Patho Unit 4 ch. 5

  1. Innate (natural) immunity
    • Born with it
    • Chemical and physical barriers
    • non-specific mechanisms
    • Non-adaptive mechanisms
  2. Adaptive (acquired) immunity
    • Exposed to it 
    • both adaptive and specific
  3. First line of defense
    • Innate (natural) (native) immunity
    • Physical barriers: skin, mucous membranes, vomiting, coughing, urination, defecation
    • Biochemical barriers: Mucus, perspiration, saliva, tears, cerumen (ear wax), chemicals derived from normal flora, sebum
  4. Second line of defense
    • Non-specific mechanisms of immunity
    •   -inflamation
    • Phagocytosis
    • search and destroy
  5. Third line of defense:
    Adaptive, specific immunity
    • Cell-mediated
    • Antibody-mediated ("humoral")
  6. Physical barriers
    Part of the first line of defense..Skin, Linings of the gastrointestinal, genitourinary, and respiratory tracts.
  7. Epithelial Cell derived chemical barriers
    Part of the first line of defense, synthesized and secreted saliva, tears, ear wax, sweat, and mucus. Antimicrobial peptides, and normal bacterial flora.
  8. Inflammation
    • Non-specific
    • Non-adaptive
    •   -A secondary exposure to a stimulus will demonstrate the same response as the initial incident
    • Immediate
    • A universal response to injury ocurring in vascular tissues of the body
    • Mediated by chemicals found in the circulation
    • Increases movement of plasma and blood cells into the tissues surrounding the injury
    • Defends against infections
    • Promotes tissue repair and healing & regeneration
    • Inflammation is necessary but can be painful and risky
  9. Local manifestation of inflammation
    • Changes in the microcirculation
    •   -Vasodiolation
    •   -Increased capillary permeability
    •   -White cell migration from the capillaries to the site of inflammation
    •   -Inflammatory chemicals stimulate nociceptors
    • Observable characeristics
    • 1. Heat- blood blow
    • 2. Redness- increased blood flow
    • 3. swelling- permiability
    • 4. Pain- chemicals
  10. Purposes and Benefits of Inflammation
    • Destroy injurious agents
    • Confine agents to limit their effects on the host
    • Stimulate components of the adaptive immune system
    • Promote regeneration and repair of tissue
  11. Systemic Manifestations of Inflammation :
    • Playing with the thermostat 
    •   -Exogenous and endogenous chemical mediators act to reset the hypothalamic thermostat
  12. Systemic Manifestations of Inflammation :
    Increases in both pro-inflammatory and anti-inflammatory plasma proteins produced by the liver
    • elevates so-called "acute-phase reactants"
    •   -Erythrocyte sedimentation rate (ESR)
    •    -rate at which red RBCs fall through plasma
    •    -reflects levels of fibrinogen and adhesion of RBCs
    •      -ESR levels increase as acute-phase reactants increase
    •   -Blood levels of C-reactive protein (CRP)
    •    -Liver produces this quickly after inflamation
  13. Systemic Manifestations of Inflammation :
    • Increases circulating neutrophils
    •   -"Shift to the left"
    •    -Increase in immature granulocytes because of mature neutrophil depletion
  14. Events of Acute Inflamation
    • Activation of three plasma protein systems:
    •  -Complement system -works with and makes better the immune system
    •    Direct or indirect destruction of cells (esp. bacteria)
    •  -Coagulation system
    •    -Isolates infections by trapping pathogens and prevents hemorrhage
    •  -Kinin system 
    •    -Interacts with the coagulation system
    •    -Pro-inflammatory
  15. Complement systetm
    • A group of plasma proteins (C1-9)
    • Participate at all levels o inflammation
    •   -Opsonization, chemotaxis, and anaphylaxis
    • Three pathways
    •   -Classical-Antibody dependent
    •     -activated by antigen-antibody complexes
    •   -Alternative and Lectin
    •     -Activated by biologic substances (bacteria, fungi, toxins)
    •     -Non-antibody dependent- recognizes self or non-self
    •     -C1 activates a cascade of C2-C5a which enhances inflammation by:
    •   -Opsonizing bacteria- Flagging for eating 
    •   -Inducing mast cell degranulation
  16. Coagulation system
    • Stops bleeding
    • Localizes microorganisms
    • Provides a meshwork for healing
  17. The Kinin system
    • Activated by coagulation system (intrinsic pathway)
    • Primary Kinin is bradykinin
    • Augments inflammation (pro-inlfammatory): vascular permeability, vasodiolation, smooth muscle contraction
  18. Cytokines
    • chemicals that are released from one cell to produce a response in another cell (cells talking to each other)
    • Can be pro- or anti-inflammatory
    • Examples: interleukins (chemicals between WBCs), interferons, chemokines,etc
  19. Interleukins
    • Cytokines produced primarily by macrophages and lymphocytes in response to microorganisms and products of inflammation
    •  -Encourages cell adhesion molecule expression
    •  -Chemotaxis
    •  -proliferation and maturation of WBCs
    •  -both pro- and anti-inflammatory
  20. Interferons
    • Natural anti-virals
    • Helps enhance our ability to kill cancer
    • Proteins produced to protect against viral infections and encourage the immune system
    •  -Defense against viral infections
    •  -Made by leukocytes to help other cells defend against viruses
  21. Mast Cells
    • Activated by antibodies
    • A critical cell in the inflammatory response
    • Large, granular cells in loose connective tissue, adjacent to blood vessels
    • Early, initial activators of the inflammatory response
