TYPE III HYPERSENSITIVITY REACTIONS : jai matha di TYPE III HYPERSENSITIVITY REACTIONS DINESH YADAV Slide 2: 10/25/2008 DINESH YADAV 2 What are type III hypersensitivity reactions ?
DEF: Hyper sensitivity reactions, in which the tissue damage is produced due to the deposition of immune complexes in the tissues are called type III hyper sensitivity reactions.
Immune complexes in type III hyper sensitivity reactions induce inflammation either directly or by activating complement system, leucocytes that are recruited, produce tissue damage by release of lysozymal enzymes & generation of free radicals. cont.... Slide 3: 10/25/2008 DINESH YADAV 3 Types of type III hyper sensitivity reactions:
Immune complex disorders can be GENERALISED or LOCALISED.
If the complexes formed in circulation are deposited in many organs, it is generalized.
eg: serum sickness
If deposited in particular organ, such as kidney, joints etc, it is localised.
eg; arthritis when in joints. cont.... Slide 4: 10/25/2008 DINESH YADAV 4 Generalized immune complex disorders:
eg: serum sickness.
Serum sickness is the prototype of systemic immune complex diseases.
It was first observed by von pirquet.
He noted that some patients developed arthritis after treated for diphtheria with serum from horses immunized with diphtheria toxin.
He also observed that symptoms appeared more rapidly with repeated injections of serum.
He concluded that this disorder is due to the immune complexes formed by anti bodies to horse serum & horse serum proteins. cont... Slide 5: 10/25/2008 DINESH YADAV 5 Pathogenesis: divided in to 3 stages.
Formation of immune complexes in circulation.
Deposition of formed immune complexes in tissues.
Initiating inflammatory reactions at the site of deposition & tissue damage.
Formation of immune complexes in circulation:
Initiated by the introduction of foreign antigen, usually a protein.
In some conditions complexes are formed with self antigens. eg; systemic lupus erythematosis(SLE).
Interaction of antigen with immuno competent cells results in the formation of anti bodies to that antigens. cont.... Slide 6: 10/25/2008 DINESH YADAV 6 Antibodies are produced approx a week after introduction of antigen.
These formed antibodies are secreted in to circulating blood.
In the blood these antibodies react with antigens still present in circulation to form antigen-antibody complex or immune complex.
Mere formation of immune complex not imply presence of disease, immune complexes are formed during many immune responses & represent normal mechanism of antigen removal.
For a immune complex to be pathogenic, usually it has to be deposited in the tissues. cont... Slide 7: 10/25/2008 DINESH YADAV 7 FOREIGN ANTIGENS B CELL AND RECEPTERS PLASMA CELLS ANTI BODIES ANTIGEN-ANTIBODY COMPLEX VASCULAR ENDOTHELIUM Formation of immune complex in circulation Slide 8: 10/25/2008 DINESH YADAV 8 2.Deposition of formed immune complexes:
Deposition of immune complexes depends on:
Size of immune complex.
Functional status of mono nuclear phagocytic sys.
i. Size of immune complex:
Size is inversely proportional to pathogenicity. because, size of complex is directly proportional to its susceptibility to phagocytosis & elimination.
Large complexes are formed when antibodies are in excess & small complexes, when antigens are in excess.
ii.Mono nuclear phagocytic system:
If functional status of phagocytic system is not effective, immune complexes persists in circulation, which aids the deposition of complexes. cont... Slide 9: 10/25/2008 DINESH YADAV 9 iii. Vascular permeability:
For the deposition of immune complexes, vascular permeability must increase.
