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72 Cards in this Set
- Front
- Back
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type I hypersensitivity
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mast cellsbind IgE via their Fc R's
on encountering allergen the IgE becomes cross linked, inducing degranulation andrelease of mediators that produce allergic rxns |
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in type IV, Ag- sensitized T cellsrelease
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lymphokines following secondary contact with the same Ag
cytokines induce inflammatory rxns and activate and attract macs, which release inflammatory mediators |
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type I immune reactant
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IgE Ab
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type I Ag
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soluble Ag
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effector mechanism of type I
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mast cell activation
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chemotaxis in type I
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eosinophils
ECF from mast cells |
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type I clinical
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allergies
asthma anaphylaxis - injected toxins, bee stings prostaglandin leukotriene - bronchiole |
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time course of type I
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immediate granules
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test for type I
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scratch
- wheel and flare |
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therapy for type I
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antihistamine
albuterol - cAMP - adenyl cyclase theophylline - phosphodiesterase epinephrine chromoglycates |
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type IV immune reactant
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T cells
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type IV antigen
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Chemical
cell associated Ag |
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effector mechanism of type IV
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mac activation and cytokines
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chemotaxis in type IV
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mac
Tc & Th1 cytokines |
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type IV clinical
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granulomatous disease
- farmers lung (chronic) - tuberculosis - parasitic infections contact hypersensitivity - poison ivy, chromates (cement), latex, many chemicals skin testing for immune reactivity - tuberculin |
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time course of IV
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48 hours
Th-1 cytokines |
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test for IV
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48 hours
Th1 cytokines chemokines mac |
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therapy for type IV
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non specific anti inflammatory drugs
immunosuppressive - cyclophosphamide - corticosteroids decrease Ab production |
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allergy
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hypersensitive state affecting about 20% of US
10% of world pop result of disorder in immune system that results in production of IgE Ab to Ag as opposed to IgG or no response |
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inheritance characteristics of allergies
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familial traits; parents with allergies and child's % chances;
- both P same allergy: 85% - different allergies: 65% - one P : 25% - neither P: 15% MHC II molecule & allergen presentation - inhereit MHC molecule from parents; need right binding place for allergen Th-2 cells TCR, cytokines IL-4 & IL-13; in absence of 10 - 10 blocks 4 and 13 from making class switch to IgE B cell cytokine Rs and signaling for EgE class switching lack of T suppressor cells: t-regs that are epitope specific genes controlling epithelial barrier function in mucosal, resp tree and gut IgA deficiency |
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hygiene hypothesis
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lack of early childhood exposre to infectious agents, symbiotic microorganisms (gut flora or probiotics & parasites) increases susceptibility to allergic disease as well as autoimmune, Chron's & inflammatory bowel disease
hypothesized that Th1, T-reg and T17 balanced responses are not induced early in life leaving the body more susceptible to developing Th2 induced diseases |
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atopy
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hereditary tendency to develop allergies
refers to clinical features of allergy: - hay fever, asthma, eczema, urticaria usually susceptible to wide range of allergens |
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allergen
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foreign material (Ag) that elicits an allergic response
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allergic rhinitis
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inflammation of mucus membranes of eye, nose and throat
common with hay fever |
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asthma
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severe alleric rxn caused by constriction of bronchials
- from histamine release |
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anaphylaxis definition
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acute type I rxn
caused by histamine and other vasoactive substances usually in asssociation with IgE generally rapid, systemic life threatening rxn |
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wheel and flare
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local response of skin to injury
characterized by wheel of edema and a flare of spreading erythema usually associated with skin testing for allergies |
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the allergic rxn
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sensitization of an atopic individual: IgE, IL4 & 13
mast cell types: IgE R's - mucosal: line respiratory and GI tract (300,000 R's / cell) - CT: ubiquitous around BV's (30,000) mediators of immediate hypersensitivity Ag-Ab processing, if right MHC binds allergen and go to TH2 cells with B cells through CD40 and CD40 L: upreg 4 & 13 produces IgE without IL10 |
