Hypersensitivity Flashcards
What mediates the four types of hypersensitivity reactions?
Type I: IgE (Th2)
Type II: Ab- mediated cytotoxicity (Th2)
Type III: immune complex (Th2)
Type IV: delayed (Th1)
*remember your ABCD:
I = Allergic Anaphylaxis
II = antiBody
III = immune Complex
IV = Delayed
Type I hypersensitivity
allergic reaction - exaggerated response to an antigen
immediate reaction
Type I hypersensitivity mechanism
- DC activates naive T cells —> Th2
- Th2 secretes IL-4 —> IgE class switching in B cells
- IgE binds Fc on mast cells and basophils
- upon secondary exposure - mast cells cross link surface IgEs, release inflammatory mediators: vasoactive (immediate) and cytokines (late phase)
these cells provide defense against parasitic worms and protozoa, and their products attract eosinophils. What are?
mast cells
what are primary (immediate) allergy mediators?
(pre-made/ stored):
- histamine and serotonin - vascular permeability, smooth muscle contraction
- neutrophil and eosinophil chemotaxis mediators
what are secondary allergy mediators?
secondary (synthesized in minutes):
- leukotrienes - vascular permeability, smooth muscle contraction
- prostaglandins - vasodilation, smooth muscle contraction, platelets activation
- bradykinin - vascular permeability, smooth muscle contraction, pain
- cytokines - recruit WBC, inflammation (causing late phase reaction)
what are the allergy mediators of late phase allergic reaction?
late phase (recruitment, up to 24hs):
- neutrophil and eosinophil inflammation
- protease damage
what are the allergy mediators of primary, secondary, and late phase reaction?
primary:
- histamine and serotonin
- neutrophil and eosinophil chemotaxis mediators
secondary:
- leukotrienes
- prostaglandins
- bradykinin
- cytokines
late phase:
- neutrophils and eosinophils
- protease damage
local vs systemic anaphylaxis manifestations
local: allergic rhinitis, asthma, urticaria (hives), eczema (atopic dermatitis), angioedema (swelling of soft tissue like lips)
systemic: disseminated mast cell activation results in increased vascular permeability, constriction of smooth muscle (—> extravasation of fluid, leading to hypotension), airway constriction, epiglottis swelling
when skin testing for an allergy, what will happen if a small amount of allergen is introduced (via intradermal injection or superficial scratching) to a patient with an allergy?
local mast cells will degranulate and cause increased permeability and fluid loss —> resulting in swelling (wheal)
and localized increased blood flow —> causing redness (flare)
so wheal (edema) + flare (red) = allergic
RAST allergy test
radioallergosorbent test (RAST): detects levels of IgE
- allergens coupled to beads
- serum is added, IgE binds beads
- labeled anti-IgE measures IgE levels
what happens on a molecular level as desensitization to an allergy occurs?
- decreases Th2
- induces Tregs
—> IL-10 and TGF-b
—> decreased IgE, suppressed mast cells, class switching to IgG and IgA
hygiene hypothesis (allergy)
developing immune system does not have enough contact with the right viruses and bacteria, so Th1 reactions are not sufficiently stimulated
immune system becomes unbalanced, with overactive Th2 response
solution: exposure to diverse environmental antigens may prevent sensitization to antigens
Type II hypersensitivity mechanism
antibody-dependent cell toxicity (ADCC) - IgM or IgG dependent
1. classical complement pathway activated
2. opsonization (IgM > IgG)
3. phagocytosis (macrophage, neutrophils)
takes a few hours (not immediate)
ADCC
antibody-dependent cell-mediated cytotoxicity: target cell opsonized, then lysed by cytolytic effector cells (NK primarily, some macrophage/neutrophils, eosinophils if parasitic/worm)
does not involve complement
dependent on prior antibody response
transfusion reactions, hemolytic disease of the newborn, autoimmunity, and drug-induced hemolytic anemia are type ____ hypersensitivity reactions
Type II: antibody-mediated cytotoxicity (via ADCC)
why does it make sense than IgM is better at opsonization than IgG?
IgM is a pentamer (more places to bind)
Graves’ disease (hyperthyroidism) is a Type ___ hypersensitivity
Type II (ADCC) hypersensitivity - leads to antibody-mediated activation of TSH (thyroid-stimulating hormone) receptors
myasthenia gravis is a Type ___ hypersensitivity
Type II (ADCC) hypersensitivity - antibodies inhibit Ach binding to receptors, leading to down-regulation of Ach receptor —> muscle weakness and paralysis
Rheumatic fever is a Type ___ hypersensitivity
Type II (ADCC) hypersensitivity - causes inflammation and macrophage activation
antibody for streptococcal cell wall antigen cross-reacts with myocardial antigen —> myocarditis, arthritis
Type III hypersensitivity
mediated by immune complex - caused by circulating antigen-antibody complexes —> lodge in small vessels and filtering organs
large complexes can be phagocytosed via complement, but small complexes get into tissues
takes 4-12 hours
Type III hypersensitivity mechanism
mediated by antigen-antibody complex (usually IgG):
- large complex—> complement activation, phagocytosis
- small complex—> accumulate in blood, get into tissues
C3a and C5a (anaphylatoxins) induce inflammatory response —> neutrophils recruitment (phagocytosis), lytic enzyme (tissue injury), platelet activation (thrombosis)
Arthus reaction
acute reaction initiated by local deposition of immune (Ab/Ag) complexes (as in Type III hypersensitivity)
takes 4-12 hours to develop - immune complexes must form and activate mast cells/ neutrophils/ complement
[faster than Type IV, but slower than Type I]
what is an example of localized and systemic Type III hypersensitivity reactions?
