Hypersensitivities Flashcards
Hypersensitivity
injurious or pathologic immune responses
occurs in two situations:
disregulation/uncontrolled
immune response directed against self
Immediate hypersensitivity
Type I
IgE and mast cell mediate reaction to certain antigens that causes rapid vascular leakage and mucosal secretions, often followed by inflammation
ALLERGIES (atopic), asthma
involves TH2 cells
has both immediate hypersensitivity phase and latent-phase reaction
Steps in immediate hypersensitivity
activation of Th2 cells by binding to B cell that has been exposed (first time) to allergen
antigen activation of TH2 cells and stimulation of IgE class switching in B cells (b/c of IL-4 and IL-13 produced by TH2 cells)
binding of the IgE to Fc receptors on mast cell
note IgE also activates eosinophils
Subsequent exposure to allergen/antigen
release of mast cell mediators
IgE
1/2 life in serum is 2 days
1/2 life bound to FcR on Mast cells and basophls is 10 days
late-phase reaction
inflammatory component of immediate hypersensitivity that occurs several hours after subsequent antigen/allergen exposure
responsible for the tissue injury that results from repeated bouts of immediate hypersensitivity
mediate by mast cell mediator and cytokines that recruit neutrophils and eosinophils to the site of the reaction
what does IgE promote
promotes TH2
how is immediate hypersensitivity a T-cell dependent adaptive immune response ?
reliant on Th2 cells to produce IL-4 and IL-13 that switch to IgE
Classical antigens
Constant challenge b/c you can’t remove allergy to a antigen
inhaled in very low doses
eaten in large doses
immunological priming
primed the system to make more memory cells
making more plasma cells with IgE
so making more IgE higher affinity binds to antigen…. loading of mast cell
what is needed in order to activate mast cell?
must cross-link IgE’s in order to get activation of cell
Clinical syndromes causes by Type I hypersensitivities
Allergic rhinitis
food allergies
bronchial asthma
Anaphylaxis
late phase reaction
part of type I immediate hypersensitivity
occurs 4-6 hours after initial type I reaction
persists 1-2 days
infiltration of PMN’s, eosinophils, macrophages, lymphocytes
due to mast cells releasing TNF alpha and IL-1 which leads to increased expression of adhesion molecules on endothelial cells
mast cells release IL-8, IL-3, IL-5, GM-CSF–> hematopoietic
antibody mediated (type II) hypersensitivity
initiating antigen is a surface
IgG, IgM, FcR, C’ SURFACE antigen
can happen by anti-tissue antibody:
- antibody/antigen complex activates C’ (classical)
- antibody/antigen complex interacts with FcR’s on effector cells (ie. neutrophil)
- alternative C’ pathway C3b on surface
effects of antibody mediated hypersensitivity
local inflammation and tissue injury
antibodies bound to Fc receptors on effector cells induce effector cells to release ROS and lysosomal enzymes that damage the tissues
complement cascade can “poke holes” by the MAC and also the away parts can induce inflammation by recruitment
hemolytic disease of the newborn
mother makes IgM b/c she sees the baby rh antigen during first pregnancy
class switches to IgG
during second pregnancy the mothers memory cells recognize another rh antigen in baby
mothers IgG attacks babies RBC’s
can treat with Rhogam which prevents B cell activaiton and memory cell formation in the first place
RhD antigen in babies is most common
Transfusion reactions
?? slide 25 hypersensitivities
Autoimmune Hemolytic anemias
see garrisons CSI
Myasthenia gravis
extreme muscle weakness
make self antibodies to acetylcholine receptors
antibody inhibits acetylcholine receptor so acetylcholine cannot activate
Type III hypersensitivites
Immune complex
IgG/IgM/FcR/C’ SOLUBLE antigen
immune complexes of Ab/Ag/C’ in circulation
complexes deposit in tissue–> leads to pathology
three groups of pathology:
- persistent infections
- autoimmune diseases
- inhalation of antigen
CR1
on RBC’s
binds immune complexes and brings them to the liver and spleen for removal
when we have more IC’s that can be cleared….
start to bring in basophils and platelets and IC’s act on them, which produce vasoactive amines (histamine)
this causes endothelial cell to get leaky, pull apart, and creates an area where the IC can settle into
increase in vascular permeability
what happens after the IC deposits into the blood vessel wall?
induces platelet aggregation and C’ activation
microthrombi form on the exposed collagen of the basement membrane of the endothelium
neutrophils are attracted to the site by the C’ products and lead to further damage of the area
Increases in blood pressure and vascular turbulence increases complex deposition
thrombocytopenia
desensitization
allergy shots
given small amounts of antigen and trying to build IgG to block bind antigen before it binds IgE
can cause arthus reaction in which there is a formation of marked edema and hemorrhage 4-10 hours after allergy shot due to Ag/Ab precipitation
can lead to necrosis
farmer’s lung
serum sickness
induced by systemic administration of a protein antigen, which elicits an antibody response and leads to formation of circulating IC’s
the individual makes antibody responses against the injected foreign antibodies
the IC’s deposit in blood vessel walls and tissues
leads to arthritis and glomerulonephritis, systemic vasculitis
type IV hypersensitivities
delayed type hypersensitivities
antigen specific T cells are the effector cells
result from inflammation caused by cytokine produced by CD4 T cells (Th1 mostly) and/or killing of host cells by CD8+ CTL’s
DTH
DTH reactions are manifested by infiltrates of T cells and blood monocytes in the tissues, edema and fibrin deposition caused by increased vascular permeability in response to cytokines produced by CD4 + T cells, and tissue damage induced by leukocyte products, mainly macrophages, activated by the T cells
representative immunopathologic disease for DTH (type IV)
contact dermatitis
granuloma formation
Three types of DTH
Contact
Tuberculin
Granulomatous
Contact DTH
48-72 hours reaction
clinical appearance is eczema
antigen is epidermal, reaction occurs at point of contact with allergen
two stages:
sensitization (10-14 days)
elicitation
Granulomatous DTH
21-28 days later
Sensitization stage of contact DTH
takes 10-14 days
hapten forms (poison oak antigen + protein)
hapten taken up by langerhan cells
goes to lymph nodes and presents to CD4+ T cells
building effector memory cells
Elicitation stage of contact DTH
CD4 T cells recruited to site of contact
CD4 (Th1 mostly) secrete IFN-gamma and other proinflammatory cytokines that activate macrophages
Tuberculin
type of DTH
induced by soluble antigen
used to test for tuberculin skin test–> looking for recall response to previously encountered Ag
also can meaure someones cell-mediate immunity and see if someone has a response
Granulomatous DTH
usually results from persistence of bacteria or virus within macrophage of intracellular microorganisms able to resist macrophage killing or other particles the cells is unable to destroy
occurs with chronic infections associated with TH1 like responses
can also occur in the absence of infection (foreign body or non-immune)
Granulomatous reaction
persistance of antigen leads to differentiation of macrophage to epitheloid cells and the fusion to form giant cells.
granuloma formation is driven by T cell activation of macrophage and is dependent on TNF
chronic diseases manifest type IV granulomatous hypersensitivities
tuberculosis
leprosy
crohn’s
