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100 Cards in this Set
- Front
- Back
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what mediates
1 2 3 4 hypersensitivities |
1. IgE immediate
2. IgG AB mediated 3. Immune Complex mediated 4. Cell mediated delayed, mediated by T |
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what type of HS is mediated by...
IgE IgG Immune Complex Cell mediated |
IgE 1 Immediate
IgG 2 Ab mediated Cell Mediated 4 delayed (t mediated) Immune Complex 3 |
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in hypersensitivity is the AG ccauseing the damage
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NOPE!
its the inappropriate IR that cauess it |
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whats the deal with hypersensitivity
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its a prolonged inappropriate humoral or CMI IR that is uncontrolled
It causes damage! |
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what hypersensitivities are humoral, what are CMI
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humoral: 1 (immediate) 2 3
CMI: 4 (delayed) |
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what is atopy
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type I immediate hypersecretion of IgE
**its IgE so we know the allergen mimics a parasite SUPER COMMON |
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is atopy common, does it ru n in families
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super!
**it is gentic and so will run in fmailies **MOST common disorder of the immune system |
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what are the phases of type I rxns
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1. sensitization (dictates the Th2 response this is when we are exposed to allergens. Th2 secreted IL4, class switch to IgE)
2. effector phase |
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what type of response is elicited by the sensitization phase of a HS I? do sx manifext
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Th2
IgE requires Th2 NO sx in sensitization |
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explain what goes on in the sensitization phase of type 1 rxns
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1. initial exposure of AG elicits Th2 response.
2. IL4 and IL13 cause IgE formation 3. IgE binds to the FceR on mast cells. the mast cell is now sensitized |
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when is a mast cell sensitized in a type I rxn
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when the mask cell has IgE bound to its FceR
**the exposure of allergen elicits a Th2 which makes IgE. The IgE binds hte mast cell and SENSITIZES IT **mast cells are located in CT close to epithelium, BV, Nerves, Airways, GI, near musouc porducing areas |
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what does it mean that location matters in a type 1 HS
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type 1, IgE, immediate, TH2 mediated
**mast cells become sensitized when IgE binds to the receptors on them **MAST cells are LOCATED in the CT near mucous producing epithelium (GI, Airway). Near BV and Nerves **becase of the location of the mast cell we will have a specific response in these areas |
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when does the effector phase of a HS 1 happen
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we we must have already has sensitization so an allergen has made a Th2 response and made LOTS of IgE, this IgE then binds to mast cells and sensitizes them
EFEFCTOR: happens when there is another exposre of hte same AG. the allergen then crosslinks the IgE bound FceR on the mast cells adn the mast cells activate and release their contents. Here we have allergic contents |
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in a type 1 HS when do mast cells degranulate
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after the second exposure!
sensitization has occured but no sx was present, when its been exposed 2 we get the effector phase where mast cells degranulate and we have histamine rleased at hte CT lining mucoous secreting epithelium. Nerves and BV |
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during the effector phase mast cells degranulate what is rleeased
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vasoactive amines: histamine
lipid mediators cytokines |
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when senssitized mast cells are activated via crosslinking if IgE bound FceR what happens
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1. DEGRANULATION: histamine, protease, heparin, TNFa
2. Prostaglandin/Leukotriene Syntheis 3. Cytokine release and synthesis |
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so what is crosslinking of mast cells for HS I
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on the mast cell there are FceR and IgE that is specific to an allergen has bound
When the allergen is seen again it binds to the IgE and crosslinks the receptors this cauess 1. degranulation 2. prostaglandin/leukotriene release/production 3. cytokine release/production |
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we know whan mast cells are activated in HS I histamine, PG/Leukotrienes, and cytokines are released what is the main fx of heac of these
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1. histamine: vasodilation
2. PG/LKT: potentiate histamine effects 3. Cytokines: WBC recruitment |
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what is the primary mediator of HS I, and why is it called such
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histamine, its made ahead of time and is stored before release. When the mast cell is activated by cross linking histamine effects are released immediatly
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is there histamine inside of a sensitized mast cell
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you bet! the cvell is sensitized and so has IgE bound but there has been no allergen to crosslink the IgE and cause histamine release
**sensitived has NO sx |
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when histamine is released from allergen activated mast in HS 1 what does it do
