Hypersensitivities Flashcards
What are the two ways hypersensitivities can arise?
Uncontrolled or abnormal response to foreign Ags
Autoimmune response against self Ags
What are the basic characteristics of a Type I hypersensitivity?
Mediated by IgE, extremely low level of Ag triggers
Results from actions of mediators secreted by mast cells
Allergies
What are the basic characteristics of a Type II hypersensitivity?
Mediated by Abs (except IgE) that bind TISSUE Ags
Cause complement dependent tissue injury
- IgG and IgM antibodies activate complement system causing production of C3a and C5a
- byproducts recruit leukocytes and induce inflammation
Abs opsonize cells leading to phagocytosis through FcRgamma or CR1 receptors –> release of inflammatory mediators= ROS and lysosomal enzymes
What are the basic characteristics of a Type III hypersensitivity?
Mediated by CIRCULATING Ag-Ab complexes that are formed in blood and deposited in vessels (kidney, lungs, liver)
Cause complement dependent tissue injury in vessel walls via Fc receptor through C5a and C3a
Complement activation and recruitment of leukocytes
Pathological features reflect site of immune complex deposition not source of antigen
What are the basic characteristics of a Type IV hypersensitivity?
Mediated by T cells (cell mediated NOT Abs)
Results from inflammation caused by cytokines produced by CD4+ Th1 and Th17, macrophages, or killing of host cells by CD8+ CTLs
What are important mast cell mediators in Type I hypersensitivity? What do they do?
Histamine= dilation of small vessels, increase vascular permeability Proteases= cause local tissue damage Prostaglandins= vascular dilation Leukotrienes= stimulate prolonged smooth muscle contraction Cytokines= induce local inflammation (late phase)
What happens during the primary exposure to an allergen?
Th2 cells are activated and secrete IL-4
Istopype switching mediated by CD40/CD40L (IgM -> IgE)= plasmas cells make IgE to allergen
IgE bind to FcRepsilong (CD23) on mast cells in tissues and basophils
What happens during secondary allergen exposure?
Ag-dependent crossing linking of membrane bound IgE causes activation of mast cells and release of inflammatory mediators
What is the immediate phase of an allergic reaction?
vascular and smooth muscle reactions within minutes –> vasodilation, congestion, and edema
Via degranulation
What is late-phase reaction of an allergic reaction?
Inflammatory infiltrate rich in eosinophils, neutrophils, and T cells
What happens in asthma? Is it local or systemic?
Airway obstruction caused by the release caused by the release of inflammatory mediators from mast cells upon –> increased capillary permeability and spasmodic contraction of smooth muscle of bronchi
Decrease in size of bronchial lumen= shortness of breath
non immunologic stimuli= cold and exercise
Local
What happens in anaphylaxis? Is it local or systemic?
exposure to allergens (normally in large amount ie. food) cause massive release of vasoactive amines and cytokines through WHOLE BODY –> contraction of smooth muscle and vasodilation of capillary endothelium
Blood pressure drops= vascular shock
Contraction of smooth muscles in the bronchi and bronchioles
Systemic
What is allergen-specific immunotherapy (SIT)
Administration of increasing dose of allergen to desensitize response –> increase threshold for mast and basophil activation
Goal is peripheral T cell tolerance of Ag by changing Th1/TH2 ratio
Th1= ifn-gamma which causes induction of IgG and IgA so making Ab to same Ag but different class and will compete with IgE so decreased histamine response
Generation of induced FOXP3+CD4+CD25+ Treg
What is the mechanism of Graves Disease?
Type II
Antibodies stimulate the activity of TSH receptor even in the absence of hormone –> hyperthyrodism
What is the mechanism of Myasthenia Gravis?
Type II
Antibody binds to ACh receptor inhibiting binding of Ach
What type of hypersensitivity mediates hemolytic reactions?
Type II
Example: ABO blood transfusion reactions
- body naturally produce ABO Abs via interactions with food aka micro flora producing IgM
- cross reactivity
What happens when a mom is Rh-neg and the baby is Rh-pos
Type II
During delivery Rh antigens enter mother’s circulation and she produces anti-Rh antibodies so when she has a second child these cross the placenta and destroy fetal RBCs
Can treat with anti (anti-Rh) immunotherapy
All involves Factor D
What is the hapten (ex. penicillin) model of drug induced hemolytic anemia?
Drugs binds directly to erythrocyte surface and induces an anti drug antibody
Hemolysis by complement or phagocytosis
Stop using drug and condition improves
What is the immune complex formation (ex. quinidine) model of drug induced hemolytic anemia
Antibodies form immune complexes with the drug which bind to erythrocyte surface through CR1
Hemolysis by complement
treat= immunosuppression of plasmapheresis
What is the autoimmune (ex. methyldopa) model of drug induced hemolytic anemia
Induces an antidrug antibody that cross-reacts with Rh antigen
Hemolysis by phagocytosis
What is autoimmune hemolytic anemia?
Opsonization and phagocytosis of erythrocytes by targeting erythrocyte membrane proteins (Rh blood group ag, I ag )
Type II
What is autoimmune thrombocytopenic purpura?
Opsonization and phagocytosis of platelets by targeting platelet membrane proteins (gpIIb/IIIA integrin)
Causes bleeding
Type II
What is Goodpasture’s syndrome?
Complement and Fc receptor mediated inflammation by targeting non-collagenous protein in basement membranes of kidney glomeruli and lung alveoli
Nephritis and lung hemorrhage
Type II
What is pemphigus vulgaris?
Antibody mediated activation of proteases, disruption of intercellular adhesions by targeting proteins in intercellular junctions of epidermal cells
Causes skin vesicles (bullae)
Type II
