Part 2: The Immune System
Prepared by: Mae Michelle F. Aguilar RN
Advanced Pathophysiology
USI – Graduate School MAN MS
A PROTECTIVE RESPONSE intended to
eliminate the initial cause of cell injury as well
as necrotic cells and tissues resulti...
Inflammatory conditions are named with adding
the suffix –itis
Two Basic Patterns
ACUTE
CHRONIC
The early reaction of local tissues and their
blood vessels to injury. Typically occurs before
the immune response.
Can be...
First Century AD , Roman physician Celsus
described the local reaction to injury.
RUBOR (Redness)
TUMOR (Swelling)
CALOR (...
2nd Century AD, Greek physician Galen added
the 5th cardinal sign
• Functio laesa (loss of
function)
Occurs as chemical mediators produced at the
site of inflammation gain entrance to the
circulatory system.
TWO COMPONENTS:...
Momentary vasoconstriction followed rapidly by
vasodilation.
Vasodilation causes Hyperemic Response: Area
becomes congeste...
Loss of proteins reduces capillary osmotic
pressure and increases interstitial osmotic
pressure.
Accompanied with an incre...
Fluid moves out of the vessels, stagnation of
flow and clotting of blood occurs.
Marked by the movement of WBCs or
leukocytes into the area of injury
GRANULOCYTES
MONOCYTES
Characterized by their cytoplasmic granules.
Three Types: Neutrophils, Eosinophils, Basophils
Neutrophils are the primary phagocyte that
arrives early at the site of inflammation.
Their cytoplasmic granules contain enzymes and other
antibacterial substances that are used in destroying and
degrading th...
Called polymorphonuclear neutrophils (PMNs)
or segmented neutrophils (segs)
Increases greatly during an inflammatory
proce...
After release from the bone marrow,
neutrophils have a lifespan of 10 hours.
LEUKOCYTOSIS
Stain red with acid
dye eosin
Increased in the
blood during allergic
reactions and
parasitic infections.
Granules contain proteins that are highly toxic
to large parasitic worms that cannot be
phagocytize.
Plays an important ro...
Stains blue with basic dye, contains histamine
and other bioactive mediators of inflammation.
MAST CELLS – resides in conn...
Monocytes are the largest
of the circulating WBC and
constitute 3 % and 8 % of
total back leukocytes.
Life span is longer ...
THREE DISTINCT STEPS
Adherence plus opsonization
Engulfment
Intracellular Killing
OPOSONIZATION – Enhanced binding of an
a...
Major mediators:
Kinins, Bradykinins - causes increased capillary
permeability and pain
Proteins of the Complement System ...
HISTAMINE AND SEROTONIN
Found in mast cells of connective tissues and
blood basophils and platelets.
Released when there i...
Histamine causes dilatation of arterioles and
increases permeability of venules.
Serotonin is a performed mediator, found ...
Injured tissue,
Inflammatory mediators
Cell membrane
phospholipids
Arachidonic acid
Lipoxygenase
pathway
Cyclooxygenase
pa...
PLATELET ACTIVATING FACTOR (PAF)
Synthesized by all inflammatory cells, endothelial
cells and injured tissue cells.
Causes...
CYTOKINES
Include colony stimulating factors that direct the
growth of immature marrow precursor cells and
the interleukin...
NITRIC OXIDE
Relaxes vascular smooth muscle, reduces platelet
aggregation and adhesion.
Regulator of leukocyte recruitment...
Serous exudates – watery fluids low in protein
content that result from entering the
inflammatory site.
Are You
SEROUS?!!!
Hemorrhagic exudates- severe tissue injury that
damages blood vessels.
Fibrinous exudates- contains large amounts of
fibrinogen and form a thick and sticky
meshwork.
Membranous or Psudomembranous – necrotic
cells in fibropurulent exudate
Purulent or suppurative exudates – contains
pus, which is composed of degraded white
blood cells, proteins and tissue debr...
Abscess- localized area of inflammation
containing a purulent exudate.
Ulceration – a site of inflammation where an
epithelial surface has become necrotic and
eroded, often associated with sube...