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intragranular and membrane derived mediators
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intragranular: histamine, proteases, heparin, ECF-A, neutrophil chemotactic factor
membrane derived: prostaglandin D2, leukotrienes C4, D4, E4, plastelet activating factor - important in chronic allergies; mast cell PM has high arachidonic acid; cox pathway leads to inflammation |
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histamine biological effects
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vasodilation
vasopermability bronchoconstriction |
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proteases biological effect
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degradation of BV BM
generation o vasoactive complement anggiotensin metabolites remodeling of CT |
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heparin biological activities
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anticoagulation
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ECF-A biological effects
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eosinophil chemotaxis
- chemokines and IL5 attract eosinophils and make major basic Protein which pokes parasites and kill thems |
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neutrophil chemotactic factor biological effects
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neutrophil chemotaxis
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prostaglandin D2 effect
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vasopermeability
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leukotrienes C4, D4, E4 effect
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bronchoconstriction
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platelet activating factoreffects
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vasopermeability
bronchoconstriction chemotaxis |
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allergy and mast cell degranulation phases
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sensitization
activation |
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sensitization phase
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result of classical Ag presentation with TH cell involvement and B cell activation
IL 4 and 13 released by Th2 cells: b cells switch to IgE production IgE produced in response to repeated mucosal contact, ingestion or injection of allergen binds rapidly to high affinity IgE c R's on tissue mast cells and blood IgE is stable for wks passive transfer of IgE containing serum will sensitized skin mast cells resulting in passive cutaneous anaphylaxis (wheel and flare)upon challenge with appropriate allergen |
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activation phase
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crosslinking of at least 2 high affinity IgE Fc R's (&bound IgE) by multivalent allergen, anti-IgE Ab, anti Fc R Ab or agregated IgE triggers mast cell (and basophill) degranulation
non-IgE activators of mast cells include C3a and C5a (anaphylatoxins) & drugs (codeine & morphine), cold, exercise, and certain neuropeptides |
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allergen cross linking of IgE bound to high affinity Fc R's leads to
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Fc R agregation, activation of protein tyrosine kinases and phosphorylation of immunoR tyrosine based activation motif (ITAMs) associated with gamma chains of high affinity IgE Fc R and PLC: 2nd messenger production
membrane phospholipid methylation activation of membrane bound adenylate cyclase cAMP levels decrease below baseline granules expand in size and decrease in density microfilaments move granules to cell surface where granules fuse with PM and granule contents are rapidly released |
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membrane phospholipid methylation causes
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increased membrane fluidity and Ca channel formation
leading to influx of Ca, as well as Ca release fom ic stores |
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activation o membrane bound adenylate cyclase leads to
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rise in ic cAMP levels and activation of cAMP-dependent kinases that alter granule permeability by phosphorylating proteins on granule membranes
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cAMP levels decrease below baseline in order for
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degranulation to occur
continued increase in ic cAMP levels will slow or halt degranulation activation of AC, is therefore, an important control mechanism |
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if activate allergic R without C3aR or IgE R what happens
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no PLC or degranulation
need ic Ca o decrease |
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allergy treatment: systemic approach
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pharmacological
antihistamines decongestants: alpha adrenergic antagonists anticholinergic Rx: stops mucus secretion ER & anaphylaxis - epinephrine alpha (smooth m constriction) & beta (increase HR) adrenergic R activation - epi activates AC theophylline and other PDE inhibitors |
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immunological approach for allergy treatment
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desensitization
encourage Th1 responses & promote IgG class switch promote development of T reg specific for allergens suppress IgE production and lower IgE memory cells |
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clinical assessment of allergies
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scratch test
- skin test for pts rxns to allergens: wheel and flare - about 1 min for response Radioallergosorbent test (RAST) lab based test: ELISA for pts IgE specific Abs to allergens |
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allergens found in
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wide variety of environmental agents, commercial preparation and food related producs
portal of entry can be through inhalation, injection or ingestion |
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types of allergens
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pollen/dust
drugs insect stings food latex |
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pollen/dust allergens
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seasonal
usually multiple pollens oak, ragweed common acute/chronic chronic is like dust & danders |
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drug allergen
