Hypersensitivty part 2 lecture 9 Flashcards Preview

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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



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



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



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


infections: influenza, mumps, measles, tb, leprosy, and others


treatment of type IV hypersensitivity

antigen avoidance

anti inflammatory drugs

immunosuppression for reactions against self antigens