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54 Cards in this Set
- Front
- Back
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What is hypersensitivity?
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An adaptive immune response that occurs in an exaggerated or inappropriate form causing tissue damage
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What is required for Type I-IV hypersensitivity reactions to take place?
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Period of sensitization after prior exposure to an antigen
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What is an allergen?
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A term synonymous with antigen in hypersensitivity reactions
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What are 4 types of hypersensitivity reactions?
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1. Type I - Immediate hypersensitivity reactions
2. Type II - Cytotoxic antibody reactions 3. Type II - Immune complex reactions 4. Type IV - Delayed hypersensitivity reactions |
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What happens, in general, during a type I hypersensitivity reaction?
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Allergen triggers IgE mast cells (or basophils) --> immediate response
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What is atopy?
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Certain allergic conditions associated with type I reactions: asthma, atompic dematitis, or allergic rhinitis
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What is the circulating levels of plasma IgE normally?
In an atopic condition? |
normal less than 1ug/ml
Atopic >1000ug/ml |
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What does IgE bind?
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high affinity IgE receptor on mast cells and basophils
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What are important factors, other than allergen exposure, in the development of the atopic state?
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1. Genes, located at many different loci
2. Environmental - pollution, diet, microbial pathogens |
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What is the hygiene hypothesis?
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Antibiotic use reducing normal gut flora, diet, sensitization to dust mites, etc. --> Th2 shift
--> allergic disease, asthma Large family size, exposure to fam animals, natural infects--> Th1 shift --> protective immunity |
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What is the high affinity IgE Fc receptor? Where is it found?
The low affinity receptor? |
FcERI - mast cells, basophils, langerhans cells, activated eosinophils
Low affinity = FcERII |
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What are the effector cells of Type I reactions?
What do they look like? |
Mast cells
Large mononuclear cells that are heavily granulated |
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What is the origin of Mast cells?
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Bone marrow origin, CD34+ progenitor cell
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What are mast cell growth factors?
Which is the most important? |
IL-3, -4, -9, -10
Stem cell factor is the most important |
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What are the newly synthesized mast cell mediators?
Time scale? |
1. Platelet activating factor
2. Arachadonic acid metabolites -Leukotrienes by lipoxygenase pathway -Prostaglandins and thromboxanes by cyclo-oxygenase pathway Made within minutes |
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What is the most important preformed mediator produced by mast cells?
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Histamine
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Mast cell mediator: Enzyme
a. Example b. Biological effects c. Released from...? |
a. Tryptase, chymase, cathepsin G, carboxypeptidase
b. Remodel connective tissue matrix c. Preformed granules |
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Mast cell mediator: Toxic mediator
a. Example b. Biological effects c. Released from...? |
a. Histamine, heparin
b. Increase vascular permeability, cause smooth muscle contraction c. Preformed granules |
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What are 3 sets of cytokines released from mast cells and what is the role of each set?
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1. IL-4, IL-13 --> Simulate and amplify Th2 cell response
2. IL-3, -5, GM-CSF --> Promote eosinophil production and activation 3. TNF-a --> Promotes inflammation, stimulates cytokine production by many cell types, activates endothelium |
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Mast cell mediator: chemokine
a. Example b. Biological effects c. Released from...? |
a. MIP-1a
b. Attracts monocytes, macrophages, and neutrophils c. Synthesized after activation |
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What are 2 sets of lipid mediators released from mast cells and what are the roles of each?
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1. Leukotrienes C4, D4, E4 --> smooth muscle contraction, increase vascular permeability, stimulate mucus secretion
2. Platelet activating factor --> attracts leukocytes, amplifies production of lipid mediators, activates neutrophils/eosinophils/platelets |
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What are the steps of IgE-dependent mast cell activation?
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Allergen binds to membrane-bound IgE --> cross links adjacent IgEs --> activation of FcERI receptor --> mediator release from mast cell
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What happens in IgE-independent mast cell activation?
What are 4 other agents that can activate mast cells this way? |
C3a and C5a can activate mast cells via complement receptors
Opiates, radiocontrast media, venoms, physical stimuli |
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What is the early phase reaction of Type I?
When does it occur? |
Always occurs in type I reactions, result of mast cell mediator release
Occurs within minutes of allergen exposure |
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What is the late phase reaction of Type I?
When does it occur? |
Some type I reactions are accompanied by a second reaction due to influx of inflammatory cells such as eosinophils, basophils, T cells, and neutrophils
Occurs 4-6 hours after early phase reaction |
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What type of reaction is an important cause of serious long-term illness like chronic persistent asthma?
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Late phase rxn, Type I
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Physiologic effects of mast cell activation on...
a. Nose and eyes b. Lungs c. Skin D. Multiple organs |
a. Allergic rhinitis (hay fever)
b. Allergic asthma c. Allergic urticaria d. Anaphylaxis |
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What are the effects of mast cell activation and degranulation on the GI system?
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Increased fluid secretion, peristalsis --> diarrhea, vomiting
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What are the effects of mast cell activation and degranulation on the airways?
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Decreased diameter, increased mucus --> congestion and blocking of airways, swelling and mucus secretion in nasal passages
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What are the effects of mast cell activation and degranulation on the blood vessels?
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Increased blood flow and permeability --> increased fluid in LN and tissues, increased cells and proteins in tissues, increased cell response in tissues
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What are 4 diseases of immediate hypersensitivity?
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1. Urticaria/angioedema
2. Allergic rhinitis 3. Asthma 4. IgE-mediated anaphylaxis due to foods, drugs, or stinging insects |
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What are 2 methods for diagnosing immediate hypersensitivity reactions?
