Stiner: Hypersensitivity Flashcards
_____:exaggerated or aberrant immune response to an antigen resulting in inflammation and tissue damage
Hypersensitivity
_____ _____:disorders that are caused by aberrant immune responses
Hypersensitivity Diseases
Type __: (immediate)
- immune reactant= IgE
- antigen= soluble antigen
- effector mechanism= mast cell activation
- ex= allergic rhinitis, asthma, systemic anaphylaxis
I
Type __:
- immune reactant= IgG
- antigen= cell or matrix associated antigen
- effector mechanism= complement, FcR+ cells (phagocytes, NK cells)
- ex= some drugs allergies (penicillin)
II
Type __:
- immune reactant= IgG
- antigen= cell surface receptor
- effector mechanism= antibody alters signaling
- ex= chronic urticaria (antibody against FCeR1a)
II
Type __:
- immune reactant= IgG
- antigen= soluble antigen
- effector mechanism= complement, phagocytes
- ex= serum sickness, arthus rxn
III
Type __:
- immune reactant= TH1 cells
- antigen= soluble antigen
- effector mechanism= macrophage activation
- ex= contact dermatitis, tuberculin rxn
IV
Type __:
- immune reactant=TH2 cells
- antigen= soluble antigen
- effector mechanism= IgE production, eosinophil activation, mastocytosis
- ex= chronic asthma, chronic allergic rhinitis
IV
Type __:
- immune reactant= CTL
- antigen= cell associated antigen
- effector mechanism= cytotoxicity
- ex= contact dermatitis
IV
Type I: -systemic anaphylaxis (most severe) Route of Entry: \_\_\_\_\_\_\_ Response: -e\_\_\_\_\_\_ -increase vascular \_\_\_\_\_\_\_ -tracheal occlusion -\_\_\_\_\_\_\_ collapse -death
intravenous edema increase vascular permeability tracheal occlusion circulatory collapse death
Type 1: -acute urticaria (\_\_\_\_\_and \_\_\_\_\_) Route of Entry: \_\_\_\_\_\_\_ Response: -local increase in \_\_\_\_\_ flow and \_\_\_\_\_ permeability
wheal and flare
through skin
increase in blood flow and vascular permeability
Type 1: -allergic rhinitis (seasonal allergies) Route of Entry: Response: -edema of \_\_\_\_\_ mucosa -irritation of \_\_\_\_ mucosa
inhalation
nasal mucosa
Type 1: -asthma (most common) Route of Entry: Response: -bronchial \_\_\_\_\_\_ -increased \_\_\_\_\_\_ production -airway \_\_\_\_\_\_\_\_\_\_
inhalation
bronchial constriction
increased mucus production
airway inflammation
Type 1: -food allergy Route of Entry: Response: -v\_\_\_\_\_\_ -d\_\_\_\_\_\_ -p\_\_\_\_\_\_(itching) -u\_\_\_\_\_\_(hives) -a\_\_\_\_\_\_(rarely)
oral vomiting diarrhea pruritis urticaria anaphylaxis
Immediate hypersensitivity is what type?
- allergy
- atopy
Type I
Occurs w/in minutes after RE-EXPOSURE to antigen/allergen:
Type 1
Rapid ____ and ____ cell mediated vascular and smooth mm rxn that is often followed by inflammation:
Type 1
IgE and mast cell
Most common disorder of immune system is what?
