non specific host defenses

1. Non-specific Host Defenses
Prepared by:
GEORGINE L. MANANTAN, RMT,RN,RM,MSN

2. Introduction:

3. Resistance
Ability to ward off disease.
The capacity of an organism
to defend itself against a
disease.
The capacity of an organism
or a tissue to withstand the
effects of a harmful
environmental agent.

4. Nonspecific Resistance:
Defenses that protect
against all pathogens.
Specific Resistance:
Protection against
specific pathogens.

5. Susceptibility:
Vulnerability or lack of resistance.
the state of being predisposed to,
sensitive to, or of lacking the
ability to resist a pathogen,
familial disease, or a drug.

6. Protection
Against
Invading

7. First Line of Defense:
 Non-specific natural
barriers which restrict
entry of pathogen.
Examples: Skin and
mucous membranes.

8. Second Line of Defense:
Innate non-specific immune
defenses provide rapid local
response to pathogen after it
has entered host.
Examples: Fever, phagocytes
(macrophages & neutrophils),
inflammation, and interferon.

9. cells

10. Third line of defense:
Antigen-specific immune
responses, specifically target
and attack invaders that get
past first two lines of
defense.
Examples: Antibodies
and lymphocytes.

11. antibodies

13. Three Lines of Defense Against Infection

14. First Line of Defense:
Skin and Mucous
Membranes

15. I. Mechanical Defenses
1. Skinhas two Layers:
A.Epidermis
 Thin outer layer of epithelial
tissue.
 Contains Langerhans cells,
dead cells, and keratin

16. B. Dermis
Thick inner layer of connective
tissue.
Infections are rare in intact skin.
Exceptions:
Hookworms can penetrate intact
skin
Dermatophytes: “Skin loving”
fungi

17. Intact Skin is an Effective
Barrier Against Most
Pathogens

18. I. Mechanical Defenses
2. Mucous Membranes
Line gastrointestinal,
genitourinary, and
respiratory tracts.

19. Two layers: Outer epithelial and inner connective
layer.
Epithelial layer secretes
mucus which maintains
moist surfaces.
Although they inhibit
microbial entry, they offer
less protection than skin.

20. Several microorganisms are capable of
penetrating mucous membranes:
•Papillomavirus
•Treponema pallidum
•Enteroinvasive E. coli
•Entamoeba histolytica

21. Papillomavirus

22. Treponema
pallidum

23. Entamoeba coli Entamoeba histolytica

24. I. Mechanical Defenses
3. Lacrimal apparatus
Continual washing and
blinking prevents
microbes from settling
on the eye surface.

25. Lacrimalapparatus

26. 4. Saliva
Washes microbes from teeth
and mouth mucous membranes.
5. Mucus
Thick secretion that traps many
microbes.

27. 6. Nose Hair
 Coated with
mucus filter
dust, pollen,
and microbes.

28. 7. Ciliary Escalator
Cilia on
mucous
membranes of
lower
respiratory
tract move
upwards
towards throat
at 1-3 cm/hour.

29. 8. Coughing and sneezing:
Expel
foreign
objects.

30. 9. Epiglottis
Covers
larynx during
swallowing.

31. Epiglottis Protects Respiratory System from Infection During
Swallowing

32. 10. Urination
 Cleanses urethra.
11. Vaginal Secretions:
Remove microbes from
genital tract.

33. B. Chemical Defenses:
Sebum:
 Oily substance produced by
sebaceous glands that forms a
protective layer over skin.
 Contains unsaturated fatty acids
which inhibit growth of certain
pathogenic bacteria and fungi.

34. pH
Low, skin pH usually between
3 and 5. Caused by lactic acid
and fatty acids.

35. Perspiration:
Produced by sweat
glands.
 Contains
lysozyme and
acids.

36. Lysozyme
Enzyme that
breaks down
gram-positive
cell walls.
Found in nasal
secretions,
saliva, and tears.

37. B. Chemical Defenses
Gastric Juice
Mixture of hydrochloric acid,
enzymes, and mucus. pH between
1.2 to 3 kills many microbes and
destroys most toxins. Many enteric
bacteria are protected by food
particles.

38. Helicobacter pylori
neutralizes stomach acid and
can grow in the stomach, causing
gastritis and ulcers.

39. Helicobacterpylori

40. Transferrins
Iron-binding proteins in
blood which inhibit
bacterial growth by
reducing available iron.
 also called Siderophilin, protein
(beta1 globulin) in blood plasma that
transports iron from the tissues and
bloodstream to the bone marrow,
where it is reused in the formation of
hemoglobin.

