2. HYPERSENSITIVITY
Exaggerated or misdirected immune response.
Results in tissue injury or other pathophysiological
changes.
Occurs when an already sensitized individual is re-exposed
to the same foreign substance.
May be immediate or delayed
3. Ensuing tissue injury may be
caused by:
1.Release of vasoactive substances
2. Phagocytosis or lysis of cells
4. 3.Activation of inflammatory & cytolytic components
of complement system
4.Release of cytokines, proteolytic enzymes and other
mediators of tissue injury or inflammation
5. CLASSIFICATION
• Gell and Coombs (1963) classified hypersensitivity reactions
into FOUR CATEGORIES based on the time elapsed from
exposure of antigen to the reaction and the arm of immune
system involved .
6. . TYPE I – IMMEDIATE, ATOPIC, ANAPHYLACTIC
TYPE II – ANTIBODY DEPENDANT
TYPE III – IMMUNE COMPLEX
TYPE IV – CELL MEDIATED / DELAYED TYPE OF
hypersensitivity
7. TYPE III (IMMUNE-COMPLEX)
HYPERSENSITIVITY
oType III reaction is mediated by antigen-antibody
immune complexes, which induce an inflammatory
reaction in tissues.
Mechanism of Immune-Complex Hypersensitivity :
• In many situations, reactions between the various
antigens and antibodies in the body give rise to
formation of immune complexes.
8. • In the normal course, these immune complexes are
normally removed by mononuclear-phagocyte system
through participation of RBC.
• However, the body may be exposed to an excess of
antigen in many conditions such as persistent infection
with a microbial organism, auto-immunity to self-components,
and repeated contact with environmental
agents .
9. • When the clearance capacity of this system is
exceeded, deposition of the complexes takes place in
various tissues.
• Immune complexes are deposited on blood vessel
walls, in the synovial membrane of joints, on the
glomerular basement membrane of the kidney, and on
the choroids plexus of the brain.
• Sometimes immune complexes are formed at the site
of inflammation itself .
10. • These in situ immune complexes in certain cases may be
beyond the reach of phagocytic clearance and hence
aggregate and cause disease.
• Immune complexes fix complement and are potent
activators of the complement system.
• Activation of the complement results in the formation of
complement components such as C3a- and C5a-
anaphylotoxins that stimulate release of vasoactive
amines.
11. • The C5a attracts neutrophils to the site, but these
neutrophils fail to phagocytose large aggregated
mass
of immunocomplexes and instead release lysosomal
enzymes and lytic substances that damage host
tissue.
12.
13. MANIFESTATIONS OF TYPE III
HYPERSENSITIVITY
Arthus reactions and
Serum sickness reactions are two typical
manifestations of type III
hypersensitivity.
14. • ARTHUS REACTIONS
• Arthus reaction is an inflammatory reaction caused by deposition of
immune complexes at a localized site.
• This reaction is named after Dr Arthus who first
described this reaction.
• He demonstrated that repeated subcutaneous injections of the
antigen such as normal horse serum to an animal, such as rabbit, till
it has high levels of serum IgG did not have any local effect.
• But when the antigen is injected subcutaneously or intradermally
into the same sensitized animal later, a local inflammatory reaction
develops.
• This reaction is edematous in the early stages, but later can become
hemorrhagic, and eventually, necrotic.
15. • Tissue damage is caused by deposition of antigen-antibody immune
complexes and complement.
• The activation of complement through its product of
activation causes vascular occlusion and necrosis.
• Hypersensitivity pneumonitis is the clinical manifestation
of Arthus reaction.
• Farmer's lung, cheese-washer's lung, wood-worker's
lung, and wheat-miller's lung are the examples of
hypersensitivity pneumonitis associated with different
occupations.
• All these conditions are caused by inhalation of fungi or
bacteria present in different products handled by the
infected people
16. • SERUM SICKNESS
• Serum sickness is a systemic inflammatory reaction caused by deposition of
immune complexes in many sites of the body.
• The condition manifests after a single injection of a high concentration of foreign
serum.
