Hypersensitivities (complete) Flashcards
What are hypersensitivities
when harmless antigens elicit an immune response. Ranging from uncomfortable to fatal
what are the 4 types of hypersensitivities
1, 2, 3, and 4,
what is another name for a hypersensitivity
allergy
what is anaphlaxis
allergic reactions that cause rapid, multiorgan inflammation, can result in death
What is type 1 hypersensitivity
Allergy and atopy
what is the immune mediator for type 1 hypersensitivity
IgE
what is the mechanism of a type 1 allergy
IgE crosslinking induced by the antigen causes the release of vasoactive mediators by basophils and mast cells
what are the manifestations of a type 1 hypersensitivity
systemic and local anaphylaxis hay fever athsma hives food allergies eczema
what is type 2 hypersensitivity
antibody-mediated hypersensitivity
what is the immune medaitor for type 2 hypersensitivities
IgG or IgM
what is the mechanism of type 2 hypersensitivities
Ab on cell surface mediates cell destruction via complement of ADCC
what are the typical manifestations of type 2 hypersensitivity
blood transfusion reactions
erythroblastosis fetalis
autoimmune hemolytic anemia
What is type 3 hypersensitivity
immune-complex mediated hypersensitivity
what is the immune mediator for type 3 hypersensitivity
immune-complexes
What is the mechanism of type 3 hyper sensitivity
Ag-Ab complexes deposited in various tissues cause activation of complement and ensuing inflammatory response, causing high levels of neutrophils coming
what are the typical manifestations of type 3 hypersensitivities
localized arthus reactions serum sickness necrotizing vasculitis SLE rheumatoid arthritis glomerulonephritis
what is type 4 hypersensitivity
delayed type hypersensitivity
what is the immune mediator for type 1 hypersensitivity
T-cells
what is the mechanism of type 4 hypersensitivities
specialized T-cells release cytokines, that activate macrophages and Cytotoxic t-cells
what are the typical manifestations of type 4 hypersensitivities
dermatitis tubercular lesions graft rejection poison ivy reaction tuberculin skin test
what type of T-cell is active is type 1 hypersensitivities
TH2 (via IgE)
do you see hypersensitivities on the first encounter with the allergen
nope, because they are antibody, or effector T-cell driven
first exposure is call sensitization
What are haptens
small organic molecules that can become covalently bound to proteins and can cause TH1 or TFH cells to become activated
what do you call a protein with a hapten bound to it
haptenated protein
how do haptens cause immune responses
they bind to proteins, and when those proteins are processed by APCs, they are presented to, and can activate Th1 and TFH cells.
what do the TH1 cells that have been activated by haptenated proteins go on and do
activate macrophages
whad to the TFH cells that have been activated by haptenated proteins go on and doo
activate B-cells to produce antibody
what does sensitization cause to happen, in immediate type (type 1 ) hypersensitivity
IgE is produced and bound to mast cells
what is the receptor on mast cells and basophils that binds the IgE
FceRI
what things are found in the granules of mast cells, and are thus released in type 1 hypersensitivity reactions
histamine
proteoglycans
proteases
TNF
what does histamine cause
vasodilation and increased vascular permeability
what are the two proteoglycans found in the granules of mast cells
heparin, chondroitin sulfate
what are the proteases found in the granules of mast cells
tryptase and chymase
how does the allergen skin test work
you inject a potential allergen into the skin, and if you are allergic the histamine will result in edema (swelling) and erythemia (redness) in the area where the allergen was placed
what does the activation of mast cells cause on other cells
TNF recruits other cells
eosinophils - perform ADCC release granules toxic for worms and TGF alpha and beta (wound healing)
basophils - make luekotrienes (attract neutrophils) and IL-4 and IL-13
TH2 cells
where do you see allergic responses
where epithelial surfaces meet the environment
how are allergies best treated
by avoiding the allergen
immunotherapy (shots)
steroids (dampen immune response)
Anti- IgE prevents IgE from binding FceRI on mast cells
are some people more genetically predisposed to allergies
yes
what besides genetic predisposition can increase the likelyhood of allergies
the timing in life of sensitization
what can cause systemic anaphylaxis
it is an allergic reaction usually caused by injected or gut absorbed allergens. (bee sting venom, penicillin, seafood, nuts)
what are the symptoms of systemic anaphylaxis
labored breathing
drop in blood pressure
contraction of smooth muscle, leading to defecation, urination, and brachial constriction
what is the treatment for systemic anaphylaxis
epinephrine injections (epi pen)
what are some common examples of haptens
penicillin
substances in latex gloves
venoms
radiocontrast media
what are the different types of Type 1 hypersensitivities
systemic anaphylaxis
localized hypersensitivity
what is localized hypersensitivity
pathology is limited to a specific tissue or organ
What are examples of localized hypersensitivity
allergic rhinitis (hay fever)
asthma
atopic dermatitis (eczema)
food allergies
what type of hypersensitivity is urticaria (hives)
behaves like type 1
asthma is associated with common allergies, but what is its root cause
dysregulated Th2 response
allergens that get into the lower airways, along with TH2 cells and Eosinophils
when can asthma begin to cause serious problems
when you have repeated episodes, and the inflammation in the lungs can’t be controlled. They can even be fatal (die from hypoxia)
what is stage one of asthma
immediate mast cell degranulation
resolved after one hour
what is stage two of asthma
4-6 hours later
newly infiltrating eosinophils, basophils, and TH2 cells
what is stage three of asthma
AIRWAY REMODELING (caused by repeated episodes) loss of epithelial cells goblet cell hyperplasia submucosal collagen build up thickening of airway walls mast cell accumulation increases in smooth muscle
What is the hygene hypothesis concerning asthma diseases
it states that children in developed countries are more likely to suffer from asthma
What do allergy injections do to help combat allergies
they increase IgG and IgG4
and decrease IgE and lymphocyte response
we know that mast cells have activating receptors (FceR1), but do they have inhibiting receptors
yes, FcyRIIB
what binds to the FceR1 receptors on mast cells
IgE (activates mast cells)
what binds to the FcyRIIB receptors on mast cells
IgG (inhibits mast cell activation)
if both bind, which wins out IgE binding to the FceR receptor, or IgG binding to FcyRIIB
IgG binding to FcyRIIB inhibits the activation of the mast cells and overrides the IgE binding to the FceR
what is the mechanisms that many drugs (not allergy shots) use to prevent hypersensitivity
maintaining high levels of cAMP (this prevents mast cell degranulation)
Are type 2 hypersensitivities cytotoxic
yep
What are examples of type 2 hypersensitivities
Transfusion reactions
hemolytic disease of the newborn
Drug-induced anemia
what is the problem in transfusion reactions, and what are the two ways that transfusion reactions can manifest
widespread destruction of RBCs
it can be IgM mediated or IgG mediated
what are the symptoms if transfusion reactions are IgM mediated
fever, chills, nausea, back pain, free hemoglobin and bilirubin in the blood, kidney and brain damage.
