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99 Cards in this Set
- Front
- Back
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Define hypersensitivity:
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Excessive or aberrant immune responses following antigen challenge
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Type I:
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IgE
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Type II:
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IgG/IgM
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Type III:
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Immune complexes
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Type IV:
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Cells
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What is Type I Hypersensitivity called?
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Immediate
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What are the pathologic immune mechanisms of Type I?
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-Th2 cells
-IgE antibody -Mast cells -Eosinophils |
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What are the mechanisms of tissue injury and disease in Type I?
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1. Mast-cell mediators
2. Cytokine mediated inflammation |
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What are 3 examples of Type I?
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-Allergic rhinitis
-Asthma -Systemic anaphylaxis |
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What tissue does Type I allergy target?
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Vascular endothelium and smooth muscle
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What is atopy?
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The propensity of some individuals to developing an allergy
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What is rhinitis?
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Hay fever
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What is a common side effect of immediate hypersensitivity?
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Late phase reaction of inflammation
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What determines Atopy?
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Genes
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What are some allergens that trigger allergy?
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-Pollen
-Foods -Insect venom -Animal dander -Drugs |
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What is the first step in develping a Type I reaction?
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Allergen exposure
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What is the initial response to allergen exposure?
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Bcell activation and Th2 cell activation via Il-4; Class switching to IgE
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What does IgE do once it is secreted by Bcells in a Type I reaction?
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Binds to Mast cells
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What is the mast cell receptor for IgE?
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Fc-epsilon-R1
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When is the real reaction seen in Type I hypersensitivity?
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Upon REPEAT exposure to the allergen
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What happens when repeat exposure to allergen occurs?
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Now the IgE that has coated mast cells get crosslinked by the allergen; this activates the mast cell and it degranulates.
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What do mast cells release when they degranulate?
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-Vasoactive amines
-Lipid mediators |
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When does immediate hypersensitivity reaction occur?
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Minutes after repeat exposure to the allergen
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When does the cytokine-stimulated late phase reaction occur?
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6-24 hours after the repeat exposure.
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What does a late phase reaction consist of?
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Recruitment of more eosinophils and PMNs - inflammation.
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What are some drugs that can cause immediate hypersensitivity?
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-Opiates
-Vancomycin -Penicillin |
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What are three important molecules that cause Bcell production to switch to IgE?
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IL-4
IL-13 CD40/CD40L costimulation |
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So the two general steps of Type I reactions are:
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1. Sensitization of mast cells
2. Activation and degranulation |
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What are 2 main types of mast cell mediators?
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1. Preformed
2. Synthesized |
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What are the preformed mediators in mast cells?
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Vasoactive amines (histamine)
Proteases (chymase) |
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What are the synthesized mast cell mediators of allergy?
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-Eicosanoids
-Cytokines |
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When are the vasoactive amines and eicosanoids released?
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Immediately - within minutes of mast cell degranulation
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When are the cytokines released?
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In the later phase.
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Why does it take longer for the cytokine release?
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Because it requires transcriptional activation of cytokine genes.
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3 cytokines that are released by mast cells:
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1. IL4
2. TNF 3. Chemokines |
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And what is the effect of IL4, TNF, and chemokines released in the late phase reaction of Type I hypersensitivity?
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Recruitment of leukocytes, so inflammation.
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Going back to early phase; What is the main vasoactive amine released by mast cells?
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Histamine
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What are the 2 effects of histamine?
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1. Vascular dilation
2. Smooth muscle contraction |
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What does the protease chymase result in?
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Tissue damage
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What are the 2 secreted lipid mediators (eicosanoids) from mast cells?
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-Prostaglandins
-Leukotrienes |
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What is the effect of prostaglandins?
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Vascular dilation
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What is the effect of leukotrienes?
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Smooth muscle contraction
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What are 3 allergens that cause Systemic Anaphylaxis?
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-Drugs
-Serums -Food |
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What are the routes of entry for systemic anaphylaxis allergens?
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Oral and IV
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What are 5 responses seen in systemic anaphylaxis?
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-Edema
-Increased vascular permeability -Tracheal occlusion -Circulatory collapse -Death |
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What is another name for Acute urticaria?
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Wheal and flare
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What are 3 allergens that cause acute urticaria?
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-Insect bites
-Allergy testing -Venom |
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What is the route of entry for the allergens that cause urticaria?
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Subcutaneous
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What is the response to acute urticaria?
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A local increase in bloodflow and vascular permeability
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What is another name for allergic rhinitis?
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Hay fever
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What causes hay fever?
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Pollen
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Route of entry for pollen
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Inhalation
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What is the response to hay fever?
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Edema and irritation of the nasal mucosa
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What are 3 allergens that cause asthma?
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-Pet dander
-Pollen -Dust mites |
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What is the route of entry for allergens that cause asthma?
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Inhalation
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What are the 3 responses to asthma inducing allergens?
