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