Vascular permeability is increased when complex binds to Fc receptors of inflammatory cells & triggers the release of vasoactive mediators & permeability enhancing cytokines
iv. Other factors:
a. charge on complex.
b. valency of antigen.
c. affinity of antigen to tissue. .
d. avidity of antibody.
e. structure of immune complex. cont.... Slide 10: 10/25/2008 DINESH YADAV 10 immune complex immuno competent cell with Fc receptor cytokines deposited immune complex deposition of formed immune complex Slide 11: 10/25/2008 DINESH YADAV 11 3.Initiating inflammation & tissue damage:
Once deposition completed, immune complexes induce inflammatory reactions & tissue damage by….
i. Activating complement cascade.
ii. Activating inflammatory cells.
iii. Aggregation of platelets.
iv. Activation of Hageman factor.
i. Activation of complement cascade:
If IgA antibodies are present in the complex, Complement cascade activates & produce inflammation by release of …. A. chemo tactic factors. B. anapylatoxins.
CHEMOTACTIC FACTORS aids migration of PMN& MONOCYTES.
ANAPYATOXINS (C3a&C5a) increases VASCULAR PERMEABILITY.
Role of complement system is observed by decrease of serum conc. in active phase of disease. cont.... Slide 12: 10/25/2008 DINESH YADAV 12 ii.Activation of inflammatory cells :
Leucocyte activation causes release of lysozymal enzymes such as proteases, collagenases, elastases etc which cause tissue damage.
Activated neutrophills produce oxygen-free radicals which also cause tissue damage.
iii. Activation of Hageman factor & iv.aggregation of platelets:
These two augment inflammation & aid formation of micro thrombi, causing ischemia & finally necrosis.
Eg: vasculitis if inflammation is produced in vessels.
Glomerulo nephritis if produced in renal glomeruli cont.... Slide 13: 10/25/2008 DINESH YADAV 13 stage of inflammation & tissue damage deposited immune complex anaphylatoxins activated leucocytes lysozymal enzymes fibrinoid necrosis aggregation of platelets chemotactic factors Slide 14: 10/25/2008 DINESH YADAV 14 Types of serum sickness:
i. Acute serum sickness. ii.chronic serum sickness
i.Acute serum sickness:
If single large dose of antigen is given, it self acts as primary dose and shocking dose & acute serum sickness develops.
Disease is self limiting. because, with rise of antibody production, complexes become larger &become more susceptible to phagocytosis & eliminated, thus all foreign antigens are eliminated.
ii. Chronic serum sick ness:
Chronic form results from repeated or prolonged exposure to antigen.. that is there should be continuous antigenemia.
eg: systemic lupus erethymatosis, which is associated with persistent antibody responses to auto antigens. cont.... Slide 15: 10/25/2008 DINESH YADAV 15 Morphology of lesion:
In acute necrotizing vasculities lesion show fibrinoid necrosis.
In glomerulo nephritis, lesion shows swelling& proliferation of endothelial & mesangial cells, accompanied by neutrophillic & monocytic infiltration.
vomiting. cont.... Slide 16: 10/25/2008 DINESH YADAV 16 LOCALISED IMMUNE RESPONSE DISEASE
eg; arthus reaction
Arthus reaction: arthus reaction is a localised area of tissue necrosis resulting from acute immune complex vasculitis, usually elicited in the skin
Reaction can be produced experimentaly by injecting antigen in a animal having circulating antibodies against that antigen.
After few hours, area of injection can be seen as area of visible edema with severe hemorrhage followed occasionally by ulceration.
This was first observed by arthus in rabbit with normal horse serum.
Mechanism: as the antigen diffuses in to vessel wall, it binds with preformed antibody & large immune complexes are formed locally .
Which precipitate on vessel walls, trigger inflammatory reactions & leucocyte-platelet thrombi formation resulting in local ischemia & necrosis cont.... Slide 17: 10/25/2008 DINESH YADAV 17 Immunoflorascent strains of arthus reaction reveals deposits of complement, immunoglobins, fibrinogen in the vessel walls, usually venules.
Histology: Show fibrinoid necrosis, inflammation & thrombus.
Arthus reaction forms a pathologic component of many clinical syndromes
eg: farmers lung.
Arthus can be passively transferred with serum cantaining precipitating antibodies like IgG, IgM in high titres. THE END