ACUTE PHASE RESPONSE
ALTERATIONS IN WBC Count (Leukocytosis
or Leukopenia)
FEVER
Systemic inflammatory response (Sepsis or...
Begins hours or days of the onset of
inflammation or infection.
Changes in plasma proteins, increased ESR,
fever, increase...
Fever
Increased number of
immature neutrophils
 Release of cytokines
IL-1, IL- 6 and TNF- α
which affect the
thermoregula...
Lethargy
Produces amino acids
that can be used in
immune response and
tissue repair
 IL-1 and TNF – α
effects on the CNS
...
Increased ESR Liver dramatically
increases synthesis of
acute-phase proteins
such as fibrinogen and
C-reactive protein.
A...
C REACTIVE PROTEIN (CRP)
The classic acute phase reactant.
Low levels of CRP in the body, which rises when
there is an acu...
Interest has focused on the use of CRP as a
predictor of risk for cardiovascular events in
persons with atherosclerotic he...
LEUKOCYTOSIS – increase in WBC especially
when caused by a bacterial infection.
15,000 to 20,000 cells/μl (4,000-10,000 ce...
Bacterial infections – neutrophilia
Parasitic and allergic responses – eosinophilia
Viral infections – neutropenia and an ...
LYMPHADENITIS – painful, palpable nodes are
commonly associated with INFLAMMATORY
process, non painful lymph nodes are
cha...
Self perpetuating and lasts for weeks, months or
even years.
A result of a recurrent or progressive acute
inflammatory res...
Infiltration of MACROPHAGES AND
LYMPHOCYTES instead of neutrophils
Proliferation of fibroblasts instead of exudates.
Agent...
Viruses, fungi, bacteria, larger parasites of
moderate to low virulence.
Presence of injured tissue such as that
surroundi...
Diffuse accumulation of macrophages and
lymphocytes at the site of the injury.
Leads to fibroblast proliferation, then sca...
A, Chronic inflammation in the lung, showing all three characteristic
histologic features: (1) collection of chronic infla...
Granuloma is a small 1-2 mm lesion in which
there is massing of macrophages surrounded by
lymphocytes.
Also called Epithel...
A response to tissue injury and represents an
attempt to maintain normal tissue structure and
function.
TISSUE REGENERATIO...
Replacement of injured tissue with cells of the
same type.
Three types:
LABILE cells – continues to divide and
replicate t...
STABLE CELLS – normally stops dividing when
growth ceases.
PERMANENT OR FIXED CELLS – cannot
undergo mitotic division. i.e...
Severe or persistent injury with damage to both
the parenchymal cells and extracellular matrix
(ECM).
Repair by replacemen...
GRANULATION TISSUE
Glistening red, moist connective tissue that
contains newly formed capillaries,
proliferating fibroblas...
Development involves Angiogenesis (growth of
new capillaries) and Fibrogenesis (formation of
scar tissue.)
Fibrogenesis involves the influx of activated
fibroblasts.
Fibroblasts secrete components of the ECM
Fibronectin, hyaluron...
Collagen synthesis – important to development
of the strength in wound healing.
Chemical mediators and Growth factors
Chemical mediators of the inflammatory
response
Growth factors control proliferation...
EXTRACELLULAR MATRIX (ECM)
Provides turgor to soft tissue and rigidity to bone.
ECM must be intact for restoration of norm...
Malnutrition
Blood flow and oxygen delivery
Impaired inflammatory or immune response
Wound separation, infection and forei...
Body temperature Maintained at 36.0 -37.5 ˚C
Regulated by the thermoregulatory center in
the hypothalamus.
FEVER – increas...
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
Inflammation, Tissue repair and fever
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Inflammation, Tissue repair and fever

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Inflammation, Tissue repair and fever

  1. 1. Part 2: The Immune System Prepared by: Mae Michelle F. Aguilar RN Advanced Pathophysiology USI – Graduate School MAN MS
  2. 2. A PROTECTIVE RESPONSE intended to eliminate the initial cause of cell injury as well as necrotic cells and tissues resulting from that injury.
