Hypersensitivity I Flashcards
Humoral?
Ig
B cells
T cells can be involved in humoral or CMI but its the final effector function that defines the type of immunity that is involved
CMI?
cellular
Cells
T cells
Four major classes of hypersensitivities…. Gel and Coombs classifications
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Type I hypersensitivity?
immediate hypersensitivity
type II hypersensitivity?
antibodies bound to cells or tissues
type III hypersensitivity?
immune complex
type IV hypersensitivity?
delayed type hypersensitivity (DTH)
which hypersensitivities are ab-mediated?
Type I, II, III
which hypersensitivities are cell mediated?
Type IV - delayed type hypersensitivity (DTH)
type I - immediate hypersensitivity
pathologic immune mechanism?
mechanisms of tissue injury and disease?
Th2 cells, IgE ab, mast cells, eosinophils
mast cell - derived mediators (vasoactive amines, lipid mediators, cytokines)
type II - ab mediated diseases
pathologic immune mechanism?
mechanisms of tissue injury and disease?
IgM, IgG antibodies against cell surface or extracellular matrix ag
complement and Fc receptor mediated recruitment and activation of leukocytes (neutrophils, macrophages)
opsonization and phagocytosis of cells
abnormalities in cellular funciton, e.g. hormone receptor signaling
type III - immune complex mediated diseases
pathologic immune mechanism?
mechanisms of tissue injury and disease?
immune complexes of circulating age and IgM or IgG abs deposited in vascular basement membrane
complement and Fc receptor-mediated recruitment and activation of leukocytes
type IV - T cell mediated diseases
pathologic immune mechanism?
mechanisms of tissue injury and disease?
- Cd4+ T cells (cytokine-mediated inflamm)
- Cd8+ CTLs ( t cell-mediated cytolysis)
- macrophage activation, cytokine-medaited inflamm
- direct target cell lysis, cytokine-mediated inflamm
Th2 type responses drive….
IgE ab production.
Most of IgE is bound to what?
high affinity Fc receptors on mast/basophils
repeat exposure to an allergen (cross-linking) of mast cells induces degranulation. The degranulation leads to the symptoms of the immediate run of the allergic response. The mast cell is activated to synthesize new mediators which make up the late phase reaction (6-24 hrs after repeat exposure to allergen).
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atopy/atopic?
prone to developing allergies due to IgE
In the late phase reaction, there is recruitment of eosinophils and T cells and neutrophils.
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the immediate reaction results in edema and vascular congestion
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a number of substances are released upon degranulation, the most prominent of which is histamine, which leads to…
vasodilation (edema) and smooth muscle contraction
most important late phase reactants?
prostaglandins and leukotrienes (similar to histamine) and cytokine synthesis (TNF is important for inflamm)
IL-4 is made - reinforces the Th2 response
late phase reaction requires de novo synthesis!!!
- leukotrienes
- cytokines (TNF-alph, IL-4, IL-5)
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Types of diagnostic tests used for Type I hypersensitivity?
- measurement of IgE levels (relatively nonspecific tho)
- measure for specific IgE Abs against specific allergens
- skin tests - look for “wheal and flare rxn”
Wheel and flare
subQ ag, low dose
mast cell activation
increased vascular permeability leads to localized swelling
have injection sites for allergen, saline, histamine
common sources of allergens….
inhaled materials?
type I
plant pollens
dander of domesticated animals
mold spores
feces of very small animals (house dust mites)
common sources of allergens…
injected materials?
Type I
insect venoms
vaccines
drugs
therapeutic proteins
common sources of allergens… ingested materials?
Type I
food (peanuts, shellfish)
orally administered drugs
drug hypersensitivity can be all four types of hypersensitivities!!
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type I hypersensitivity causes
allergic rhinitis sinusitis (hay fever)
food allergies
bronchial asthma
anaphylaxis (may be drugs, bee sting, or food)
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allergic rhinitis sinusitis (hay fever)
type I
increased mucus secretion
inflammation of upper airways
sinuses
food allergies
type I
increased peristalsis due to contraction of intestinal muscles
bronchial asthma
type I
airway obstruction caused by bronchial smooth muscle hyperactivity
inflamm and tissue injury caused by late-phase rxn
anaphylaxis
fall in blood pressure (shock) caused by vasodialtion
airways obstruction due to laryngeal edema
epinephrine works on what type of receptors?
adrenergic!
Key cytokines in a Th2 response?
why is Th2 response important?
