Flashcards in Hypersensitivity Deck (60):
What are hypersensitivities?
inappropriately vigorous host immune response to antigen
What are the four types of hypersensitivities?
Type I = anaphylaxis
Type II = Antibody-mediated cytotoxicity
Type III = Immune complex disease
Type IV = Delayed hypersensitivity
What is a type I hypersensitivity? How is it brought about?
Anaphylaxis - brought about by antigen binding to the surface of IgE-coated basophils or mast cells, causing release of histamine
How fast is a type I hypersensitivity?
Seasonal allergies are what type of hypersensitivity?
Type I (IgE mediated)
What does it mean for an individual to be atopic?
those that have an increased tendency to develop allergies
IgE is mostly made to fend off against what type of antigen? What is its role in anaphylaxis?
Made for parasites, but released in response to allergens in atopic individuals
What is the default pathway in the absence of inflammation: Th1 or Th2? What is the significance of this in anaphylaxis?
Th2-- IgE production is the outcome of the lack of inflammation as seen in anaphylaxis
What is the "hygiene hypothesis"?
decreased exposure to pathogens early in life (which would favor the development of Th1-mediated immune responses), leading to the development of strong Th2-mediated immunity and subsequent IgE production
What are most respiratory allergens?
small molecules that are carried on larger particles such as pollen grains or mite feces
What sort of delivery method to the body do most respiratory allergens go through? What does this elicit?
Transmucosal delivery, causes Th2 IgE responses
Physiologic responses to parasites usually occur where?
Skin, airways, gut
What are basophils?
Granulocytes withgranules present in cytoplasm
Where are basophilis usually found?
Are basophils phagocytic?
How are basophils related to mast cells?
Similar, but arise from different cells
Where are mast cells usually located?
Near small blood vessels and post capillary venules in mucosal tissues
What is on the surface of mast cells that binds to IgE released during anaphylaxis? Binding to this area causes what?
Fc receptors--binding = histamine release and degranulation
How do anaphylatic reactions come about (what leads to hypersensitivity)?
1st exposure stimulates IgE production. Subsequent exposure to the allergen binds to the surface bound IgE and activates the cells to release their granule contents.
What are the two major chemicals in mast cells that mediate anaphylaxis?
How does the amount of eosinophils in allergic individuals compare to that of non-allergy prone people?
What are the four major Leukotrienes, and what are their effects?
LTC4, LTD4, and LTE4.
Most potent substances known that cause smooth muscle contraction and increased vascula rpermeability
How long does it take leukotrienes to be synthesized? How do they compare to histamine?
Released more slowly than histamine, but have a longer effect
Where do eosinophils accumulate?
Nasal and bronchial mucosa in respiratory allergies, and in intestinal mucosa during certain worm infections
What is the function of eosinophils in the gut?
Attach to worms and release granules containing hydrolytic enzymes
When does the late response phase develop?
6-8 hours after immediate reaction
What are the chemicals that are released in the late phase response?
What is the cell type(s) responsible for the late phase response?
What are the four events that occur in the late phase response?
1. 2nd phase muscle contraction
2. sustained edema
3. recruitment of eosinophils and Th2 cells
4. Remodeling of tossue
Eosinophils contain granules that have what?
hydrolytic enzymes that can be used to destroy certain parasites.
What synthesizes leukotrienes C4, D4 and E4?
Activated basophils and mast cells
What is the only treatment that can reverse anaphylaxis?
What is the mechanism of action of Epi?
binds to beta-adrenergi receptors to increase cAMP. This relaxes bronchial smooth muscles, tightens endothelial cell junctinos, and stimulates the heart
What is the mechanism of action of histamines?
Binds to histamine receptors to block further binding of histamine
What is the mechanism of action of Cromolyn sodium and theophylline?
What are the preventative treatments for anaphylaxis? How does it work?
Repeated treatments of anti-IgE. leads to development of Th1 cell mediated (IgG), downregulated Th2
What is type II hypersensitivity?
When antibodies bind to a cell surface to destroy it
What are the four types of antibody mediated reactions?
3. Hemolytics disease of newborn
4. Non-cytotoxic reaction
What is involved in the complement mediated reactions of type II hypersensitivity?
Antibodies of the IgG or IgM classes activate the classical complement cascade, which is a sequentially activated series of proteins that can lyse cells. (e.g. blood transfusions)
What is involved in the ADCC mediated reactions of type II hypersensitivity?
Tumor cells or virus-infected cells are bound by IgG and are lysed by natural killer cells, monocytes or neutrophils via recognition through their Fc receptors.
What is involved in the hemolytic disease of the newborn reactions of type II hypersensitivity?
a mother makes IgG antibodies specific to the Rh blood group antigen expressed by the red blood cells of her child.
Are the IgG antibodies produced by the mother in hemolytic disease of newborns cytotoxic?
No, but antibodies coat RBCs, and these are destroyed = anemia
What is the treatment for erythroblastosis fetalis?
Anti-Rh antibodies given to mother bind to the fetal cells in the mother's circulation, causing their removal by spleen and liver phagocytic cells, thereby preventing sensitization of the mother's immune system
What type of hypersensitivity are Grave's disease and Myasthenia gravis?
What is the mechanism of action in Grave's disease?
Antibodies to the thyroid-stimulating hormone receptor cause the overproduction of thyroid hormones and the resulting hyperthyroidism
What is the mechanism of action in Myasthenia gavis?
antibodies to the acetylcholine receptor blocks nerve impulse transmission to muscles
What are the four ways immune complex diseases (Type III hypersensitivities) are induced?
1. Autoimmune diseases
2. Drug reactions
3. Infectious disease
4. Inhaled allergens
What is the pathogenesis of Type III hypersensitivities?
Formation of immune complexes, which lodge into tissues. Complement is then activated via classical pathway. C5a recruits lysosomal enzymes which release damaging enzymes to tissues
What is serum sickness?
Repeat injection of large amounts of foreign serum, causing immune complexes...
What normally removes the immune complexes? What chemical do these cells have that aid in this process? What happens to remove the immune complexes.
RBCs that bear complement receptor 1 protein (CR1), which binds C3b and C4b. These removed by liver
What happens to the RBCs in type III hypersensitivities that prevents them from removing complement?
What protein is present on the glomerulus that cause issues in type III hypersensitivities?
CR1 proteins that bind immune complexes
How long does it take to develop type IV hypersensitivity?
PPD test for TB is an example of what type of hypersensitivity?
What is the pathogenesis of Type IV hypersensitivites?
Small molecules complex with skin proteins, become internalized and expressed on class II MHC. CD4+ Th cells activated, lead to CTLs and interferon-gamma production.
When PPD is injected intradermally, macrophages present to T cells via class II MHC. What is the response of endothelial cells?
upregulate expression of vascular cell adhesion molecule-1 (VCAM-1)
What is the action of VCAM-1 in the PPD test?
alerts the circulating memory T cells that inflammation is occurring in the adjacent tissues and they bind and migrate into the tissues
When memory T cells have migrated to the PPD area, what happens?
Interferon gamma increaes macrophages. Tissue damage ensues, leading to positive test
Why don't PPD negative individuals develop immunity to the antigen?
Dose is too small to initiate primary immune response, and no memory cells generated.