  3. 3. Inflammatory conditions are named with adding the suffix –itis Two Basic Patterns ACUTE CHRONIC
  4. 4. The early reaction of local tissues and their blood vessels to injury. Typically occurs before the immune response. Can be triggered by: infections, immune reactions, blunt and perforating trauma, physical or chemical agents and tissue necrosis.
  5. 5. First Century AD , Roman physician Celsus described the local reaction to injury. RUBOR (Redness) TUMOR (Swelling) CALOR (Heat) DOLOR (Pain)
  6. 6. 2nd Century AD, Greek physician Galen added the 5th cardinal sign • Functio laesa (loss of function)
  7. 7. Occurs as chemical mediators produced at the site of inflammation gain entrance to the circulatory system. TWO COMPONENTS: VASCULAR STAGE AND CELLULAR STAGE
  8. 8. Momentary vasoconstriction followed rapidly by vasodilation. Vasodilation causes Hyperemic Response: Area becomes congested causing redness and warmth. Accompanied by an increase in vascular permeability with outpouring of protein-rich fluid (exudates) into the extravascular spaces.
  9. 9. Loss of proteins reduces capillary osmotic pressure and increases interstitial osmotic pressure. Accompanied with an increase in capillary pressure causes outflow of fluid and its accumulation in tissues and spaces produce swelling, pain and impaired function.
  10. 10. Fluid moves out of the vessels, stagnation of flow and clotting of blood occurs.
  11. 11. Marked by the movement of WBCs or leukocytes into the area of injury GRANULOCYTES MONOCYTES
  12. 12. Characterized by their cytoplasmic granules. Three Types: Neutrophils, Eosinophils, Basophils
  13. 13. Neutrophils are the primary phagocyte that arrives early at the site of inflammation.
  14. 14. Their cytoplasmic granules contain enzymes and other antibacterial substances that are used in destroying and degrading the engulfed particles Contains oxygen dependent metabolic pathways that generate toxic oxygen and nitrogen products that destroy pathogens.
  15. 15. Called polymorphonuclear neutrophils (PMNs) or segmented neutrophils (segs) Increases greatly during an inflammatory process especially during bacterial infections.
  16. 16. After release from the bone marrow, neutrophils have a lifespan of 10 hours. LEUKOCYTOSIS
  17. 17. Stain red with acid dye eosin Increased in the blood during allergic reactions and parasitic infections.
  18. 18. Granules contain proteins that are highly toxic to large parasitic worms that cannot be phagocytize. Plays an important role in allergic reactions by controlling release of specific chemical mediators.
  19. 19. Stains blue with basic dye, contains histamine and other bioactive mediators of inflammation. MAST CELLS – resides in connective tissue throughout the body.
  20. 20. Monocytes are the largest of the circulating WBC and constitute 3 % and 8 % of total back leukocytes. Life span is longer that granulocytes. Arrive at the inflammatory site within 24 hours and by 48 hours Monocytes and macrophages are the predominant type Also plays a role in chronic inflammation
  21. 21. THREE DISTINCT STEPS Adherence plus opsonization Engulfment Intracellular Killing OPOSONIZATION – Enhanced binding of an antigen due to antibody or complement Intracellular killing of pathogens is accomplished by lysosomal enzymes and oxygen-dependent mechanisms.
  22. 22. Major mediators: Kinins, Bradykinins - causes increased capillary permeability and pain Proteins of the Complement System – cascade of plasma proteins that plays an important role in immunity and inflammation Complement System contribute to inflammation 1. Causes vasodilation and increasing vascular permeability 2. Promoting leukocyte activation, adhesion and chemostaxis 3. Augmenting Phagocytosis
  23. 23. HISTAMINE AND SEROTONIN Found in mast cells of connective tissues and blood basophils and platelets. Released when there is trauma and immune reactions involving binding of immunoglobulin E (IgE) antibodies to mast cells.