    •   -Degranulation: Quick release of performed mediators -Histamine and chemotactic factors
    •   -Synthesis of inflammatory mediators
  22. Mast Cell Degranulation
    • Released from granules:
    • -Histamine 
    • - Mast cell protease (cleave basement membrane)=tryptase
    • -Proteoglycans (increase endothelial cell permeability)
  23. Effects of Histamine
    • This relates to the type of histamine receptors on the cells
    • -Inflamation
    •   -Causes vasodiolaiton of capillaries
    •   -Increases vascular permeability
    • -Contracts smooth muscle in the bronchi, GI tract, and uterus
    • -Increases bronchial, intestinal, and saivary secreations
    • -Dilation of cerebral blood vessels (headache)
    • -Stimulates secretion of gastric juices
    • -Stimulates nerve endings to cause pain and itching
  24. Mast Cell Mediator synthesis
    • these are made by the mast cell when it is stimulated
    • Lipid mediators -chemicals that are stimulated and released
    •  -Prostaglandins
    •  -Leukotrienes
    •  -Platelet-activating factor (PAF)
  25. Leukotrienes
    • Produce histamine-like effects
    • Slower, more prolonged response
    • play an important role in the pathophysiology of asthma
    • Leukotriene inhibitors (found in inhalers) used for more severe forms of asthma and also to prevent exercise-induced asthma; may be helpful in allergic rhinitis 
    •   -Montelukast
    •   -Zafirlukast
    •   -Zileuton
  26. Prostiglandins (PGs)
    • Encourage vascular permeability, chemotaxis, and pain
    • Made by enzymes called cyclo-oxygenase (COX)
    • Non-steroidal anti-inflammatory drugs (NSAIDs, such as aspirin) are COX inhibitors
  27. Phagocytosis and Phagocyte migration
    • Rolling: cells slowed by interaction with endothelium
    • Margination: increased stickiness by producing adhesion proteins on the cell
    • Diapedesis: emigration through the retracted entothelial junctions and basement membrane
    • Exudation
    • Phagocytosis
  28. Neutrophils
    • 70% of WBCs, live 5 days on average (die by apoptosis)
    • Dive into puss and die
    • Phagocytose invaders, then drop chemical bombs on them to kill them
  29. Macrophages
    • Migrate into tissues, where they lie in wait as macrophages
    • Enter the site after 24 hours to help replace neutrophils 
    • Survive longer than neutrophils
    • Professional antigen presenting cells
  30. Chronic inflammation
    • Last longer than acute inflammation
    • usually last longer then 2 weeks
    • it is often the result of unsuccessful acute inflammation
    • Occurs when the body fails to remove the cause of the inflammation
    •   -weak pathogens
    •   -Large, resistant or persistent pathogens
    •   -Weak immune response
  31. Histological differences between chronic and acute inflammation
    • Chronic inflammation demonstrates a dense infiltration of lymphocytes and macrophages
    •  -if macrophages cant protect the tissue from damage, the body will protect itself walling off the infected site, forming a granuloma 
    • Granulomas are formed by macrophages which join together like bricks in a wall to encircle the offender
  32. Wound healing:
    Regeneration of the tissue
    • the goal of healing in inflammation
    • results in the restoration of the structure, therefore function
    • regeneration replaces the damaged tissue with the same kind of functional tissue that was there before
  33. Wound healing:
    • The replacement of destroyed tissue with scare tissue
    •   -scare tissue restores strength, but not function
    • If a tissue isn't able to adequately regenerate because the wound is large, fibrin persists in the lesion, or if granulomas form, the wound will likely be repaired , not regenerated
  34. Wound healing:
    • clean up the wound by phagocytizing particulate matter (fibrin, microorganisms, RBCs, and dead cells)
    • Afterwords, healing continues
    •  -Filling in the wound
    •  -Covering/sealing the wound
    •  -Shrinking the wound
  35. Wound healing:
    Simple wounds (Minimal tissue loss)
    • Regenerated and healed by primary intention
    •  -Examples: paper cut, incised wounds, sutured laceration
  36. Wound healing:
    Open wound
    • requires more tissue replacement and healing occurs through secondary intention
    •  -Examples: pressure sores, non-sutured laceration, burns
  37. Regeneration and Repair statges
    • Phase I: Inflammation
    •   -coagulation and infiltration of cells to facilitate healing
    •   -Debridement and angiogenesis
    • Phase II: Proliferation and New Tissue Formation
    •   -Fibroblast proliferation, collagen synthesis, and epithelialization
    • Phase III: Remondeling and Maturation
    •   -Cellular differentiation, scar tissue remodeling, capillaries removed from scare tissue
  38. Dysfunctional Wound healing
    • Dysfunction during inflammatory phase
    •   -Hemorrhage
    •   -Infection
    •   -Chronic inflammation (excess granuloma formation)
    • Affected by:
    •   -Diabetes, hypoxia, nutritional deficiency, reactivation of inflammatory responses, and anti-inflammatory medications
    • Impaired collagen synthesis from nutritional deficiency
    •   -Lack of vitamin C (scurvy), iron, calcium, and copper
    • Excessive collagen synthesis
    •   -Adhesions, hypertropic (remains within the boarders of the original wound) and keloid scars (extends beyond the boarders of the original wound
    • Wound disruption
    •   -reopening (dehiscence) due to collagen disruption
    •    -wound healing by primary intention is now healing by secondary intention
    • Excessive wound contraction
    •   -vasoconstiction- or nerve constriction
Card Set
Patho Unit 4 ch. 5
Patho Unit 4 ch. 5