Do all immune complexes lead to tissue injury? - Large complexes are removes by phagocytes
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Transcript of Do all immune complexes lead to tissue injury? - Large complexes are removes by phagocytes
Do all immune complexes lead to tissue injury?
- Large complexes are removes by phagocytes
- Medium and small complexes are pathogenic
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
Type IV Hypersensitivity (Cell mediated)
Participants:
- Antigen presenting cells (macrophages)
- T lymphocytes
- Cytokines
Two types:
1) Delayed type Hypersensitivity:
Mediated by CD4+ T cells
(helper)
2) Direct T cell cytotoxicity:
Mediated by CD8+ T cells
(cytotoxic)
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
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
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
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
Clinical situations (DTH):
- Intracellular pathogens (TB, leprosy, fungi, parasites)
- Transplant rejection
- Tumor immunity
- Contact dermatitis
- Autoimmune diseases like Type I diabetes and Multiple sclerosis
T Cell-Mediated Cytotoxicity:- Role of CD8+ T cells (cytotoxic T Lymphocytes), Class I MHC
Clinical situations (CTL):
- Transplant rejection
- Resistance to viral infections
- Tumor immunity