Hypersensitivity and Autoimmunity Flashcards
What cells are involved in innate immunity
Phagocytes Eosinohpils Basophils Mast cells APCs
What receptors are involved in innate immunity
Fc Complement Toll-like Mannose Cytokine
What molecules are involved in innate immunity
Complement
Acute phase reactants
Inflammatory mediators
Cytokines
What cells are involved in adaptive immunity
B cells
T cells
What receptors are involved in adaptive immunity
Ig TCR HLA Cytokine Complement Toll-like
What molecules are involved in adaptive immunity
Immunoglobulins
Cytokines
What does immunity involve
Recognition Interaction Response Elimination Control and regulation
What is hypersensitivity
A group of disorders where the normally beneficial components of the immune response act in an exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage.
What is responsible for the tissue damage caused by hypersensitivity
The exaggerated response directed at the antigen
How can humans come into contact with allergens
Inhaled
Ingested
Injected
Contact
Describe the pathogenesis of an allergen
Allergen leaches on cell Enters to form APC which has MHC, a class II protein and epitope T helper cell helps B cells IgE produced IgE binds to inflammatory cell Causes clinical effects
(Allergen could attach straight to Fc epsilon receptor to cause a response)
What can T helper CD4 cells form
Th 1 - found in type IV (IL-2, gamma-IFN, TNF)
Th2 - found in type I (IL-4,6,10,13)
Define Atopy
A genetic tendency to produce IgE to normally innocuous, common environment allergens
How many people does atopy affect
About 40% of the population
Define allergy
A clinical expression of the atopic tendency
How many people does allergy affect
15-20% of the population
State some specifc IgE triggers
Insect venom Pollen Mould spores Animal dander Food allergens
State some non-specific allergy and atopy triggers
Exercise Acetylsalicylic acid Tobacco Sulphur dioxide Cold air Temperature Pressure Water Food items
What are some of the symptoms of allergy and atopy
Anaphylaxis Asthma Rhinitis and conjunctivitis Urticaria Gastrointestinal
What can cause allergy
Genes Environment (allergen) Immune dysregulation Environment (other) Internal influences
What types of mast cell mediators are there
Preformed
Newly synthesised
Name some preformed mast cell mediators
Histamine Heparin Tryptase Chymase Eosinophil/neutrophil chemotactic factors
Name some newly synthesised mast cell mediators
Prostaglandins
Leukotrienes
Describe the pathogenesis of type I hypersensitivity
Allergen exposure trigger mast cells and IgE
This causes degranulation of preformed mediators and synthesis of new mediators
Response includes: mucosal oedema, secretions, vasodilation, capillary leakage and smooth muscle contraction.
When does an early phase response occur
Within minutes using preformed mast cell mediators
When does a late phase response occur
Takes hours using newly synthesised mediators, Th2 cytokines and eosinophil mediators
Describe type II hypersensitivity
IgG/IgM mediated and its target antigens are either found on the cell surface or fixed in certain tissues
Involves immune effectors/target cell interactions
How can tissue damage arise in type II hypersensitivity
Complement activation
Fc binding of immunogloubin and stimulation of phagocytes
Antibody-dependent cellular cytotoxicity (ADCC)
Effects on target cell function (inhibition of function or stimulation)
What is the function of the immune complex
When formed under normal/physiological conditions has protective mechanisms including opsonisation, transportation and destruction
When formed under pathological conditions it has antigen factors and host response factors
How can the immune complex form
In circulation causing systemic deposition in tissues (serum sickness)
Locally in tissues (arthus reaction)
What is type III hypersensitivity
When there is an excessive or abnormal immune complex formation causing complement activation and the recruitment of inflammatory cells which leads to tissue damage
How long does it take for type IV hypersensitivity to occur
Over 24 hours
Th1 mediated
How does type IV hypersensitivity occur
An exogenous hapten (low molecular weight antigen) and endogenous protein (carrier) or microorganism cause antigen presenting cells (HLA class II) to form this stimulates Th1 cytokine production and causes inflammation
Define automimmunity
A large group of clinical disorders which are characterised by tissue or organ damage mediated through aberrant immunological mechanisms which are directed against autoantigens
What type of selection does central tolerance have
Positive or negative selection
What is peripheral tolerance dependent on
Tregulatory cells Antibody idiotype regulation Immune complex formation Oral tolerance Th17 cells
What causes autoimmune disease
The interaction of: Genetic factors Immune regulatory factors Hormonal factors Environmental factors ‘Other’ factors
What does MHC stand for
Major histocompatibility complex
What type of effector mechanisms are there
Cell - mediated Antibody - mediated Antibody + complement Immune complex - mediated Recruitment of innate components
Describe how an autoimmune disease occurs
An event initiates the process (e.g. infection) coupled with genetic susceptibility
Causes the breakdown of self-tolerance
Auto-reactivity occurs to cause either a humoral or cellular response
Leads to tissue damage
What can autoimmune diseases range between
Organ specific to non-organ specific
Where can organ specific autoimmune diseases occur
Thyroid
Stomach
Adrenal glands
Pancreas
Name some autoimmune thyroid diseases
Hashimoto’s thyroiditis
Primary myxoedema
Thyrotoxicosis
Name an autoimmune stomach, adrenal and pancreatic disease
Stomach - pernicious anaemia
Adrenal - Addison’s disease
Pancreas - juvenile diabetes
Where can non-organ specific autoimmune diseases occur
Muscle - dermatomyositis
Kidney - SLE
Skin - scleroderma
Joints - rheumatoid arthritis
How many types of hypersensitivity mechanisms are there
4 Type I Type II Type III Type IV
How are Types I, II and III hypersensitivity mediated
Through antibodies
What is type IV hypersensitivity caused by
By the inappropriate actions of Th1 cells
What is type I hypersensitivity also known as
Allergy
How does type I hypersensitivity arise
Through inappropriate synthesis of IgE by the immune system
IgE is directed at allergens
Why does type I hypersensitivity arise
Due to a combination of interacting genetic factors, environmental influences, hormonal and neurological influences and immune regulatory factors
Where can the antigens triggering type II and III sensitivity be derived from
External (exogenous)
Self (therefore almost an autoimmune disease)
How do clinical conditions arise in type III hypersensitivity
Due to abnormal:
Deposition of formed antigen (Ag)
Antibody (immune) complexes in tissues
Where to immune complexes go once formed
Bloodstream - kept soluble in blood
Transported (usually attached to red cells) to the liver and spleen where fixed phagocytes (e.g. Kupffer cells) take up and destroy them