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Immediate release with FAST effects, primary mediator bc its already made
binds H1 R (NO H1R on BV so BV still dilate!) 1. SM contraction of ilium, brinchi, and uterus 2. Vasodilation/vascular permiability 3. Increased mucus secretion |
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what causes
SM contraction Vasodilatio Mucus secretion |
binding of histamine to H1 receptors
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how can we block the SM contraction, vasodilation, and mucus secretion that is seen when Histamne Binds H1 R when allergen activated mast cells secretehistamine
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ANTIHistamine
first generation enter the brain and make you tired second generation dont enter the brain and wont make you tired Block h1 receptor |
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what are antihistamines? do they totally reverse inflammation
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block H1 Receptor
dont totally reduce bc there are other inflammatory mediators |
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what are some OTC 1 and 2 generation antihistamines. what are they used to TX
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Allergic Rhinitis
1: make you tired: benedryl, phenergan, atraxm vistrail 2. wont make you sleepy: claritin, clariex, zyrtec, allegra Pill, liquid, nasal spray, eye drosp |
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allergic Rhinitis can be treated what what class of drugs
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antihistamines, blocj the H1 R so histamine cant 1. constrict SM, vasodilate, or produce mucus
**1 make you tired **2 dont make you tired **Antihistamines wont totally block the inflammation bc there are other inflammatory mediators |
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when mast cells are activated HS 1 and li[pid mediators are released what happens?
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inflammation is potentiated!
2 mediators, NOT preformed! (recall histamine was a primary and it was preformed) membrane phosplolipids degenerate, and PLA2 converts to AA that is then made into PGD2 nad Leukotrienes C4,D4, E4 by COX nad lipooxygenase |
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what are the 2 mediators of the mast cell activation in HS 1
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lipid mediators: mast phosphilipids break down. PLA2 makes AA. AA is used to make PGD2, adn LTC4, LTD4, LTE4.
PGD2: vasodilation, bronchoconstriction, bring PMN and eosinophiles LT: slower to begin but last much longer, same as histamine |
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IN HS1 what causes PMN and eosinophiles to flood the area
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lipid mediators PGD2
also causes bronchoconstriction and vasodilation |
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what does PGD2 do?
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its a prostaglandin li[pid mediator of HS 1.
causes vasodilation, bronchoconstriction, adn brings PMN nad eosinophiles to the area |
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what allows prolonged vasodilation, SM constriction and mucus secretion in HS1
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leukotrienes
LTC4 TLD4 LTE4 slow reacting substances of anaphylaxis. do the same things as histamine but happen alter and effects last longer |
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we said antihistamines can prevent Histamine from binding to H1 R, BUT that wasnt the end all bc there were other inflammatory mediators. what are these mediators and how are they TX
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leukotriens (the ones that make histamines effects really last a long time)
LTD4 R inhibitors (D and E will bind, C has its own R) pill to block airway constriction Singulair, Accilate, Ultair |
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what are LTD4 inhibitors
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inhibit the leukotriene effects of HI1 Rxns
**block the LTD/E4 from binding and prolonging vasidilation, mucus secretion and SM constriction **pills, especially useful in airway mgmt **singulair, accolate, ultair |
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what are mast cell stabilizers
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inhibit mast cell activation!
good, dont even let it be a problem Must be taken prophylactically, once its activated these wont do anything (cant reverse sx) given as inhalers or eye drops |
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so we have antihistamines, LT inhibitors, adn Mast cell stabilizers. what WONT help if we have an active response
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mast cell stabilizers. they need to be given prophylatically to PREVENT activation, once activated there is nothing we can do
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so when a mast cell is activated by allergen crosslinking in HS 1 we have hte release of histamine, LT and what else? what does this last thing do
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Cytokines
**de novo synthesie, (not prestored same as LT) TNFa can be preformed LATE PHASE repsonse, wont occur for several hours and the effects last several days **bring eisinophiels and PMN to the area |
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what are the cytokines that are made with mast cell release in HS 1? are mast hte ONLY ones htat make these sytokines
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IL1
IL3 hematpoesis IL4 IL5 IL6 ECF: eosiniphile chemoattractant factor NCF: neutrophile chemoattractnat factor TNFa: NOT made de novo as others, can be made and stored **Th2 can also make some of thse |
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what is responsible for the last phase HS 1 rxn (ocurs after house of exposure and can last several days)
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cytokines IL1,3,4,5,6,TNFa, ECA, NCA
causes accumulations of Eosinophiles and Neutrophiles |
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when cytokines are released and eosinophiles and neutrophiles are stim to build up what happens?
