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Citation Key
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Mechanisms of Immune-Mediated
Disorders
(4- types)
J. Fantone: Host Defense
2/17/09
10:00-12:00am
Winter 2009
The four types of hypersensitivity reaction
type l type ll
allergen
cell surface antigen
lgG
target
K cell
lgE
cytotoxic action
Fc receptor antibody
complement target
mast cell degranulation complement cell
mediator release mediated lysis
type lll type lV
immune-complex
deposition antigens
complement T
inflammatory lymphokines
mediators
tissue
blood basement
membrane activated macrophage
vessel
Source Undetermined
Type I Anaphylactic Type
• Prototype • Immune
Disorders Mechanisms
– Allergic rhinnitis – IgE-Mast cells
– Allergic asthma – Vascular
– Anaphylaxis permeability
(insect venom) – Eosinophils
Type II, Cytotoxic Type
• Prototype Disorders • Immune
– Hemolytic reactions Mechanisms
– Goodpastures – IgG
Syndrome – Complement
– Myasthenia Gravis – Phagocytic cells
– Grave’s Disease – ADCC
(hyperthyroidism)
Type III, Immune Complex
Disease
• Prototype Disorders • Immune Mechanisms
– Post-streptococcal – Ab-Ag reactions
glomerulonephritis – Complement
– Vasculitis – Neutrophils
• Polyarteritis nodosa – Fibrin, hemorrhage
Type IV, Cell-Mediated
(Delayed) Hypersensitivity
• Prototype Disorders • Immune
– Poison Ivy Mechanisms
– Tuberculosis – T-lymphocytes
(granulomatous – Monocyte/macro-
inflammation)
phage
– Cytotoxic T-cell
• Dr. King’s lectures
Antibody-Mediated Cell and Tissue
Injury: IgE Mediated Hypersensitivity
Reactions
Objectives:
antigen
pharmacological effects
blood vessels
processing airways etc.
APC
and presentation cell infiltration
(see Fig. 19.22)
mast cell
antigen presentation lgE production mediator release clinical effects
activation
Source Undetermined
Sensitization to Ag
Second Ag challenge
Source Undetermined
Serologic Tests: RAST -
Radioallergosorbent Test -
Specific IgE
+ Patient’s
serum
Anti-human
(Ab)
Bead with Ag IgE
J. Fantone
RIST - Radioimmunosorbent
Test - Total IgE
+ Patient’s serum
(Ab)
• Antibody: IgE
• Effector Cells: Mast Cell &
Eosinophil
• Complement: No
• Reaction: Minutes
Antibody-Mediated Cell and
Tissue Injury
(Type II and Type III Reactions)
The four types of hypersensitivity reaction
type l type ll
allergen
cell surface antigen
lgG
target
K cell
lgE
cytotoxic action
Fc receptor antibody
complement target
mast cell degranulation complement cell
mediator release mediated lysis
type lll type lV
immune-complex
deposition antigens
complement T
inflammatory lymphokines
mediators
tissue
blood basement
membrane activated macrophage
vessel
Source Undetermined
Pathophysiology
• Cytotoxic or Type II Reactions: Binding of
Antibody (IgG or IgM) with cell membrane or
tissue antigens
– Red blood cell membrane antigens - hemolytic
anemias
– Platelet antigens - thrombocytopenia cell
membrane - petechial hemorrhage
– Basement Membrane - Goodpasture’s
syndrome
• Kidney - proteinuria
• Lung - hemorrhage
Mechanisms
Pregnant woman
Rh-
RBC hemolysis
• Hemoptysis
• Pulmonary infiltrates
• Renal failure
• Anemia
Pathology
PMNs
J. Fantone
proteases
Lung: hemorrhage, hemoptysis, oxygen metabolites
alveolar infiltrates
J. Fantone
J. Fantone
J. Fantone
The four types of hypersensitivity reaction
type l type ll
allergen
cell surface antigen
lgG
target
K cell
lgE
cytotoxic action
Fc receptor antibody
complement target
mast cell degranulation complement cell
mediator release mediated lysis
type lll type lV
immune-complex
deposition antigens
complement T
inflammatory lymphokines
mediators
tissue
blood basement
membrane activated macrophage
vessel
Source Undetermined
Type III: Immune Complex Mediated Tissue Injury
antibody antigen
Ag-Ab complex
Complement Monocyte/macrophage
activation activation
Cytokines
C5a
(e.g. TNF, chemokines)
Neutrophil influx
J. Fantone
Summary: Immune Complex Mediated Tissue Injury
Neutrophil influx
Tissue injury
J. Fantone
Pathology of Immune
Complex Injury
• Fibrinoid necrosis
• Hemorrhage
• Neutrophils
• Antibody + Complement deposition
• EM: Electron dense depositis
• Granular immunofluorescence
Type III Hypersensitivity: Local I.C. Disease
The Arthus reaction
complement
lysosomal
enzymes
endothelial
cell retraction
platelet
aggregation
vasoactive
antibody amines
Source Undetermined
Immune Complex-Mediated
Hypersensitivity (Type III) (cont.)