-affecting ~20% of pop
Type 1
1st time exposure to allergen= sensitivity
2nd time exposure to allergen= _______
hypersensitivity
Type 1 Hypersensitivity:
1) initial exposure to antigen and production of ___ antibodies (Ab)= ________
- TH2 cells secrete IL’s (causing class switching)
- TH2 cell _____ binds to B Cell _____ (activating B Cell)
IgE
sensitization
CD40L
CD40
Type 1 Hypersensitivity:
2) binding of ____ Ab to ___ receptors on ____ cells (activation of mast cells causing degranulation)
IgE binds to Fc receptors on mast cells
Type 1 Hypersensitivity:
3) cross linking of bound _____ upon reexposture to allergen
IgE
Type 1 Hypersensitivity:
4) release of ___ cell mediators
mast
Type 1 Hypersensitivity: biphasic response
5) ______ effects: dilation of blood vessels, increased vascular permeability, smooth mm contraction
immediate
Type 1 Hypersensitivity: biphasic response
6) _____ response: inflammation by cytokines (need time to be produced)
late
Type 1 Hypersensitivity:
Mast cell degranulation-
-immediate response= _____ _____ (histamine and serotonin ) and _____–> initiate tissue damage
–synthesis and secretion of _____ mediators (prostaglandins and leukotrienes made from arachidonic acids)
vasoactive amines
proteases
lipid
Type 1 Hypersensitivity:
Lipid Mediators of Immediate Response=
________:
-vascoconstriction in lungs or dilation in vascular smooth mm (depends on receptor)
-constriction or dilation of bronchioles
-cause aggregation or disaggregation of platelets
prostanglandins
Type 1 Hypersensitivity:
Lipid Mediators of Immediate Response=
_______:
-powerful inducers of bronchoconstriction, increased vascular permeability
-refereed to as slow reacting substance of anaphylaxis (SRS-A)
leukotrienes
Type 1 Hypersensitivity:
Mast cell degranulation-
-late phase rxn= synthesis and secretion of cytokines (___ _, ___ ___, ____ ____, ____-____)
and chemokines (_____-___)
-infiltration of eosinophils (release ROS/major basic proteins), monocytes, neutrophils
TNF alpha
IL 4
IL 5
GM-CSF
MIP-1 alpha
-
-
coughing
wheezing
shortness of breath
Common asthma triggers:
- a
- r
- p
- c
- a
air allergens respiratory infections physical activity cold air air pollutants/irritants
Response Triggered By Dust Mite Allergens:
- ____ jnx seal the barrier of airway epithelium
- enzyme ___ _ _ cleves occuldins in jxn
- enzyme is taken up by _____ cells for antigen presentation and TH2 priming
- enzyme specific _____ binds to mast cell; enzyme triggers MAST CELL DEGRANULATION=INFLAMMATORY RESPONCE
tight
Der p 1
dendritic cells
IgE
Treatment Strategies for Asthma:
-long term control medications= inhaled ________ and ______ modifiers
corticosteroids
leukotriene
Dose and Rts of Entry of Allergens determine the Type of IgE mediated Allergic Rxn that Results:
….
Type 1 Hypersensitivity: Key Pts
-all clinical and pathologic features of immediate hypersensitivity rxns are driven by mediators produced by _____ cells
mast
Type 1 Hypersensitivity: Key Pts
-mediators produced in different amounts and in different tissues are responsible for ______ immediate hypersensitivity syndromes
different
Type 1 Hypersensitivity: Key Pts
-the most severe form of immediate hypersensitivity is ______
anaphlaxis
_______: response driven by the systemic release of vasoactive amines and lipid mediators from mast cells
anaphylaxis
______: causes life threatening drop in BP accompanied by severe bronchoconstriction
anaphylaxis
_____: treated w/ epinephrine (vasoconstrictor and bronchodilator) and antihistamine
anayphylaxis
Type ___ Summary:
-sensitization
-events that occur as a result of mast cell activation
1. mast cell degranulation
2. synthesis and secretion of lipid mediators
delayed-last phase response
3. cytokine release- leads to recruitment of neutrophils and eosinophils to the sire of inflammation
Type 1
Type II Hypersensitivity:
- antibodies produced by the immune response that bind to antigens on our own cell surfaces
- -primarily ____ and ____ isotypes
IgG (own)
IgM
Type II Hypersensitivity:
-host Ab binds foreign Ab on cell surfaces or binds ____ ___
self Ag
Type II Hypersensitivity:
- can activate ______ resulting in membrane attack complex formation
- -leads to _______ of cells, inflammation, or interfere with normal cellular fnx
complement
destruction
Type II Hypersensitivity or _______ hypersensitivity
cytotoxic
Type II Hypersensitivity:
______ ____ of the Newborn (Erythroblastosis fetalis)
–maternal Ab’s target fetal RBC’s for destruction
(Rh positive or negative)
Hemolytic Disease of the Newborn
Type II Hypersensitivity:
________ _____-
-auto antibodies are produced against self Ag’s on the surface of RBC’s
-this triggers the rapid destruction of RBC’s leading to anemia
Hemolytic anemia
Type II Hypersensitivity:
____ ____ _____-
-host anti blood grp Ab’s target transfused RBC’s for destruction
blood transfusion rxn
Type II Hypersensitivity:
_____ _____-
-TSH receptor Ab’s stimulate TSH receptor to over produce thyroid hormone
Graves Disease
Type II Hypersensitivity:
_______ _______-
-Ach receptor Ab’s bind to and block the Ach receptor
Myasthenia Gravis
Therapeutic Strategies:
Autoimmune Hemolytic Anemia-
______ or _____ _______
prednisone
blood transfusion
Therapeutic Strategies:
HDNB-
_____-_____ ___
anti-Rh Ab
Therapeutic Strategies:
Graves disease-
radioactive _____, anti-____ drugs, or ____ removal
iodine
anti thyroid drugs
thyroid removal
Therapeutic Strategies:
Myasthenia Gravis-
________ inhibitors and _________
cholinesterase
corticosteroids
Type ___ Summary:
- host Ab binds foreign AG on cell surfaces or binds self Ag
- IgG (some IgM)
2
Type III Hypersensitivity: (____-____ mediated)
-Ag-Ab complexes ___ and deposit in blood vvs or tissues attracting an _____ inflammatory rxn
immune- complex mediated
clump
acute
Type III Hypersensitivity:
-an ____ _____ consists of an Ag (allergen) binding to its specific Ab (IgG/IgM)
immune complex
Type III Hypersensitivity:
- larger aggregates fix _____ and are cleared from circulation by _______
- small complexes formed in Ag ____ deposit in vvs or tissues (ligate ___ receptors on leukocytes, leading to activation and tissue damage)
complement
phagocytes
excess
Fc
Type III Hypersensitivity:
-how long does it occur after activation?