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-Bronchial constriction
-Increased mucus production -Airway inflammation |
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What is the therapy for systemic anphylaxis?
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Epinephrine
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What are 2 treatments for asthma?
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-Corticosteroids
-PDE inhibitors |
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What are 4 treatments for most allergic diseases?
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-Densitization
-Anti-IgE antibody -Antihistamines -Cromolyn |
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What does cromolyn do?
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Inhibits mast cell degranulation
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What is Type II hypersensitivity mediated by? Type III?
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Type II: antibody
Type III: immune complex |
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How does opsonization and phagocytosis work?
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1. Ab binds and coats antigen
2. Fc region binds FcR on phagocyte 3. Activates lysozyme, ROS, NO production for better killing |
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What are the antibodies in Type II and III hypersenstivity often directed against?
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Self antigens - like in the ECM or in the bloodstream circulation
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What types of disorders result from auto-antibody induced hypersensitivity?
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Chronic disorders
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Why do auto-antibodies develop in the first place?
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Because of a breakdown in tolerance
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What is the isotype of antibodies in type II hsn?
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Igm or IgG
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Where do the IgM or IgG antibodies deposit in Type II hsn?
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In tissue expressing the antigen
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What is the nature of the disorder then in type II Hsn?
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Local
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What is an example of an antigen that causes type II hsn?
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Drugs that bind to cell surfaces or the ECM.
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What are 4 treatments for Ab-mediated HSN diseases?
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1. Corticosteroids to limit inflammation and damge
2. Plasmapheresis 3. Blocking CD40/CD40L contact 4. Splenectomy for AIHA |
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What are 3 diseases that are Type III HSN?
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1. SLE
2. Polyarteritis nodosa 3. Post-streptococcal glomerulonephritis |
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What is the Antibody specificity in Systemic lupus?
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Anti-DNA, Anti-nucleoproteins, and others
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What are the clinicopathologic manifestations of SLE?
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-Nephritis
-Arthritis -Vasculitis |
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What is the antibody specificity in Polyarteritis nodosa?
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Anti-Hepatitis B virus surface antigen
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What is the clinicopathologic manifestation of polyarteritis nodosa?
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Vasculitis
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What is the antibody specificity in post-strep glomerulonephritis?
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Anti-streptococcal cell wall antigen
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What is the clinicopathologic manifestation of Post-strep glomerulonephritis?
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Nephritis
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What is the mechanism of all 3 diseases?
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Complement and Fc-receptor mediated inflammation
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What causes serum sickness?
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The result of injecting a large dose of antigen like Penicillin or antibiotics
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What is the reaction that occurs in serum sickness?
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-IgG/antigen complexes stimulate classical complement cascade
-C3a activates mast cells |
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What is the treatment for serum sickness?
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-Corticosteroids to blunt inflammation
-Self limiting - as the antigen gets cleared. |
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What is the other name for Type IV HSN?
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Delayed type hypersensivitity
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What are all Type IV HSN's mediated by?
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Tcells
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What is the classic example of DTH?
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The PPD skin test for TB
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How is the TB skin test done?
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-Inject Mycobacterial protein subcutaneously
-Local APCs process/present it -Th1 response results in inflammation, visible lesion |
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What do we call DTH that is not on purpose?
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Contact hypersensitivity
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What are 3 antigens that stimulate contact hypersensitivity?
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-Haptens
-Small metal ions -Topical drugs |
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What are the consequences of contact hypersensitivity?
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-Local epidermal reaction
-Erythema, cell infiltrate, intraepidermal abcesses |
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What is a hapten?
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A small chemical which only becomes antigenic after its coupled to a protein carrier
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What is the classic time duration for presentation of poison ivy?
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2 days after exposure
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What is Pentadecacatechol?
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The chemical in poison ivy leaves that stimulates a T-cell response.
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When a person first brushes against poison ivy, what happens?
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The pentadecacatechol oil gets on the skin cells, and a self protein haptenates them.
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What happens to the haptenated poison ivy oil?
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They are taken up by Langerhan's dendritic cells, processed, and presented on MHCII to T cells
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What type of Tcells respond to poison ivy haptenated complexes?
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Th1
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But what do we know about the types of immunity elicited in poison ivy infections?
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Both Th1 and CTLs respond
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How do CTLs get stimulated by poison ivy?
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The pentadecacatechol is membrane permeant so becomes intracellular and presented on MHC I as well!
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What are the forms of treatment for poison ivy contact dermatitis?
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-Corticosteroids
-Benadryl |
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What is benadryl? what is it for?
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Antihistamine - it blocks the products released by mast cells.
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What are 4 other types of Tcell-mediated HSN that are not contact dermatitis?
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1. IDDM (type I diabetes)
2. Rheumatoid arthritis 3. Exper. Allergic Encephalomyelitis 4. Inflammatory bowel disease |
