MECHANISMS OF SELF-DEFENSE

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MECHANISMS OF SELF-DEFENSE Part 1

• Charlotte A. Richmond, PhD, RN

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INNATE DEFENSES

• Bodys 1st line of defense anatomic barriers
• The skin mucous membranes
• If these defenses are penetrated
• Mechanical clearance
• 2nd line of defense Inflammatory response

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IMMUNE RESPONSE

• 3rd Line of defense Immune Response
• Slower specific compared to inflammatory
  response
• Inflammatory immune responses complement each
  other interact in complex ways

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THE IMMUNE SYSTEM

• Extraordinary complex system
• Elaborate dynamic communication network
• Recognizes responds to antigens

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Cells molecules of the immune system protect
the nose from attack by a virus
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CHARACTERISTICS OF IMMUNE RESPONSE

• Immunity
• State of protection, primarily against infections
• Characterized by memory specificity
• Antigens
• Chemical substances that react with preformed
  components of the immune response
• Immunogens
• Antigens that induce an immune response
• Haptens
• Antigens must be bound to carriers to induce an
  immune response

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CHARACTERISTICS OF IMMUNE RESPONSE

• Self-Antigens
• Antigens on host cells
• Not recognized as immunogenic by hosts immune
  system
• A condition called tolerance

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INDUCTION OF IMMUNE RESPONSE

• Most immune system cells are WBCs
• Immunocytes (lymphocytes) are 1 type of WBC
• 2 major classes of immunocytes
• T lymphocytes (T cells) B lymphocytes (B
  cells)
• Immune response is characterized by the
  activation of B cells T cells

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B CELLS

• Develops from a stem cell that matures under
  hormonal control in bursal-equivalent tissues
  (bone marrow)
• Develops into a mature plasma cell capable of
  producing antibody against a specific antigen
• Antibody marks the antigen for destruction by
  other immune cells

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ANTIBODIES

• Plasma glycoproteins
• Classified by chemical structure biologic
  activity
• IgG, IgM, IgA, IgE, or IgD
• Protect host from harmful antigens
• Recognize and bind with antigens
• Functions
• Opsonize bacteria, neutralize toxins viruses
• Activates inflammatory response

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ANTIBODY CLASSIFICATION

• IgG 80 plasma Ig, in all body fluids,
  secondary response, activates complement
• IgM Primary response, large molecule, vascular
  system, activates complement
• IgA 95 of body secretion Ig, respiratory and
  GI tract, coats bacteria some viruses
• IgD Plasma, B cell surfaces, antigen receptor
• IgE Hypersensitivity and allergic reactions
  (asthma)

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T CELLS

• Develop from stem cells that mature under
  hormonal control in thymus
• Make up the cell-mediated immune response
• Help to destroy infected cells
• Coordinate the overall immune response

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TYPES OF T CELLS

• Cytotoxic T cells
• Kill target cells directly
• Delayed hypersensitivity T cell
• Produces lymphokines that affect other cells
  (especially macrophages)
• Helper T cell
• Induces B cells to produce antibody
• Recognize antigen fragments
• Suppressor T cell
• Suppresses antibody production immune function

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T-CELL RECEPTOR

• T cell has molecule on its surface called T-cell
  receptor
• Interacts with molecules called MHC (major
  histocompatibility complex)

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T cell (lymphocyte) with a T-cell receptor on its
surface
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ANTIBODY PRODUCTION

• Final stage of the process
• Requires interaction of
• B cells
• Helper T cells
• Antigen-presenting cells

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Histocompatibility Antigens (Human Leukocyte
Antigens)

• Proteins found on the surface of nearly every
  cell in the body
• Recognizes substance is foreign

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Major Histocompatibility Complex (MHC)

• MHC (or HLA complex)
• Major group of genes producing the HLA antigens
• 4 closely linked foci located on short arm of
  chromosome 6 (A, B, C D complex)
• Antigens produced by A, B C loci found on
  surface of most cells except erythrocytes
• D complex consists of 3 independent loci (DR, DP,
  DQ)
• Confined to B cells, macrophages, some epithelial
  cells some stimulated T lymphocytes

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INNATE IMMUNITY

• Nonspecific (species specific)
• First line of defense
• Present at birth
• Found in multi-cellular organisms
• Permanent immunity
• Not product of immune response

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INNATE IMMUNITY

• Effectors
• Neutrophils
• Macrophages
• Eosinophils
• NK cells

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INNATE IMMUNITY

• Main Mediators
• Lysosomal enzymes
• Cytokines
• Complement proteins
• Acute phase proteins

