Hypersensitivity Flashcards
Which type is the immediate type?
Type I
Which type is modified self?
Type II
Which type is due to immune complex disease?
Type III
Which type is delayed type?
Type IV
Which type is IgE mediated?
Type I
Which type is IgG mediated?
Type II and III
Which type is T cell mediated?
Type IV
What is the effector mechanism of Type I?
Mast cell activation
What is the effector mechanism of Type II?
If cell/matrix associated Ag: complement and cells containing Fc receptors (phagocytes and NK cells)
If cell surface receptor bond to Ag:Ab alter signaling
What is the effector mechanism of Type III?
Complement and Phagocytes
What is the effector mechanism of Type IV?
Th1 cells activate macrophages, Th2 cells activated eosinophils, or CTLs induce apoptosis
What are some examples of Type I?
Allergic rhinitis, asthma, systemic anaphylaxis
What are some examples of Type II w/ cell or matrix associated Ag?
Durg allergies, namely penicillin
What are some common sources of allergens?
- Inhaled:plant pollens, pet dander, mold spores, feces of very small animals (dust mites)
- Injected: insect venoms, vaccines, drugs, therapeutic proteins
- Ingested: food, orally administered drugs
- Contacted: plant leaves, industrial products made from plants, synthetic chemicals in industrial products, metals
What are some examples of Type II w/ cell surface receptor bound to Ag?
chronic urticaria
What are some examples of Type III?
serum sickness, arthus rxn
What are some examples of Th1 mediated Type IV?
contact dermatitis, tuberculin rxn
What are some examples of Th2 mediated type IV?
chronic asthma, chronic allergic rhinitis
What are some examples of CTL mediated Type IV?
contact dermatitis
Will a hypersensitivity rxn occur upon first encounter w/ Ag?
No, the first exposure will prime the allergic response. The hypersensitivity rxn will not take place until second exposure
Can Th1 cells lead B cells to release IgE?
No
How long does it take for a Type I to occur?
minutes
What type of inhaled Ag promotes the priming of Th2 cells to drive an IgE response?
protein Ag b/c only they can induce T cell responses
What type of function do those Ag’s have? refer to an Ag that is required to prime a Th2 cell to drive an IgE response
These allergens are often proteases
T or F. High doses of inhaled Ag promotes the priming of Th2 cells to drive and IgE response. (refer to an Ag that is required to prime a Th2 cell to drive an IgE response)
F. Low doses favor activation of Il-4 producing CD4 T cells
Do inhaled allergens have a high or low molecular weight? (refer to an Ag that is required to prime a Th2 cell to drive an IgE response)?
low molecular weight so they can diffuse out of particle and into mucus
Do inhaled allergens have a high of low solubility (refer to an Ag that is required to prime a Th2 cell to drive an IgE response)?
high solubility that is readily eluted from particle
Are inhaled allergens highly stable (refer to an Ag that is required to prime a Th2 cell to drive an IgE response)?
yes so they can survive in a desiccated particle
Do inhaled allergens contain peptides that bind to host MHC class II molecules (refer to an Ag that is required to prime a Th2 cell to drive an IgE response)?
yes, this is required for T cell priming
What causes mast cell degranulation?
cross linking of IgE bound on mast cell surface w/ Ag
What enzymes do mast cells release?
tryptase, chymase, cathepsin G, carboxypeptidase
What toxic mediators do mast cells release?
histamine and heparin
What cytokines do mast cells release?
TNF-alpha, IL4, IL3, IL13, Il5, GM-CSF
Which chemokine do mast cells release?
CCL3
What lipid mediators do mast cells release?
Leukotrienes C/D/E4s and PAF
What is the role of histamine (and heparin)?
toxic to parasites, increases vascular permeability, and causes smooth muscle contraction
What is the role of the enzymes released by mast cells?
to remodel the connective tissue matrix
What does TNF-alpha do when released by mast cells?
promotes inflammation, stimulates cytokine production by many cell types, and activates endothelium. It is pro-inflammatory
What do Il-4 and IL-13 do when released by mast cells?
Stimulate and amplify Th2 cell response
What do Il-3, Il-5, and GM-CSF do when released by mast cells?
promotes eosinophil production and activation
What does CCL3 do when released by mast cells?
chemotactic agent for monocytes, macrophages, and neutrophils
What do the leukotrienes C4, D4, and E4 do when released by mast cells?
causes smooth muscle contraction, increase vascular permeability, and causes mucus secretion
What does PAF do when released by mast cells?
- Chemotactic agent for leukocytes. Amplifies production of lipid mediators. Activates neutrophils, eosinophils, and platelets.
What does local degranulation of mast cells cause?
Hives (also known as wheal and flare reactions). Urticaria.
What are the effects of mast cell degranulation on the GI tract?
Increased fluid secretion and increased peristalsis. Leads to expulsion of contents aka diarrhea and vomiting
What are the effects of mast cell degranulation on the airways?
Decreased diameter and increased mucus secretion. Leads to expulsion of contents aka phlegm and coughing.
What are the effects of mast cell degranulation on blood vessels?
Increased blood flow and increased permeability. Leads to edema, inflammation, increased lymph flow, and carrying of Ag to lymph nodes.
What happens if Ag enters the bloodstream?
It enters tissues throughout the body causing systemic activation of connective tissue mast cells
What does systemic activation of mast cells result in?
anaphylaxis
What are the effects of anaphylaxis on the heart and vascular system?