3-10 hrs
Type III Hypersensitivity:
-can be caused by exogenous (____) or endogenous (____) Ag
foreign
self
Type III Hypersensitivity:
-deposits tend to accumulate at sites where antigens are ______ or at sites of turbulence (_______) or high pressure (_______)
localized
vessel brs
kidneys
–vasculitis, arthritis, nephritis
Type III Hypersensitivity:
Mechanisms- immune complexes trigger inflammation via 3 mechanisms:
1. ___ ___ ____
mast cell activation
Type III Hypersensitivity:
Mechanisms- immune complexes trigger inflammation via 3 mechanisms:
2. macrophages release _____-___ and ____-___ that induces the inflammatory ______
TNF-alpha
IL-1
inflammatory cascade
Type III Hypersensitivity:
Mechanisms- immune complexes trigger inflammation via 3 mechanisms:
3. ____, ____, ____=stimulate mast cells to release more histamines, serotonin, and chemotactic facts
=attracts monocytes, neutrophils, leukocytes
C3a
C4a
C5a
Type III Hypersensitivity:
Mechanisms-
= cells bearing ____ receptors for IgG/IgM/IgE may be crucial for antibody complex mediated hypersensitivity
Fc receptors
Type III Hypersensitivity: Arthus Rxn
- triggered in the ____ by Ig___
- immune complexes form
- complexes bind to ___ receptors on ____ cells/leukocytes
- -local ____ rxn w/ vascular permeability
- -fluid and cells enter site
- -____ activates leukocytes once they arrive
skin IgG
Fc mast
inflammatory
C5a
Type III Hypersensitivity: Arthus Rxn
- typically occurs in _____ walls, pleura, pericardium, synovium, glomeruli
- at repeated subcutaneous infection sites
- local
vessel
Type III Hypersensitivity: Arthus Rxn
- symptoms:
- swelling/pain/edema
- treatment:
- ________
anti-inflammatory agents
Type III Hypersensitivity: Serum Sickness
-ex of ____ ____ immune complex mediated syndrom
transient systemic
Type III Hypersensitivity: Serum Sickness
- caused by an injection of ____ protein leading to an Ab response
- -Ab form immune complexes with prot.–>deposit in small blood vvs–>activate complement and phagocytes
foreign
Type III Hypersensitivity: Serum Sickness
- symptoms occur w/in ___ or ____
- -chills, fever, rash ect.
- -rash= mast cell degranulation caused by immune complex ligation of ______
days or weeks
FcRy
Type III Hypersensitivity: Serum Sickness
Causes:
_______: (serum from horses immunized w/ snake venoms)- source of neutralizing Ab to treat ppl w/ poisonous snake bites
antivenin
Type III Hypersensitivity: Serum Sickness
Causes:
______: immunosuppressive agent used for transplant recipients
anti-lymphocyte globulin
Type III Hypersensitivity: Serum Sickness
Causes:
____: penicillin, cephalosporin
anti-biotic
Type III Hypersensitivity: Serum Sickness
Causes:
_____: (a bacterial enzyme(- used as thrombolytic agent to treat heart attack pts
streptokinase
Type III Hypersensitivity and Autoimmune: SLE (Lupus)
- Ig___ Ab against ubiquitous ____ Ag in all nucleated cells
- large amounts of small complexes deposits
- phagocytes activated by ____ receptors
- auto reactive T cells involved = more Ab produced, effector fnx destroys cells–>death
IgG
self
Fc
Type III Hypersensitivity: Ther. Strag- Athus Rxn
avoidance or anti inflammatory agents
Type III Hypersensitivity: Ther. Strag- Serum Sickness
drug avoidance, antihistamines, corticosteroids
Type III Hypersensitivity: Ther. Strag- Lupus
NSAID’s, corticosteroids, immunosuppressive agents
Type _____ Summary:
- Ag-Ab complexes clump and aggregate in or near blood vessels attracting an acute inflammatory rxn
- -primarily IgG (IgM/IgE)
- -immune complex
- -ex. arthus rxn, serum sickness, SLE
III
Type IV Hypersensitivity: Delayed Time
- Cell mediated rxn:
- mediated by Ag specific ___ Cells which induce macrophage infiltration in a ____ individual
- _____ response to injected or absorbed Ag
- occurs w/in ___-___ days
T cells
sensitized
DTH= delayed time hypersensitivity
2-3 days
Type IV Hypersensitivity:
-tuburculin type hypersensitivity (_____ into the skin)
