Immune Injury Flashcards
what does immune response protect against?
invaders and toxins
hypersensitivity reactions
excessive/inappropriate immune response
types of hypersensitivity reactions
types I, II, III, IV
autoimmune disorders
misdirected immune response
immunodeficiency disorders
deficient immune respone
type I hypersensitivity aka
anaphylaxis, immediate hypersensitivity
type I hypersensitivity results from what
antigen binding to IgE on mast cell/basophil surfaces
“allergen”
type I hypersensitivity-what happens after antigen binds to IgE?
degranulation with histamine (and other mediator) release into tissues
type I hypersensitivity reaction time
reaction immediate and over within hours
type I hypersensitivity-what must happen before allergy manifests?
mast cells/basophils must be “primed”
type I hypersensitivity-what does first exposure result in?
1st exposure results in IgE production and binding to mast cells/basophils
type I hypersensitivity-what does subsequent exposure result in?
mast cell/basophil degranulation
type I hypersensitivity-what is the most prominent mediator?
histamine
type I hypersensitivity-what does histamine produce?
vasodilation
increased capillary permeability
bronchial smooth muscle contraction
type I hypersensitivity-what does IgE normally protect against?
parasitic worm infections
type I hypersensitivity-what manifestations are designed to expel a worm?
itching sneezing coughing vomiting diarrhea
type I hypersensitivity-what do mast cells also release (besides histamine)?
eosinophil and neutrophil chemotactic factors
type I hypersensitivity-acute phase
seconds to minutes after exposure
-histamine release with immediate/transient effects
type I hypersensitivity-late phase timeline
hours after acute phase
type I hypersensitivity-late phase steps
infiltration of tissues by lymphocytes and eosinophils
release of leukotrienes (C4, D4, E4) and prostaglandins (D2)
similar effects to histamine but prolonged
type I hypersensitivity local reactions examples
generally not dangerous
urticaria (hives)-wheal and flare effect of histamine (e.g. mosquito bite)
allergic rhinitis (hay fever)-sneezing, itchy eyes from airborne allergies
allergic (extrinsic) asthma-bronchoconstriction from inhaled allergens
type I hypersensitivity local reactions-how to treat
treated with antihistamines or steroids
type I hypersensitivity generalized reactions importance and examples
are life threatening
anaphylaxis, penicillin injections, certain foods
type I hypersensitivity generalized reactions sx
whole-body vasodilation/capillary leak
anaphylactic shock
edema of tongue/larynx can obstruct airway
intense bronchoconstriction
type I hypersensitivity generalized reactions tx
epinephrine mainstay of treatment
-vasoconstrictor and bronchodilator
food allergies
are real
local or systemic type I reactions
200 deaths/year
eggs, nuts, shellfish
what causes histamine release in everyone?
chocolate, strawberries, codeine
non-IgE mediated
those with greater release are “allergic”
testing methods for allergies
skin testing better (prick, injection) used in diagnosis
wheal and flare response
radioallergosorbent test (RAST)
detects IgE, less sensitive and specific
type II hypersensitivity definition
antibodies bind to “fixed” antigens present on cell membranes
-IgM or IgG mediated
cell bearing the antigen then destroyed (or function altered)
type II hypersensitivity mechanisms of destruction
complement activation and cell lysis/phagocytosis
antibody-dependent cell cytotoxicity
complement- and antibody-mediated inflammation
type II hypersensitivity what can also occur?
antibody-mediated cell dysfunction
what is type II hypersensitivity pathogenesis of?
many autoimmune diseases
type II hypersensitivity complement activation
Ag-Ab complex fixes complement
target cell lysed by MAC
Ab and/or C3b act as opsonins
target cell engulfed
type II hypersensitivity-hemolytic transfusion reactions
ABO incompatibility
ready-made IgM
hemolytic disease of newborn
requires sensitization and involves IgG
type II hypersensitivity antibody-dependent cell cytotoxicity
involves elements of innate and adaptive immunity
Ab bound to target cell attracts NK cell
NK cell binds Ab and induces apoptosis
examples of type II hypersensitivity antibody-dependent cell cytotoxicity diseases
hashimoto’s thyroiditis
autoimmune adrenalitis
type I diabetes mellitus?
type II hypersensitivity complement and antibody-mediated inflammation
Ag-Ab complex fixes complement
C3a/C5a attract neutrophils
neutrophils bind Ab
acute inflammation occurs
type II hypersensitivity-goodpasture’s syndrome
Ab binds to lung and glomerulus basement membranes
acute inflammation destroys alveoli and nephrons
example of type II hypersensitivity injury
transfusion-related lung injury (TRALI), plasma transfusion
type II hypersensitivity-antibody-dependent cell dysfunction
Ab binds cell membrane receptor
blocks or activates receptor
type II hypersensitivity-myasthenia gravis
Ab binds and blocks ACh receptor at neuromuscular junction
prevents muscle stimulation
type II hypersensitivity-graves’ disease
Ab binds and stimulates TSH receptor at thyroid gland
produces hyperthyroidism
type III hypersensitivity
antibodies (IgM and IgG) bind to soluble antigens in plasma when each present in the right proportions
what is formed during type III hypersensitivity?
