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71 Cards in this Set
- Front
- Back
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Definition of hypersensitivity
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innappropriate immune response;
not always increased, but inappropriate |
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immediate hypersensitivity:
-initiators -manifested how soon after ag-encounter |
anaphylactic reactions within the humoral branch, initiated by antibody or ag-ab complexes.
-symptoms manifest w/in min/hr or even days |
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dth
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delayed type hypersensitivity;
delayed symptoms - days after exposure. cell-mediated |
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humoral types of hypersensitivity:
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1. IgE mediated
2. Ab-mediated 3. immune complex-mediated. |
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Allergen
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nonparasitic antigens that stimulate type 1 hypersensitivity.
humans are not usually stimulated by these ag, but are genetically predisposed to inappropriate stimulation of IgE. |
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which cells have Fc receptors and induce tpe 1 hypersens.
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Mast cells (in tissue)
Basophils (in circulation) both release vasoactive and smooth-muscle-contracting mediators. |
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categories of allergens that induce type 1 hypersens:
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proteins
plant pollens drugs (penicillin, anesthetis) foods insect products (bee venom, dust mites) mold spores animal hair/dander |
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what causes the allergic response in type 1 hyps?
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the crosslinking of IgE that is on the membrane of basophils and mast cells. this causes degranulation and release of stimulating factors.
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describe the sensitization phase of Type 1 hypersensitivity:
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First exposure to antigen stimulates Ab production, class-switching to IgE. These bind to mast cells/basophils
Second exposure antigens cross-link IgE and induce degranulation of the mast cells and basophils. |
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why does IgE bind mast cells and basophils?
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they have Fc receptors for the antibody.
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Type 1 Hypersens. is really just a normal humoral response... but what is the key distinguishing feature?
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Plasma cells secrete IgE
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What are the two main effects of degranulation?
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-Smooth muscle contraction
-Vasodilation Either systemic or local depending on amount of antigen, degree of toxicity |
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Requirement of Antigens in order to crosslink IgE:
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Must be divalent, not monovalent
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What role do cytokines play in Type 1 hypersens.?
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-They are inflammatory mediators like histamine and leukotriene, released from granules of MAST cells and eosinophils; recruit inflammatory cells, neutrophils and eosinophils.
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What are the 4 mediators of the inflammatory response in type 1 hypersensitivity?
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Histamine
Leukotrienes Prostaglandins Cytokines |
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what is allergic rhinitis?
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hay fever
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what is atopy?
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the inherited tendency to manifest localized anaphylactic reactions to an allergen
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4 types of common IgE-mediated disorers - Type 1 Hypersensitivity:
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-Hay fever
-Food allergy -Asthma -Atopic dermatitis Eczema |
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Symptoms of hay fever, caused by what?
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Runny nose and eyes, sneezing.
Due to localized vasodilation and increased capillary permeability from mast cell degranulation |
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What triggers Asthma, where does the reaction occur?
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Mast cell degranulation; in the lower respiratory tract. Causes broncho-constriction, airway obstruction.
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why is there a difference in the late and early asthmatic responses?
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Early response primarily consists of constitutive inflamm. mediators - hist, prostagl., lktrienes. these vasodilate, bronchoconstrict.
Late response shows action of mediators synthesized after allergen exposure - cytokines, chemotactic, and PAF. These increase CAMS ad recruit inflamm. cells |
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two types of inflammatory mediators produced in Type 1 hypers. based on time
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primary - stored in granules, released immediately -- histamine
secondary - synthesis is activated upon degranulation; prostaglandins/ leukotrienes broken from phospholipids. |
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what are the effects of histamine, how are they mediated?
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-contraction of bronchial/intestinal smooth muscles
-vasodilation binding to H2 receptors on mast cells is negative feedback, inhibits degran. |
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why are leukoriene/prostaglandin effects seen after histamine?
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degranulation induces their production from phospholipids.
longer lasting effects than histamine. bronchoconstriction, vascular permeability. |
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What does epinephrine do?
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increases cAMP levels; prevents degranulation
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4 main symptoms of early asthmatic response:
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vasodilation
increased endothelial permeability mucus production bronchoconstriction |
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2 main symptoms of late asthmatic response:
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-cell influx
-tissue damage |
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what are the steps of degranulation?
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1. Crosslinking activates PTK, transmembrane signalling.
2. Phospholipid methylation; increased Ca2+ channels. Arachidonic a. forms -> prostagl.leukotr. 3. Transient incr/decr of cAMP - necessary for degranulation |
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5 drugs for treating type 1 hypersens:
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Antihistamines
Cromolyn sodium Theophylline Epinephrine Cortisone |
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Action of Antihistamine:
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blocks H1 and H2 receptors on target cells
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Action of Sodium cromolyn
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blocks ca2+ influx into mast cells
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Action of theophylline
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prolongs high cAMP levels; decrease is necessary for degranulation so this does not occur
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method of epinephrine in preventing Type 1 hypersens:
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stimulates caMP production
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Action of cortisone:
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prevents histamine production, stimulates cAMP production
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is antihistamine alone sufficient to treat asthma? why?
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no. because leukotrienes/prostaglandins are also released; these are more potent in action than histamine.
more effective for hay fever |
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what is the choice treatment for systemic anaphylaxis - what should you reach for first?
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EPI PEN -> epinephrine increases muscle tone fast and prevents continued vasodilation.
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Hallmark of Type 2 hypersensitvity:
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RED BLOOD CELL LYSIS
-Ab binding Ag on RBC surface -Transfusion reaction |
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2 types of incompatibility that cause type 2 hypersens:
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ABO incompatibility of RBC
Allotypic incompatibility of RBC. |
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What is the principle of a type 2 hypersens. response? What is it really?