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late phase HS 1 Rxn
Eosinophile: 30% of total cells there, their mediators cause tissue damage PMN: 30% of total cells there. tissue damage TISSUE DAMAGE |
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are eosinophiles and pmn the only cells recruited by cytokiens in a late phase HS 1 response
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nope, thises are major and indice TONS of TISSUE damage
Th2, Basophiles, Macrophages |
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what characterizes the early nad latephase of the HS 1
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EARLY:
vascular and SM changes (sm contraction, vasodilation, mucus secretion. Histamine. PGD2, LT LATE: Inflammation!!! IL4,TNFa, IL5, NCF,ECF. leukocyte migration and activation. |
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inflaminflammation is characterized what what phase of hte HS 1 rxn, what characterizes the otehr
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Inflammation: LATE (cytokines)
EARLY: vascular and SM changes (histamine, PHD2, LTC,D,E4) |
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what prevents the late phase response of HS1
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corticosteroids (anti-inflammatory)
inhibits PLA2 so no AA can be made so NO PGD2 or LT can be made ---> decreased cytokine production, decreased infiltration of eosinophiles and PMN, decreased MHC II |
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what effect does corticosteroids have on HS 1
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prevent/minimize late phase rxn
**inhibit PLA2, NO AA, this means less IL2 IL1, decreased infiltration by eosinophiles nad PMN, also decreased MHC 2 |
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why are there so many different ways that corticosteroids can be given to prevent hte late phase of HS1 RXNs *name 4 administrations
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because location matters in type 1!!!!
1. InhaledL control asthma (long term asthma releif) 2. Oral: systemic, tx SEVERE asthma (fast asthma releif) 3. Nasal/Eye Drops: allergic rhinitis. Rhinocort, flonase, nasonex, beconase 4. Topically: atopic dermitis |
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asthma, allergic rhinitis, and atopic dermitis are all what type of HS? how can each be tx with the same class of med
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HI 1
can use CORTICOSTEROIDS to tx all bc they are delivered differently. LOCATION MATTERS Asthma: oral for short term releif of severe problems. or inhiled to long term control Allergic Rhinitis: nose spray Atopic Dermiti: topical administration |
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why do immediate HS rxns (HS1) manifest in so many dif ways (asthma, atopic dermitis, allergic rhinbitis)
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based on the LOCATION of allergen in the body
site of allergen exposure and thus location of mast cell degranulation (can be serious or mild) 1. Respiratory: allergic rhinitis, asthma 2. Skin/Mucosa: atopic dermitis, atopic urticaria 3. GI allergies: food allergies 4. Systemic Anaphylaxis |
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waht happens when the site of allergen exposeure of a HS 1 occurs at..
respiratory skin/mucosa GI Systemic Anphylaxis |
allergic rhibitis asthma
atopic dermitis, urticaria food allergies systemic anaphylaxis: |
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waht can we do to detect HS 1? what are pros and cons
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skin tsts
Inject allergen intradermally good bc its cheap and can test lots of allergens, can be bad bc we just sensitized an individual to new allergens Also can use: RIST RAST DBPCFC |
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waht is DBPCFC
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double blind placebo controlled food challenge
**present suspected food allergens in a controlled hospital environement to test for HS 1 |
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what is RIST?