Increased capillary permeability and entry of fluid into tissues causing swelling of tissues including tongue. Loss of blood pressure. Reduced oxygen to tissues. Irregular heartbeat. Anaphylactic shock. Loss of consciousness
What are the effects of anaphylaxis on the respiratory tract?
Contraction of smooth muscle. Constriction of throat and airways. Difficulty in swallowing and breathing. Wheezing
What are the effects of anaphylaxis on the GI tract?
Contraction of smooth muscle. Stomach cramps. Vomiting. Fluid outflow into gut. Diarrhea.
What is used to treat anaphylaxis?
epinephrine
What are the IgE-mediated allergic reactions?
Systemic anaphylaxis, wheal and flare reactions, allergic rhinitis (hay fever), bronchial asthma, food allergies.
Which type of Ag will elicit a Type I HS?
Protein, low concentration, extracellular.
Which cytokines drive proliferation of T cells in Type I HS?
IL 4 and IL5
T or F. Type II hypersensitivities are the result of Ab’s specific for altered host proteins
True
A penicillin-induced HS is of which type?
Type II
When penicillin binds to RBCs what happens?
it changes the self determinants present on the RBC
After the change from #59 has taken place what happens?
Complement is deposited on RBCs and they are phagocytosed by macrophages.
After #60 happens which cell gets activated?
Macrophages present peptides from the phagocytosed RBCs and activate Th2 cells.
After becoming activated by Th2 cells and the penicillin Ag on RBCs, what happens to B cells/what do they do?
B cells are activated to plasma cells that secrete penicillin-specific IgG that binds to the modified RBCs
What 2 things can happen to RBCs once penicillin-specific IgG binds to the penicillin-modified protein determinants on RBCs?
MAC formation on RBCs causes lysis or C3b deposition leads to phagocytosis. Activation of complement is the common factor.
T or F. There is a rash associated with a penicillin allergy
True
What type of Ig is involved in the immune complexes associated with Type III HS?
IgG
What is the underlying cause of problems associated with Type III?
deposition of immune complexes in the vasculature and tissues
Which organ is most susceptible to damage in a Type III HS?
Kidney
T or F. Immune complexes can cause mast cells to degranulate.
True
What receptor on mast cells do immune complexes bind to?
Fc-gammaRIII
What other mediator in Type III HS can elicit mast cell degranulation?
C5a. The immune complexes activate the complement cascade and results in production of the anaphylatoxin C5a.
What is the time course for a Type III?
1-2 hours
A high dose of IV Ag results in what 3 diseases? What are the sites of immune complex deposition in each of them?
Vasculitis- blood vessel walls. Nephritis- renal glomeruli. Arthritis- joint spaces.
What reaction is elicited when subcutaneous Ag elicits a Type III? Where is the site of immune complex deposition in this case?
Arthus reaction. Perivascular area.
What disease results with inhaled Ag that elicits a Type III? Where is the site of immune complex deposition in this case?
Farmer’s Lung. Alveolar/capillary interface.
What are the 2 most common Type III HS?
Famer’s Lung and Bird-Fancier Disease
What is the responsible allergen in Farmer’s Lung?
mold from hay
What is the responsible allergen in Bird-Fancier Disease?
feathers and droppings from birds
What are some types of Bird-Fancier Disease?
pigeon breeder’s disease, poultry worker’s lung, bird breeder’s disease
Type IV HS are also known as what?
delayed type
What cell type mediates Type IV?
T cells
What is the time course for a Type IV?
24-72 hours
T or F. In a Type IV, Ag is processed by tissue macrophages which stimulate Th1 cells.
true
What do Th1 cells secrete in a Type IV?
Chemokines. Cytokines: IFN-gamma, IL-3, GM-CSF. Cytotoxins: TNF-alpha and LT.
What is the role of the secreted chemokines in a Type IV?
Recruit macrophages to site of Ag
What is the role of IFN-gamma in a Type IV?
Activates macrophages thus increasing release of inflammatory mediators.
What is the role of TNF-alpha and LT in a Type IV?
Local tissue destruction. Increased expression of adhesion molecules on local blood vessels.
What is the role of IL-3 and GM-CSF in a Type IV?
Monocyte production by bone marrow stem cells
What is the most widely studied example of a Type IV HS?
Tuberculin reaction aka TB skin test
What is the process in a TB skin test?
Inject small amount of the MTB protein subq. Wait 24-72 hours and look for local inflammatory response (raised bump at site of injection).
What is the mechanism of eliciting a positive TB skin test?
The injected subq MTB Ag will be processed by local APCs presented to Th1 cell Th1 cell recognizes cognate MTB Ag releases cytokines that act on vascular endothelium recruitment of T cells, phagocytes, fluid, and protein to site of Ag injection causes visible lesion for reading of TB skin test.
What is the most well known example of a Type IV HS?
Poison Ivy reaction.
What is the mechanism for poison ivy reacion?
Active ingredient of poison ivy penetrates skin covalently binds to host proteins forms new “non-self” Ag’s effector T cells (CD4+ and CD8+) specific for these new “non-self” Ag’s are produced.
What is the active ingredient in poison ivy that elicits the Type IV HS?
Pentadecacatechol
T or F. The first exposure to poison ivy usually elicits a reaction.
F: first exposure will prime subsequent responses.
