Glossary of Hypersensitivity
Other Decks By This User
- Definition of hypersensitivity
- innappropriate immune response;
not always increased, but inappropriate
- immediate hypersensitivity:
-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
- delayed type hypersensitivity;
delayed symptoms - days after exposure.
- humoral types of hypersensitivity:
- 1. IgE mediated
3. immune complex-mediated.
- nonparasitic antigens that stimulate type 1 hypersensitivity.
humans are not usually stimulated by these ag, but are genetically predisposed to inappropriate stimulation of IgE.
- which cells have Fc receptors and induce tpe 1 hypersens.
- Mast cells (in tissue)
Basophils (in circulation)
both release vasoactive and smooth-muscle-contracting mediators.
- categories of allergens that induce type 1 hypersens:
drugs (penicillin, anesthetis)
insect products (bee venom, dust mites)
- what causes the allergic response in type 1 hyps?
- the crosslinking of IgE that is on the membrane of basophils and mast cells. this causes degranulation and release of stimulating factors.
- describe the sensitization phase of Type 1 hypersensitivity:
- 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.
- why does IgE bind mast cells and basophils?
- they have Fc receptors for the antibody.
- Type 1 Hypersens. is really just a normal humoral response... but what is the key distinguishing feature?
- Plasma cells secrete IgE
- What are the two main effects of degranulation?
- -Smooth muscle contraction
Either systemic or local depending on amount of antigen, degree of toxicity
- Requirement of Antigens in order to crosslink IgE:
- Must be divalent, not monovalent
- What role do cytokines play in Type 1 hypersens.?
- -They are inflammatory mediators like histamine and leukotriene, released from granules of MAST cells and eosinophils; recruit inflammatory cells, neutrophils and eosinophils.
- What are the 4 mediators of the inflammatory response in type 1 hypersensitivity?
- what is allergic rhinitis?
- hay fever
- what is atopy?
- the inherited tendency to manifest localized anaphylactic reactions to an allergen
- 4 types of common IgE-mediated disorers - Type 1 Hypersensitivity:
- -Hay fever
-Atopic dermatitis Eczema
- Symptoms of hay fever, caused by what?
- Runny nose and eyes, sneezing.
Due to localized vasodilation and increased capillary permeability from mast cell degranulation
- What triggers Asthma, where does the reaction occur?
- Mast cell degranulation; in the lower respiratory tract. Causes broncho-constriction, airway obstruction.
- why is there a difference in the late and early asthmatic responses?
- 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
- two types of inflammatory mediators produced in Type 1 hypers. based on time
- primary - stored in granules, released immediately -- histamine
secondary - synthesis is activated upon degranulation; prostaglandins/ leukotrienes broken from phospholipids.
- what are the effects of histamine, how are they mediated?
- -contraction of bronchial/intestinal smooth muscles
binding to H2 receptors on mast cells is negative feedback, inhibits degran.
- why are leukoriene/prostaglandin effects seen after histamine?
- degranulation induces their production from phospholipids.
longer lasting effects than histamine.
bronchoconstriction, vascular permeability.
- What does epinephrine do?
- increases cAMP levels; prevents degranulation
- 4 main symptoms of early asthmatic response:
increased endothelial permeability
- 2 main symptoms of late asthmatic response:
- -cell influx
- what are the steps of degranulation?
- 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
- 5 drugs for treating type 1 hypersens:
- Action of Antihistamine:
- blocks H1 and H2 receptors on target cells
- Action of Sodium cromolyn
- blocks ca2+ influx into mast cells
- Action of theophylline
- prolongs high cAMP levels; decrease is necessary for degranulation so this does not occur
- method of epinephrine in preventing Type 1 hypersens:
- stimulates caMP production
- Action of cortisone:
- prevents histamine production, stimulates cAMP production
- is antihistamine alone sufficient to treat asthma? why?
- no. because leukotrienes/prostaglandins are also released; these are more potent in action than histamine.
more effective for hay fever
- what is the choice treatment for systemic anaphylaxis - what should you reach for first?
- EPI PEN -> epinephrine increases muscle tone fast and prevents continued vasodilation.
- Hallmark of Type 2 hypersensitvity:
- RED BLOOD CELL LYSIS
-Ab binding Ag on RBC surface
- 2 types of incompatibility that cause type 2 hypersens:
- ABO incompatibility of RBC
Allotypic incompatibility of RBC.
