Schein - Hypersensitivity Flashcards
What is stored in a mast cell and what is synthesized upon activation?
Stored (primary) - histamine, serotonin, chemo taxis mediators for neutrophils and eosinophils, proteases
Synthesized (secondary) - leukotrienes, PGs, bradykinin, cytokines
Skin Testing for allergy
Physician will inject a small amount of allergen right beneath the surface. Because the IgEs are already in position on the Fc receptors, the mast cells will degranulation upon exposure to antigen.
- it is possible also that the person has never been exposed to the antigen so next time maybe they will have a reaction
Wheal and Flare
What you will see on a skin test. The wheal is the localized edema causing the bump and the flare is the redenning around the wheal due to vasodilation.
RAST testing for allergy
You have a bead with the allergen on it. You then add some of the patients serum to see if they have antibodies that will bind to the antigen. Then you add a radiolabeled anti-immunoglobulin antibody. The more it lights up the more antibodies it has against that antigen.
Desensitization for allergies (allergy shots)
basically what this is is that they give you a shot with an increasing amount of antigen each time. With each time there is more class switching from IgE to IgA and IgD In the mucous membranes. Therefore, when you actually come in contact with the antigen, it is neutralized and can’t bind to the IgE on the mast cells.
Type II Hypersensitivity
- takes 4-12 hours
- antibody dependent (IgG or IgM). They bind to antigens located on the cell surface and opsonize them.
- They will then be killed by phagocytosis by neutrophils and macrophages
- This will also activate the complement pathway and activate the MAC complex
- this will also activate the Antibody Dependent Cell-mediated Cytotoxicity (ADCC) which basically means that the NK cells will recognize the target cell dressed with antibodies and kill them.
ADCC
When target cell are coated with antibodies they are lysed by various mechanisms
- NK, macrophages, neutrophils
Some examples of Type II reactions
- Transfusion reactions
- hemolytic disease of the newborn, erythroblastosis fetalis
- autoimmune diseases
- drug induced hemolytic anemia - antibiotics can sit o nthe membrane of a cell and can be viewed as foreign. - cell membranes act as carrier to hapten-carrier complex, which sit on membranes
Type III. Hypersensitivity
- 4-12 hours
- It is an immune complex disease. So basically what happens is that you have these circulating antigen-antibody complexes (usually IgG) that get lodged into small vessels and filtering organs. Then the anaphlatoxins (C3a and C5a) from complement will find these complexes lodged and induce mast cell degranulation, inflammatory markers, neutrophil recruitment, and release of lytic enzymes.
- small/medium size complexes are more problematic because the larger ones can fix complement easier and can be phagocytized.
- has An Arthur reaction
Arthus reaction
Type of Type III sensitivity that look a lot like the wheal and flare. It would be a Type I, but because it takes so many hours to occur it is type III. It is also Ag/Ab complex, which is type III
Type IV Hypersensitivity
Delayed type hypersensitivity.
- TAKES 48-72 HOURS TO SEE IT
- antibody independent. Basically what happens is that the Th1 cells recruit macrophages and monocytes and a granuloma is created. It activated CTL and cell killing.
- TB is the classic example - person will have a wheal and flare after 48-72 hours
Examples of Type IV. Hypersensitivity
TB
Allergy to metals/salts
Rejection of organ transplant
Urishiol from poison ivy and other skin contact rxns
Mnemonic for the hyper sensitivities
ACID A - anaphylaxis C - cytotoxic I - Immune complex D - Delayed type
Type I hypersensitivity
Will occur immediately - allergies, asthma, hay fever
1) You have sensitization from a previous exposure
2) It activates Th2 and makes more IgE
3) The circulating IgE binds to the Fc receptor on mast cells
4) upon secondary exposure, the IgEs are already there so a multivalent antigen will cross-link the receptors and cause mast cell degranulation.