Lecture 19 Flashcards
where does central tolerance occur
primary lymphoid tissue
what does central tolerance do
eliminate clones that recognise self
what are the 3 mechanisms for lymphocytes that recognise self
apoptosis, helper cells become Treg cells and B cells may ingest their receptor and undergo receptor editing
what are T cell populations based on
1) TCR has right sequence and shape so it can bind MHC
2) Can recognise a foreign peptide in grove of MHC and not self peptide
what happens to majority of thymocytes
80% die via neglect as most thymocytes that dont bind self dont get provided a signal during maturation
what happens to the thymocytes that bind strongly to self
20% of T cells die via apoptosis as they bind too strongly
where do Treg cells come from
small amount of thymocytes that bind strongly to self peptide turn into Treg cells
what thymocytes are positively selected
the 1-2% of thymocytes that dont react with self peptides
how are Treg cells formed
small subset of negatively selected are presented with a self peptide however they dont receive signals to die
What do Treg cells do
provide peripheral tolerance mechanisms and if deleted provides autoimmunity
what are the mechanisms for periphreal tolerance
Normal T cell response, Anergy, Suppression, Deletion, Ignorance
what is normal T cell response
produces effector and memory T cells
what is suppression
when there is a block in activation so Tregs control self reactive cells
what is deletion
apoptosis
what is anergy
functional unresponsiveness
Where does central tolerance in B cells occur
Bone marrow
what happens if they dont receive signals
die via apoptosis
What are B cells able to do if they bind self
B cells can ingest their receptor and edit it. It is then redisplayed as a different receptor.
what happens if the B cells arent able to edit their receptor
it dies via apoptosis
What happens if the B cell escapes out into the periphery
it becomes anergic (unresponsive) due to its low binding affinity
what is periphreal tolerance
a back up mechanism that silences any lymphocytes that recognise self
what is clonal anergy
self reactive lymphocytes that are not activated properly and become resistant to stimulation
what does T cell tolerance lead to
B cell tolerance
what is the breakdown of tolerance
failure of an organism to recognize its own parts as self due to loss of tolerance
what are the 4 mechanisms for the breakdown of tolerance
genetic suceptibility, infections, influx of self reactive lymphocytes and activation of self reactive lymphocytes
what are susceptibility genes
1) complement genes are impared immune complex clearance
2) immunogoblin and TCR are antigen receptor genes
3) cytokines and co stimulators are regulatory genes
4) antigen presenting enes are class 1 and class 2
what is sympathetic ophthalmia
damage to eye after trauma which results in the release of intracellular antigens which active T cells in both eyes
what is molecular mimicry
body generates lymphocytes that display bacterial pathogen
what are 2 examples of molecular mimicry
acute rheumatic fever and multiple sclerosis
what is acute rheumatic fever
group A streptococcus post infection complication
what is multiple sclerosis
affects brain and spinal cord
how does multiple scierosis work
autoimmune attack against myelin sheat that sorrounds nerve fibres of brain and spine. the immune response causes gradual destruction of myelin and damage to nerve axons
what are the symptoms of multiple scierosis
change in sensation, visual problems, muscle paralysis
how does acute rheumatic fever work
M protein in cell wall protein shares epitopes with proeins in heart mucles and valve
how do you prevent acute rheumatic fever
long term dose of antibiotics
what is type 1 diabetes
immune system attacks beta islets cells of pancreas
what effect does type 1 diabetes have of Treg cells
normal levels of Treg cells with decreased function
how do you combat type 1 diabetes
daily injections of insulin
what is rheumatoid arthritis
autoimmune attack on synovial tissue and cartilage in joints
what are the symptoms of rheumatoid arthritis
ligament, tendon and bone degradation with pain
what effect does rheumatoid arthritis have on Treg cells
increased levels of Tregs with decreased function
what is a distinctive feature of rheumatoid arthritis
presence of rheumatoid factor in patient serum
what is rheumatoid factor
autoantibodies that bind to own IgG
what is coeliac disease
abnormal reaction to gliadin
what is gliadin
gluten protein found in wheat
how does coeliac disease work
inflammatory reaction flattens villi of intestine which interferes with nutrient absorbtion and frequently leads to anemia
how do you combat coeliac disease
removal of gluten from diet
3 ways to treat autoimmune disease
replacement, infection treatment, remove trigger
what is biologics
more targeted approach to suppress the immune system
what is biologics used for
rheumatoid arthritis
what is NSAIDs and what does it do
non steroidal anti inflammatory drug which blocks symptoms like pain or swelling
what is DMARDs and what does it do
disease modifying anti-rheumatic drugs which are slow acting immune suppressants
what are examples of corticosteroids
NSAIDs and DMARDs
what do corticosteroids do
reduce inflammation
what does removing the trigger work on
coeliac disease by removing gluten from the diet
what is an example of infection treatment
penicillin injects for rheumatic fever
what is an example of replacement treatment
replace lost secretions or inhibit endocrine function such as type 1 diabetes with their insulin injections