  24. 24. Histamine causes dilatation of arterioles and increases permeability of venules. Serotonin is a performed mediator, found in platelets, that has actions similar to those of histamine . ARACHIDONIC ACID METABOLITES
  25. 25. Injured tissue, Inflammatory mediators Cell membrane phospholipids Arachidonic acid Lipoxygenase pathway Cyclooxygenase pathway Leukotrinenes (LTC4, LTD4, LTE4) Prostaglandins (PGI2, PGF2a Thromboxane (TxA2) Smooth muscle contraction Constricts pulmo airways Increases microvascular permeability Vasodilation and bronchoconstriction Inhibits inflammatory cell function Vasoconstriction Bronchoconstriction Promotes platelet function c c c Corticosteroid Medication Aspirin, NSAIDs
  26. 26. PLATELET ACTIVATING FACTOR (PAF) Synthesized by all inflammatory cells, endothelial cells and injured tissue cells. Causes Platelet Aggregation and enhances functions of neutrophils and monocytes. A potent eosinophil chemoattractant. A potent vasodilator
  27. 27. CYTOKINES Include colony stimulating factors that direct the growth of immature marrow precursor cells and the interleukins (IL), Interferons (IFN) and Tumor necrosis factor (TNF)
  28. 28. NITRIC OXIDE Relaxes vascular smooth muscle, reduces platelet aggregation and adhesion. Regulator of leukocyte recruitment and aids in killing microbes by Phagocytic cells.
  29. 29. Serous exudates – watery fluids low in protein content that result from entering the inflammatory site. Are You SEROUS?!!!
  30. 30. Hemorrhagic exudates- severe tissue injury that damages blood vessels.
  31. 31. Fibrinous exudates- contains large amounts of fibrinogen and form a thick and sticky meshwork.
  32. 32. Membranous or Psudomembranous – necrotic cells in fibropurulent exudate
  33. 33. Purulent or suppurative exudates – contains pus, which is composed of degraded white blood cells, proteins and tissue debris.
  34. 34. Abscess- localized area of inflammation containing a purulent exudate.
  35. 35. Ulceration – a site of inflammation where an epithelial surface has become necrotic and eroded, often associated with subepithelial inflammation.
  36. 36. ACUTE PHASE RESPONSE ALTERATIONS IN WBC Count (Leukocytosis or Leukopenia) FEVER Systemic inflammatory response (Sepsis or septic shock)
  37. 37. Begins hours or days of the onset of inflammation or infection. Changes in plasma proteins, increased ESR, fever, increased leukocyte count, skeletal muscle catabolism, and negative nitrogen balance. Due to release of cytokines (IL -1, IL- 6 and TNF-α)
  38. 38. Fever Increased number of immature neutrophils  Release of cytokines IL-1, IL- 6 and TNF- α which affect the thermoregulatory center in the hypothalamus IL – 1 and other cytokines stimulate the bone marrow.
  39. 39. Lethargy Produces amino acids that can be used in immune response and tissue repair  IL-1 and TNF – α effects on the CNS Skeletal muscle catabolism
  40. 40. Increased ESR Liver dramatically increases synthesis of acute-phase proteins such as fibrinogen and C-reactive protein. Acute phase proteins dampen the repulsive effect of like charges on red blood cells causing them to clump or aggregate, forming stacks (rouleau formations)
  41. 41. C REACTIVE PROTEIN (CRP) The classic acute phase reactant. Low levels of CRP in the body, which rises when there is an acute inflammatory response. Function is protective, binds to the surface of invading microbes and targets them for destruction through complement and phagocytosis Has an anti-inflammatory function.
  42. 42. Interest has focused on the use of CRP as a predictor of risk for cardiovascular events in persons with atherosclerotic heart disease.
  43. 43. LEUKOCYTOSIS – increase in WBC especially when caused by a bacterial infection. 15,000 to 20,000 cells/μl (4,000-10,000 cells/ μl) “shift to the left” in WBC differential count refers to the increase in immature neutrophils seen in severe infections
  44. 44. Bacterial infections – neutrophilia Parasitic and allergic responses – eosinophilia Viral infections – neutropenia and an increase in lymphocytes (lymphocytosis) Infections in persons with debilitating diseases such as cancer – Leukopenia.