Ag-Ab complexes (“immune complexes”) that precipitate
type III hypersensitivity-where do immune complexes?
blood vessel walls (close by)
glomerulus (proteins are more concentrated)
skin (precipitation faster due to cooler temperature)
lungs (same as skin)
synovial membranes
type III hypersensitivity what do immune complexes do?
fix complement and induce inflammation
type III hypersensitivity manifestations dependent on what?
manifestations dependent on location of immune complex deposition
examples of type III hypersensitivity manifestations
vasculitis
glomerulonephritis
arthritis
type III hypersensitivity examples
neutrophils have nothing to attack (but attack anyway)
systemic lupus erythematosus
serum sickness
malaise hours after immunization
what is involved in type IV hypersensitivity?
no antibodies, T cells
what happens in type IV hypersensitivity?
Th cells are presented Ag by APC (with MHC II)
Th then activate Tc cells and macrophages
Th cells selectively destroy cells bearing same Ag with MHC I
angry macrophages destroy normal tissues as well
no complement involved
type IV hypersensitivity what could activated T cells also destroy?
activated T cells may destroy normal cells bearing similar Ag to one provoking response
what is type IV hypersensitivity great for?
eliminating parasite-infected cells
viruses
mycobacteria
what can type IV hypersensitivity also eliminate?
some tumor cells
what is type IV hypersensitivity a mechanism of?
one mechanism of acute transplant rejection
examples of type IV hypersensitivity
contact dermatitis (nickel, poison ivy, etc.) tb skin test
type IV hypersensitivity tb skin test
extract of M. tuberculosis injected into dermis
if sensitized (previously exposed), type IV reaction occurs
-memory Th and Tc cells spring to life
-macrophages recruited
angry macrophages destroy some normal tissue at site
“lump” of fibrin macrophages at 48-72 hours
don’t test someone with known exposure
anergy
defects in Th cell number or function can inhibit type IV response
examples of causation of anergy
AIDS, sarcoidosis, wasting diseases
how to test for anergy?
skin tests with common antigens candida, mumps, tetanus often done in conjunction with TB test people with normal T cell function should have a bump no bump=anergic
transplant rejection
donor tissues/organ seen as foreign by recipient with immune destruction
matching done on basis of synergy between donor/recipient HLA antigens
autograft
donor and recipient are the same
isograft
donor and recipient are different but have same genes
allograft
donor and recipient are different and have different genes
xenograft
donor and recipient are different species
what is required for graft survival with allografts and xenografts?
immunosuppression
transplant rejection-hyperacute rejection
due to premade (or almost immediately made) antibodies
antibodies directed against HLA antigens on the graft
type II and III injury occurs
transplant rejection-acute cellular rejection
months or years after transplantation
mediated by T cells, type IV injury
transplant rejection-acute humoral rejection
months or years after transplantation
mediated by antibodies with both type II and III injury
why is it important to distinguish cellular transplant rejection from humoral?
they are treated differently
graft vs. host disease
can occur when immune cells are transplanted into immune-disabled recipient
-bone marrow, liver
graft v. host disease-what cell attacks antigens of recipient?
T cells (probably NK) in graft attack HLA antigens of recipient
what cells are most commonly injured in graft vs. host disease?
epithelial cells
skin-exfoliative dermatitis
GI tract-bloody diarrhea, malabsorption
liver (biliary ducts)-jaundice
autoimmune disease
the immune system attacks its owner
loss of tolerance
is autoimmune disease localized?
it can be localized or affect many organs?
how are self antigens attacked in autoimmune disease?
the same mechanisms as protective immunity or hypersensitivity
type I rare
what are autoimmune diseases typically linked to?
a particular HLA I (A, B or C) or HLA II (DR) antigen but not both
what is the strongest autoimmune disease and HLA link?
HLA B27 and ankylosing spondylitis
which associations for autoimmune disease are more common in men?
HLA I
which associations for autoimmune disease are more common in women?
HLA II
what type of diseases are autoimmune diseases?
diseases of exacerbations and remissions
what are systemic autoimmune diseases known as
collagen vascular diseases
examples of autoimmune collagen vascular diseases
SLE, RA, JRA, ankylosing spondylitis, scleroderma, Sjogrens, etc. etc.
what are many autoimmune diseases characterized by?
the presence of antibodies
SLE
systemic lupus erythematosus
systemic lupus erythematosus
common, mostly affects young women, slightly more common in blacks
unknown etiology
what kind of involvement in SLE?
systemic involvement, exacerbations and remissions
how is SLE diagnosed?
critical criteria
what autoantibodies are present against antigens in most cells with SLE?
Anti-dsDNA Anti-Ro/SSA (an RNA polymerase) Anti-Smith (nuclear proteins) Anti-blood cell, anti-neuron, anti-phospholipid many more
variable presentations in SLE
fever, skin changes, arthritis, kidney damage, inflamed serous membranes, mental changes, vasculitis, blood cytopenias
what is SLE often a diagnosis of?
exclusion
SLE smell vessel vasculitis
type III injury
accelerated atheroslerosis
SLE glomerular injury
type III injury
decreased renal function
SLE skin lesions and photosensitivity
malar rash
discoid (demarcated) rash
SLE arthritis
type III injury
rarely mutilating
SLE serositis
pleuritis, effusions and scarring
pericarditis effusions and scarring
SLE nonbacterial verrucous endocarditis
libman-sacks endoarditis
any valve, most often mitral
SLE related problems
blood cytopenias
fatigue, mental changes
hypercoagulability and strokes
SLE diagnosis
often delayed often diagnosis of exclusion new criteria 2019 positive ANA greater than or equal to 10 points from different domains
SLE death
death usually from kidney failure, infection heart or brain damage
