Transcript Type IV hypersensitivity

Type II
Cytotoxic hypersensitivity •
Reaction time is minutes to hours •
mediated by antibodies of IgM or IgG •
class and complement
Phagocytes and NK cells may also play a role •
(ADCC).
Diagnostic tests include detection of •
circulating antibody against tissues involved and
the presence of antibody and complement in the
lesion (biopsy) by immunofluorescence
Directed against cell surface or tissue antigen •
Clinical Examples
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Transfusion reactions
Autoimmune Hemolytic anemia
Hemolytic disease of newborn
Drug induced hemolytic anemia
Autoimmune thrombocytopenia
Pemphigus vulgaris(desmoglein )
Goodpastures syndrome
Myasthenia gravis
Graves disease
Insulin resistant diabetes
Pernicious anemia
others
Drugs that can cause this type of
hemolytic anemia include:
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Cephalosporins (a class of antibiotics)
Levodopa
Methyldopa
Penicillin and its derivatives
Quinidine
Some nonsteroidal anti-inflammatory
drugs (NSAIDs)
Type III
• The reaction may be general (e.g., serum
sickness) or may involve individual organs
including skin ( Arthus reaction), kidneys,
lungs, blood vessels , joints or other
organs.
Type III
• It is mediated by soluble immune
complexes
• The reaction may take few hours after
exposure to the antigen
• The lesion contains primarily neutrophils
Immune complex mediated
diseases
• Immune complexes cause disease only:
1-in excessive amounts
2- not efficiently cleared
3- become deposited in tissues
a) intermediate complexes tend to be
deposited in vessels
b) Cationic antigens bind to negatively
charged components of the basement
membranes of blood vessels and
glomeruli,joints
Tissue injury mechanisms
• Antibodies may opsonize cells or
activate the complement system
Production of complement proteins that
opsonize cells.
These cells are phagocytosed and
destroyed by phagocytes that express FcR
and CR
Main mechanism in autoimmune hemolytic
anemia and thrombocytopenia and
hemolysis in transfusion reactions.
Cell Mediated Immunity
• The effector cells involved in these
processes are cytotoxic T-lymphocytes
(CTLs), NK-cells and Th cells
Phagocytosis and killing of intracellular
pathogens
Direct cell killing by cytotoxic T cells
Direct cell killing by NK and K cells
• These responses are especially important for
destroying intracellular bacteria, eliminating viral
infections and destroying tumor cells
• Response to microbes residing within the
phagosomes is mediated by effector CD4
Th1 cells
• Microbes that infect and replicate in
nonphagocytic cells,is mediated by CD8
• T cell dependent macrophage activation
and inflammation may damage normal
tissues
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Th1(IFN- )
Th2(IL-4,IL-5)
Th17(TGF-,IL-1,IL-6)
The most differentiation –inducing stimuli
are IFN- ,IL-12 and IL-4
Killing by cytotoxic T cells
• release some substances known as
perforin ,Granzyme A,B ,C and serglycin
and granulysin
• the CTL may release lymphokines and/or
cytokines
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Recognition
Activation
Lethal hit
Release(cathepsin B)
Type IV hypersensitivity
Type IV hypersensitivity
• DTH (Delayed type hyper sensitivity)
• Is a T cell mediated inflammatory response ,in which
stimulation of T cells leads to macrophage activation and
localised inflammation and edema within tissues.
• This effector T cell response is essential for the control
of intracellular and other pathogens.
• If the response is excessive it can damage host tissues
• Subsequent exposure of the sensitised individual to the
exogenous Ag results in the recruitment of specific T
cells to the site and development of a local inflammatory
response over 24-72 hrs.
Interferon  production
TDTH formation
variants of type IV HS
There are 3 variants of type IV HS reaction
• Contact HS
• Tuberculin type HS
• Granulomatous HS
Contact hypersensitivity
• Occur within 72 hrs of Ag challenge
• Characterized by an eczematous reaction
in the skin at the point of contact with an
allergen
• Organic chemicals and inorganic metals
such as nickel , chromate and rubber
accelerator in latex gloves
Contact hypersensitivity
Has 2 stage
• Sensitization
• elicitation
TUBERCULIN TYPE
• Is induced by soluble antigens from organisms
such as M.Tuberculosis and Leprae and
leishmania tropica
• Following ID tuberculin challenge memory T
cells are recruited and activated to secrete IFN-
,which activates Macrophages to produce TNF
and IL-1
• The initial influx at 4 hrs is neutrophils but
replaced at 12 hrs by monocytes and T cells.
PPD skin test
Granulomatous HS
• Clinically the most important form of type
IV HS.
• If the Ag persist(intracellular micro.,other
particles such as ziconium and beryllium
,talc ,silica) ,chronic activation of T cells
and macrophages lead to granuloma
formation and tissue damage.
Granulomatous HS
The Granuloma contains :
• Epithelioid cells (secret TNF)
• Langhans giant cells(low ER and
degeneration of lysosomes and
mitochondria)
• Macrophages
IFN- and TNF are essential for granuloma
formation
Granulomatous HS
• Crohn disease(chronic inflammatory
disease of ileum and colon)
• Leishmaniasis
• Sarcoidosis
• Leprosy
• tuberculosis