Hypersensitivity Flashcards
four types of hypersensitivity
type I: allergy and atopy
type II: antibody-mediated
type III: immune complex-mediated
type IV: delayed-type
type I hypersensitivity is mediated by
mast cells
sensitization phase
IgE antibody production and binding to Fc receptors on mast cells
activation phase
on second exposure to antigen, antigen cross-links membrane bound IgE molecules
effector phase
activated cells degranulate releasing pre-formed mediators and release newly synthesized lipid mediators
localized allergic symptoms
late phase
~48 hours later
cytokines and chemokines newly produced by mast cells recruit and activate other leukocytes
histamine
generated by decarboxylation of the amino acid histidine
most histamine is stored in
mast cells
histamine binds to
histamine receptors
the action of histamine on a cell depends on
the receptor and the cell type
exposure in gastrointestinal tract
increased fluid secretion and peristalsis - vomiting and diarrhea
exposure in airways
decreased diameter and increased mucus secretion - congestion and airway blockage
exposure to blood vessels
increased blood flow and permeability -swelling, more protein in tissues (can increase effector response)
reducing symptoms of Type I hypersensitivity
avoiding exposure
asthma meds
anti-histamines block histamine receptors on target cells
corticosteroids
epinephrine
desensitization
how does desensitization/hyposensitization therapy work
decreases IgE production by shifting antibody class to IgG and IgA
type II hypersensitivity
antibodies bind antigens on surface of cells
usually foreign cells (donated blood, transplanted organ (HLA))
activates NK cells by Fc receptor binding
activation of complement
can be autoimmune
type III hypersensitivity
immune complexes
large amounts of small, soluble antigen create very small and soluble immune complex
evade clearance and can deposit in tissues
activate complement and lead to recruitment of neutrophils
excessive degranulation damages tissues - free radical generation
passive immunity
provides strong, immediate, short-lived protection
-maternal antibodies
-convalescent serum
- therapeutic monoclonal antibodies
active immunity
develops slowly, sometimes requires multiple exposures
-natural infection
-vaccination
long lasting and has memory
maternal antibodies
trans-placental IgG during gestation
IgA in breast milk coats mucosal surfaces
window of susceptibility
anti-toxins immunoglobulin
anti-serum contains antibodies that bind to and inhibit bacterial exotoxins
rapid acting and life-saving for diphtheria and tetanus toxin - protection is temporary
originally generated in horses
type II reactions cause pathology in what autoimmune diseases
systemic lupus erythematosus - antibodies binding DNA or RNA from leukocytes
rheumatoid arthritis - immune complexes in the joints
immune complexes in skin lead to
arthus reaction
what causes farmer’s lung
complexes in lungs from Actinomycetes spores in hay
allergic alveolitis
molecular mimicry
can stimulate Type III reactions against host tissues - post group A streptococcal disease after S. pyrogenes infection
serum sickness
immune complexes form in blood from foreign proteins
immune complexes accumulate in blood vessel walls, joints and kidneys
this is why antibody therapies are humanized
type IV delay type hypersensitivity
takes a while for response to initiate
requires T cells activation and recruitment of other cells
cell mediated - no antibodies required
usually Th1 response but can be Th17 as well or be driven by CD8+ T cells
can cause extensive tissue damage if prolonged
type IV hypersensitivity - sensitization
APC endocytosis/phagocytosis antigen and presents on HLA II to helper T cells
in response to intracellular bacteria
helper cells differentiate and clonally expand to generate effector and memory subsets
Th1 cells responsible
type IV hypersensitivity - effector phase
Th1 memory cells in tissues encounter APC displaying same activating epitope
activated memory TH cells release cytokines that attract and activate macrophages and other inflammatory response cells, which clear the infected, epitope-bearing cells
24=72h needed for macrophages and T cells to migrate to and proliferate at the antigen site
responses not visible until 24-72h after encounter
