an autoimmune condition?
Mutated results in defective complement activation results in defective clearances of immune complexes and apoptotic cells
Associated with systemic lupus arythematosus
Describe the structure of MHC (HLA) genes?
MHC is a group of genes resulting in HLA proteins
MHC gene can be split into class 1, class 2 and class 3 genes
Each class is polygenic - contains multiple different genes
Each gene is polymorphic - multiple possible copies of each allele to inherit.