INFLAMMATION AND HYPERSENSITIVITY

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INFLAMMATION AND HYPERSENSITIVITY

• Dr. Carol Gardner
• cgardner_at_eohsi.rutgers.edu

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INFLAMMATION
SEQUENCE OF SPECIFIC PHYSIOLOGICAL BEHAVIORS THAT
OCCUR IN RESPONSE TO A NONSPECIFIC AGENT. ACTS
TO 1) NEUTRALIZE OR DESTROY OFFENDING AGENT 2)
RESTRICTS TISSUE DAMAGE TO SMALLEST
POSSIBLE AREA 3) ALERTS BODY TO THREAT OF TISSUE
INJURY 4) PREPARES INJURED AREA FOR
HEALING CAUSES EXOGENOUS OR ENDOGENOUS
TRAUMA, SURGERY, INFECTION, CAUSTIC CHEMICALS,
EXTREMES OF HEAT OR COLD, IMMUNE RESPONSES,
ISCHEMIC DAMAGE
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INFLAMMATION HOT THING
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CARDINAL SIGNS OF ACUTE INFLAMMATION
Heat Redness Swelling
Pain Loss of function
Celsius (30 BC) Virchow
(1902)
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Acute Inflammation Components
Physiological Symptoms Responses
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
Heat (calor) Redness (rubor) Swelling
(tumor) Pain (dolor)
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Acute Inflammation Components
Physiological Symptoms Responses
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
Heat (calor) Redness (rubor) Swelling
(tumor) Pain (dolor)
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Acute Inflammation Components
Physiological Symptoms Responses
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
Heat (calor) Redness (rubor) Swelling
(tumor) Pain (dolor)
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Acute Inflammation Components
Physiological Symptoms Responses
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
Heat (calor) Redness (tubor) Swelling
(tumor) Pain (dolor)
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Acute Inflammation Components
Physiological Symptoms Responses
Release of soluble mediators Vasodilation Increa
sed blood flow Extravasation of fluid
(permeability) Cellular influx
(chemotaxis) Elevated cellular metabolism
Heat (calore) Redness (tubor) Swelling
(tumor) Pain (dolor)
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ACUTE INFLAMMATION SHORT TERM RESPONSE INVOLVES
HEMODYNAMIC CHANGES EXUDATE
FORMATION PRESENCE OF GRANULAR
LEUKOCYTES CHRONIC INFLAMMATION
PERSISTANT INVOLVES PRESENCE OF NONGRANULAR
LEUKOCYTES RESULTS IN MORE EXTENSIVE SCARRING.
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MECHANISMS OF INFLAMMATION
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STAGES OF INFLAMMATION
I. NEUROLOGIC RESPONSE - SYMPATHETIC NERVOUS
SYSTEM, CAUSES CONSTRICTION OF BLOOD
VESSELS II. VASCULAR RESPONSE - INCLUDES TRIPLE
RESPONSE A. VASODILATION B. CAPILLARY
PERMEABILITY, EDEMA C. PAIN TRIPLE RESPONSE
1) 3-50 SEC. - THIN RED LINE (VASODILATION
OF CAPILLARIES) 2) 30-60 SEC. - FLUSH
(VASODILATION OF ARTERIOLES) 3) 1-5 MIN -
WHEAL (INCREASED VASCULAR PERMEABILITY,
EDEMA) WHEAL - PALE, SOFT,
SWOLLEN AREAS ON THE SKIN CAUSED
BY LEAKAGE OF FLUID FROM THE CAPILLARIES
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PATTERNS OF INFLAMMATORY RESPONSE
IMMEDIATE TRANSIENT RESPONSE RESPONSE TO MINOR
INJURY IMMEDIATE SUSTAINED RESPONSE RESPONSE
TO MORE SERIOUS INJURY, CONTINUES FOR
SEVERAL DAYS, DAMAGE TO VESSELS DELAYED
RESPONSE INCREASES IN CAPILLARY PERMEABILITY,
DELAYED 4-24 HR, RADIATION INJURIES, SUNBURN
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III. CELLULAR RESPONSE A. MARGINATION AND
PAVEMENTING OF WHITE BLOOD CELLS B.
EMIGRATION C. CHEMOTAXIS D. PHAGOCYTOSIS
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Emigration of Neutrophils
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MARGINATION OF NEUTROPHILS
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PAVEMENTING
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EMIGRATION OF NEUTROPHILS
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Extravasation of Neutrophils
Diapedesis ?
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CHEMOTAXIS
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PHAGOCYTOSIS
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PHAGOCYTOSIS
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IV. INFLAMMATORY EXUDATES CONTAIN PLASMA,
CELLS AND FLUID A. SEROUS LARGELY PLASMA,
LOW IN PROTEIN, OCCURS EARLY OR IN
MILD INFLAMMATION B. FIBRINOUS LARGE
AMOUNTS OF FIBRINOGEN, FORMS A THICK,
STICKY MESHWORK. ONLY REMOVED BY
FIBROLYTIC ENZYMES. FAILURE OF REMOVAL
LEADS TO INFLUX OF FIBROBLASTS AND
SCAR TISSUE FORMATION C. PURULENT
CONTAINS PUS (REMAINS OF WBCs, PROTEIN
AND TISSUE DEBRIS). D. HEMORRHAGIC DAMAGE
TO BLOOD VESSELS, OCCURS WITH OTHER
FORMS OF EXUDATE. E. CATARRHAL MUCUS
HYPERSECRETION THAT ACCOMPANIES
INFLAMMATION OF A MUCUS MEMBRANE.
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SEROUS EXUDATE
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FIBRINOUS EXUDATE
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PURULENT EXUDATE
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Inflammation Outcome - Resolution
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CHRONIC INFLAMMATION
SELF PERPETUATING, MAY DEVELOP IN THE COURSE OF
RECURRENT OR PROGRESSIVE ACUTE INFLAMMATION OR
LOW GRADE IRRITANTS THAT FAIL TO ELICIT AN ACUTE
RESPONSE
ACUTE VS CHRONIC

