Hypersensitivity Part 1 lecture 8 Flashcards
Hypersensitivity
immunity as sensitivity. Based on the observation than an individual who has been exposed to an antigen exhibits detectable reaction
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
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.
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
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
T cell mediated: Type VI
- Cd4T cells (Th1 and Th17)
- CD8 CTLs
Cytokine mediated inflammation and direct target cell killing cytokine-mediated inflammation
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
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
Release of mast cell mediators TYpe I
Histamine/lipid mediators: Vascular smooth muscle responses
Inflammation in the late phase
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
Late phase reaction Type I
IL5 from mast cells and Th2 cells recruit and activate eosinophils (parasitic infections)
disease associations type I
allergic rhinitis, allergic asthma, eczema or atopic dermatitis, food allergy, drug allergy, insect venom allergy
localized reactions
allergic rhinitis sinusitis (hay fever): increased mucus secretion; inflammation of upper airway sinuses
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
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
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.
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 (???)
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.
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.
mechanism of Type II hypersensitivity
abnormal physiologic responses without cell/tissue injury
antibody stimulates receptor without hormone
antibody inhibits binding of neurotransmitters to receptor
disease associations Type II
transfusion reaction, hemolytic disease of the newborn, autoimmune hemolytic anemia, good pasture syndrome, pemphigus
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)
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
transfusion reaction
fever, low Bp, nausea and vomiting, back and chest pain
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.
SX of hemolytic disease
stuff
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
Autoimmune hemolytic anemia (AIHA)
d
Pephigus vulgaris
proteins in intracellular junction of epidermal cells (epidermal cadherin)
blistering and rare
goodpasture syndrome
basement of
test for detecting Type II reactions
good pastures syndrome anti GBM antibody is detected. Ant
treatment of goopasture
remove the antiGBM
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