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radioimmunosorbent test
**radioimmunoassay that can detect super small levels of IgE **contrast with RAST that can detect small levels of IgE specific for a given allergen |
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waht is RAST
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radioimmunosorbent test
**detect small amts of IgE in serum that is specific to an allergen |
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how are RIST and RAST different
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A stands for allergen
**RIST tests for small amts of allergen in serum. RAST tests for small amts of AG specific IgE in serum both are radiolabeled immuno assays |
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what is the best prophylatic tx for HS 1
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stay away from the allergen
allergy shots can also be given *hyposensitization, desensitization by injecting allergen you switch from IgE hypersecretion to IgG secretion |
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what are allergy shots? what type of hypersensitivity to they halp for? do they always work
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HS 1, not helpful in all ppl
They give weekkly/monthly injections of allergen adn this desensitizes ppl. they start to make IgG instead of IgE. the IgG then BLOCKS the allergen from activating mast cells by binding to it |
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what is a way to tx allergic rhinitis, mites, pollen, animal dander allergies (HS 1(
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allergy shots, give allergen to desensitize
Make IgG rather than IgE. The IgG then neutralizes the allergen so the allergen cant activate mask cells |
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1. what cell is initially secreting the mediators that elicit HS 1
2. what activatees the mast cell 3. The first preformed mediator that is released within a few min of activation is 4. what are the effects of histamines interaction with H1 receptors 5. What secondary lipid mediators are most important in HS 1 6. What is the effect of mast cell cytokine secretion |
1. mast
2. alleren crosslinking IgE on the mast cell 3. histamine 4. dilation, SM contraction, mucus secertion 5. PGD2, LTC,D,E4 6. bring eisoniophiles/PMN this damages the tissue |
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tell me abotu HS 2
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IgM or IgG hypersecretion
**binds to allergens that are CELL BOUND **still ab mediated (all are except 4 which is T and macro) |
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we know in HS 2 its a cell associated allergen that elicits the hypersecretion of IgG or IgM. what kinds are AG are cell bound
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1. intrinsic cmpds: blood group
2. drugd that adhere |
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does HS2 have a sensitization and effector stage
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yep!
Sensitization: exposure to allergen creastes IgG/M secretion Effector: reexposure causes IgG/M to bind cell surface and elicit compliment/ADCC which makes the cell die |
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what type of HS has the killing of a cell bc it has an allergen attached to ir
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HS 2
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what type of HS is a blood transfusion rxn
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type 2
we respond to a CELL BOUND Allergen adn make IgG/M to activate compliment and ADCC **massive hemolysis of RBC **IgM mediated |
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what mediates a type 2 blood transfusion rxn
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IgM
preexisting IgM AB |
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are delayed hemolytic transfusion rxns IgM mediated
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NOPE!
IgG **not as severe, seen in ppl with repeated transfusions. they have the right ABO type but minor components may not be a perfect match |
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so massive intravasculat hemolysis that causes fever chills nauesua renal failure is associated with transfustion rxnx (mismatch ABO)
**what does drug induced hemolytic anemia cause |
some drugs can complex with RBC (like a hapten thing) and become immunogenic
**IgM/G mediated killing of RBC **anemia resolves when drug is removed Type II HS |
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what is drug induced thrombocytopenia
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decreased platelets bc drugs coat platelets adn then IgM/G kill the platelets
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what autoimmune disorders are HS II
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1. myesthenia gravis: AB binds and blocks Ach from getting to its receptor
2. graves disease: AB acts to stim TSH R on thyroid to make T3/T4 3. hashimotos 4. goodpasture |
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what again detected HS 1? what detects HS 2
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HS1:
skin prick, RIST, RAST, DBPCFC HS 2: Coombs test. Detects AB on the surface of pts RBC. hemaagglutination |
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what type of HS will do hemolytic diesase of newborn
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HS 2
**kill the Rh factor. |
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what does the coombs test look for?
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look for IgG bound to RBC (NOT a normal finding!)
we take BRC and give it the coobs reagent which is anti IgG, if we have agglutination we know its a + coombs and there is HS2 |
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what does hte indirect and direct coombs test for which is mroe sensitive
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Direct: tests to see if IgG is on pts RBC, hemagglutinatoin is +
Indirect: MORE sensitive, test to see if tehre is IgG in PLASMA |
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explain whats going on in a HS 3
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well we still ahve LOTS of IgG/M secretion (like 2) but this time it makes small immune complexes that cant be cleared by phago as large complexes are. These small complexes are deposited in the joints nad kidneys and activate inflammation and compliment
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does HS3 have sensitization and effector phase
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BUT sensitization is NOT always necessary for HS3
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what is the sensitization phase of HS3
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small insoluble immune complexes are deposited into tissues (not always necessary for this)
Effector: immune complex activation and recriutment of inflammatory cells and more immune complexes for deposition |
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what is the effector phase of HS 3
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first we have sensitization where small INSOLUBLE immune complexes are deposited in tissue
EFFECTOR: immune activation of complimant and recruitment of inflammatory cells and increased vascular permiability to let more immune complexes in |
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what type of HS ccan cause thrombi, edema, hemmorage and necrossi
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HS 3
insoluble immune complexes ppt in joints and things, this causes tissue damage and platelet aggregation |
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during the effector phase of HS 3 we have lots of things going on, what are they
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more complexes accumulate
compliment activates PMN release ROS platelet aggregation Thrombi, hemmorage, edema, necrosis |
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what is the arthus rxn, what HS?