• Systemic immune complex disease
Foreign Ag injected I.V.
Immune response w/Ab production (IgM, IgG)
Circulating immune complexes formed
Tissue deposition w/complement fixation
Arteritis
Glomerulonephritis (w/proteinuria)
Source Undetermined
Immune Complex-Mediated
Hypersensitivity (Type III) (cont.)
• Pathology
– Light microscopy: neutrophils,
hemorrhage, edema
– Electron microscopy: electron dense
deposits
– Immunofluorescence: immunoglobulin and
complement deposition, granular
immunoflouresence pattern
Immune Complex-Mediated
Hypersensitivity (Type III) (cont.)
• Clinical - depends on target organ and/or site
of immune complex deposition
– Synovium - rheumatoid arthritis
– Kidney - glomerulus
• Post-streptococcal glomerulonephritis
• Systemic lupus erythematosus
– Blood vessel walls - vasculitis
• Polyarteritis nodosa
• Early transplant rejection
– Lung - hypersensitivity pneumonitis
J. Fantone
J. Fantone
J. Fantone
J. Fantone
Source Undetermined
Immune Complex Disease
(post-streptococcal
glomerulonephritis)
target
K cell
lgE
cytotoxic action
Fc receptor antibody
complement target
mast cell degranulation complement cell
mediator release mediated lysis
type lll type lV
immune-complex
deposition antigens
complement T
inflammatory lymphokines
mediators
tissue
blood basement
membrane activated macrophage
vessel
Source Undetermined
Type IV: Cell-Mediated Immune
Reactions
• Objective
– To define the primary mechanisms involved
in contact hypersensitivity and delayed type
hypersensitivity reactions
– To review mechanisms of T-Cell mediated
cytotoxicity (see Dr. King)
• Cell Components
– Mononuclear inflammatory cells:
lymphocytes, monocytes/macrophages and
antigen presenting cells
Source Undetermined
Source Undetermined
Source Undetermined
Source Undetermined
Source Undetermined
Source Undetermined
J. Fantone
J. Fantone
J. Fantone
Granulomatous Inflammatory
Reactions
J. Fantone
J. Fantone
Summary: Type IV Reaction
• Antibody: No
• Effector Cells: T-lymphocytes,
Monocyte/Macrophage
• Complement: No
• Reaction: 48-72 hours (skin test)
Type IV: T-Cell Mediated
Cytotoxicity
(see Dr. King’s presentation)
• Mechanisms
– CD8+ lymphocyte
– Antigen expressed with Class I MHC
– Interleukin-2 clonal expansion
– Cytotoxic effector cell
• Recognizes Ag+ class I MHC
T-Cell Mediated Cytotoxicity
(cont.)
• Initiates programmed cell death
(apoptosis)
• Perforins/cytolysins
• Proteolytic enzymes: granzymes
• FAS-induced apoptosis: CD8+ T cell: FAS
ligand target cell:FAS receptor
• Cytokines
– Interferon
– Tumor Necrosis Factor a and b
The four types of hypersensitivity reaction
type l type ll
allergen
cell surface antigen
lgG
target
K cell
lgE
cytotoxic action
Fc receptor antibody
complement target
mast cell degranulation complement cell
mediator release mediated lysis
type lll type lV
immune-complex
deposition antigens
complement T
inflammatory lymphokines
mediators
tissue
blood basement
membrane activated macrophage
vessel
Source Undetermined
Additional Source Information
for more information see: http://open.umich.edu/wiki/CitationPolicy