- What is the principle of a type 2 hypersens. response? What is it really?
- 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.
- 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
- Clinical manifestation of ABO incompatibility:
- Huge lysis of RBC via complement; Within hours can see:
-toxic bilirubin levels
-fever, chills, blood clots,
-acute tubular necrosis
- Clinical manifestation of allotypic incompatibility:
- fever, hemoglobinemia, bilirubin, mild jaundice, anemia. less severe response than ABO because IgG is less efficient in activating complement.
- What type of hypersensitivity causes hemolytic disease of the newborn?
- type 2
- hemolytic newborn disease is aka
- erythroblastosis fetalis
- what causes eryth. fetalis?
- 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.
- How does Rhogam work?
- Binds any rH antigen in mom's circulation just after delivery; prevents immune response or production of any antibody.
- Why do type 3 hypersensitivity responses develop?
- 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)
- what is a great example of a localized type 3 hypersensitivity reaction?
- Arthus reaction - subcutaneous or epidermal injection of Ag.
Immune complex forms; complement activates, inflammation occurs. Tissue damage, IgG response
-TB skin test, Insect bite
- what is the name for systemic Type 3 hypersensitivity?
- Serum sickness
- what is serum sickness caused by?
- large amounts of Ag-Ab complexes in the circulatory system --> wherever they deposit is where an inflammatory response will develop with much tissue damage.
- what can induce serum sickness?
- injection of antibody from another species (horse antiserum)
- what autoimmune diseases, drug reactions, or infectious diseases are examples of type 3 response
post strep glomerulonephritis
- manifestation of type 3 hyp in lupus:
- red face -> small arteries are damaged by Ab/Ag complexes deposited in the kidney.
- Why does glomerulonephritis develop in type 3 hyp?
- Circulatory Ag-Ab complexes are deposited in the basement membrane; chemotactic factors call inflamm. response resulting in tissue damage.
- what type of hypersens. response occurs after insect bite in a sensitive person?
- initially type 1 -> crosslink of IgE
but 4-8 hrs later, Type 3 -> edema, buildup of pus, etc!
- what is the major difference between type 3 and type 4 hypersens. cells recruited?
- Type 3 calls up neutrophils
Type 4 calls up macrophages.
- How is it that Type 4 hypersens. is INNATE and NONSPECIFIC, but it's CELL-MEDIATED?
- Starts off by activated Th cells. They secrete cytokines that tell monocytes to adhere to endothelial cells, extravasate into tissues and differentiate into Macrophages.
- When is DTH good, and when is it bad?
- 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
- 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.
- What type of response results in Mycobacterium Tuberculosis infections?
- DTH --> tubercle forms --> this is a huge granuloma of macrophages surrounding the infected cell. causes lung tissue damage.
- what are the 2 APC in DTH?
- langerhans cells
- what type of bacteria is DTH especially effective in combating?
- intracellular --> antigen is presented on MHC2 and activates Th cells; subsequent exposure causes cytokine release and inflammation
- what type of hypersensitivity is induced during a TB skin test?
- Type 4; injection of bacterium antigen causes release of cytokines and influx of macrophages.
- cytokines secreted by Th cells in DTH:
- IFN-y, TNF-a/B, IL-2, Chemokines
- What is the effect of activating macrophages?
- 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.
- what types of substances cause contact dermatitis?
- chemicals, nickel, hair dye, poison oak/ivy
- what is contact dermatitis?
- small molecules complex w/ skin protein;
after phagocytosis of complex, it's presented as Ag on APC. Activates Th1 cells for DTH response.
- Role of TNF-a in type 1 hyp:
- -secondary mediator that stimulates chemotaxis of neutrophils and eosinophils;
-contributes to systemic anaphylactic shock
- what do the early and late responses of asthma generally consist of?
- early: histamine/leukotriene/prostagl.
late: cytokines (IL-4,5,6, Eosin chemotactic factor, PAF) to increase endothelial CAMS and recruit inflammatory cells
- 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
- WHY is IgE the mediator of Type 1?
- PAtient suffers regulatory defects for IgE;
nonparasitic antigens can stimulate inappropriate activity of IgE.
You must Login or Register to add cards