Hypersensitivity & Autoimmunity Flashcards
Define Hypersensitivity
immune response acts in exaggerated or innapropriate fashion to environmental antigens and cause tissue damage (bystander damage)
Which types of hypersensitivity are mediated by antibodies?
Types I, II & III
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?
Triggers mast cells to release inflammatory mediators like histamine & prostaglandins
(prostaglandins = lipids made at sites of tissue damage/infection, involved in dealing with injury and illness)
What are the consequences of type 1 hypersensitivity?
Mucosal Oedema
Capillarly leakage
vasodilation
(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 isn’t the presence of IgE alone enough for an allergic reaction to occur?
Clinical allergy arises through many factors not just immune regulatory factors
IgE can or be associated with symptoms or might not
What is it called when IgE is present but no symptoms occur?
Atopy
State of sub-clinical immune sensitisation
What antibodies mediate Type 2 hypersensitivity?
IgG & IgM antibodies
Why is the line between type 2 hypersensitivity & autoimmune blurred?
In type 2, IgG & IgM antibodies can bind to exogenous or self antigens
(exogenous antigens = antigens that have entered body from outside)
How does type 2 hypersensitivity occur?
- IgG & IgM antibodies target antigens on surface of cells or within tissues
- 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
- ADCC (antibody dependant cellular cytotoxicity)
- inhibit/stimulate cell function
What is immune complex formation?
Antigens & antibodies from complexes together
Transported to liver/spleen and destroyed by phagocytes.
How does type 3 hypersensitivity occur?
Predisposing factors in Ag or Ab cause 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?
Environmental substance with phagocytic resistance or infectious micro-organism that evades immune system
Th1 cells overreact (having trouble destroying the foreign substances)
Inappropriate action of Th1 cells.
Why do non-infectious enviromental agents need to bind to a host protein to triger type 4 hype?
Non-infectious EV agents Too low molecular weight to produce substantial antigenic stimulus in order to trigger immune response.
What is a Hapten? (think type 4 hype)
non-infectious EV agent bound to host protein
What is a Carrier? (think type 4 Hype)
host protein bound to low mw EV agent
Define an autoimmune disease.
tissue/organ damage controlled by abnormal cellular or humoral immunological mechanisms against autoantigens
Describe autoantigen specificity
Systemic - diffuse, spread throughout body, affects multiple organs
Organ specific - directed against 1 organ
Define tolerance?
Immune system avoids producing damaging reaction against self-antigens
(Unresponsiveness of immune system toward certain substances or tissues that are normally capable of stimulating immune response)
Define central tolerance:
Deletion of auto-reactive T&B cells during cell maturation
(auto reactive = produced by organism and acting against own cells or tissues)
Define peripheral tolerance:
Inhibiting activity of autoreactive cells that escape central tolerance.
In what cases is immune self-recognition not damaging?
T cells can recognise antigens complexed to self molecules
Antibodies can recognise and bind to eachtoher to regulate production and activity
What is physiological autoimmunity
processes of self-recognition that are normal & beneficial
What factors make up the aetiology of autoimmune disorders?
- Genetic factors
- immune regulatory factors
- hormonal factors
- environmental factors
Age
Trauma
Malignant disease
what are immune regulatory factors that help cause autoimmune disorders?
defective central or peripheral tolerance mechanisms
What is an early phase response?
Occurs within minutes
Involves preformed mast cell mediators (e.g histamine, heparin & chemotactic factors)
Whats a late phase response?
Takes hours or days
Newly synthesised mediators like prostaglandins
Th2 cytokines
Eosinophil mediators
What immune effector mechanisms can go wrong to cause an autoimmune disease?
- Cellular (T cell) & antibody (B cell) activity
- autoantibody activation of complement-mediated inflammation
- immune complex formation (type 3 hype)
- recruitment of innate immune components (phagocytes/cytokines/Nkc etc)
Summary of the steps of an autoimmune disorder:
- initiating EV agent [infection] and genetic susceptibility factors e.g. inheritance of particular HLA (Human leukocyte antigen) alleles.
- breakdown of self tolerance
- auto-reactivity (humoral/cellular)
- Tissue damage
Do autoimmune disorders only cause damage?
Some cause hyperfunction (hyperthyroidism)
How do overlap disorders occur?
Autoimmune disorders often occur together
Can/cannot be organ specific
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)
- Addison’s disease (adrenal insufficiency)
- Hashimotos thyroiditis (thyroid insufficiency)
- Primary myxoedema (thyroid shrinking)
- Thyrotoxicosis (overactive Thyroid)
List some non-organ specific diseases:
-Muscles = Dermatomyositis (muscle shrinking/skin rash)
- Skin = Scleroderma
- Kidneys = SLE (lupus)
- Joints = Rheumatoid arthritis
