The document provides an overview of the immune system and inflammation. It discusses the inflammatory response process, including the vascular and cellular stages. It describes the signs of inflammation (rubor, tumor, calor, dolor, functio laesa) and cells involved in inflammation like neutrophils, eosinophils, basophils, and monocytes. It also discusses mediators of inflammation like kinins, complement system, histamine, serotonin, arachidonic acid metabolites, platelet activating factor, cytokines, and nitric oxide. Finally, it covers acute phase response, types of inflammation (acute vs chronic), and factors that influence wound healing.

1. Part 2: The Immune System
Prepared by: Mae Michelle F. Aguilar RN
Advanced Pathophysiology
USI – Graduate School MAN MS

2. A PROTECTIVE RESPONSE intended to
eliminate the initial cause of cell injury as well
as necrotic cells and tissues resulting from that
injury.

4. Inflammatory conditions are named with adding
the suffix –itis
Two Basic Patterns
ACUTE
CHRONIC

5. 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.

6. First Century AD , Roman physician Celsus
described the local reaction to injury.
RUBOR (Redness)
TUMOR (Swelling)
CALOR (Heat)
DOLOR (Pain)

7. 2nd Century AD, Greek physician Galen added
the 5th cardinal sign
• Functio laesa (loss of
function)

8. Occurs as chemical mediators produced at the
site of inflammation gain entrance to the
circulatory system.
TWO COMPONENTS: VASCULAR STAGE AND
CELLULAR STAGE

9. 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.

10. 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.

11. Fluid moves out of the vessels, stagnation of
flow and clotting of blood occurs.

12. Marked by the movement of WBCs or
leukocytes into the area of injury
GRANULOCYTES
MONOCYTES

13. Characterized by their cytoplasmic granules.
Three Types: Neutrophils, Eosinophils, Basophils

15. Neutrophils are the primary phagocyte that
arrives early at the site of inflammation.

16. 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.

17. Called polymorphonuclear neutrophils (PMNs)
or segmented neutrophils (segs)
Increases greatly during an inflammatory
process especially during bacterial infections.

18. After release from the bone marrow,
neutrophils have a lifespan of 10 hours.
LEUKOCYTOSIS

19. Stain red with acid
dye eosin
Increased in the
blood during allergic
reactions and
parasitic infections.

20. 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.

21. Stains blue with basic dye, contains histamine
and other bioactive mediators of inflammation.
MAST CELLS – resides in connective tissue
throughout the body.

22. 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

24. 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.

25. 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

26. 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.

27. 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

28. 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

29. 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

30. 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)

31. NITRIC OXIDE
Relaxes vascular smooth muscle, reduces platelet
aggregation and adhesion.
Regulator of leukocyte recruitment and aids in
killing microbes by Phagocytic cells.

33. Serous exudates – watery fluids low in protein
content that result from entering the
inflammatory site.
Are You
SEROUS?!!!

34. Hemorrhagic exudates- severe tissue injury that
damages blood vessels.

35. Fibrinous exudates- contains large amounts of
fibrinogen and form a thick and sticky
meshwork.

36. Membranous or Psudomembranous – necrotic
cells in fibropurulent exudate

37. Purulent or suppurative exudates – contains
pus, which is composed of degraded white
blood cells, proteins and tissue debris.

38. Abscess- localized area of inflammation
containing a purulent exudate.

39. Ulceration – a site of inflammation where an
epithelial surface has become necrotic and
eroded, often associated with subepithelial
inflammation.

40. ACUTE PHASE RESPONSE
ALTERATIONS IN WBC Count (Leukocytosis
or Leukopenia)
FEVER
Systemic inflammatory response (Sepsis or
septic shock)

41. 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)

42. 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.

43. 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

44. 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)

45. 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.

46. Interest has focused on the use of CRP as a
predictor of risk for cardiovascular events in
persons with atherosclerotic heart disease.

47. 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

48. 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.

49. LYMPHADENITIS – painful, palpable nodes are
commonly associated with INFLAMMATORY
process, non painful lymph nodes are
characteristics of NEOPLASMS

50. 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.

51. 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)

52. Viruses, fungi, bacteria, larger parasites of
moderate to low virulence.
Presence of injured tissue such as that
surrounding a healing fracture.

53. 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.

54. 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

55. 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.

59. A response to tissue injury and represents an
attempt to maintain normal tissue structure and
function.
TISSUE REGENERATION
FIBROUS TISSUE REPAIR

60. 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.

61. 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.

62. 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.

63. GRANULATION TISSUE
Glistening red, moist connective tissue that
contains newly formed capillaries,
proliferating fibroblasts and residual
inflammatory cells.

64. Development involves Angiogenesis (growth of
new capillaries) and Fibrogenesis (formation of
scar tissue.)

65. 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

66. Collagen synthesis – important to development
of the strength in wound healing.

67. 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

68. EXTRACELLULAR MATRIX (ECM)
Provides turgor to soft tissue and rigidity to bone.
ECM must be intact for restoration of normal
structure.

70. Malnutrition
Blood flow and oxygen delivery
Impaired inflammatory or immune response
Wound separation, infection and foreign bodies

72. 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.