Hypersensitivity Flashcards
What is hypersensitivity?
over-reactions to foreign agents, harmful or benign
What mediates a type I hypersensitivity and what is it mediated by?
immediate hypersensitivity (minutes)
mediated by IgE, mast cells and eosinophils
what are some respiratory examples of type I hypersensitivity?
hay fever, asthma
what are the events in a type I reaction?
sensitization phase
action phase
immediate effector phase (mast cells)
late effector phase (eosinophils)
what happens in the sensitization phase?
-activation of T helper 2
-production of IL 4
-activation of B lymphocytes
-Production of IgE
-generation of memory responses
what occurs during the activation phase?
-IgE binds to high affinity IgE specific Fc receptors
-receptors cross linked by allergens
-IgE activates basophils and mast cells (from blood vessels, CT, gut, lungs etc)
what occurs in the immediate effector phase?
-activation of mast cells (Ca influx in mast cells)
-decrease in cAMP, increase cGMP
-activation of prostaglandins and leukotrienes
-production of cytokines and chemotactic factors
-degranulation of mast cells
-increase infiltration of eosinophils
what are some functions of the mediators released in immediate effector phase?
-vasodilation
-inflammation
-smooth muscle contraction
-modulate adaptive immunity
-tissue damage
slide 286–go back over it
what occurs in the late effector phase?
4-12 hours production of cytokines
Mast cells produce eosinophil chemotactic factor that recruits eosinophils
rxn persists for days
what activates eosinophils?
IgE binds and activates eosinophils by FceRII
what is the major activity of eosinophils?
anti-parasitic activity
-major basic protein- destroys parasites
-eosinophilic cationic protein- form ROS
-leukotrienes from mast cells cause smooth muscle contraction to expulse the parasite
what is atopy? Which hypersensitivity is it associated with?
allergic reaction due to the inhalation of allergens
what is anaphylaxis? Which hypersensitivity is it associated with?
systemic reaction to allergin
what is wheal and flare skin reaction test?
intradermal challenge with antigens that leads to
-Flare: dilation of blood vessels
-wheal-raised area due to released serum in tissue
what is the time required for a result for the flair and wheal test?
15 mins
positive test will show a raised wheal with well defined edges
what types of interventions are there for hypersensitivity?
environmental
pharmacological
immunological
what are some examples for the pharmacological interventions to hypersensitivity?
epinephrine
corticosteroids
leukotriene antagonist
phosphodiesterase inhibitor
desensitization
anti- IgE antibodies
antihistamines
(good chart on slide 291)
what is a type II hypersensitivity mediated by?
IgM and IgG
what are some examples of Type II?
IgM: blood transfusion rxn
IgG: hemolytic disease of the newborn
what is the general mechanism for damage in type II?
-antibody directed against surface molecules on targets activates complement system
(this can cause activation of the lytic path, anaphylatoxins, inflammation and production of inflammatory and tissue destructive mediators)
what causes blood transfusion reactions?
-different polysaccharides
(Blood type=antigen you have, antibody will by opposite ex. type A blood, A antigen, anti- B antibody)
in a type II hypersensitivity, environment carbohydrates induce the production of _____ in a _______manner?
IgM
T Cell independent
what effect does IgM have in blood transfusion reactions?
Igm binds to blood group antigens on donated blood cells which are mismatches and transfused causing massive agglutination and destruction of donor cells
what is a key symptom for differentiating blood transfusion reactions from other types or reactions?
RBC debris causing damage in the kidney (has many other symptoms but they are more generic and harder to narrow down the different conditions)
what happens to cause hemolytic disease of the newborn?
mother is Rh-, father is Rh+, baby is Rh+
first pregnancy is fine, second will cause destruction of baby blood cells VIA IGG because it can cross the placenta
what are some symptoms of hemolytic disease of newborn?
enlargement of liver, spleen, hemorrhages and elevated bilirubin
Hw is HDNB diagnosed?
indirect coombs test (anti human IgG)
determines whether the mothers serum has anti Rh antibody’s
what is the treatment for HDNB?
Rhogam after first delivery to prevent mother from developing immune response to fetal blood cells
wat is a type II hypersensitivity mediated by?
antibody complexes (antigen and IgG)
what is the mechanism of damage for type III?
antigen and IgG complexes form persistent microbial infection or chronic exposure to extrinsic antigens (ex molds)
what does damage does the antigen/igg complexes cause?
immune responses get deposited in tissues because they failed to clear, immune complexes activate the complement cascade causing inflammation
what are some examples of type III?
arthus reaction (localized)
serum sickness (systemic)
what is arthus reaction?
after repeated injection of antigens in the same location there is a high level of antibody in that area causing formation of antigen/antibody complexes activating complement IN THE TISSUES
what is serum sickness
when arthus reaction occurs but the antigen/antibody complexes are in the blood
(think the snake bite, give you horse protein to reduce the snake venom but our body attacks the horse protein resulting in large reaction that become deposited in basement membranes and cause nephritis/arthritis, then the complexes get cleared and the person recovers)
what is a type IV hypersensitivity?
mediated by Th1 cells
(aka delayed type hypersensitivity cells)
rxn occurs 24-48 hours after contact
What is the general mechanism for damage in type IV?
cell mediated inflammatory and cytotoxic response
antigen in tissues presented to CD 4 Th 1 cells
what do activated CD4 Th1 cells produce?
cytokines, IFNy, TNFB, IL3 GM-CSF and chemokines
Th1 cells activate what other type of cell?
CH 8 or cytotoxic T cells (phagocytes CTL and inflammation lead to development of lesions)
what are the three types of DTH?
- contact dermatitis
- tuberculin reactions
- granulomatous reactions
what is contact dermatitis caused by?
CONTACT with irritant such as poison ivy, metals or chemicals (like in a detergent)
INFECTION- via viruses like chicken pox
what is the mechanism behind poison ivy dermatitis?
pentadecacatechol (from ivy) touches skin activating cutaneous rxn
presented BY Langerhans cells and keratinocytes TO Th1 cells
what happens after pentadecacatechol is presented to Th1 cells by langerhans cells and keratinocytes?
Th1 produce cytokines
IFNy activates macrophages that produce destructive enzymes and activate more Th1 cells elevating rxn
what is a tuberculin skin test?
test used for determining previous exposure to mycobacterium tuberculosis
injection of soluble antigens (PPD) under the dermis
what occurs with a tuberculin rxn?
antigen presented by dendritic cells and macrophages activate Th1 production of chemokines and cytokines
what is the visual difference between the three skin tests?
1- well defined circular bump appears in MINUTES
3- Aurthers, diffused redness, HOURS
4- red indurated lesion DAYS
what is a granulomatous rxn?
immune mechanism to confine what it finds hard to eliminate by walling them by surrounded the by layers of macrophages Th1 and fibroblast cells
How does a granuloma usually end?
cell trapped in the center becomes necrotic and dies due to lack of nutrients, when it dies the surrounding cells disperse
(tuberculosis and asbestos)
what is leishmaniasis?
parasite can be killed by macrophages so it lives inside the macrophages forming granulomas to form around the infected kupffer cells in the liver
what is Hanson disease? (leprosy)
mycobacteria lepra is very tough to destroy etiological agent
what are some examples of novel therapies for HS?
blocking:
-CD8 CD80/86
-signal transduction
-cytokines/chemokines receptors
-adhesion molecules
what does antihistamine do?
competitively blocks histamine from binding to histamine receptors on smooth muscle cells
