Hypersensitivty part 2 lecture 9 Flashcards
Type III hypersensitivity
involves immune complexes formed from antibody and soluble antigen complexes which deposit in tissue
complement activated
neutrophils attracted to the area
cause local damage
involves IgG or IgM antibodies that react with soluble antigens to form immune complexes that are deposited in tissues.
consequence: complement and Fc mediated inflammation which leads to tissue damage
type III reactions can be systemic or localized
immune complex deposition
mechanisms of type III reactions
complement and FC receptor mediated inflammation
site of deposition of immune complexes lead to complement and Fc receptor mediated recruitment and activation of inflammatory cells, vasculitis.
in addition platelet aggregation occurs and leads to microthrombus formation.
immune complexes as trigger for increasing vascular permeability
immune complexes act on basophils and platelets to produce vasoactive amine release
amines cause endothelial cell retraction and increase vascular permeability
deposition of immune complexes
kidneys, joins, and small vessels, heart, and skin
types of antigens: infectious agents, innocuous substances, self antigen, persistence of ag facilitates IC formation
what makes immune complexes deposit?
size: large immune complexes are cleared. Small immune complexes are formed that do not fix complement and do not get cleared in complement
other variables
charge of the immune
class of immune complex
antigen characteristics
disease assocations
associated with many human diseases.
serum sickness
drug reaction
prominent rheumatic disese: rheumatoid, lupus, post streptococcal GN, and polyarteritis nodosum
serum sickness
antigen antibody complexes rom in circulation and deposit in tissues
complement levels in serum derease due to activtion
eventually excess (free ) antibody limits formation of complexes.
SX: rash, fever, arthralgia or arthritis
type III vs type II
type III circulating immune complexes. Deposition in tissue. Lumpy and bumpy immunofluorescence pattern
type II: circulating antibody to tissue. Linear immunofluorscence pattern.
pathologic lesions
lesions occurs in vessels (vasculitis), kidneys (glomerulonephritis), joints (arthritis)
chronic immune complex disease
repeated antigen exposure
results in formation of immune complexes which deposit in many tissues, see in many tissues
see in many autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus
drug reaction (serum sickness)
a type of serum sickness caused by hypersensitivity to an intravenous injection of drug
penicillin most commonly implicated although many drugs
caused by drug specific immune complexes
small drug molecules may serve as haptens that bind to serum proteins then develop antibody response either to the hapten or the hapten protein conjugate
rheumatoid arhtirits
autoimmune disease characterized by inflamed synovium
role of rheumatoid factor
IgM which has specificity for determinants on the Fc portion of ht patients own IgG
this IgM antibody is called rheumatoid factor and is deposited in joints
also has a type IV component
lupus
chronic inflammatory disease targeting mainly joints, kidneys, heart, skin and lung.
immunologic features: auto antibodies to multiple nuclear antigens including double stranded DNA.
Antigen/antibody complex damage tissues by activating complement and by engaging Fc receptors on immune cells expressing these receptor
Post strep glomeruloephrtis
associated with infection group A strep
immunogloic features: immune complexes deposit in the lipid bilayer of the glomerular basement membrane. ACtivation of the classical complement pathway leads to damage to basement membrane
abrupt onset of symptoms 1-4 weeks after infection leads to dark or smoky colored urine
Localized type III reaction: arthus reaction
skin reaction which shows classic finding of Type III reaction
antigen injected intradermally in the presence of preformed antibody
get area of tissue necrosis and caused by antibody excess. Results from immune complex deposition. tetnus and diptheria
measurement of immune complexes
measure levels of complement
will be decreased with active deposition of immune complexes. Simple test. readily available. indirect measure.
treatment of type III hypersensitivity
immunosuppression for reactions against self antigen
antigen avoidance
type IV hypersensitivity: T cell mediated
describe all hypersensitivity reaction which took more than 12 hours to develop
Delayed type hypersensitivity
include classic DTH reaction and T cell mediated.
