Mechanisms Of Hypersensitivity Flashcards
Which of the hypersensitivities involves complement and Fc receptor-mediated recruitment and activation of leukocytes and results in immune complex deposition in vascular basement membrane?
Type III (immune-complex mediated diseases)
Which of the hypersensitivities involves IgM and IgG antibodies against cell surface or extracellular matrix antigens?
Type II (antibody-mediated diseases)
Which of the hypersensitivities is T cell mediated and involves macrophage activation and direct target cell lysis?
Type IV (T cell mediated diseases)
In Type IV hypersensitivity, which type of T cell is the basis for DTH?
CD4+ T cells
Which of the hypersensitivities is Th2 mediated, as well as IgE antibodies, mast cells, and eosinophils?
Type I (Immediate hypersensitivity)
T/F: Each cell involved in an immediate hypersensitivity response is restricted to carrying a receptor of a single antigen specificity
False! They carry a range of IgE representing that present in the circulation; thus they are not restricted to carrying a receptor of single antigen specificity
What must occur prior to someone having a type I hypersensitivity response to an allergen?
They must be sensitized to it in an initial exposure (priming)
What type of cell involved in type I hypersensitivities is especially prominent in skin and mucosa?
Mast cells
What type of receptor is present on mast cells that make them integral to a type I hypersensitivity response?
High affinity Fc receptors for IgE (FceRI = CD23a)
What do mast cells contain that make them potent type I hypersensitivity cells?
Preformed pro-inflammatory mediators (granules): histamine, serotonin, heparin, serine proteases
Newly formed lipid mediators (eicosanoids): prostaglandin D2, leukotrienes
What role do pre-formed mediators like histamine and heparin from mast cells play in type I responses?
Toxicity to parasites
Increase in vascular permeability
Smooth muscle contraction
Which cytokines play a role in type I hypersensitivities?
IL-4, IL-13: amplify Th2 response
IL-3, IL-5, GM-CSF: promote eosinophil production and activation
TNF-a: pro-inflammatory, activation of endothelium
Which chemokine plays a role in type I hypersensitivities?
CCL3 - Attracts monocytes, macrophages, and neutrophils (not as potent as IL-8)
What is the major contributor to tissue damage in type I hypersensitivities?
Eosinophils –> lead to chronic allergic inflammation
What receptor’s expression is inducible on eosinophils, making them a big player in type I hypersensitivities?
FceRI
What enzymes contained by eosinophils contribute to type I hypersensitivities?
Eosinophil peroxidase - triggers histamine release from mast cells
Eosinophil collagenase - remodels CT matrix
Matrix metalloproteinase-9 - matrix protein degradation
What toxic proteins are contained by eosinophils that cause major tissue damage in type I hypersensitivities?
Major basic protein (MBP) - toxic to parasites and mammalian cells, triggers histamine release from mast cells
Eosinophil cationic protein - toxic to parasites, neurotoxin
Eosinophil-derived neurotoxin
What cytokines are associated with eosinophils in a type I hypersensitivity response?
IL-3
IL-5
GM-CSF
TGF-alpha and beta
chemokine: IL-8
What type of mediators associated with mast cells and eosinophils are considered SRS-A’s (slow reactive substances of anaphylaxis)?
Leukotrienes
What are some examples of leukotrienes?
LTC4
LTD4 (very potent)
LTE4
LTB4 (pro-inflammatory)
Leukotrienes have overlapping activities with ___________.
They are associated with ________ onset, but _______ powerful and _______ duration as compared to histamine in bronchoconstriction.
They cause a __________ in capillary permeability and mucous production.
Histamine
Slower; more; longer
Increase
Which cytokine is considered a Th2 growth factor?
IL-4
What are the 2 primary functions of IL-4 in Th2 responses?
Isotype switching to IgE
Increase in VCAM-1
Which cytokine is associated with airway eosinophilia, mucous gland hyperplasia, and airway fibrosis and remodeling?
IL-13
What cytokine is the regulator of Eo production and survival?
IL-5
Which cytokine is in charge of recruitment and activation of inflammatory cells and causes altered function and growth of airway smooth muscle cells?
TNF
What is the half life of IgE binding to receptors? Is this considered long or short as compared to other isotypes?
Half life = 2 days in serum, up to 10 days when sequestered on FceRI on mast cells and basophils
This is short as compared to other isotypes (like IgG which has 21-23 day half life)
IgE is produced in ______ amounts to a very select group of antigens called _________
Small; allergens
_______ cells and ________ have high affinity Fc receptors for IgE called FceRI or CD23a
Mast cells; basophils
FceR receptors are only found in human cells that contain _______
Histamine
Allergens are small, ______ soluble antigens that are carried on _____ particles.
They can elicit responses in the absence of acute __________
Highly; dry
Inflammation
Mucosal challenge to allergens at ____ dose leads to _______ cell processing and presentation, and eventual ______ response
Low; dendritic; Th2
Allergens are often _____, meaning they are enzymatically active
Proteases
What do allergens contain that are required for T-cell priming?
Peptides that bind MHC class II
What occurs on first exposure to an allergen?
Priming - which results in IgE binding to mast cells, leading to sensitization to the allergen
DOES NOT result in allergic symptoms
Do allergens easily diffuse across mucosal epithelium?
Yes