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Antibody-mediated cell destruction:
1. by activating complement MAC attack, 2. opsonization for phagocytosis 3. ADCC -> NK cells, granulytic cells bind Fc of antibody, cause lysis. |
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ABO antibody is what isotype?
Allotypic antibody is what isotype? |
IgM - induced by intestinal organisms w/ similar epitopes. result is within hours.
IgG - induced by repeated blood transfusions with minor allelic difernces that stimulate minor Ab production. result is days later |
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Clinical manifestation of ABO incompatibility:
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Huge lysis of RBC via complement; Within hours can see:
-hemoglobinuria -toxic bilirubin levels -fever, chills, blood clots, -acute tubular necrosis |
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Clinical manifestation of allotypic incompatibility:
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fever, hemoglobinemia, bilirubin, mild jaundice, anemia. less severe response than ABO because IgG is less efficient in activating complement.
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What type of hypersensitivity causes hemolytic disease of the newborn?
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type 2
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hemolytic newborn disease is aka
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erythroblastosis fetalis
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what causes eryth. fetalis?
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Baby is rH+ and mom is rH-.
Mom exposed during delivery; develops Anti-rH IgM antibody. 2nd pregnancy, anti-rH IgG can cross placenta and lyse baby's cells. |
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How does Rhogam work?
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Binds any rH antigen in mom's circulation just after delivery; prevents immune response or production of any antibody.
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Why do type 3 hypersensitivity responses develop?
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Antigen-antibody complexes are not cleared, but still activate complement. cleaved compl. products are chemotactic/inflammatory mediators, so wherever the complex is deposited, lytic enzymes cause much damage. Can be local or generalized (serum)
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what is a great example of a localized type 3 hypersensitivity reaction?
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Arthus reaction - subcutaneous or epidermal injection of Ag.
Immune complex forms; complement activates, inflammation occurs. Tissue damage, IgG response -TB skin test, Insect bite |
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what is the name for systemic Type 3 hypersensitivity?
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Serum sickness
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what is serum sickness caused by?
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large amounts of Ag-Ab complexes in the circulatory system --> wherever they deposit is where an inflammatory response will develop with much tissue damage.
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what can induce serum sickness?
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injection of antibody from another species (horse antiserum)
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what autoimmune diseases, drug reactions, or infectious diseases are examples of type 3 response
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lupus
rheumatoid arthritis penicillin allergy post strep glomerulonephritis meningitis hepatitis mono malaria |
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manifestation of type 3 hyp in lupus:
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red face -> small arteries are damaged by Ab/Ag complexes deposited in the kidney.
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Why does glomerulonephritis develop in type 3 hyp?
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Circulatory Ag-Ab complexes are deposited in the basement membrane; chemotactic factors call inflamm. response resulting in tissue damage.
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what type of hypersens. response occurs after insect bite in a sensitive person?
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initially type 1 -> crosslink of IgE
but 4-8 hrs later, Type 3 -> edema, buildup of pus, etc! |
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what is the major difference between type 3 and type 4 hypersens. cells recruited?
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Type 3 calls up neutrophils
Type 4 calls up macrophages. |
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How is it that Type 4 hypersens. is INNATE and NONSPECIFIC, but it's CELL-MEDIATED?
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Starts off by activated Th cells. They secrete cytokines that tell monocytes to adhere to endothelial cells, extravasate into tissues and differentiate into Macrophages.
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When is DTH good, and when is it bad?
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Good: buildup of phagocytic cells destructs intracellular pathogens nonspecifically. Eliminates pathogen.
BAD: when pathogen won't eliminate; persistant buildup leads to tissue necrosis via GRANULOMA |
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What is a granuloma?
why is it bad? |
a fused ball of activated macrophages that formed a multinucleated giant cell.
Displaces normal tissue, releases lytic enzymes, destroys tissue. |
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What type of response results in Mycobacterium Tuberculosis infections?
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DTH --> tubercle forms --> this is a huge granuloma of macrophages surrounding the infected cell. causes lung tissue damage.
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what are the 2 APC in DTH?
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langerhans cells
macrophages |
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what type of bacteria is DTH especially effective in combating?
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intracellular --> antigen is presented on MHC2 and activates Th cells; subsequent exposure causes cytokine release and inflammation
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what type of hypersensitivity is induced during a TB skin test?
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Type 4; injection of bacterium antigen causes release of cytokines and influx of macrophages.
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cytokines secreted by Th cells in DTH:
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IFN-y, TNF-a/B, IL-2, Chemokines
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What is the effect of activating macrophages?
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Increased MHC2 enhances Ag presentation
Increased TNF receptors enhances phago. Increased O2 radicals and Nitric oxide enhance respiratory burst for killing bacterial cells during phagocytosis. |
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what types of substances cause contact dermatitis?
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chemicals, nickel, hair dye, poison oak/ivy
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what is contact dermatitis?
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small molecules complex w/ skin protein;
after phagocytosis of complex, it's presented as Ag on APC. Activates Th1 cells for DTH response. |
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Role of TNF-a in type 1 hyp:
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-secondary mediator that stimulates chemotaxis of neutrophils and eosinophils;
-contributes to systemic anaphylactic shock |
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what do the early and late responses of asthma generally consist of?
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early: histamine/leukotriene/prostagl.
late: cytokines (IL-4,5,6, Eosin chemotactic factor, PAF) to increase endothelial CAMS and recruit inflammatory cells |
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what do skin lesions in Type 1 atopic dermatitis contain?
What about in Type 4? |
Thelper2 cells and eosinophils
Macrophages and not many Th1 cells |
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WHY is IgE the mediator of Type 1?
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PAtient suffers regulatory defects for IgE;
nonparasitic antigens can stimulate inappropriate activity of IgE. |
