2.1.2 Hypersensitivity Flashcards
What is a hypersensitivity?
Excessive or aberrant pathologic immune reactions
What is the Gel and Coombs classification for Type I hypersensitivities?
Immediate hypersensitivity Mast cell-derived mediators
What is the Gel and Coombs classification for Type II hypersensitivities?
Antibody-mediated cytotoxicity IgM or IgG antibodies against cell surface or extracellular matrix antigens
What is the Gel and Coombs classification for Type III hypersensitivities?
Immune complex-mediated diseases Deposition of immune complexes in vascular basement membrane. Soluble Ags
What is the Gel and Coombs classification for Type IV hypersensitivities?
T cell-mediated T cells and autoimmunity
Type I hypersensitivity is mediated by what?
IgE-mast cell
Type I hypersensitivities are characterized by what?
Allergy or atopy; Rapid vascular leakage (inflammation); Hay fever, food allergies, asthma, or anaphylaxis
Upon activation Mast cells degranulate, what are they releasing?
Histamine
What are some of the lipid mediators that mast cells release?
Prostaglandin and leukotrienes
What is an important cytokine that mast cells release when activated?
TNF-alpha
What is the pathway that happens in a type I hypersensitivity upon exposure to pollen?
First exposure to the allergen will cause binding to the B cell. This will lead to signaling to the Th2 cells and stimulate IgE class switching in B cells. IgE will be produced, and will bind to the Fc-epsilon-RI on mast cells. Upon second exposure to this allergen, the allergen will bind to multiple receptors on the mast cell signaling for the release of mediators.
Upon FceRI crosslinking by antigen on a mast cell what signaling occurs?
Phosphorylation of Lyn kinase then subsequent phosphorylation of Syk kinase
Phosphorylated Syk will carry out what function?
Phosphorylation of PLC-gamma
PLC-gamma activation will then do what in mast cells?
Create IP3 and DAG
What will occur upon IP3 activation?
Activation will lead to Ca2+ mobilization from ER stores and thus degranulation
Activation of DAG will have what effect in mast cells?
This will lead to activation of PKC, which will affect transcription factors that will lead to the release of cytokines.
MAPK activation in the mast cells will have what effects?
MAPK will activate phospholipid A which will then mediate lipid mediators
Release of ECF-A/NCF-A by mast cells leads to what?
Chemotaxis for eosinophils and neutrophils
Release of TNF-alpha/IL-1 by mast cells leads to what?
ICAM-1 upregulation
Release of PAF by mast cells does what?
Aids in platelet aggregation
Release of heparin granules by mast cells does what?
This helps with anticoagulation
How do mast cells mediate complement activation?
Protease (granules) cleavage of C3a, 4a and 5a
IL-3 and IL-4 release by mast cells is intended for what?
Mast cell survival
IL-4, IL-5 and IL-13 by what cells in the late phase of a T1 hypersensitivity?
Th2 cells
What is the role of tryptase release by mast cells?
Aids in mucus secretion
What is the role of histamine in the immediate reaction during type I hypersensitivity?
Histamine leads to dilation of small blood vessels, increased vascular permeability, and transient contraction of smooth muscles
What are the roles of prostaglandins in the immediate reaction?
Vascular dilation
What is the role of leukotrienes in the immediate reaction of type I hypersensitivity?
Prolonged smooth muscle contraction
What cytokines are released by mast cells that work in the late phase hypersensitivity?
TNF-alpha, IL-4 and IL-5
What ILs work in the late phase that affect Th2 cells?
IL-4, 5 and 13
What leukocytes are recruitmented in the late phase of type I hypersensitivities?
Neutrophils and eosinophils
What is this an image of?
Mast cell
What is this an image of?
Eosinophil
Type I hypersensitivities can result in anaphylaxis, what are the symptoms of this?
Systemic reaction caused by widespread mast cell degranulation. Edema can lead to an airway obstruction and a fall in blood pressure can result from vascular dilation.
What is the point of a skin test for Type I?
This is looking for a wheal and flare reaction on the skin. Epicutaneous skin test followed by an intradermal test
The antigen is ragweed, does this person appear to have a hypersensitivity to ragweed? Also what are the three dots?
This person does have a ragweed allergy. The top is the antigen, the middle is a negative control, and the bottom is the positive control
What is the difference between the intradermal and epicutaneous test? How does this image help explain that?
The intradermal skin test is more sensitive and is semiquantitative. The image shows increasing dilutions of the antigen to show a difference in immune responses.
Why is an epicutaneous skin test done before an intradermal skin test?
There is a risk of anaphylaxis with the intradermal test
What is the process of immunocap to test Type I hypersensitivity?
IgE from patient sample will bind to allergen covalently attached to the well. Enzyme labeled anti-IgE will be added, and then a color change will be measured to quantify how much was bound
How would you treat anaphylaxis from a Type I hypersensitivity?
Epinephrine to increase cardiac output and relax airway muscles
What would you use to treat asthma caused by a type I hypersensitivity?
Bronchodilators, corticosteroids to reduce inflammation, leukotriene antagonist, and histamine receptor antagonist
Anti-IgG - IgG is not involved in the type I hypersensitivity reaction
Type II hypersensitivity is characterized by?
Antibodies against cells or extracellular matrix proteins;
OR
Microbial antigens that cross-react with self-tissue
What is an example of type II hypersensitivity caused by an microbial antigen?
Rheumatic fever caused by streptococcus
Type II diseases with tissue injury utilizes what mechanisms?
Complement activation, Fc Receptor activation on neutrophils and macrophages, and opsonization of cells
Type II diseases without tissue injury do what?
Antibodies with specificity for a receptor can be agonist or antagonist.
Myasthenia gravis - Blocking antibodies against the acetylcholine receptor
How is myasthenia gravis an example of a type II disease?
MG blocking antibodies against the acetylcholine receptor
How is Graves disease an example of type II disease without tissue damage?
Antibodies against the TSH receptor to stimulate thyroid cells
What is a type III hypersensitivity?
Immune complexes deposited in vessels attract and activate leukocytes. IgG and antigen:antibody aggregates.
What is the Arthus reaction?
Antigen is injected into an immune individual with IgG antibody. Local immune-complexes form. Activation on mast cells leads to degranulation leading to edema necrosis and activation of complement. Can lead to blood vessel occlusion.
What is serum sickness?
Antibodies are formed to foreign proteins. Immune complexes form and are deposited in membranes, where they fix complement leading to tissue damage.
How is post-streptococcal glomerulonephritis an example of a type III hypersensitivity?
Cross-reactive and anti-streptococcal antibodies can lead to nephritis
How is systemic lupus erythematosus an example of type III hypersensitivity?
Antibodies against DNA and nucleoproteins leading to nephritis
What are some treatments against type II and type III hypersensitivities?
Corticosteroids, IVIG, Anti-CD20 to deplete B cells, CD40 ligand (CD154) antagonists
Type IV issue injury is mediated by?
CD4 T cells secreted cytokine induced inflammation. Th1 - secretes IFN gamma
Th17 secretes IL-17
Type IV hypersensitivity is characterized by?
Sensitized T cells encounter antigen and then release cytokines that lead to macrophage activation and tissue damage
What are some examples of type IV hypersensitivities?
TB, contact dermatitis, and some autoimmune diseases
How is the DTH skin test different than the type I skin test?
This is looking for a delayed hypersensitivity in response to purified protein derivative. The type I hypersensitivity will take minutes to get a result
How to treat type IV hypersensitivity?
Corticosteroids, Anti-TNF and costim blockade
