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

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

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

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

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

Mechanical Barrier Normal skin G.I. Mucosa Respiratory mucosa

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).

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

Hansbrough 1984 - show that immediate eschar excision avoided immunosupression.

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.

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

Nonspecific Immune Responce A- Vascular component B- Cellular component C- Humoral component

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.

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

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

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

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

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

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

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)

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)

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

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

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

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

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

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

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

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

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

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