=mediated by ____ ____
injected into the skin
TH1 cells
Type IV Hypersensitivity:
-contact dermatitis (_____ by the skin)
=mediated by ____ ___ and or _____
absorbed
TH1 cells and or CTL’s
Type IV Hypersensitivity:
-chronic asthma (______)
=mediated by _____ ______
inhaled
TH2 cells
Type IV Hypersensitivity:
- gluten-sensitive enteropathy (_______)
=still poorly understood but evidence suggests response involves ___ and ___
digested
TH1 and TH2
Type IV Hypersensitivity:
-graft rejection
=mediated by ___ ____
T cell
Type IV Hypersensitivity:
-what are the effector cells in the DTH response? (3)
macrophages
CD8T cells
NK cells
Type IV Hypersensitivity:
- initiated by ______ (antigens that usually do not initiated responses)
- small molecules that must become bound to a larger carrier molecule in order to illicit an immune or inflammatory response
haptens
Type IV Hypersensitivity:
- Ag presented by APC’s activates ____ cells after the initiation of haptens
- -these cells then secrete cytokines which will activate macrophages
TH
Type IV Hypersensitivity: TB Test
Tuberculin Test (Mantoux PPD test)
-test to determine previous exposure/infection w/ ______ ______
-small amounts injected intradermally
-w/in ___-___ hrs a local t cell mediated inflammatory rxn evolves in individuals previously exposed to M. TB
==response mediated by ____ cells
mycobacterium tuberculosis
24-72 hrs
TH1
Type IV Hypersensitivity:
Major DTH Mechanism= Ag Presentation
-Antigen is processed by _____ and stimulates by ____ cells
macrophages
TH1
Type IV Hypersensitivity: Contact Dermatitis
- highly reactive small molecules (____) complexed w/ skin _____ and internalized by _____ in the skin
- elicited by ____ or ____ T cells
- inflammation occurs by inflammatory response initiated by T cells
- 2 phages of contact: _____ and ______
hapens proteins APC's CD4 or CD8 t cells sensitization and elicitation
Type IV Hypersensitivity:
_________
-occurs during 1st exposure to Ag
-takes ___-___ days to develop
-langerhan’s cells in skin
-APC of skin take up Ag and present to T cells
-formation of CD4+ memory t cells specific for the AG
Sensitization
10-14
Type IV Hypersensitivity:
________
-upon reexposure to Ag
-develops w/in ___ - ___ hrs
-involves LC Ag presentation to memory T cells at site of Ag entry
-T cells release IFNgamma and pro inflammatory cytokines
-cytokines recruit macrophages, CTL, NK, and other effectory cells (inflammatory response continues)
Elicitation
24-48 hrs
Type IV Hypersensitivity: Poison Ivy
- example of ____ ____
- response requires a sensitization period and elicitation of the allergic response on subsequent interactions w/
contact dermatitis
Type IV Hypersensitivity: Chronis Asthma
- mast cell degranulation leads to ____ (IL-5) and esosinophil influx
- eosinophils active and degranulate
- -damaging tissue/recruiting more cells
- chronic inflammation can cause irreversible damage and death
–ppl can have type 1 and type 4 (leads to tissue damage)
TH2
Type IV Hypersensitivity: Crohn’s Disease
- type of IBD in terminal ileum
- chronic _______ of the bowel mucosa or submucosa
- symptoms due to unresolved ____
- initial presentation may be in ____ cavity (6%)
inflammation
DTH
oral
Type IV Hypersensitivity: Ther. Str.
__ ____ _____
-self limiting= will pass/not long
TB Test Injection
Type IV Hypersensitivity: Ther. Str.
____ _____
-limit exposure, corticosteroids, antihistamines
Contact hypersensitivy
Type IV Hypersensitivity: Ther. Str.
_____ _____
-corticosteroids, bronchodilates, cromolyn
Chronic Asthma
Type IV Hypersensitivity: Ther. Str.
_____ _____
corticosteroids, immunosuppressants
Crohn’s Disease
Type ___ Summary:
-cell mediated rxn
-by Ag specific ___ cells which induce macrophage infiltration in a sensitized individual
–DTH response to injected or absorbed AB
-2-3 days
ex TB test, contact dermatitis, chronic asthma, crohn’s
4
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