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ACQUIRED IMMUNITY

• Highly specific, inducible discriminatory,
  unforgetting
• T lymphocyte- dependent
• Gained after birth

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ACQUIRED IMMUNITY

• Active
• Natural exposure
• Immunization

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ACQUIRED IMMUNITY

• Passive
• Doesnt involve hosts immune response
• Antibodies T cells transferred to recipient
• Temporary immunity

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IMMUNE RESPONSE

• Primary
• 5 7 days after exposure
• Dominated by IgM
• Lesser amounts of
• IgG

• Secondary
• 2nd challenge by same antigen
• Rapid production of
• antibody
• IgM same production
• as primary
• IgG predominant

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HUMORAL IMMUNITY

• Antigens stimulate B cells ? plasma cells
• Mediated by antibodies secreted by B cells

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CELL-MEDIATED IMMUNITY

• Activation of sensitized T cells
• T cells secrete cytokines
• T cells become cytotoxic cells
• T cells kill virus-infected or abnormal host cells

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ACUTE INFLAMMATORY RESPONSE

• Rapid nonspecific
• Protective response to cellular injury
• Occurs only in vascularized tissue

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MACROSCOPIC HALLMARKS OF INFLAMMTION

• Redness
• Heat
• Pain
• Loss of function of the inflamed tissues

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MICROSCOPIC HALLMARKS OF INFLAMMATION

• Accumulation of fluid and cells at the
  inflammatory site

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MAST CELLS

• Most important activator of inflammatory response
• Releases biochemical mediators
• Histamine
• Chemotactic factors
• Synthesizes other mediators
• Prostaglandins
• Leukotrienes
• Platelet-Activating Factor (PAF)

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MAJOR VASOACTIVE AMINES OF INFLAMMATION

• Histamine serotonin
• Effects
• Constricts vascular smooth muscles
• Dilation of capillaries
• Retraction of endothelial cells lining
  capillaries
• Increases vascular permeability

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ACUTE PHASE RESPONSE

• Systemic changes present if inflammation is
  severe enough
• May be transient, dissipating with recovery or
  persistent in chronic disease
• Mediated by inflammation-associated cytokines
• Changes in concentrations of large number of
  plasma proteins

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ACUTE PHASE RESPONSE

• Fever
• Somnolence
• Anorexia
• Changes in plasma protein synthesis
• Altered synthesis of endocrine hormones

• Hormones effected
• CRH
• Glucagon
• Insulin
• ACTH
• Cortisol
• Catecholamines
• Growth Hormones
• TSH, Thyrpxine
• Aldosterone
• AVP

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ACUTE PHASE PROTEINS

• Major acute phase proteins (APP)
• C-Reactive protein (CRP)
• Serum amyloid A (SAA)
• Negative APP
• Albumin
• Transthyretin
• Transferrin

• Other positive APP
• Complement proteins
• Ferritin
• ?-1- antitrypsin (antiprotease)
• Fibrinogen
• Fibronectin
• Hempexin
• Haptoglobin
• Ceruloplasmin

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C-REACTIVE PROTEIN

• Influences inflammatory tissue repair processes
• Recognizes some foreign pathogens
• Activates complement system
• Bonds to phagocytic cells
• Induces production of inflammatory cytokines
• Main initiator of blood coagulation
• Net effect may be antiinflammatory

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PLASMA PROTEIN SYSTEM

• Inflammation is mediated by 3 key plasma proteins
  systems
• Complement system
• Clotting system
• Kinin system

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COMPLEMENT SYSTEM

• The complement cascade (Fig 7-7)
• Activated by antigen-antibody reactions (classic
  pathway)
• Activated by other products especially bacterial
  polysaccharides alternate (nonantibody) pathway
• Produces biologically active (anaphylactic or
  chemotactic) fragments
• Produces target cell lysis
• Phagocytosis
• Increases vascular permeability

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CLOTTING SYSTEM

• Extrinsic Intrinsic pathways (Fig 7-9)
• Stops bleeding
• Localizes microorganisms
• Provides a meshwork for repair healing

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KININ SYSTEM

• Bradykinin most important kinin protein
• Dilates vessels (low dosage)
• Induces pain (along with prostaglandins)
• Contracts extravascular smooth muscle
• Increases vascular permeability
• May increase leukocyte chemotaxis (Fig 7-6)

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INHIBITORY INFLAMMATORY ENZYMES