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HS 3
localized tissue necrosis after repeated injection of allergen into the skin Preformed IgG form immune complexes in BV near injection site |
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what is it called when you get tissue necrosis due to preformed IgG molevules forming IC in BV near sites of repeated injections
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arthus rxn
Type 3 |
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serum sickness is what type of HS? how does it differ than other HS rxns
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3, immune complex formation
This is systemic, all others were local Happens after antitoxin.antivenom is injected or can be drug induced Sx: rash, fever, arthritus, kidney complications Immune complexes ppt out |
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what can cause serum sickness
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can happen after antitoxin or antivenom is given. also can be drug induced
sx include: rash, fever, arthritis, glomerulonephtritis hs3 |
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what autoimmune diseases are hs 3
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sle
ra autoreactive AB are detected in pts serum |
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SLE and RA are what type of Autoimmune HS diseorrders
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HS 3, immune complexes
autoreactive AB in pts serum |
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what are delayed HS? why do they take longer
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type 4
**mediated by Th1 (Th2 was HS1) and macro **require AG presentatoin |
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wht do Th1 cells do, waht is another name for them
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type 4 delayed.
AKA Tdth (T delayed type HS) |
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is there a sensitization phase for ALL HS rxns
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you bet
Type 3 doesnt always have a sensitization |
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what goes on in the sensitization phase of HS4
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initial contact exposure to AG
(AG complexed with protein in the skin) procvess/present AG to T cells Th1 are activated |
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what is the effector phase of a HS 4
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APC activation of Th1 MEMORY when reexposed to AG
release chemokines/cytokiens recruit/activate macro and PMN TISSUE DESTRUCTION |
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is there a specific test to detect HS3
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not really, we can run an elisa to see if there are any autoantibodies
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Th1 in HS4 does what
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IFNg to recruit macrophages
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what are the cytokine reelasd adn what do they do when a Th1 memory is activated in a HS 4? why do we get a Th1 response in this HS
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IFNg: recruit macro
TNFa: recruit PMN allergen binds TRL, APC secretes IL12 adn IL12 causes Th1 differentiona (Th1=Tdth) |
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what is a common type 4 rxn
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TB test, this is why we have to wiat, its a T cell response
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what kind of HS is TB test
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4, t cell response
**the injected bug is a hatpen and will complex with protein in the skin |
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how can HS 4 track AIDS progress
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indicate T cell fx
Tdth declines as AIDS progresses. Use an AG that the individual WILL respond to, if we dont see a rxn the T cell activity has declines |
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contact dermatitis is what type of HS
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4
hapten complexes with protein in the skin and causes blistering *usually takes 48 hrs. its a delayed type hypersensitivity |
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why type of sensitivity causes poison ivy
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type 4, delayed type
poision oak, ivy, sumac **complexes with langerhan cells, APC to Th1 and cause IFNg and TNFa to bring macro and PMN |
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whats the deal with granuloma formation
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type 4 HS that cant clear the pathogen
**persistant stimulation of inflammation |
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how are HS 4 detected
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PATCH test
cloth with allergen is put on your back and left for 48 hrs. if there is a response you know your type 4 allergic |
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what dioes a patch test do
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detect HS 4
**put allergen on a patch and then place on the back, your allergic if you react |
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waht are common manifestations of HS
1 2 3 4 |
1: systemic/localized anaphylaxis, hay fever, asthma, hives, food allergies, eczema
2. blood transfusions, erythroblasoisis fetalis, autoimmune autolytic anemia 3. arthus, serum sickness, necrotizing vasculitis, kidney disease, RA, SLE 4. contact dermitic, TB, graft rejection |
