EX2 Hypersensitivity - Stiner Flashcards
This is an exaggerated or aberrant immune response to an antigen resulting in inflammation and tissue damage
hypersensitivity
This is caused by an intravenous route of entry (oral absorption) and results in edema, increased vascular permeability, tracheal occlusion, circulatory collapse, and death
systemic anaphylaxis
This is caused by through skin route of entry and results in local increase in blood flow and vascular permeability
acute urticaria (wheal-and-flare)
This is caused by inhalation and results in edema and irritation of the nasal mucosa
allergic rhinitis (hay fever)
This is caused by inhalation and results in bronchial constriction, increased mucous production, and airway inflammation
asthma
This is caused by oral aborption and results in vomiting, diarrhea, pruritis, urticaria, and anaphylaxis (rarely)
food allergy
This is often referred to as allergy, atopy, or immediate hypersensitivity
Type 1 hypersensitivity
Type 1 hypersensitivity occurs when
within minutes of RE-EXPOSURE to antigen/allergen
What is the immune response during a type 1 hypersensitivity reaction
rapid IgE and mast cell mediated vascular and smooth muscle reaction that is often followed by inflammation
True or False
The reaction of type 1 hypersensitivity depends on the route of allergen entry
True
True or False
Type 1 hypersensitivity is the most common disorder of the immune system, affecting 20% of the population
True
What is the sensitization step during type 1 hypersensitivity
it is the initial exposure to antigen and production of IgE antibodies
TH2 cells secrete ILs
TH2 cell CD40L binds to B cell CD40 (B cell activation)
What are the 6 steps to type 1 hypersensitivity
- sensitization
- binding of IgE Ab to Fc receptors on mast cells
- cross-linkning of bound IgE upon re-exposure (degranulation)
- release of mast cell mediators
- immediate effects (dilation of bv, etc.)
- late response (inflammation)
The release of mast cell mediators triggers what
a biphasic response
- immediate effects
- late response
During the immediate response of mast cell degranulation what is secreted/occurs
vasoactive amines (histamine/serotonin) and proteases synthesis and secretion of lipid mediators (prostaglandins and leukotrienes)
What three things do prostaglandins stimulate
vasoconstriction in the lungs (or dilation in vascular smooth muscle)
constriction or dilation of bronchioles
aggregation or disaggregation of platelets
During the late phase response of mast cell degranulation what is secreted/occurs
synthesis and secretion of cytokines and chemokines
leading to infiltration and eosinophils, monocytes, and neutrophils; leading to inflammation and tissue damage
What is the overview of type 1 hypersensitivity
IgE on surface of the cell with allergen triggers activation and production of cyotkines, histamines, and lipid mediators
What are some common triggers for asthma
airborne allergens (pollen, dust mites, etc) respiratory infections physical activity cold air air pollutants
How many people suffer from asthma worldwide
235 million (22 million adults and 7 million children in the USA)
The dust mite allergen triggers asthma via which enzyme
Der p 1, it occludes tight junctions and triggers mast degranulation
What are some treatment strategies for asthma
inhaled corticosteroids
leukotriene modifiers
The dose and route of entry of allergens determine what
the type of IgE-mediated allergic reaction that results
This is a response riven by the systemic release of vasoactive amines and lipid mediators from mast cells causing a life-threating drop in blood pressure accompanied by severe bronchoconstriction
anaphylaxis
How would you treat anaphylaxis
with epinephrine (vasoconstrictor and bronchodilator) and antihistamine
What events occur as a result of mast cell activation
mast cell degranulation
synthesis and secretion of lipid mediators
cytokine release (late phase)
This is when antibodies produced by the immune response bind to antigens on our own cell surfaces
primarilay IgG and IgM
type II hypersensitivity
True or False
In type II hypersensitivity, host antibodies bind foreign Ag on cell surfaces or binds self Ag
True
What is the result of type II hypersensitivity
it can activate complement resulting in MAC formation
leading to the destruction of cells, inflammation, or interference with normal cell function
The target antigens of this disease are erythrocyte membrane proteins and platelet membrane proteins, of which causes opsonization/phagocytosis of them, and results in hemolysis, anemia, and bleeding
autoimmune hemolytic anemia
autoimmune thrombocytopenic purpura
The target antigen of this disease is the acetylcholine receptor which inhibits acetylcholine binding causing muscle weakness and paralysis
myasthenia gravis
The target antigen of this disease is thyroid stimulation hormone (TSH), causing stimulation of TSH receptors causing hyperthyroidism
Grave’s disease
Type II hypersensitivity is also known as
cytotoxic hypersensitivity
In this disease, maternal antibodies target fetal RBCs for destruction
hemolytic disease of the newborn (erythoblastosis fetalis) (Rh factor)
In this disease, host anti-blood group antibodies, target transfused RBCs for destruction
blood transfusion reactions
What are the therapeutic strategies for autoimmune hemolytic anemia HDNB Grave's disease myasthenia gravis
prednisone or blood transfusion
anti-Rh antibodies
radioactive iodine, anti-thyriod drugs, thyroid removal
cholinesterase inhibitors or corticosteriods
This is when Ag-Ab complexes (immune complex) clump and deposit in blood vessels or tissues attract an acute inflammatory response
type III hypersensitivity
What happens when immune complexes are large, and are small?
large ones fix complement and are cleared from circulation by phagocytes
small complexes formed in Ag excess deposit in vessel or tissue
What are some examples of type III hypersensitivity
lupus, arthus reaction, serum sickness, and rheumatoid arthritis
When does type III hypersensitivity occur
3-10 hours after exposure
can be caused by exogenous or endogenous Ag (foreign/self)
Where does the immune complex accumulate
at the sites where antigen is localized or at sites of turbulence and/or high pressure (vessel branches, kidneys, etc.)