Type III - mediated by Ab/Ag complex
localized:
- local deposition of complex in blood vessels
- insect bites
- drugs/vaccines (—> Arthus rxn)
- inhaled bacterial spores/ fungi (Farmer’s lung)
systemic:
- serum sickness (circulating immune complexes)
- autoimmunity (autoantigens) - SLE (systemic Lupus erythematosus), rheumatoid arthritis
Farmer’s lung is a type ___ hypersensitivity
Type III (Ab/Ag) mediated
intrapulmonary reaction due to inhaled bacterial spores or fungi
serum sickness is a type ___ hypersensitivity
Type III (Ab/Ag) - circulating immune complexes
SLE and rheumatoid arthritis are both a type ____ hypersensitivity
Type III (Ab/Ag mediated)
SLE (systemic lupus erythematosus) and rheumatoid arthritis are both autoimmune diseases
Type IV hypersensitivity
delayed - symptoms begin 24h after exposure, peaks between 48 and 72 hours
mediated by antigen-specific Th1 cells, antibody independent
major injury due to inflammation - CD4 Th, cytokines, T cell cytotoxicity
how do Th1 cells induce Type IV hypersensitivity?
Type IV - delayed, antibody independent
Th1 secrete inflammatory cytokines, activate neutrophils and macrophages, recruit monocytes/macrophages/granuloma formation
Th1 can activate CTL (CD8+) killing
Type IV hypersensitivity mechanism
- Th1 activation via MHC II APC and IL-12
- Th1 secrete INF-y —> activates macrophages
- macrophages produces IL-1, IL-6, IL-23
- activated Th17 recruit neutrophils via IL-17
what happens upon secondary exposure in Type IV hypersensitivity (Th1 mediated)
memory T recognize antigen, secrete inflammatory cytokines, recruit macrophages (—> tissue damage) and neutrophils
macrophages —> granulomatous inflammation
CD8+ —> cytotoxicity
symptoms begin 24h after secondary exposure and peak between 48 and 72 hours
what occurs following skin test for type IV hypersensitivity?
Type IV is delayed, so reactivity is evident between 48 and 72 hours
skin lesions form as a result of infiltration of inflammatory cells to site
[remember in skin test, antigen is introduced via intradermal injection or scratching]
what kind of hypersensitivity reaction is utilized in diagnosis of tuberculosis?
Type IV (delayed - remember that you return for reading 48-72 hours later!)
positive Type IV reaction in dermis indicates prior exposure
allergy to metal salts or other haptens causing contact dermitis to coins, jewelry, or nickel is an example of type ___ hypersensitivity
Type IV (delayed, Th1 mediated)
urushiol, or poison ivy, is an example of Type ___ hypersensitivity
Type IV (delayed, Th1 mediated)
which type of hypersensitivity is anaphylactic?
Type I (IgE mediated) - immediate reaction
which of these is a type of Type I hypersensitivity?
a. Arthus reaction
b. Hay fever
c. ABO mistmatch
d. contact dermititis
b. Hay fever: type I (IgE, anaphylactic) hypersensitivity
Arthus rxn: Type III
ABO: Type II
contact dermititis: Type IV
which of these is a type II hypersensitivity?
a. Arthus reaction
b. Hay fever
c. contact dermititis
d. Rh hemolytic disease of newborn
d. Rh hemolytic disease: Type II hypersensitivity (as is ABO mismatch) - ADCC mediated
Arthus rxn: Type III
Hay fever: Type I
contact dermititis: Type IV
from this list, pick out the Type II hypersensitivities:
a. chronic transplant rejection
b. ABO mistmatch/ Rh (newborn)
c. contact dermititis
d. Graves’
e. hyperacute transplant rejection
f. allergy
g. myasthenia gravis
h. rheumatic fever
i. tubercular lesions
j. hemolytic anemia
Type II (ADCC) hypersensitivity:
b. ABO/Rh
d. Graves’
e. hyperacute transplant rejection
g. myasthenia gravis
h. rheumatic fever
j. hemolytic anemia
a farmer’s respiratory problems related to an allergy to moldy hay is indicate of type ____ hypersensitivity
type I (anaphylactic/allergy)
a chest x-ray showing nodular opacities in both lung apices is indicative of type ____ hypersensitivity
type IV (cell mediated) - granulomas form in tissues
hay fever is a type ____ hypersensitivity
type I (anaphylactic)
A patient comes into the emergency room with severe bleeding due to a car accident. They need a transfusion right away, but their blood type on file is wrong and they begin to experience a type ___ hypersensitivity
type II (cytotoxic/ADCC) hypersensitivity
A patient complains of allergy symptoms that begin to occur a few hours after they arrive to work, at a factor that processes natural fibers. Their symptoms improve on the weekends. This is indicative of a type ___ hypersensitivity
Type III (immune complex) hypersensitivity
this is describing Farmers lung - reaction to spores in fibers
Which products of activated complement bind to receptors on mast cells and stimulate release of inflammatory mediators?
C3a and C5a
A boyscout allergic to poison ivy develops an itchy rash 2 days after a camping trip. What process below plays the largest role in this type of reaction?
a. CD8+ CTL killing
b. CD4+ Th cytokine secretion
c. proliferation of NK cells
d. activation of neutrophils
b. CD4+ Th cytokine secretion
remember that Type IV hypersensitivity is mediated by Th1
Six months after transplantation, a transplanted kidney shows signs of acute rejection. What immune mechanism is responsible?
a. deposition of immune complexes
b. IgG production
c. anti-ABO antibodies
d. mast cell degranulation
e. cell-mediated immune response
e. cell-mediated immune response (T cell mediated) to donor MHC antigens not present in the recipient
