Hadassah University Hospital

1. Hadassah University Hospital Dr. Slosser Plastic Surgery Seminars June 15, 2001 BURN IMMUNOLOGY

2. Introduction In history burn injury described as an “ internal inflammation”.

3. Causes of death: • 90% due to INFECTION • 60% pneumonia • 40% sepsis (Gram N) • < 10% wound sepsis

4. 3 LINES of Resistance: • Mechanical barrier • The nonspecific immune response • The specific immune response

5. SUPRESSION OF THE IMMUNE RESPONCE • Open contaminated wound • Increase metabolic requirements • Decrease nutritional intake

6. Mechanical Barrier • Normal skin • G.I. Mucosa • Respiratory mucosa

7. SKIN • Burn damages the skin ( physical barrier allowing microbial invasion). • All lines - entry points to offending organisms. • Eschar - ideal ground for microorganisms (avascular tissue is not accessible to most systemic antibiotics).

8. ESCHAR Toxic ProductsLipid Protein Complex (LPC) • LPC - is produced by cross linkage of a complex of 6 skin cell membrane- lipid- associated proteins. • Damages cell ultrastructure and its metabolic function. • Inhibits T-cell proliferation. • Inhibits IgG production. • LPC effects continue until eschar excision

9. Hansbrough 1984 - show that immediate eschar excision avoided immunosupression.

10. G.I. Mucosal Barrier • Translocation of microbes and endotoxins occurs rapidly+extensively after burn injury. - 1 hour after burn - proportional to the severity. • Translocation increases with parenteral nutrition and reduced with enteral feeding.

11. Respiratory Mucosal Barrier • In inhalation injury, damaged epithelium allows bacterial invasion. • Intubation allows for colonization of airway with opportunistic organisms.

12. Nonspecific Immune Responce • A- Vascular component • B- Cellular component • C- Humoral component

13. A- VASCULAR COMPONENT • Minor thermal injury - Local vasodilatation. - Increase capillary permeability. - Chemotaxis of PMN & monocytes. • Severe thermal injury - Venous stasis. - Microvascular thrombosis. - Endothelial cell slough.

14. B- CELLULAR ROLE • Phagocytes ( blood born and tissue) • Neutrophils (PMN) • Macrophages - monocytes - fixed phagocytic cells of RES

15. C- HUMORAL ROLE • Arachidonic acid metabolites • Endotoxines • Thromboxane • Complement system • Fibronectin

16. Chemical mediators • Serotonin -from platelets, mast cells • Histamine- mast cells, basophils • Platelet activating factor (PAF) - basophils, neutrophils, macropages • Hyaluronidase • Peroxides, free radicals

17. Chemical mediators • Neutrophil chemotactic factor (NCF) -mast cells • IL-8 -monocytes, lymphocytes • C3a - complement C3 • C5a - complement C5 • Bradykinine - kinin system (kininogen) • Fibrinopeptides - clotting system

18. Chemical mediators • Prostaglandin E2 (PGE-2) - cyclo-oxygenase pathway • Leukotriene B4 (LTB-4) -lipoxygenase pathway • Leukotriene D4 (LTD-4) -lipoxygenase pathway

19. Effect of Endogenous Mediators on Inflammation Postburn • Increased microvascular permeability Vasoactive amines (histamine) Kinin system (bradykinine) Acidic lipides ( Pg, Pc, Leukotrienes C-4, D-4, E-4. Complement system byproducts C3a

20. Effect of Endogenous Mediators on Inflammation Postburn • Leukocytic infiltration ( chemotaxis) Complement system byproducts -C5a Acidic lipids ( Leukotriens B4) Lysosomal components (cationic proteins) • Tissue damage Lysosomal components (neutral proteases)

21. SPECIFIC Immune Responce COMPOSED OF TWO COMPONENTS • Cell mediated immunity component (T-lymphocytes and its subgroups) • Humoral immunity component (B- lymphocytes and its product antibodies)

22. CELL MEDIATED Immunity • T-lymphocytes subdivided according to function into: Cytotoxic T-cells (killer) Helper T-cells Supressor T-cells

23. CELL MEDIATED Immunity • Cytokines - intracellular signalling proteins which amplify the nonspecific defence response and recruit other noncommitted lymphoid cells as well as monocytes, neutrophils and eosinophils. • Macrophages play a key role

24. CELL MEDIATED Immunity • Some key lymphokines are: Interleukin 1 Interleukin 2 TNF

25. HUMORAL Mediated Immunity • B-cells under influence of the T-cells committed to become antibody producing cell when stimulated by the presence of particular antigens

26. FUNCTIONS of ANTIBODIES • Opsonization of bacteria • Neutralization of viruses and bacterial toxins • Bactericidal antibodies lyse bacteria on contact in presence of compliment

27. Effect of BURN on the Specific Immune Responce • CELL MEDIATED IMMUNITY -Prolonged survival of skin allografts -Altered skin test reactivity - energy -T-lymphocytes (A)-decrease in total count (B)-depressed primary and secondary responses to T-dependent antigens -Blast transformation- diminished response to mitogens/ MLS -Cytotoxity - reduced activity -T-cell subpopulations - increase in nonspecific supressor T-cells

28. Postburn Alteration in Humoral Immunity • B-lymphocytes - increase in number with a T- or B-cell shift • Immunoglobulins - reduction in IgG with lesser reductions in IgA and IgM • Antibody responce - increase in anamnestic secondary responce; decrease in primary humoral antibody responce • Proteins - increase in levels of acute phase reactants (C-active protein, haptoglobine); decrease in alpha2- macro globulin and prealbumin

29. IMMUNIZATION THERAPY • ACTIVE IMMUNIZATION -Psedomonas aeruginosa -dominant pathogen in burn patients • PASSIVE IMMUNIZATION -Administration of immunoglobulins

30. IMMUNOMODULATION • A - General support - Fluid resuscitation -Early nutrition -Early excision • B - Remove supressors ( Plasma exchange, early wound excision, topical Cerium nitrate, Polymyxin B ) • C - Stimulate target cells

31. Immunomodulating Agents • Killed vaccine of Corynebacter parvum • IL-1, IL-2 • FFP • Vitamin A and Vitamin E • Thymosin • Levamisole • TP-5 ( Thymopentin) • Fibronectine • Cyclophosphamide