week 2 Flashcards
what is the principle cause of type 1 hypersensitivity - e.g. asthma , ecxema, hayfever
IgE mediated, it is atopic .
characteristics of type 1 hypersensitivity
response to challenge occurs immediately
tends to increase in severity with repeated challenge
predominantly mediated by IgE bound to mast cells
Process of allergy
-Sensitisation Mast cells primed with IgE -Re-exposure to antigen -Antigen binds to IgE associated with mast cells -Mast cells degranulate releasing: Toxins (i.e. histamine) Tryptase Pro-inflammatory cytokines Chemokines Prostaglandins Leukotrienes Pro-imflammatory process stimulates and amplifies future responses
tissue effects from early phase of type hypersensitivity
occurs within mins of exposure to antigen
occurs largely as a result of histamine and prostaglandins - smooth muscle contraction and - increased vascular permeability
tissue effects from late phase of type 1 hypersensitivity
occurs over hours to days after exposure to antigen
principally mediated through recruitment of T cells and other immune cells to site
results in
- sustained smooth muscle contraction/hypertrophy
- tissue remodelling
what is anaphylaxis
severe systemic type 1 hypersensitivity . can be rapidly fatal.
- widespread mast cell degranulation caused by systemic exposure to antigen.
- vascular permeability is principle immediate danger : soft tissue swelling threatens airway ; loss of circulatory volume causing shock
type 2 hypersensitivity caused by …
binding of antibodies directed against human cells - IgG usual cause .
it is a common cause of autoimmune diseases
type 2 hypersensitivity reaction
- sensitisation
- opsonisation of cells
- cytotoxicity ; complement activation , inflammation, tissue destruction
- (in some cases)- direct biological activation with antigen - i.e receptor activation impaired enzyme action)
type 3 hypersensitivity is mediated by?
immune complexes bound to soluble antigen - its a cause of autoimmune disease and drug allergy
how do the complexes bound to soluble antigens form in type 3 hypersens?
aggregate in small blood vessels ; - direct occlusion
- complement activation
- perivascular inflammation
what is type 4 hypersensitivity is mediated
by the action of lymphocytes infiltrating area
what is type 4 hypersensitivity also known as
delayed type hypersensitivity
- presents several days after exposure
what is an autoimmune disease
harmful inflammatory response directed against ‘self’ tissue by the adaptive immune response
- organ specific / systemic
type 1 diabetes
selective autoimmune destruction of the pancreatic beta cells (often a mix of type ii and iv)
- causes profound insulin deficiency and death if not treated with insulin replacement
- inflammation of the islets of Langerhans precedes symptoms by many years
What is myasthenia gravis
syndrome of fatigable muscle weakness .
caused by IgG against acetylcholine receptor
antibody blocks receptor and prevents signal transduction
pathophysiology of RA
Rheumatoid factor -
- IgM and IgA directed against IgG Fc region
- forms large immune complexes
- high conc within synovial fluid
- inflammation leads to release of PAD from inflamm cells
- alters variety of proteins by converting alanine to citrulline
- in RA , anti-citrullinated protein/peptide antibodies are common.
describe the nature of infliximab and its target
monoclonal antibody
soluble cytokine
nature of etanercept and its target
soluble receptor
soluble cytokine
nature of rituximab and its target
monoclonal antibody
surface marker
presence of what strongly predicts RA
antibodies of citrullinated proteins
how do citrullinated proteins develop
they develop due to action of enzymes induced during inflammation
complications from an MI
Death Arrythmia Pericarditis Myocardial rupture Mitral valve prolapse Left ventricular aneurysm +/- thrombus* Heart Failure * *longer term
