Hypersensitivity, Allergy, and Chronic Inflammation Flashcards
what is anaphylaxis
a severe, immediate and system-wide harmful immune response to a non-pathogenic antigen
what is a hypersensitivity reaction
an immediate or delayed immune response to innocuous antigens(often, but not always) resulting in healthy tissue damage.
-the antigen should not be harmful normally
how many types of hypersensitivity reactions are there?
4
what types are humorally mediated?
type 1-3
what types are cellular mediated?
type 4
what is type 1 hypersensitivity?
mast cell degranulation
what is type 2 hypersensitivity?
due to IgG and IgM that initiate a complement response or a ADCC
what is type 3 hypersensitivity?
anti body complex deposistion
what is type 4 hypersensitivity?
T cell sensitization
Allergy: A type I hypersensitivity reaction
Allergen-IgE activation of granulocytes -Mast cells -basophils -eosinophils immediate hypersensitivity localized
what is an allergen?
a non-pathogenic antigen that illicit hypersensitivity reactions
- proteins or glycoproteins
- enzymatic activity
- interact with PRR
- low, persistent concentrations at mucosal surfaces
what is the mechanism of a type I allergy?
Ag induces cross linking of IgE bound to mast cells and basophils with release of vasoactive mediators
typical manifestations of type I allergy
systemic anaphylaxis localized anaphylaxis -hay fever -asthma -hives -food -eczema
what cells is the Th2 effector cell in parasite immunity?
Granulocytes
how does the body deal with parasitic diseases, 3 ways?
degranulation
sequestration
excretion (proteolytic enzymes)
How does mast cell degranulation drive inflammation?
- histamine/heparin-increase vascular permeability, SM contraction
- TNF alpha- promotes inflammation
- Tryptase, chymase, cathepsin G, carboxypeptidase remodel CT matrix
mast cell deregulation effect on the GI, Airways and blood vessels
GI- increased fluid excretion
Airway- decreases diameter, increased mucous secretion
Blood vessels- increases blood flow, increased permeabil
Eosinophil degranulation is?
toxic
what causes eosinophil degranulation?
mast cell and Th2 cytokines
-express Fc receptors upon activation
what do the granules of the eosinophils do?
they are highly toxic and promote further inflammation
what is the hygiene hypothesis?
reduced early developmental immune pressure causes poor immune education and an inappropriate pathogen identification, leading to allergy and autoimmune disorders
-basically lack of parasites leads to allergies and autoimmune disease
Development of type I hypersensitivity causes immediate what?
mast cell degranulation of histamine, heparin, TNF alpha, and proteases
-also recruit eosinophils
allergic reactions occur in two phases what are they?
- immediate-mast cells are activated leading to localized swelling. Looks like a hive
- late- the inflammatory process leading to a typical response with leukocytes and such
anaphylactic shock:
rapid, systemic and deadly allergic reactions
- basically a hyper immediate response
- systemic mast cell degranulation
what halts anaphylactic shock?
epinephrine- due to a sympathetic response, which basically reverses the allergic response
epi-pens
what are some therapeutic interventions that can resolve type I allergies?
allergy shots antihistamines leukotriene antagonists corticosteroids immunotherapeutics
what is hyposensitization?
repeated exposure to escalating dosage of allergens to reduce a type I response
what are the two possible models of how hyposensitization work?
- tolerance is built up by the production of T reg cells
2. Desensitization- IgG4 inhibit inflammatory response by binding up Fc receptors on macs
Type II hyper sensitization: Antibody-mediated reactions
- IgG response to small molecules bound to cell surfaces
- *-complement or Ab-directed cellular cytotoxicity
- Abs against self antigen
- drug allergies
- graft rejection
- autoimmunity
what is Newborn hemolytic disease?
Type II hypersensitivity reaction
- Rh- mother caries an Rh+ fetus leads to anti-Rh IgG in 1st pregnancy
- future Rh+ fetuses are targeted by maternal IgG
what prevents newborn hemolytic disease?
Rhogam- binds the Rh+ on the fetus
Type III hypersensitivity: immune complex reactions
inefficient immune complex clearance
-Ag-Ab lattices
-Ags with high affinity for tissue surfaces
-highly charged antigens
-compromised phagocytosis
complexes deposited in blood vessels and tissues
-Innate inflammatory response
what are some manifestations of type III hypersensitivity?
clot formation fever skin rash Rheumatoid arthritis lupus
mechanism for type III hypersensitivity?
Ag-Ab complexes deposited in various tissues induce complement activation and an ensuing inflammatory response mediated by massive infiltration of neutrophils
Type IV hypersensitivity: cell-mediated delayed type hypersensitivity
contacted materials function as adjuvants
- chemically modify human antigens
- complex initiates an immune response
- *cell mediated NOT humoral
what are the two cells responsible for type IV hypersensitivity?
CD4 and macrophage mediated
what are the two phases of type IV hypersensitivity?
- sensitization-priming step usually no reaction
- effector-the reaction that happens days later
type IV hypersensitivity mechanism?
sensitized CD4 T cells release cytokines that activate macs which mediate direct cellular damage
how is poison ivy a type IV delayed hypersensitivity?
the pentadecacatechol oil of the ivy combines with skin protein as an adjuvant.
- this is no antigenic to the human
- next exposure leads to a effector response
chronic inflammation cytokines
IL-6
TNF alpha
IL-1 beta
IL-18
non-infectious causes of chronic inflammation?
obesity
tissue damage
heart disease and atherosclerosis
infectious causes of chronic inflammation
unresolved infection
intestinal microbes
chronic inflammation can lead to what two changes?
metabolic
tissue
*both of which can lead to systemic diseases
Periodontitis is a result of what?
polymicrobial dysbiosis (pathogenic bacteria present rather than commensals) which causes chronic inflammation
T/F periodontitis may be linked to systemic inflammation and disease?
True
-has been shown to aid in hypertension, DM, cardiovascular diseases
Chronic inflammation produces IL-6, which means what?
acute phase proteins released from liver
-can lead to atherosclerosis, gut diseases, pregnancy complications
