Flashcards in 03/09i Complement, Hypersensitivity I & II Deck (46)
What are the three pathways of complement activation?
At what point does the complement system get amplified?
What are the functions of complement?
1) Opsonization and phagocytosis
2) Formation of the Membrane Attack Complex
3) Release of soluble inflammatory mediators C3a and C5a - chemoattractants, activate macrophages
What distinguishes the lectin complement pathway from the classical pathway?
Instead of using antibodies, it used mannose-binding lectins or ficolins to bind carbohydrates on pathogen surfaces
Why is the alternative pathway also considered the 'spontaneous' pathway?
C3 convertase can be activated spontaneously on cell surfaces
Does not require C1 or MBP
If complement can be activated spontaneously, why don't we do it all the time?
Endogenous complement inhibitors - Decay Accelerating Factor (DAF), Membrane Cofactor Protein (MCP), and C1 Inhibitor
What are the anaphylatoxins?
C3a, C5a, and C4a - mediators of inflammation
Initiate inflammatory processes
Increase vascular permeability and smooth muscle contraction, histamine release from mast cells, chemotaxis, and cell activation
What are the functions of C5a?
Mediator of inflammation
Activation of phagocytosis by macrophages
What is the most common regulator of complement?
Why doesn't the Membrane Attack Complex work on our cells?
We have CD59, which inhibits its formation
What happens if you lack certain components of complement? List three complement deficiencies and their associated diseases
C1 Inhibitor deficiency - hereditary angioedema
C3 deficiency - recurrent infections, SLE
C2 and C4 deficiency - immune complex diseases
What are the two phases of a hypersensitivity reaction?
What are the four types of hypersensitivity reactions? By what antibodies or cells are they mediated?
Type 1 - immediate (IgE/mast cell)
Type 2 - antibody (IgG or IgM)
Type 3 - immune complex
Type 4 - T cell
What are the hallmarks of a Type 1 hypersensitivity reaction?
Activation of Th2 cells and production of IgE - inappropriate anti-helminthic-like response
IgE binds to mast cells
Re-exposure to the antigen results in release of mediators from mast cells, and subsequent effects
What are the mediators of Type 1 hypersensitivity? What are their effects?
Histamines - vasodilation, vascular permeability
Lipid mediators - bronchoconstriction, intestinal hypermotility, inflammation
Cytokines (TNF) - inflammation
Enzymes - tissue damage
What are some possibly causes of Type 1 hypersensitivity reactions?
Nature of the antigen
Hygiene hypothesis - lack of exposure to bugs!
What are the clinical manifestations of immediate hypersensitivity?
Abdominal pain, diarrhea
What does the degree of immediate hypersensitivity reaction that develops depend upon?
Route of allergen exposure
Dose of allergen exposure
Frequency of allergen exposure
What are the characteristics of the immediate phase of Type 1 hypersensitivity?
Mast cell degranulation
What causes the immediate reaction of type 1 hypersensitivity?
Dependent on cross-linking of IgE and granule contents of mast cells
What is the Wheal and Flare Reaction?
Immediate phase of a Type 1 hypersensitivity reaction
Caused by injection of an allergen under the skin
Wheal = bump of inflammation, flare = vasodilation
What are the characteristics of the late phase of a type 1 hypersensitivity reaction?
Develops in 2-4 hours
Symptoms are due to the accumulation of inflammatory cells - neutrophils, eosinophils, basophils, and Th2 cells
May occur without a detectable immediate hypersensitivity reaction
What are some common examples of allergic diseases in humans? List five
Urticaria and atopic dermatitis
What is anaphylaxis?
A systemic hypersensitivity reaction
Characterized by systemic edema, drop in blood pressure, vasodilation and increased permeability
Clinical symptoms - constriction of airways, laryngeal edema, hypermotility of the gut, outpouring of mucous, and hives
How is anaphylaxis treated?
Systemic epinephrine - reverses bronchoconstriction, improves cardiac output
Steroids - prevent a late-phase reaction
What is bronchial asthma?
Intermittent and reversible airway obstruction caused by repeated immediate-phase hypersensitivity and late-phase allergic reactions in the lung
What are the characteristics of bronchial asthma?
Chronic bronchial inflammation
Bronchial smooth muscle cell hypertrophy and hyperreactivity
Increased production of thick mucous
What happens in the early phase of asthma?
What happens in the late phase of asthma?
Inflammation and leukocyte activation
Fibrosis and repair