transferred by cells, not serum
Type IV 2
reaction is initiated by antigen specific TH1 cells
activated t cells and macrophages are the major cellular mediators of these reactions
cytokines are very important in amplifying and continuing the response
CD8 t cells- mediate direct killing
hallmarks of a type IV reactions
delay in time required for the reaction to develop to re exposure to antigen
the recruitment of macrophages as opposed to neutrophils
extensive tissue damage
association with cytokines
Important in killing viruses and tumor antigens: destroy target cells by CD8 cells
lysis of targets cells are specific and dependent on Class I HLA antigens.
target antigens
innocuous environmental antigens- often seen in contact dermatitis
self antigens: associated with autoimmune disease
intracellular pathogens that are hard to clear: mycobacterium
disease associations type IV
contact dermatitis
autoimmune diseases: multiple sclerosis, type I diabetes, rheumatoid arthritis
graph rejection
tumor immunity
infectious diseases manifesting delyaed hypersensitivity
many due to infectious agents: mycobacteria, protozoa, and fungi
diseases: TB, leprosy, leishmaniasis, listeriosis, deep fungal infection, sarcoidosis, and parasitic infections
viral hepatitis
contact hypersensitivity
allergen is placed in contact with the skin
area of crusting with erythema at the site of contact with the allergen
reaction is maximal at 48 hours
induced by haptens such as nickel and chromate
bind to normal skin proteins and ecome antigenic
commonly caused by rubber, poison oak and ivy.
contact hypersensitivity 2
sensitizing substance is often a hapten that complexes with skin proteins (carrier)
target organ is skin
antigens: substances like nickel, poison ivy, drugs
histologic features
langerhans’ cells are the principal antigen presenting cells
cytokines are crucial in mediating and continuing the reaction
test for detecting type IV reactions Patch test
an in vivo test to assess person’s reactivity to contact antigens
sensitizing antigen is place on the skin and convered with dressing
examined 48-72 hours later
testing for detecting type IV reactions DTH test
an in vivo test to assess immunologic memory for specific antigens
antigen injected intradermally
reaction peaks at 48 to 72 hours
positive reaction only means person has been sensitized
a nonreactive person is called anergic
DTH tests
measure induration, not simply erythema
antigens: PPD (purified protein derivative from mycobacterium tuberculosis), candida, teatanus, diphtheria
positive DTH skin test only tells you that there are sensitized t cells present
gives you no information on whether the disease is active
tuberculin type hypersensitivity
classic DTH response
occurs as an erythematous indurated lesion
maximal 48-72 hours after challenge with tuberculin antigen in a sensitized individual
antigen applied intradermally
TB test from blood
several tests now available for testing for TB exposure on whole blood
test for release of interferon gamma after incubation with TB antigen
called interferon gamma release assays
2 are fda approved: Quantiferon - TB gold in tube test; T spot
IFGA
does not differentiate past from present infection
just demonstrates the presence of sensitized t cells
need to coreelate with clinical presentation to determine if the disease is active
what are advantages of IGRAs?
requires a single patient visit to conduct the test
results can be available within 24 hours
does not boost responses measured by subsequent tests
prior BCG (bacillus calmette-guerin) vaccination does not cause a false positive IGRA test result; this is seen with in vivo DHT PPD testing
What are limitations of IGRAs?
samples must be processed within 8-30 hours after collection while white blood cells are still viable
eroros in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of IGRAs
limited data on the use of IGRAs to predict who will progress to TB disease in the future
Other things to consider
limited data on the use of IGRAs for children younger than 5 years, persons recetnly exposed to M. Tuberculosis, immunocompromised persons, serial testing
test may be expensive
appearance of the three main injection initiated skin tests
Wheal and flare: raised with well defined edge; soft wheal ~15mins
arthus reaction: larger reaction site and less defined edges ~5-12 hours
DTH reaction: Red undurated lesiion peaks at 48 to 72 hours
anergy
inability to react to common skin antigens
this is tested by performing DTH skin tests, using a panel of commonly encountered antigens
disease associataed with anergy
congenital imunodeficiencies; secondary or acquired immunodeficiency such as AIDS
autoimmune diseases: rheumatoid arthritis
malignancies: hodgkin’s disease, lymphoma, chronic lymphocytic leukemia
sarcoidosis
infections: influenza, mumps, measles, tb, leprosy, and others
treatment of type IV hypersensitivity
antigen avoidance
anti inflammatory drugs
immunosuppression for reactions against self antigens