41. Cellular Elements of Blood
Cell Type # Cells/mm3 Function
Erythrocytes (RBC) 4.8-5.4 million Transport O2 and CO2
Leukocytes (WBC) 5,000-10,000 Various
A. Granulocytes:
1. Neutrophils (70% of WBC) Phagocytosis
2. Basophils (1%) Produce histamine
3. Eosinophils (4%) Toxins against parasites
some phagocytosis
B. Monocytes/Macrophages (5%) Phagocytosis
C. Lymphocytes (20%) Antibody production (B cells)
Cell mediated immunity (T cells)
Platelets 300,000 Blood clotting

42. Composition of Human Blood

43. Platelets Form Blood Clots

44. II. Second Line of Defense

45. 1. Phagocytosis
Derived from the Greek words
“Eat and cell”.
Phagocytosis is carried out by
white blood cells:
macrophages,
neutrophils,
occasionally eosinophils.

46. Neutrophils
predominate early in
infection.

47. Wandering macrophages
Originate from monocytes that
leave blood and enter infected
tissue, and develop into
phagocytic cells.

48. Fixed Macrophages (Histiocytes):
Located in liver, nervous
system, lungs, lymph
nodes, bone marrow, and
several other tissues.

49. 1. Chemotaxis
Phagocytes
are
chemically
attracted to
site of
infection.

50. Phagocytic Cells: Macrophages (Monocytes), Neutrophils, and
Eosinophils
(Macrophages)

51. Stages of
Phagocytosis

52. Phagocytes are Attracted to Site of Infection by
Chemotaxis

53. 2. Adherence:
Phagocyte plasma membrane
attaches to surface of pathogen
or foreign material.
Adherence can be inhibited by
capsules (S. pneumoniae) or M
protein (S. pyogenes).

54. Opsonization:
Coating process with opsonins
that facilitates attachment.
Opsonins
include antibodies and
complement proteins.

55. 3. Ingestion
Plasma membrane of
phagocytes extends
projections (pseudopods)
which engulf the microbe.
Microbe is enclosed in a sac
called phagosome.

56. 4. Digestion
 Inside the cell, phagosome fuses with
lysosome to form a phagolysosome.
Lysosomal enzymes kill most bacteria within
30 minutes and include:
• Lysozyme: Destroys cell wall
peptidoglycan
• Lipases and Proteases
• RNAses and DNAses
After digestion, residual body with
undigestable material is discharged.

57. Process of Phagocytosis

58. Inflammatio
nTriggered by tissue damage due
to infection, heat, wound, etc.

59. Functions of
Inflammation
1. Destroy and remove pathogens
2. If destruction is not possible, to limit
effects by confining the pathogen and its
products.
3. Repair and replace tissue damaged by
pathogen and its products.

60. HOST DEFENSE

61. HOST DEFENSE
POLYMORPHONUCLEAR
LEUKOCYTES
Neutrophils
Eosinophils
Basophils
CELLULAR PARTICIPANTS

62. POLYMORPHONUCLEAR LEUKOCYTES
Neutrophil Eosinophil
Basophil

63. HOST DEFENSE
MONONUCLEAR
LEUKOCYTES
Lymphocytes
Monocytes
CELLULAR PARTICIPANTS

64. LYMPHOCYTES

65. MONOCYTE/HISTIOCYTE/MACROPHAGE

66. PLATELETS

67. I
n
t
e
n
s
i
t
y
Time
Neutrophils
Lymphocytes
Macrophages
Fibroblasts
Fibrosis
Acute Chronic Scar
HOST DEFENSE
INJURY REPAIR

68. ACUTE
INFLAMMATION

69. ACUTE INFLAMMATION
INJURY Acute
inflammation
Mediators

70. ACUTE INFLAMMATION

71. Inflammation
Major Symptoms of Inflammation:
LOCAL MANIFESTATION
1. Redness
2. Pain
3. Heat
4. Swelling
5. Loss of function

72. Fever
Chills
Myalgia
Malaise
ACUTE INFLAMMATION
SYSTEMIC MANIFESTATIONS

73. • Leukocytosis
(granulocytosis vs. lymphocytosis)
• Elevated serum acute phase proteins
(C-reactive protein, fibrinogen, etc)
• Increased ESR
(erythrocyte sedimentation rate)
• Hypercoagulability
ACUTE INFLAMMATION
LABORATORY MANIFESTATIONS

74. ACUTE INFLAMMATION
SEQUELAE
INJURY
RESOLUTION
Autoimmune disease
Chronic inflammation
Acute inflammation
Viral infection
Chronic irritation
Mediators
Mediators

75. ACUTE INFLAMMATION

76. Vasoconstriction
Vasodilation
Increased
vascular
permeability
Hemoconcentrati
on and stasis
Phagocytosis
Leukocyte
Adhesion
Transmigration
Chemotaxis
Aggregation
ACUTE INFLAMMATION
SEQUENCE OF EVENTS

77. Stages of Inflammation
1. Vasodilation
 Increase in diameter of blood
vessels.
 Triggered by chemicals released
by damaged cells: histamine,
kinins, prostaglandins, and
leukotrienes.