• Little signs - Fibrosis
• Chronic inflammatory cells Lymphocytes,
  Macrophages
• Neo-vascularization
• No/less exudation
• Prominent fibrosis

• Flush, Flare Wheal
• Acute inflammatory cells - Neutrophils
• Vascular damage
• More exudation
• Little or no fibrosis

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CHRONIC INFLAMMATION
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• NONSPECIFIC CHRONIC INFLAMAMTION-
• DIFFUSE ACCUMULATION OF MACROPHAGES AND
• LYMPHOCYTES AT INJURY SITE
• MACROPHAGES FROM 3 SOURCES
• 1) RECRUITMENT
• 2) LOCAL PROLIFERATION
• 3) PROLONGED SURVIVAL
• B. GRANULOMATOUS-
• GRANULOMA FORMATION MASSING OF
• MACROPHAGES SURROUNDED BY LYMPHOCYTES
• SOME ASSOCIATED WITH FOREIGN BODIES
• DEPOSTION OF ANTIGENIC MATERIAL, TYPE IV
• HYPERSENSITIVITY REACTION

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GRANULOMA FORMATION
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GIANT FOREIGN BODY CELL
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GRANULOMA
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• INFLAMMATORY MEDIATORS
• HISTAMINE 1st mediator of initial inflammatory
  response, causes dilation of arterioles and an
  inc. in permeability of capillaries and venules.
• SEROTONIN Causes vasodilation and inc.
  vascular permeability

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INFLAMMATORY MEDIATORS

• PLASMA PROTEINS
• BRADYKININ Causes an inc. in capillary
  permeability and pain, may inc. leukocyte
  chemotaxis
• COMPLEMENT COMPONENTS Make up 10 of
  circulating serum proteins, chemotactic to
  neutrophils and monocytes, complement cascade
  can damage bacteria
• COAGULATION SYSTEM Responsible for making
  a fibrous network at the site of a lesion to
  trap exudate, microorganisms, and foreign
  bodies, stops bleeding and provides a framework
  for repair to begin.