IgM mediated transfusion reactions are due to ABO antigens
what are the symptoms if the transfusion reactions are IgG mediated
delayed
Jaundice and anemia\
IgG mediated transfusion reactions are due to Rh, and other antigens
why are transfusion reaction problems delayed when mediated by IgG
because the RBCs are destroyed at extravascular sites by phagocytosis
What is hemolytic disease of the newborn
when an RH- mother has had a RH+ baby, her body made antibodies against the RH antigen. so the next time she has an RH+ baby, her antibodies attack the RH antigen of the baby and destroys the RBCs
how is hemolytic disease of the newborn treated
transfusion of the fetus, plasmaresis of mother
how do you prevent hemolytic disease of the newborn
Rhogam
what is drug induced anemia
chemicals get absorbed onto RBCs, and those stimulate complement-mediated destruction
what is another name for hemolytic disease of the newborn
erythroblastosis fetalis
what type of hypersensitivity is mediated by immune complexes
type 3
how do immune complexes cause a hypersensitivity
ones that aren’t cleared get deposited in tissues, and those can trigger the release of inflammatory mediators, and vasoactive mediators (they can also activate platelets to form clots)
What are symptoms of type 3 hypersensitivity (immune complex mediated)
fever, rash, joint pain, lymph node enlargement, and protein in the urine
what are examples of type 3 sensitivity
vasculitis (if the complex deposited in the blood vessel)
glomerulonephritis (if the complex is in the kidney)
Arthritis (if the complex is in the joints)
what happens to immune complex mediated hypersensitivities over time
they can eventually resolve over time as the complexes are cleared as long as the Ag goes away.
what can cause type 3 hypersensitivities to not resolve with time
autoantigens
What type of hypersensitivity is SLE
type 3
What type of type 3 hypersensitivity (localized or generalized) is an arthus reaction
localized type 3 hypersensitivity
what are the characteristics of type 4 hypersensitivity
- Purely cell related, not antibody mediated
- Initiated by T-cells
- Delayed reaction
- macrophage recruitment to the inflammation site
what is the most common example of a type 4 hypersensitivity
Poison Ivy contact dermatitis
What is another name for type 4 hypersensitivity
delayed type hypersensitivity (the first exposure just causes sensitization)
what type of T-cell is created during the sensitization of type 4 hypersensitivity
CD4+ TH1 cells
what happens when there is a second exposure to the antigen in type 4 hypersensitivity
with the second exposure the TH1 cell produces cytokines that activate macrophages, and the destruction of substances begins
what type of hypersensitivity gives rise to tuberculin response, allergic contact dermatitis, celiac disease, and graft rejection
type 4 hypersensitivity
what kind of MHC class, and thus T-cell, is usually generated by lipid soluble antigens
MHC class 1, and CD8+ cytotoxic t-cells this is because the lipid soluble antigens can cross the plasma membrane and are now endo- (come from within the cell)
celiac disease is a type of which type of hypersensitivity
type 4
what causes celiac disease
the binding of glutamic acids to HLA-DQ2 or HLA-DQ8 (found in the mucosal surface of the small intestine) this initiates a TH1 response against and the destruction of the mucosal surface of the small intestine
What are the two types of inflammatory bowel disease, and what is the difference between them
Crohn's disease (located in the terminal ileum and ascending colon) Ulcerative Colitis (located in the colon and rectum)
What is the cause of inflammatory bowel disease
an aberrant immune reactivity to normal intestinal flora
what disease (hypersensitivity type 4) is associated with crypt abscesses, the rectum and colon, and a dysregulated Th2 response
ulcerative colitis
What things can cause chronic inflammation
- continual microbial invasion
- ineffectively cleared microbes
- DAMPS (noninfectious)
- Obesity
how does obesity lead to chronic inflammation
visceral adipocytes are secretors of proinflammatory cytokines TNF-alpha and IL-6
how does obesity lead to insulin resistance
TNF-alpha and IL-6 released by visceral adipose inhibit the ability of insulin receptors to function
can chronic inflammation lead to increased tumor growth? how?
yes, because inflammation increases the ability of blood vessels to be produced.