IL-4 —-> IgE response
IL-5 —-> eosinophil activation
IL-13 overlapping function with IL-4 (involved with airway hyper-responsiveness)
importnat in IgE mediated responses (allergy/asthma) and responses to helminths (parasitic infections)
IL-4/ IL-13 also involved in…
alternative macrophage activation (enhanced fibrosis/tissue repair)
intestinal mucus secretion and perstalsis
IL-13 and eosinophils seem to have prominent roles in asthma also
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the type of clinical manifestations seen when exposed to an allergen depend on the route of exposure to the allergen!
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Intervention for Type I hypersensitivity?
avoidance (food, pets, regional)
desensitization (allergy shots)
pharmacologic
anaphylaxis therapy?
epinephrine - causes vascular smooth muscle contraction and increases CO (to counter shock)
relaxes airway muscle, inhibits mast cell degranulation
bronchial asthma therapy?
corticosteroids (reduce inflamm)
leukotriene antagonists (relax bronchial smooth muscle and reduce inflamm)
phosphodiesterase inhibitors (relax bronchial smooth muscle)
various allergic diseases therapy?
desensitization - unknown mechanism
anti-IgE ab
antihistamines
cromolyn - inhibits mast cell degranulation
antihistamines are not Abs against histamine! They are pharmacological antagonists that bind to the histamine receptors and compete with histamine.
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For HAE airway obstruction, administer..?
C1INH
always administer epi first because you do not know if its an anaphylactic rxn or not
anaphylactic edema is likely to e accompanied by urticaria and itching
Type II hypersensitivity… Ag is found…?
found on surface of tissue, cell, or ECM
Type II is tissue/organ specific
Type III - immune complex and systemic!
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Type III leads to vasculitis as there is deposition of immune complexes as it circulates
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C5a attracts what?
neutrophils
Type II hypersensitivity reactions activate complement. Inflammatory mediators can also be released to attract neutrophils and other inflamm cells leading to tissue damage
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Type II hypersensitivity can have antibody stimulate the receptor without the hormone… aka Ab serves as agonist for what receptor in what disease?
TSH receptor
Grave’s disease (hyperthyroidism)
Type II hypersensitivity can have antibodies that inhibit binding of neurotransmitter to receptor.. this happens in what disease?
myasthenia gravis!
the antibody is antagonistic to AchR
two autoimmune diseases associated with type II?
graves disease
myasthenia graves
type II
autoimmune hemolytic anemia
erythrocyte membrane proteins (Rh antigens)
opsonization and phagocytosis of erthyrocytes
hemolysis, anemia
type II
goodpasture’s syndome
non=collagenous protein in BM of kidney glomeruli and lung alveoli
complement and Fc receptor mediated inflamm
nephritis, lung hemorrhage
type II
grave’s disease
thyroid-stimulating hormone receptor
ab-mediated stim of TSH recap
hyperthyroidism
type II
myasthenia gravis
acetylcholine receptor
ab inhibits acetylcholine binding
down-modulates receptors
muscle weakness, paralysis
type II
rheumatic fever (caused by infection)
streptococcal cell wall antigen; ab cross-reacts with myocardial antigen
inflamm, macrophage activation
myocarditis, arthritis
Type II - drug induced hemolytic anemia
this is a case where a hapten (penicillin) couples to an RBC (carrier) making it immunogenic
destruction of the rbc can be through a combination of opsonization and complement mediated lysis
form opsonins (phagocytosis) or complement that is carried to spleen for destruction or activation of membrane attack complex
Mother with Graves disease makes anti-TSHR antibodies
During preg, these ab cross the placenta to fetus
Newborn also suffers from Graves
Plasmaperesis removes maternal anti-TSHR ab and cures the infant’s disease
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Rheumatic fever is caused by what bacteria?
Group A Streptococcus pyogenes
Its cell wall stimulates ab response
Some ab cross-react with heart tissue, causing rheumatic fever
Type III hypersensitivity - formation of circulating immune complexes.
In excess levels, the immune complexes will deposit along blood vessels systemically leading to vasculitis. As immune complexes accumulate, complement will be activated which leads to an inflammatory reaction
originally, they are soluble but when they deposit they begin to activate complement because of the concentration of Fc receptors
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ex. of Type III hypersensitivity from tetanus talk?
serum sickness with equine serum
example of a tissue where immune complexes after concentrate?
the kidneys!
immune complexes occur when there is a large amount of ag in the system
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Three examples of type III reactions?
ab spec and manifestations in each?
1) systemic lupus erthematosus
- ab spec: DNA, nucleoproteins, others
- nephritis, arthritis, vasculitis
2) serum sickness (clinical and experimental)
- ab spec: various protein ag
- systemic vasculitis, nephritis, arthritis
3) arthus reaction (experimental)
- ab spec:various protein ag
- leads to cutaneous vasculitis
