Autoimmunity Overview Flashcards
What is the name given to the process whereby T cells are formed from precursor thymocytes?
Where does this process occur?
Thymocytes education or central tolerance
In the thymus gland
What are the steps of thymocytes education?
Where do each of these steps occur?
Thymocytes rearrange T cell receptor genes in thymus to create new T cell receptors
Functional T cell receptor?
Positive selection for self (thymic cortex)
Negative selection for too much self (high affinity self reacting self) (thymic medulla)
How are apoptosis T cells who have failed thymocytes education destroyed?
Where does this take place?
They are phagocytosed by macrophages in the thymocytes cortex
What is the acronym for the 4 hypersensitivity reactions?
What does it stand for?
ACID
A - allergy
C - cytotoxic (antibody)
I - immune complex
D - delayed
How does type 1 hypersensitivity work?
IgE antibodies to certain allergens are overproduced and bind to mast cells
When the allergen enters the body it binds to the IgE and cross links it, which causes the mast cell to release its mediators (histamine) resulting in the symptoms of allergies
How does type 2 hypersensitivity work?
This involves antigens from host tissue (e.g. a specific organ or tissue)
The antibody/antigen complex activates complement which works to:
- opsonise antigen
- recruit neutrophils via chemotaxis
- form a membrane attack complex (MAC)
Give 4 examples of type 2 hypersensitivity reactions and explain what they are.
1) goodpastures syndrome = auto-antibodies are produced to the collagen of the basement membrane (e.g. in the glomeruli of the kidneys or alveoli of the lungs)
2) autoimmune haemolytic anaemia = auto-antibodies to RBC’s
3) graves thyroiditis = auto-antibodies to the thyroid hormone receptor, which inhibits negative feedback of thyroxine causing hyperthyroidism
4) myasthenia gravis = auto-antibodies to muscle acetylcholine receptors, destroying them causing weakness and fatigue
How does type 3 hypersensitivity work?
They key for this is the antigen has to be SOLUBLE, as an antibody/antigen complex for type 3 hypersensitivity reaction needs to be an IMMUNE COMPLEX, which is the name given to a solvable antigen/antibody complex
These complexes deposit in blood vessel walls and activate compliment
Give 2 examples of type 3 hypersensitivity reactions and explain what they are.
1) serum sickness = a reaction to anti-serum of some sort (e.g. anti-venom post-snake bite) which the body produces antibodies to and binds with to for, immune complexes
2) SLE = antibodies to DNA which forms many small immune complexes
How does type 4 hypersensitivity work?
Takes several days to develop
It is the only type NOT antibody mediated, but instead cell mediated (CD4 T cells Th1 recognise self as antigen)
Give MANY examples of type 4 hypersensitivity reactions and explain what they are.
1) contact dermatitis
2) rheumatoid Arthritis
3) asthma
4) Hashimoto’s thyroiditis = thyroglobulin antigen leading to hypothyroidism
5) type 1 DM
6) IBD
7) graft rejection
What is the strongest genetic link of any autoimmune disease?
What is the relative risk and what does this mean?
Ankylosing spondylitis = HLA-B27
RR = 87 (times more likely to develop the disease if you are positive for HLA-B27)
What is the female:male ratio of:
1) Ankylosing spondylitis
2) multiple sclerosis
3) rheumatoid Arthritis
4) SLE
What does this grossly tell us?
1) 0.3
2) 10
3) 3
4) 10-20
Females seem to be at greater risk of autoimmune diseases than males
Goodpastures is an auto-immunological syndrome whereby auto-antibodies are produced against the collegen in basement membrane.
Why do these patients not get ear problems?
What is the name given to these parts of the body?
There is a physical barrier preventing the auto-antibodies for reaching the cochlear basement membrane.
These areas are called ‘immune privileged sites’
Why do autoimmune conditions occur, what is the gross cause?
A loss of peripheral tolerance mechanisms