Type III hypersensitivity manifest as
vasculitis, arthritis, or nephritis
What are the three mechanisms of which immune complexes trigger inflammation
- mast cell activation
- macrophages release TNF-α and IL-1 which induces the inflammatory cascade
- cells bearing Fc receptors for IgG/IgM/IgE
What is the Arthus reaction triggered by and what does it form
triggered in the skin by IgG, forms immune complexes of which bind to Fc receptors on mast cells and other leukocytes
Where does the Arthus reaction occur and as a result of what
occurs in vessel walls, pleura, pericardium, synovium, or glomeruli
can occur as a result of repeated subQ inject of tetanus toxoid containing or dipthetia toxoid containing (rare)
and upon subsequent exposure to an Ag for which a person has high circulating levels of IgG, complexes can be found in localized vasculature
What are the symptoms of an Arthus reaction
swelling, induration, pain, edema, hemorrhage, and occasionally necrosis
occurs a couple hours after exposure
What is the treatment for Arthus reaction
anti-inflammatory
This is a classic example of transient systemic immune complex mediated syndrome
serum sickness
What causes serum sickness and what are the symptoms
an injection of a foreign protein or proteins which leads to an antibody response
symptoms occur within days or weeks after injection; chills, fever, rash, etc.
What can specifically cause serum sickness
antivenum
anti-lymphoyte globulin (immunosuppressant)
antibiotics
streptokinase (bacterial enzyme)
What is the mechanism behind SLE
IgG antibodies against self antigen in all nucleated cells
large amounts of small complexes deposit in blood vessels, kidneys, joints, and other tissues
What happen in SLE due to the immune cells
phagocytosis activated by Fc receptors
auto-reactive T cells become involved
damage can lead to death
What are the therapeutic strategies for
Arthus reaction
serum sickness
lupus
avoidance and anti-inflammatories
drug avoidance, antihistamines, corticosteriods, etc.
NSAIDs, corticosteroids, immunosuppressive drugs, etc.
What is the overview of type III hypersensitivity
Ag-Ab complexes clump and aggregate attractive an inflammatory response
primarily IgG
immune complex
This is mediated by Ag specific T cells which induce macrophage infiltration in a sensitized individual
type IV hypersensitivity
How long does it take for type IV hypersensitivity to take place
2-3 days; due to it taking longer than antibody mediated
Turburculin type hypersensitivity is mediated by which type of cells (TB test)
Th1
contact dermatitis is mediated by which type of cells
Th1 and/or CTLs
chronic asthma is mediated by which type of cells
Th2
gluten-sensitive enteropathy is mediated by which type of cells
Th1 and Th2, but still poorly understood
graft rejection is mediated by which type of cells
T cells
Type IV hypersensitivity is also called what
delayed type hypersensitivity (DSH)
True or False
Type IV hypersensitivity is antibody mediated
False; it is cell mediated, mostly Th cells
What are the important cells in DTH response
macrophages
CD8 T cells
NK cells
Type IV hypersensitivity is generally initiated by what
haptens (small molecules)
Ag presented by APCs activate Th cells
Th cells secrete cytokines which activate macrophages
contact dermatitis involve this complexing with skin proteins and activating this
haptens (itching can push these further in skin)
elicited by CD4 and CD8
What are the two phases of contact hypersensitivity
sensitization and elicitation
When/Where does sensitization occur during type IV hypersensitivity
first exposure; 10-14 days
in the Langerhans cells, creation of CD4 memory T cells
When/Where does elicitation occur during type IV hypersensitivity
upon re-exposure, 24-48 hours
presentation to memory T cells
release of IFN-γ and pro-inflammartory cytokines
inflammation
What is the mechanism of chronic asthma
mast cell degranulation leads to Th2 and eosinophil influx
eosinophils activate and degranulate resulting in more eosinophils and tissue damage
can cause irreversible damage and death
Granulomatous inflammation/Crohn’s disease are which type of hypersensitivity
Type IV; thought to be due to unresolved DTH
initially presents in oral cavity
What are the therapeutic strategies for TB test contact hypersensitivity chronic asthma Crohn's disease
self-limiting
limit exposure, corticosteroids, antihistamines, etc
corticosteriods, bronchodilators, etc.
corticosteriods, immunosuppressants, etc.
What is the overview of type IV hypersensitivity
cell mediated by Ag specific T cells which induce macrophage infiltration
DTH response to injected or absorbed Ab
2-3 days
