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1

Hypersensitivity

immunity as sensitivity. Based on the observation than an individual who has been exposed to an antigen exhibits detectable reaction

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Gell and Coombs

1960s

applied to drug hypersensitivity reactions

the role of T lymphocytes, MHC restriction, and cytokines were largely unknown

despite that, system persisted

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Immediate type I

Mediated by IgE antibody

mast cell, eosinophils and their mediation (vaso active amines, lipid mediation, cytokines)

Atopy: unusual but really not so unusual now.

4

antibody mediated: type II

IgM, IgG antibodies against cell surface or extracellular matrix antigens

Opsonization mediated phagocytosis of cells

complement and Fc receptor mediated recruitment and actiation of leukocytes. Abnormalities in cellular function (hormone receptor signaling, neurotransmitter receptor blockade

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Immune complex mediated: Type III

Immune complex of circulating antigens and IgM or IgG antibodies

Bind to antigens that are soluble and causes a complex to deposit in diferent tissues. Complement or Fc mediated recruitment of leukocytes

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T cell mediated: Type VI

1. Cd4T cells (Th1 and Th17)
2. CD8 CTLs

Cytokine mediated inflammation and direct target cell killing cytokine-mediated inflammation

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Sensitization

Developing the immediate type reaction. Not necessarily sure when they develop this. Maybe getting the allergen through the skin instead of orally and the development of that allergy will occur.

IL4 induces class switching to IgE

IgE bind to Fc epsilon Receptor

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Activation of mast cells

repeat exposure to allergen occurs

activation of mast cells: release of mediators

Immediate hypersensitivity reaction (mins)

late phase reaction (6-24 hours) after repeat exposure to allergen

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Release of mast cell mediators TYpe I

Histamine/lipid mediators: Vascular smooth muscle responses

Inflammation in the late phase

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Biological effects of mast cell mediators Type I

biogeni amines (histamine) and lipid mediators (PAF, PGD2, LTC): vasodilation, vascular leak, broncho constriction, intestinal hypermotility

Cytokine and lipid mediators: inflammation

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Late phase reaction Type I

IL5 from mast cells and Th2 cells recruit and activate eosinophils (parasitic infections)

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disease associations type I

allergic rhinitis, allergic asthma, eczema or atopic dermatitis, food allergy, drug allergy, insect venom allergy

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localized reactions

allergic rhinitis sinusitis (hay fever): increased mucus secretion; inflammation of upper airway sinuses

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systemic anaphylaxis

heart and vascular system: increased capillary permeability, entry of fluid to tissue, swelling, low BP.

respiratory tract: contraction of smooth muscles and constriction of smooth airways. Difficulty in swallowing, bloating, and wheezing

gastrointestinal tract: contraction of smooth muscle, diarrhea

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allergic march

progression of allergic symptoms with age

chronic asthmatics have atopic dermatitis

sensitivity to food in infants can be associated with appearance of allergy to inhalants later in life

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how to test for immediate hypersensitivity

history

In vivo: skin testing: sweeling or wheals

In vitro: allergen specific IgE levels and total IgE levels. Plate (solid phase) coated with allergen. Patient's serum added. Labeled anti epsilon added.

Total serum IgE levels: Elisa method: solid surface coated with IgE antibody. Patient's serum added and labled anti epsilon added.

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TX Type I

avoid allergen possible

anaphylaxis: epinephrine

bronchial asthma: corticosteroids, leukotriene antagonist, or phosphodiesterase inhibitors

various allergic disease: desensitization, anti IgE antibody, antihystmine, cryo (???)

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Immunotherapy

increasing doses of allergen are administered

typically injected subcutaneous; also sublingual and intralymphatic routes

general, this results in rise in serum IgG blocking antibody levels (IgG4)

currently only available for environmental aeroallergens

current research into area of oral immunotherapy for foods is extensive although still not FDA approved.

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ADCC

IgG antibodies serve as bridges to link target cells to effector cell. Lead to other actions.

complement and Fc receptor mediated inflammation and opsonization and phagocytosis.

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mechanism of Type II hypersensitivity

abnormal physiologic responses without cell/tissue injury
antibody stimulates receptor without hormone

antibody inhibits binding of neurotransmitters to receptor

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disease associations Type II

transfusion reaction, hemolytic disease of the newborn, autoimmune hemolytic anemia, good pasture syndrome, pemphigus

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tests for Type II

Coombs test: detects anti-RBC abs

direct: picks up antibodies directly on the surface of the red blood cell.

Red blood cells coated with antibody and given anti Ig which results in clumping. Helps diagnose hemolytic thing

indirect coombs: measures in the serum. RBC not coated with antibody and serum with antibody to RBC. Antibody coated RBC and anti Ig which leads to agglutination of RBC. Mainly used in blood banking (cross matching, blood typing)

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transfusion reaction

ABO transfusion reaction can cause type II response

group O cannot receive A, B, AB cells

Group A receive like blood

Group B receive like blood

AB receive any type of blood

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transfusion reaction

fever, low Bp, nausea and vomiting, back and chest pain

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hemolytic disease of the newborn

dramatic type II reaction

called erythroblastosis fetalis

antigen present on the surface of the red cell

called rhesus (RhD)

baby is RhD+ and mom is RhD- and forms antibodies. Normally occurs due to trauma and the blood of the baby enters mom, the mom will attack the baby.

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SX of hemolytic disease

stuff

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Anti D tx

inject Rh - mothers with preformed antiRHD at 28 weeks gestation or within 3 ays of potential exposure from miscarriage trauma or delivery

these abs destroy RhD + fetal cells in maternal circulation. Trick body into thinking that it had made anitbodies

repeat each pregnancy

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Autoimmune hemolytic anemia (AIHA)

d

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Pephigus vulgaris

proteins in intracellular junction of epidermal cells (epidermal cadherin)

blistering and rare

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goodpasture syndrome

basement of

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test for detecting Type II reactions

good pastures syndrome anti GBM antibody is detected. Ant

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treatment of goopasture

remove the antiGBM

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crossreactivity from infectious agents

acute rheumatic fever: infection with group a streptococcus; antibody crross reacts with myocardial antigen. Cause inflammation and macrophage activation.

migratory arthritis

molecular mimicry