• Histaminase
• Carboxypeptidase
• C1 esytrase inhibitor
• ?1-antitrypsin

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CELLULAR COMPONENTS OF INFLAMMATION

• Phagocytic leukocytes
• Neutrophils
• Macrophages
• Eosinophils
• Platelets
• Lymphocytes

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PHAGOCYTIC CELLS

• Engulf destroy microorganism (Fig 7-16)
• Enclose in phagocytic vacuoles (phagolysosomes)
• Toxic products degradative lysosome enzymes
  kill digest

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OPSONINS

• Antibody complement component (C3b) coat
  microorganisms (Fig 7-15)
• This makes them more susceptible to phagocytosis
• Binds microorganism more tightly to the phagocyte

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ENDOTHELIAL CELLS

• Line the blood vessels capillaries
• Retract during inflammation
• Permit fluid, nutrients phagocytic cells into
  area of injury

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POLYMORPHONUCLEAR NEUTROPHIL (PMN)

• Predominant phagocytic cell in early inflammatory
  response
• Enters inflammatory site within 6-12 hours
• Attracted by chemotactic factors
• Short lived
• Gradually replaced by macrophages lymphocytes
• Primary role removal of debris phagocytosis

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MONOCYTES

• Largest normal blood cell
• Produced in bone marrow
• Enters circulation migrates to inflammatory
  site
• Develops into a macrophage

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MACROPHAGES

• Larger more active phagocyte
• Characterizes chronic inflammation
• May appear within 24 hours of injury
• Usually arrive 3-7 days later
• Attracted by chemotactic factor released by PMN
  monocytes
• Survive longer at site

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ROLE OF MACROPHAGES

• Responsive to products secreted by T cells
• Participate in activating the immune response
• Stimulates the growth differentiation of
  granulocytes monocytes in bone marrow
• Produce inflammatory cytokines
• Secrete substances to promote wound healing
• Phagocytic activity

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EOSINOPHILS

• Release products to control inflammatory response
• Contain biochemical mediators to control effects
  of histamine serotonin
• Contains a caustic protein that dissolves surface
  membranes of parasites
• Induced by IgE-mediated mechanisms of
  hypersensitivity (Fig 7-18)

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CELLULAR PRODUCTS

• Interleukins
• Lymphokines
• Chemokines
• Interferon
• See Fig 7-19

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INTERLEUKINS

• Biochemical messengers
• Cytokines produced by macrophages or lymphocytes
• Stimulated by antigens or inflammation
• Stimulate other leukocytes to proliferate (?
  immune function)
• Chief effect ? the immune response

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LYMPHOKINES

• Cytokines produced by T cells
• Also biochemical mediators
• Most important effects on macrophages
• Tumor necrosis factor (TNF)

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CHEMOKINES

• Generally proinflammatory cytokines
• Effects on leukocytes
• Chemotaxis
• Growth
• Activation
• Release stored chemicals from intracellular
  storage granules (degranulation)

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INTERFERON

• Defense against viral infections
• Cytokine produced released by host cells
  invaded by virus
• Prevents virus from infecting healthy cell
• Stimulates uninfected cells to produce antiviral
  proteins (Fig 7-20)
• INF-? INF-? are antiinflammatory
• INF-? is proinflammatory and enhances
  cell-mediated immunity

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CHRONIC INFLAMMATION

• Lasts 2 or more weeks
• Can occur without much acute inflammation
• Dense infiltration of lymphocytes macrophages
• Granulomas form to isolate tissue damage

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RESOLUTION REPAIR

• Begin during inflammation (debridement)
• Phagocytosis
• Dissolution of fibrin clot
• 2 phases reconstruction maturation
• Resolution
• Restoration of original structure function
• Repair
• Replacement of destroyed tissue with collagen
• Fill in the wound
• Cover or seal wound
• Shrink the wound

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WOUND HEALING

• Primary Intention
• Conditions of minimal tissue loss
• Clean incision
• Paper cut
• Surgical incision

• Secondary Intention
• Healing requiring more tissue replacement
• Wound healing takes longer
• Open wound
• Stage IV decubitus

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NEONATAL CONSIDERATION

• Immature depressed immune function
• Transient depressed inflammatory function
• Partially deficient in complement (components of
  alternative pathway)
• Develop severe sepsis meningitis when infected
  with bacteria with no transferred maternal
  antibody

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GERIATRIC CONSIDERATIONS

• Impaired wound healing
• Associated with chronic illness
• Medications that interfere with healing
• Diminished immune function
• Decrease perfusion to the skin