INNATE IMMUNITY:
NONSPECIFIC
DEFENSE OF HOST
TOPIC OUTLINE
▪ IMMUNITY
▪ CONCEPTS OF IMMUNITY
▪ FIRST LINE OF DEFENSE
▪ PHYSICAL FACTORS (Skin and Mucus membrane)
▪ CHEMICAL FACTORS
▪ NORMAL MICROBIOTA AND INNATE IMMUNITY
▪ SECOND LINE OF DEFENSE
▪ FORMED ELEMENTS IN BLOOD
▪ LYMPHATIC SYSTEM
▪ PHAGOCYTE
▪ INFLAMMATION
▪ FEVER
▪ ANTIMICROBIAL SUBSTANCES
GUIDE QUESTIONS
▪ First white blood cells to be involved in acute
inflammation by pyogenic cocci
a. Macrophages
b. Polymorphonuclear leukocytes
c. Basophils
d. Lymphocytes
GUIDE QUESTIONS
▪ Helminth infections will cause an increase in
a. NK cells
b. Dendritic macrophages
c. Eosinophils
d. Pre-B cells
IMMUNITY (BIGGER PICTURE)
▪ FIRST LINE OF DEFENSE
▪ Keeps the pathogen outside or neutralizes infection before it begins
▪ Physical factors (Skin and MM, mucus, cilia, cerumen, flow of urine, and vaginal
secretion) and Chemical factors (Perspiration, Saliva, Gastric juices, Urine,
Vaginal secretion)
▪ SECOND LINE OF DEFENSE
▪ Slows or contains the infection when the first line of defense fails
▪ Includes defensive cells (phagocytic cells), inflammation, fever, antimicrobial
substances
▪ THIRD LINE OF DEFENSE
▪ Targets specific pathogens for destruction when second line of defense fails
▪ Memory component → allows the body to effectively combat the same
pathogens in the future
IMMUNITY (BIGGER PICTURE)
▪ WHITE BLOOD CELL COUNT
▪ Number of leukocyte found in the blood
▪ Differential WBC (Neutrophils, Lymphocytes,
Monocytes, Eosinophils, Basophils)
CONCEPTS OF IMMUNITY
▪ INNATE IMMUNE SYSTEM
▪ Defense present at birth
▪ Rapid but non-specific
▪ No memory component
▪ ADAPTIVE IMMUNE SYSTEM
▪ Slow and specific
▪ Memory component (rapid and stronger
response to same pathogen at a later date)
CONCEPTS OF IMMUNITY
▪ Response of INNATE SYSTEM are activated
by PROTEIN receptors in the plasma
membrane of phagocytic cell (E.g. Toll-
like receptor)
▪ Activated by pathogenic compounds called
Pathogen-Associated Molecular Patterns
(PAMPs) (E.g. LPS, Peptidoglycan, DNA and
RNA)
▪ Binding of TLR and PAMPs → Cytokines
FIRST LINE OF DEFENSE
▪ PHYSICAL FACTORS
▪ INTACT SKIN
▪ Epidermis consist of many layer of tightly packed
epithelial cells; topmost layer is dead and contains
protective layer (keratin)
▪ Periodic shedding and dryness of the skin
▪ MUCUS MEMBRANE
▪ Non-keratinized epithelial cells that lines RT, GIT, GUT
▪ Secretes mucus
▪ LACRIMAL APPARATUS
▪ Manufactures and drains tears
▪ Washing action of the keeps microorganisms & irritating
substances
▪ SALIVA
FIRST LINE OF DEFENSE
▪ PHYSICAL FACTORS
▪ MUCUS
▪ Traps microorganisms
▪ NASAL HAIR (mucus coated)
▪ Filters the inhaled air and traps particles
▪ CILIA
▪ Traps smaller particles
▪ Propels microorganisms and particles in the
mucus upward, towards the throat (mucociliary
escalator)
FIRST LINE OF DEFENSE
▪ PHYSICAL FACTORS
▪ EPIGLOTTIS
▪ Small lid of cartilage that closes the larynx during
swallowing
▪ EARWAX
▪ FLOW OF URINE
▪ Prevents colonization
▪ Obstruction of flow (Catheterization) → Infection
▪ FLOW OF VAGINAL SECRETION
▪ PERISTALSIS, DEFACATION, VOMITING, DIARRHEA
FIRST LINE OF DEFENSE
▪ CHEMICAL FACTORS
▪ SEBUM
▪ Unsaturated FA + lactic acid → make the skin
slightly acidic which inhibits the growth of
pathogenic microorganisms
▪ PERSPIRATION
▪ Lysozyme → breakdown of CW of G(+) >> G (-)
bacteria
▪ Tears, saliva, Tissue fluid, urine
▪ EARWAX
▪ Contains sebum
FIRST LINE OF DEFENSE
▪ CHEMICAL FACTORS
▪ SALIVA
▪ Lysozyme, amylase, and IgA
▪ GASTRIC JUICES
▪ Capable of destroying bacteria and most toxins, except C. botulinum & S. aureus
▪ H. pylori neutralizes stomach acid
▪ URINE SECRETION
▪ Lysozyme
▪ VAGINAL SECRETION
▪ Lactic acid (Lactobacillus)
FIRST LINE OF DEFENSE
▪ NORMAL FLORA & INNATE IMMUNITY
▪ PROVIDES RESISTANCE IN 3 WAYS
▪ Competes for available space and nutrients (competitive exclusion)
▪ Produces substances that inhibits or kill pathogens
▪ Stimulates immune system development
▪ PROBIOTICS
▪ Live microorganism that exerts beneficial effects
