Hypersensitivity & Autoimmunity Flashcards
Define Hypersensitivity
Disorders where normally beenficial parts of an immune response act in an exaggerated or innapropriate fashion to enviromental antigens and cause tissue damage. (bystander damage)
Which types of hypersensitivity are mediated by antibodies?
Types I, II & III
What causes type IV hypersensitivity?
Innapropriate action of Th1 cells.
What is type 1 hypersensitivity also called?
“allergy”
How does Type 1 hypersensitivity arise?
enviromental antigens (allergens) are mistaken for pathogens & IgE is innapropriately synthesised.
What does the allergen-specific IgE released during type 1 hypersensitivity do?
It trigers mast cells to release inflammatory mediators like histamine & prostoglandins.
What are the consequences of type 1 hypersensitivity?
Mucosal Oedema Capillarly leakage vasodilation ETC (basically inflammation
What factors influence allergic problems? (think what factors all immune responses arise from)
- Genetic factors
- Hormonal & neurological influences
- Enviromental Influences
- Immune regulatory factors
Why isnt the prescnce of IgE alone enough for an alleric reaction to occur?
A clinical allergy arises through many factors not just immune regulatory factors so IgE can be associated with symptoms or not.
What is it called when IgE is present but no smptoms occur?
Atopy
A state of sub-clinical immune sensitisation
What antibodies mediate Type 2 hypersensitivity?
IgG & IgM antibodies
Why is the line between type 2 hypersensitivy & autoimmune blurreD?
Because in type 2 the IgG & IgM antibodies can bind to exogenous or self antigens.
How does type 2 hypersensitivity occur?
- IgG & IgM antibodies target antigens on the surface of cells or within tissues.
- They cause tissue damage
How do antibodies in type 2 hype cause tissue damage?
- complement activation triggers cell lysis
- Fc receptors on phagocytes bind to immunoglobulin & phagocytic activity is stimulated
- antibody dependant cellular cytotoxicity (ADCC)
- inhibit/stimulate cell function
What is immune complex formation?
antigens & antibodies from complexes together.
They are normally transported to the liver/spleen where theyre destroyed by phagoctytes.
How does type 3 hypersensitivity occu?R
Predisposing factors in the Ag or the Ab cause the immune complex to precipitate into tissues & cause inflammation
What are the 2 types of inflammation in type 3 hypersensitivty?
Serum sickness (immune complexes deposited throughout many tissues) Arthus reaction (complexes formed locally in tissues)
What causes type 4 hypersensitivity?
There is an enviromental substance thats strucutrally hard to destroy or an infectious micro-organism that evades the immune system.
The Th1 cells overreact because theyre having trouble destroying the foreign substances.
Why do non-infectious enviromental agents need to bind to a host protein to triger type 4 hype?
Theyre generally of too low a molecular weight to produce a substantial antigenic stimulus in order to incite an immune resposne.
What is a Hapten? (think type 4 hype)
The non-infectious enviromental agent bound to the host protein
What is a Carrier? (think type 4 Hype)
The host protein bound to a low mw enviromental agent.
Define an autoimmune disease.
Clinical disorders characterised by tissue/organ damage mediated by aberrant cellular and/or humoral immunological mechanisms against autoantigens.
Are specific autoantigens organ-specific?
They can be localised to certain tissues/organs or spread all over the place.
Define tolerance?
Process where immune system avoid producing damaging reaction againsts self-antigens.
Define central tolerance:
Deletion of autoreactive T&B cells during cell maturation
Define peripheral tolerance:
Inhibiting activity of autoreactive cells that escape central tolerance.
In what cases is imune recognition of self not damaging?
T cells can recognise antigens complexed to self molecules
Antibodies can recognise/bind to eachtoher to regulate production/activity.
What is physiological autoimmunity
processes of self-recognition that are normal & beneficial
What 5 factors make up the aetiology of autoimmune disorders?
- Genetic factors
- immune regulatory factors
- hormonal factors
- enviromental factors
- “other”
what are immune regulatory factors that help cause autoimmune disorders?
defective central or peripheral tolerance mechanisms
What “other” factors affect autoimmune disorders?
Age
Trauma
Malignant disease
What is an early phase response?
One that ccurs within minutes
involves preformed mast cell mediators (e.e.g histamine, heparin & chemotactic factors)
Whats a late phase response?
One that takes hours or days
Involves newly synthesised mediators like prostoglandins
Also Th2 cytokines
Eosinophil mediators
What immune effector mechanisms can go wrong to cause an autoimmune disease?
- Cellular (T cell) & antibody (B cell) activity
- autoantibody acitivation of complement-mediated inflammation
- immune complex formation (e.g. type 3 hypersensitivity mechanisms)
- recruitment of innate immune components (phagocytes/cytokines/Nk cells etc)
Quick summary of the steps of an autoimmune disorder:
- initiating (enviromental) event [e.g infection] and genetic (susceptibility) factors e.g. inheritence of particular HLA alleles.
- breakdown of self tolerance
- autoreactivity (humoral and/or cellular)
- Tissue damage
Do autoimmune disorders only cause damage?
No some cause hyperfunction rather than hypo (e.g. hyperthyroidism)
How do overlap disorders occur?
OFten autoimmune disorders will often occur together if they are both very organ speciic or very not.
What factors are involved in the aetiology of autoimmune diseases?
- Immune regulatory
- Genetic
- Hormonal
- Enviromental
What are the pathogenic mechanisms of autoimmune disease?
- Immune complex formation
- Antibody mediated
- Cell-mediated
- Recruitment of innate immune components (neutrophils, macrophages etc)
- complement system
List some oran specific diseases:
- Pernicious anaemia (stomach)
- Adidsons disease (adrenal)
- Hasimotos thyroiditis, primary myxoedema, thyrotoxicosis (Thyroid)
List some non-organ specific diseases:
- Muscles = Dermatomyositis
- Skin = Scleroderma
- Kidneys = SLE
- Joints = Rheumatoid arthritis
Name 3 thyroid specific diseases:
- Hashimotos thyroiditis
- Primary Myxoedema
- thyrotoxicotis
