Do all immune complexes lead to tissue injury? - Large complexes are removes by phagocytes
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Do all immune complexes lead to tissue injury?
- Large complexes are removes by phagocytes
- Medium and small complexes are pathogenic
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Disease Antigen Features
Systemic lupus eryth. DNA, Nucleoproteins Nephritis, Arthritis, Vasculitis
Polyarteritis nodosa Hepatitis B Surface Antigen Vasculitis
Post streptococcal G N Streptococcal wall antigens Nephritis
Acute glomerulonephritisBacteria (treponemes), parasites (malaria), tumor
Nephritis
Reactive arthritis Bacteria (yersinia) Acute Arthritis
Arthus reaction Foreign proteins Cutaneous vasculitis
Serum sickness Injected proteins Nephritis, Arthritis, Vasculitis
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Type IV Hypersensitivity (Cell mediated)
Participants:
- Antigen presenting cells (macrophages)
- T lymphocytes
- Cytokines
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Two types:
1) Delayed type Hypersensitivity:
Mediated by CD4+ T cells
(helper)
2) Direct T cell cytotoxicity:
Mediated by CD8+ T cells
(cytotoxic)
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1) Delayed type Hypersensitivity (DTH):Tuberculin test is the prototype
24-72 hrs24-72 hrs24 - 72 hrs
- Mononuclear cells around blood vessels
- Increased vascular permeability
- Escape of plasma proteins & fibrin
- Endothelial swelling and hypertrophy
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1) Delayed type Hypersensitivity (DTH):
- Exposure to TB protein
- Differentiation of CD4+ T cells to sensitized TH1 cells
- Injection of PPD into skin (re-exposure to antigen)
- Recruitment of sensitized TH1 cells, secretion of
cytokines
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Cytokines involved in DTH:
- IL-12:
Produced by macrophages and dendritic cells
Responsible for induction of TH1 response
- IFN-ϒ:
Key mediator for macrophage activation
Responsible for formation of granuloma
- IL-2:
Causes proliferation of T cells at site of DTH
- TNF and lymphotoxin:
Through prostacyclin increase blood flow
Through P-E selectins promote margination and diapedesis
Induces other chemotactic factors
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Persistent / non-degradable antigens (eg. TB bacilli in lungs / tissues)
- Accumulation of macrophages over 2-3 weeks
- Macrophages transform to “epithelioid cells”
- Granuloma formation occurs
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Clinical situations (DTH):
- Intracellular pathogens (TB, leprosy, fungi, parasites)
- Transplant rejection
- Tumor immunity
- Contact dermatitis
- Autoimmune diseases like Type I diabetes and Multiple sclerosis
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T Cell-Mediated Cytotoxicity:- Role of CD8+ T cells (cytotoxic T Lymphocytes), Class I MHC
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Clinical situations (CTL):
- Transplant rejection
- Resistance to viral infections
- Tumor immunity