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

2. described as an “ internal inflammation”.
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 Products Lipid 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 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