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penicillin
haptens systemic anaphylaxis |
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insect sting allergens
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order
hymenoptera bees, wasps, ants venom access to circulation risk of systemic anaphylaxis |
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food allergens
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nuts, berries, milk proteins, grains
anaphylaxis incidence CDC says more than 3 million americans are allergic to peanuts or tree nuts nearly 7 million allergic to seafood combined, food allergies cause 30,000 cases of anaphylaxis; 2000 hospitalizations, and 150 deaths annually |
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latex allergens
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proteins rubber tree
can be type I or IV or both spina bifida susceptible |
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delayed hypersensitivity mediated by
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primed T lymphocytes (never Ab)
lesions in which lymphocytes and macs are usually prominent, do not appear until about 24 hours after contact of a sensitized subject with Ag |
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lymphocytes that play major role in DTH rxns
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mac chemotactic factor
- chemo attractant for mac to accumulate in tissue at site of injury mac migration inhibition factor - promotes various adhesion molecule production & other factors to localize macs mac activating factor - various cytokine: INF-g, TNF, IL12 produced and secreted by lymphoid cells; primarily Th1 cells and mac themselves, but also non lymphoid cells: keratinocytes |
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DTH is major mech of defense against various
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IC pathogens, including mycobacteria, fungi, and certain parasites
it occcurs in transplant rejection and tumor immunity synonymous with cell mediated immunity Th1, T cytotoxic cells and macs |
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DTH rxn types
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granulomatous hypersensitivity
contact hypersensitivity skin testing |
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granulomatous hypersensitivity
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persistent inectious agents
chronic localized stimulation of CMI response; DTH generates granuloma |
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contact hypersensitivity chemical agents called
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haptens
skin rxn to chemical allergens (haptens) defined delayed term in DTH poison ivy |
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skin testing
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clinical visualization of previous exposure to pathogens or assessment of immune status
following transplantation Tuberculin hypersensitiity |
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granulomatous hypersensitivity more frequently used to refer to localized collection of macs that result in
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accumulation and mutual compression gives appearance that stimulates focus of epithelial cells
hence these compressed macs are often called epitheloid cells cells often fuse forming giant cells and if stimulus continues many of the cells may die fibrosis, calcification and "walling Off" may occur granulomas |
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initiating Ags of granulomatous DTH characteristics
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most are infectious agents
cell walls components not good Ags, lipids, polysaccharids and sometimes waxy (Ab and complement ineffective in early stages of infection) - type III hypersensitivty at this stage agents extremely resistant to phagocytic process organisms have IC phases and grow in phagosome |
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pathogenesis of DTH granulomatous
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mac phagocytosis
- organism's IC phase - MHC I & II presentation cytotoxic T cells TH1 amplification epitheloid cell granuloma - fused membranes, multinucleated giant cells - fibroblasts GF's, calcification, etc many have early type III phase; farmers lung initated as III and clincially presents as IV |
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allergic contact dermatitis is an inflammation of skin characterized by
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erythematous vesiculouus lesions
caused by immunologic DTH to variety of external agents applied to or coming into contact with skin |
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initiating Ags in contact DTH
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chemicals on skin: hapten
- ind to cell surface and CT proteins - alter structural chemical features create epitopes (haptens) |
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langerhan's cells in contact DTH
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take up, and present process protein hapten conjugates: MHC II
cell surface (MHC ii) may be altered |
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lymph node sensitization in contact DTH
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Ag transport
T cell rich areas Th0 helper cell proliferation no free Ags; no sIg's no b cells no B cell activation |
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second exposure in contact DTH
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langerhan's cells present Ag/hapten in tissue to sensitization Th1 cells: memory, mac recruitment, amplification of lesion and generates more sensitized T cells
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clinical features of contact DTH
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acute: skin rxns lesion well demarcated, fimharrdened inflammation and little edema
- mostly chemical (haptnes) = plants, metals, tanning industry, paints, latex proteins chronic: long term, continuous exposure to initiating material and occupational related - chromates in cement, latex in paint, chemicals in leather tanning industry. - presents with severe eczema & respiratory ailments - can result in organ (lung) failure - Tx: difficult as condition caused as "part of pts job" - use steroids and immunosuppresents |
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skin testing for contact DTH
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DTH rxn: intradermal injection of small amount of test Ag
- read rxn 24 hours later contact hypersensitivty: patch test. apply (tape) smamll amount of test substance on skin - read rxn 24 hours later |