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COMPLEMENT CASCADE
ALTERNATIVE PATHWAY
CLASSICAL PATHWAY
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COAGULATION CASCADE
TF tissue factor HK high-molecular-weight kini
nogen PK prekallikrein PL phospholipid
PT prothrombin TH thrombin.
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LIPID MEDIATORS
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WHITE BLOOD CELL PRODUCTS NEUTROPHILS -
LTs, PROTEASES, REACTIVE OXYGEN
INTERMEDIATES, THROMBOXANE A2, PGE2,
HYDROLASES MONOCYTES/MACROPHAGES -
REACTIVE OXYGEN AND NITROGEN
INTERMEDIATES, LTs, IL-1, IL-6, TNF-",
COLONY STIMULATING FACTORS LYMPHOCYTES
T HELPER CELLS - IL-2, IL-3, IL-4, IL-5, IL-6,
IL-7, IL-8, (-INTERFERON, COLONY
STIMULATING FACTORS, TUMOR NECROSIS
FACTOR - T CYTOTOXIC CELLS
TUMOR NECROSIS FACTOR - , PERFORINS B
CELLS - IMMUNOGLOBULIN
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T CELL MEDIATED KILLING
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MAST CELLS HISTAMINE, SEROTONIN, LTB4,
PROSTAGLANDINS, PLATELET ACTIVATING FACTOR,
IL-8, EOSINOPHIL CHEMOTACTIC FACTOR EOSINOPHILS
CONTROL MEDIATORS THAT ARE RELEASED BY
MAST CELLS
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TISSUE HEALING AND REPAIR
HEALING BY FIRST OR SECOND INTENTION I. FIRST
INTENTION a. MINIMAL TISSUE LOSS b. NO
GRANULATION FORMATION II. SECOND INTENTION a.
SIGNIFICANT TISSUE LOSS b. GRANULATION
TISSUE c. SLOW HEALING d. SCAR
TISSUE REGENERATION - DEPENDS ON TISSUE
TYPE A. LABILE Capable of lifelong
regeneration B. STABLE Tissue can regenerate
when stimulated C. PERMANENT No regenerative
ability
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GRANULATION TISSUE
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GRANULATION TISSUE
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HYPERSENSITIVITY
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TYPE I HYPERSENSITIVITY
A. TYPE I ALLERGIC RESPONSES - IMMEDIATE, IgE
MEDIATED, CAUSES RELEASE OF HISTAMINE,
LEUKOTRIENES AND PROSTAGLANDINS FROM MAST CELLS
AND BASOPHILS, ATOPIC (FAMILIAL
PREDISPOSITION)  1. IgE BINDS TO MAST CELLS 2.
ANTIGEN CROSSBRIDGING 3. HISTAMINE RELEASE
(MAST CELL DEGRANULATION)
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IgE Production
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EFFECTS OF MAST CELL DEGRANULATION
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EFFECTS OF MAST CELL DEGRANULATION ON CELLULAR
COMPONENTS
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• EFFECTS OF MAST CELL DEGRANULATION
• HISTAMINE INCREASES VASCULAR PERMIABILITY,
• EOSINOPHIL CHEMOTACTIC FACTOR
• B. LEUKOTRIENES SLOW REACTING SUBSTANCES OF
• ANAPHYLAXIS, CONTRICTION OF SMOOTH MUSCLE
• C. PLATELET ACTIVATING FACTOR PLATELET
• AGGREGATION AND LYSIS, MACROPHAGE AND
• NEUTROPHIL ACTIVATION.
• EXAMPLES ACUTE ANAPHYLAXIS, HAY FEVER, FOOD
• ALLERGIES

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ACUTE ANAPHYLAXIS
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TYPE II HYPERSENSITIVITY
B. TYPE II CYTOTOXIC REACTIONS - IgG OR IgM
MEDIATED, COMPLEMENT INVOLVED, REACTIONS MOST
OFTEN EFFECT CELLULAR ELEMENTS IN INTIMATE
CONTACT WITH CIRCULATING PLASMA EXAMPLES
HEMOLYTIC ANEMIA, TRANSFUSION REACTIONS
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TYPE III HYPERSENSITIVITY

• C. TYPE III IMMUNE COMPLEX REACTIONS
• IgG OR IgM MEDIATED, COMPLEMENT INVOLVED,
• CHARACTERIZED BY FORMATION OF IMMUNE
• COMPLEXES, TISSUE DAMAGE
• EXAMPLES
• SERUM SICKNESS - DISEASE CAUSED BY ANTIBODY
• PRODUCED TO HORSE OR BOVINE SERUM USED IN
• ANTITOXINS. AGGREGATES OF IgG ACTIVATE
• COMPLEMENT
• 2) ARTHUS REACTION - DERMAL INFLAMMATORY
• RESPONSE, CAUSED BY REACTION OF ANTIBODY
• TO ANTIGEN IN SKIN.

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TYPE IV HYPERSENSITIVITY
D. TYPE IV - CELL MEDIATED OR DELAYED
HYPERSENSITIVITY T-CELL MEDIATED, SENSITIZED TO
LOCALLY DEPOSITED ANTIGEN. REACTION MEDIATED
BY RELEASE OF LYMPHOKINE AND/OR
DIRECT CYTOTOXICITY EXAMPLES CONTACT
SENSITIVITY (POISON IVY)
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CONTACT DERMATITIS