78. ACUTE INFLAMMATION
VASODILATION

79. ACUTE INFLAMMATION
VASODILATION

80. Increasein
Permeability
Time
ACUTE INFLAMMATION
INCREASED VASCULAR PERMEABILITY
Histamine (Mast Cells)
Seratonin (Platelets)

81. Normal flow
Stasis
ACUTE INFLAMMATION
HEMOCONCENTRATION AND STASIS

82. ACUTE INFLAMMATION
LEUKOCYTE ADHESION

83. ACUTE INFLAMMATION
LEUKOCYTE ADHESION

84. ACUTE INFLAMMATION
EMIGRATION (TRANSMIGRATION)

85. ACUTE INFLAMMATION
EMIGRATION (TRANSMIGRATION)

86. ACUTE INFLAMMATION
CHEMOTAXIS

87. ACUTE INFLAMMATION
AGGREGATION

88. ACUTE INFLAMMATION
PHAGOCYTOSIS - ATTACHMENT

89. ACUTE INFLAMMATION
PHAGOCYTOSIS - ENGULFMENT

90. ACUTE INFLAMMATION
PHAGOCYTOSIS – KILLING AND DEGRADATION

91. ACUTE INFLAMMATION

92. 2. Phagocyte Migration and
Margination
Margination is the process in which
phagocytes stick to lining of blood
vessels.
Diapedesis (Emigration):
Phagocytes squeeze between
endothelial cells of blood vessels
and enter surrounding tissue.

93. Phagocytes are attracted to site of
infection through chemotaxis.
Phagocytes destroy microbes, as
well as dead and damaged host
cells.
3. Tissue Repair
Dead and damaged cells are
replaced.

94. Process of Inflammation

95. Serous
Catarrhal
Fibrinous
Hemorrhagic
Suppurative
Gangrenous
Pseudomembranou
s
ACUTE INFLAMMATION
PATTERNS

96. ACUTE INFLAMMATION
SEROUS

97. ACUTE INFLAMMATION
SEROUS

98. ACUTE INFLAMMATION
CATARRHAL

99. ACUTE INFLAMMATION
FIBRINOUS

100. ACUTE INFLAMMATION
HEMORRHAGIC

101. ACUTE INFLAMMATION
SUPPURATIVE / PURULENT

102. ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - ABSCESS

103. ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - ABSCESS

104. ACUTE INFLAMMATION
SUPPURATIVE / PURULENT - EMPYEMA

105. Thomas McGovern M.D.
ACUTE INFLAMMATION
ULCERATIVE

106. ACUTE INFLAMMATION
GANGRENOUS

107. ACUTE INFLAMMATION
GANGRENOUS
Appendix Gallbladder

108. Atlanta South Gastroenterology, P.C.
ACUTE INFLAMMATION
PSEUDOMEMBRANOUS

109. Antimicrobial Substances:
I. Complement System:
Large group of serum proteins that
participate in the lysis of foreign
cells, inflammation, and
phagocytosis.

110. II. Interferons:
Antiviral proteins that interfere with viral
multiplication.
• Small proteins (15,000 to 30,000 kDa)
• Heat stable and resistant to low pH
• Important in acute and short term
infections.
• Have no effect on infected cells.
• Host specific, but not virus specific.

111. Interferon alpha and beta: Produced
by virus infected cells and diffuse
to neighboring cells. Cause
uninfected cells to produce antiviral
proteins (AVPs).
Interferon gamma: Produced by
lymphocytes. Causes neutrophils
to kill bacteria.

112. Two mechanisms of
complement activation:

113. 1. Classical Pathway: Initiated by an
immune reaction of antibodies.
2. Alternative Pathway: Initiated by
direct interaction of complement
proteins with microbial
polysaccharides.
 Both pathways cleave a complement protein
called C3, which triggers a series of events.

114. Classical Complement Pathway is
Triggered by Antibodies Binding to
Foreign Cells

115. Both Classical and Alternative Complement Pathways
Trigger the Cleavage of C3

116. Consequences of
Complement Activation

117. 1. Cytolysis: Due to the formation
of a membrane attack complex
(MAC) which produces lesions
in microbial membranes.
2. Inflammation: Complement
components (C3a) trigger the
release of histamine, which
increases vascular permeability.

118. 3. Opsonization: Complement
components (C3b) bind to
microbial surface and promote
phagocytosis.
4. Inactivation of Complement:
Regulatory proteins limit damage
to host cells that may be caused
by complement.

119. Classical and Alternative Complement Pathways
Cause Inflammation, Opsonization, and Cytolysis

120. Cytolysis Caused by Membrane Attack
Complex

121. Thank you…