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Testing for IgE antibodies by...
1. In vivo prick testing 2. enzyme-based immunoassays (formerly used radioallergosorbent test) |
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How do we determine whether there has been a systemic mast cell activation, like in anaphylaxis?
What can/cannot these tests actually tell us? |
Measure mast cell mediators like serum tryptase or histamine metabolites
Cannot tell us if Type I reaction, but indicates systemic mast cell activation |
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What are the 3 tiers of allergic disease treatment?
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1. Environmental intervention (avoid allergen!)
2. Pharmacological: antihistamine, cromolyn sodium, corticosteroids, epinepherine, leukotriene modifying agents 3. Immunologic interventions: immunotherapy or desensitization |
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What are 4 similarities between Type Ii and Type III hypersensitivity reactions?
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1. Ab mediated
2. IgG and IgM 3. Exaggeration of normal immune response 4. Time course 4-24 hrs |
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What are 2 differences between Type II and type III hypersensitivity rxns?
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1. Type II = Ab directed against surface antigens on cells/tissues; Type III = Ab against soluble antigens
2. Type II = damage localized to specific cells and tissues Type III = Damage to organs where immune complexes deposit |
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What occurs in type II Hypersensitivity reactions (Ab-dependent cytotoxicity)?
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Ab binds to cell surface or tissue antigens on Fab end, effector cells with FcR on Fc end
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What are 5 types of effector cells involved in type II rxns? To what do they bind?
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1. NK cells (IgG)
2. Neutrophils (IgG) 3. Eosinohils (IgE) 4. Monocyte/Macrophage (IgG) 5. platelets (IgM, IgG) |
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What are 2 examples of Type II hypersensitivity? Examples of each?
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1. Hypersensitivity to circulating cellular antigens - transfusion, hemolytic disease of newborn, autoimmune hemolytic anemia
2. Hypersensitivity to tissue antigens: Goodpasture's and Myasthenia Gravis |
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What type of hypersensitivity rxn happens in Myasthenia gravis?
What occurs in Myasthenia Gravis? |
Type II
Autoantibodies bind Ach receptors --> muscles can't receive neuronal impulses |
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Type II hypersensitivity rxns
a. Antibody b. Effector cells |
a. IgG, IgM
b. cells with Fc receptors |
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Type III hypersensitivity rxns
a. Antibodies b. Effectors |
a. IgG, IgM
b. Neutrophils |
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What are the steps of a type III hypersensitivity rxn?
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Ab-Ag immune complex --> complement activation --> C3a and c5a released --> chemoattract leukocytes and simulate basophil and platelets to release histamine and serotonin --> increase vascular permeability --> platelet aggrgation
--> microthrombus --> immune complexes deposit on walls --> Neutrophils get "frustrated" trying to phagocytose ICs, spit out toxic metabolites and enzymes |
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What is an Arthus reaction?
What does it require? (4) |
Type III: Acute hemorrhagic-necrotic reaction in the skin of an immunized animal following antigen injection
Requires: 1. Large amounts of IgG and IgM that can stimulate complement 2. PMNs 3. Large amounts of antigen 4. ICs (antigens in slight excess) |
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What is one-shot experimental serum sickness?
What are the 3 phases? |
Serum sickness-like reaction in rabbits given large amounts of antigen
1. Equilibrium of antigen between vascular and extravascular spaces 2. Catabolic clearance of Ag, formation of ICs 3. Rapid clearance of antigen due to more ICs, symptoms form |
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What are 4 clinical examples of Type III hypersensitivity?
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1. Human serum sickness
2. Systemic lupus erythematosus 3. Hypersensitivity pneumonitis 4. Infection associated IC disease |
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In human serum sickness, what are 2 common antigens?
What are 4 clinical features? |
Common antigens:
1. Drugs (penicillin) 2. Exogenous animal sera clinical (after 7 days): 1. cutaneous rashes b. arthralgias/myalgias 3. lymphadenopathy 4. Fever/malaise |
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How are Type IV reactions different than 1,2, and 3?
What are they mediated by? |
Not Ab-mediated
Specific effector T-cell mediated |
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What are 3 names of Type IV?
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1. Tuberculin rxn
2. Delayed-type hypersensitivity rxns 3. Cell-mediated immunity |
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What is allergic contact dermatitis?
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Most common clinical manifestation of Type IV
Target organ (skin) experiences inflammation in response to an allergen (hapten) that contacts skin (poison ivy, nickel) |
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What is the process of sensitization of allergic contact dermititis?
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Hapten binds self-proteins --> Lcs process --> migrate to node to increase adhesion and class II molecules --> antigen-bearing LCs --> IDCC, release cytokines for T cells to expand and differentiate into CD4 Th1 and CD8 Th1 --> memory cells, home to skin
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What is the efferent or allergen challenge phase of contact dermatitis?
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Repeat exposure to allergen, processed by LC and keratinocytes --> cytokines released --> upreg. adhesion molecules --> memory T cells extravasate into dermis --> LC present allergen to memory Th1 or memory CD8 T cells --> cytokines --> recruits macrophages and T cells --> dermatitis
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What are 3 diagnostic features of contact dermatitis?
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1. Eczema-weepy and scaly, itchy, red
2. Location and distribution 3. History of contact |
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What is patch testing?
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Tests for allergic contact dermatitis to poison ivy
Allergen applied to skin, secured with tape, examined at 48 and 96 hours |
