Hypersensitivty part 2 lecture 9 Flashcards by Benja Lamyaithong

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

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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.

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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

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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

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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

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other variables

charge of the immune

class of immune complex

antigen characteristics

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disease assocations

associated with many human diseases.

serum sickness

drug reaction

prominent rheumatic disese: rheumatoid, lupus, post streptococcal GN, and polyarteritis nodosum

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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

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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.

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pathologic lesions

lesions occurs in vessels (vasculitis), kidneys (glomerulonephritis), joints (arthritis)

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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

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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

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rheumatoid arhtirits

autoimmune disease characterized by inflamed synovium

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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

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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

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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

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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