▪ PREBIOTICS
▪ Chemicals that selectively promotes the growth of beneficial bacteria
SECOND LINE OF DEFENSE
▪ Includes defensive cells (Basophils,
Eosinophils, Mast cells, Neutrophils,
Monocytes/Macrophages, Dendritic cells, Natural
killer cells) inflammation, fever, and
antimicrobial substances
SECOND LINE OF DEFENSE
▪ FORMED ELEMENTS IN BLOOD
SECOND LINE OF DEFENSE
▪ LYMPHATIC SYSTEM
SECOND LINE OF DEFENSE
▪ PHAGOCYTES
▪ Cells that are capable of phagocytosis
▪ PHAGOCYTOSIS – ingestion of a microorganism/other
substances by cell
▪ When infection occurs, granulocytes and monocytes
migrates to infected area
▪ FIXED MACROPHAGES
▪ KUPFFER’S CELL
▪ ALVEOLAR MACROPHAGE
▪ MICROGLIA
▪ FREE (WANDERING) MACROPHAGES
SECOND LINE OF DEFENSE
▪ 4 MECHANISMS/PHASES OF PHAGOCYTOSIS
▪ CHEMOTAXIS
▪ Chemical attraction of phagocytes to microorganism (microbial product, WBC component,
cytokines, peptide from complement
▪ ADHERENCE
▪ Attachment of phagocytes PM to foreign material
▪ PAMP + TLR or Opsonization
▪ INGESTION
▪ PM of phagocyte extends projection (pseudopods) surrounds the foreign material forming
phagosome
▪ DIGESTION
▪ Phagosome fuses with lysosome to form phagolyososome
SECOND LINE OF DEFENSE
▪ INFLAMMATION
▪ Local defensive response
▪ Infection, physical agent, chemical agent
▪ Associated with certain signs and symptoms
▪ PIRSH (Pain, Redness, Immobilization secondary to loss of function, Swelling, Heat)
▪ 3 FUNCTIONS
▪ Destroy injurious agent and remove its by products from the body
▪ Wall off or confine if destruction is impossible
▪ Repair/replace tissue damage
SECOND LINE OF DEFENSE
▪ INFLAMMATION
▪ 2 TYPES
▪ ACUTE INFLAMMATION
▪ Develops rapidly (days to weeks)
▪ Self-limiting
▪ Neutrophils/PMN
▪ CHRONIC INFLAMMATION
▪ Develops more slowly (months to years)
▪ Often severe and progressive
▪ Macrophages
SECOND LINE OF DEFENSE
▪ INFLAMMATION
▪ 3 STAGES OF INFLAMMATION
▪ VASODILATION AND INCREASE PERMEABILITY OF BLOOD VESSELS
▪ Caused by a number of mediators (Histamine)
▪ Vasodilation → Redness and Heat; Increased permeability → Edema
▪ PHAGOCYTE MIGRATION AND PHAGOCYTOSIS
▪ MARGINATION
▪ Phagocyte begins to stick to the inner surface of the endothelial lining
▪ DIAPEDESIS
▪ Phagocyte begins to squeeze between endothelial cells
▪ TISSUE REPAIR
▪ The ability to regenerate/repair depends on the type of cell/tissue
SECOND LINE OF DEFENSE
▪ ANTIMICROBIAL SUBSTANCES
▪ COMPLIMENT SYSTEM
▪ Enhances cell of immune system in destroying microbes
▪ Not adaptable, never changing
▪ It can be recruited by the adaptive immune system
▪ Destroy microbes by cytolysis, opsonization, and inflammation
▪ Acts in cascade
▪ 3 pathways: Classical, Alternative, and Lectin pathways
SECOND LINE OF DEFENSE
▪ ANTIMICROBIAL SUBSTANCES
▪ COMPLIMENT SYSTEM
▪ OUTCOMES OF COMPLIMENT ACTIVATION
1. CYTOLYSIS
▪ Formation of membrane attack complex
(C5bC6C7C8C9)
▪ G (-) are more susceptible to cytolysis
2. OPSONIZATION
▪ Promotes attachment of phagocyte to microbes
(C3b)
3. INFLAMMATION
▪ Histamine release (C3a, C5a) or Chemotactic factor
(C5a)
SECOND LINE OF DEFENSE
▪ ANTIMICROBIAL SUBSTANCES
▪ COMPLIMENT SYSTEM
▪ REGULATION
▪ CD59 – Prevents assembly of MAC
▪ EVADING THE COMPLIMENT SYSTEM
▪ Salmonella – inhibits MAC formation
▪ N. gonorrhea, B. pertussis, Influenzae – inhibits MAC formation
▪ G (+) cocci – breaks down C5a
SECOND LINE OF DEFENSE
▪ ANTIMICROBIAL SUBSTANCES
▪ INTERFERONS
▪ IFN α, β → stimulates NK cells
▪ IFN γ → induces PMN and macrophage maturation
▪ IRON-BINDING PROTEINS
▪ Transferrin, Lactoferrin, Ferritin, Hemoglobin
▪ ANTIMICROBIAL PEPTIDES
▪ Dermcidin, Defensins and Cathelicidins,
Thrombocins
▪ OTHER FACTORS
▪ Genetic resistance
▪ Age
GUIDE QUESTIONS
▪ First white blood cells to be involved in acute
inflammation by pyogenic cocci
a. Macrophages
b. Polymorphonuclear leukocytes
c. Basophils
d. Lymphocytes
GUIDE QUESTIONS
▪ Helminth infections will cause an increase in
a. NK cells
b. Dendritic macrophages
c. Eosinophils
d. Pre-B cells