  45. 45. LYMPHADENITIS – painful, palpable nodes are commonly associated with INFLAMMATORY process, non painful lymph nodes are characteristics of NEOPLASMS
  46. 46. Self perpetuating and lasts for weeks, months or even years. A result of a recurrent or progressive acute inflammatory response or from failure of the acute response.
  47. 47. Infiltration of MACROPHAGES AND LYMPHOCYTES instead of neutrophils Proliferation of fibroblasts instead of exudates. Agents: low grade fever, persistent irritants that are unable to penetrate deeply or spread rapidly. (i.e. talc, asbestos, silica)
  48. 48. Viruses, fungi, bacteria, larger parasites of moderate to low virulence. Presence of injured tissue such as that surrounding a healing fracture.
  49. 49. Diffuse accumulation of macrophages and lymphocytes at the site of the injury. Leads to fibroblast proliferation, then scar formation that replaces connective tissue or the functional parenchymal tissues of the involved structures.
  50. 50. A, Chronic inflammation in the lung, showing all three characteristic histologic features: (1) collection of chronic inflammatory cells (*), (2) destruction of parenchyma (normal alveoli are replaced by spaces lined by cuboidal epithelium, arrowheads), and (3) replacement by
  51. 51. Granuloma is a small 1-2 mm lesion in which there is massing of macrophages surrounded by lymphocytes. Also called Epithelioid cells. Associated with foreign bodies such as splinters, sutures, silica, and asbestos and microorganisms that cause tuberculosis, syphilis and sarcoidosis, deep fungal infections and brucellosis.
  52. 52. A response to tissue injury and represents an attempt to maintain normal tissue structure and function. TISSUE REGENERATION FIBROUS TISSUE REPAIR
  53. 53. Replacement of injured tissue with cells of the same type. Three types: LABILE cells – continues to divide and replicate throughout life. i.e. Surface epithelial cells of skin, oral cavity, vagina and cervix, Columnar epithelium of GI, uterus, and fallopian tubes. Transitional epithelium of bone marrow and urinary tract.
  54. 54. STABLE CELLS – normally stops dividing when growth ceases. PERMANENT OR FIXED CELLS – cannot undergo mitotic division. i.e. Nerve cells, skeletal muscle cells, cardiac muscle cells.
  55. 55. Severe or persistent injury with damage to both the parenchymal cells and extracellular matrix (ECM). Repair by replacement of connective tissue, process involving generation of granulation tissue and formation of scar tissue.
  56. 56. GRANULATION TISSUE Glistening red, moist connective tissue that contains newly formed capillaries, proliferating fibroblasts and residual inflammatory cells.
  57. 57. Development involves Angiogenesis (growth of new capillaries) and Fibrogenesis (formation of scar tissue.)
  58. 58. Fibrogenesis involves the influx of activated fibroblasts. Fibroblasts secrete components of the ECM Fibronectin, hyaluronic acid, proteoglycans, collagen. Scar formatio: 1. Emigration and proliferation of fibroblasts into sites of injury 2. deposition of ECM by these cells
  59. 59. Collagen synthesis – important to development of the strength in wound healing.
  60. 60. Chemical mediators and Growth factors Chemical mediators of the inflammatory response Growth factors control proliferation, differentiation and metabolism of cells during wound healing Contribute the generation of ECM, stimulate angiogenesis and assist in inflammatory processes Examples of GF: PDGF, FGF, EGF
  61. 61. EXTRACELLULAR MATRIX (ECM) Provides turgor to soft tissue and rigidity to bone. ECM must be intact for restoration of normal structure.
  62. 62. Malnutrition Blood flow and oxygen delivery Impaired inflammatory or immune response Wound separation, infection and foreign bodies
  63. 63. Body temperature Maintained at 36.0 -37.5 ˚C Regulated by the thermoregulatory center in the hypothalamus. FEVER – increase in body temperature due to resetting of the hypothalamic thermoregulatory set point as a result of endogenous pyrogens released from host macrophages or endothelial cells. An adaptive response to bacterial and viral infections or to tissue injury. The growth rate of microorganisms is inhibited and immune function is enhanced.

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