• It appears a few days to 2 weeks after injection of foreign serum or certain drugs
such as penicillin.
• Unlike type I hypersensitivity reaction, a single injection acts as both priming
and shocking doses.
• Fever, lymphadenopathy, rashes, arthritis, splenomegaly, and eosinophilia are
the typical manifestations.
• Disease is self-limited and clears without sequelae.
• However, serum sickness is considered as an immediate hypersensitivity
reaction, because symptoms appear immediately after formation of immune
complex
17. TYPE IV DELAYED (CELL-MEDIATED)
HYPERSENSITIVITY
• Type IV hypersensitivity reaction is called delayed type
hypersensitivity (DTH) because the response is delayed.
• It starts hours or days after primary contact with the antigen
and often lasts for days.
• The reaction is characterized by large influxes of nonspecific
inflammatory cells, in particular, macrophages.
• It differs from the other types of hypersensitivity by being
mediated through cell-mediated immunity.
• This reaction occurs due to the activation of specifically
sensitized T lymphocytes rather than the antibodies.
18. . Initially described by Robert Koch in tuberculosis as a localized
reaction., this form of hypersensitivity was known as tuberculin
reaction.
• Later, on realization that the reaction can be elicited in various
pathologic conditions, it was renamed as delayed type
hypersensitivity.
19. • MECHANISM OF DTH
• The DTH response begins with an initial sensitization phase of 1-2
weeks after primary contact with an antigen.
• TH1 subtypes CD4 are the cells activated during the
sensitization phase.
• A variety of antigen-presenting cells (APCs) including Langerhans
cells and macrophages have been shown to be involved in the
activation of a DTH response.
• These cells are believed to pick up the antigen that enters through
the skin and transport it to regional lymph nodes, where T cells are
activated by the antigen.
20. • The APCs present antigens complexed in the groove of
major histocompatibility complex (MHC) molecules
expressed on the cell surface of the APCs.
• For most protein antigens or haptens associated with
skin
DTH, CD4 + T cells are presented with antigens
bound to MHC class II alleles, human leukocyte antigen
(HLA)-DR, HLA-DP, and HLADQ.
21. • Specific MHC class II alleles are recognized to produce excessive
immune activation to antigens.
• On subsequent exposure, the effector phase is stimulated.
• The TH 1 cells are responsible in secreting a variety of cytokines
that recruit and activate macrophages and other non- specific
inflammatory cells.
• The response is marked only after 2-3 days of the second exposure.
• Generally, the pathogen is cleared rapidly with little tissue
damage.
• However, in some cases, especially if the antigen is not easily
cleared, a prolonged DTH response can itself become destructive to
the host, as the intense inflammatory response develops into a
22.
23. • TYPES OF DTH REACTIONS
• DTH reactions are of two types: contact hypersensitivity and tuberculin-
type hypersensitivity reactions.
• CONTACT HYPERSENSITIVITY
• Contact hypersensitivity is a manifestation of DTH occurring after
sensitization with certain substances.
• These include drugs such as sulfonamides and neomycin, plant products
such as poison ivy and poison oak, chemicals such as formaldehyde and
nickel, and cosmetics, soaps and other substances.
• This reaction manifests when these substances acting as haptens enter
the skin and combine with body proteins to become complete antigens to
which a person becomes sensitized .
24. • TUBERCULIN-TYPE HYPERSENSITIVITY
REACTION
• Tuberculin reaction is a typical example of delayed hypersensitivity to
antigens of microorganisms which is being used for diagnosis of the
disease.
TUBERCULIN SKIN TEST: This test is carried out to determine
whether an individual has been exposed previously to M.
tuberculosis or not.
• In this test, a small amount of tuberculin (PPD), a protein
derived from the cell wall of M. tuberculosis, is injected
intradermally.
25. • Development of a red, slightly swollen, firm lesion at
the site
of injection after 48-72 hours indicates a positive test.
• A positive test indicates that the person has been
infected
with the bacteria but does not confirm the presence of
the
disease, tuberculosis.
