INNATE

IMMUNITY
Outline
• Concept of Immunity?
• What is Innate Immunity?
– Level of defenses

• The mechanism of Phagocytosis

• Inflammation
• Fever
• What are antimicrobial substances
– The complement system
IMMUNITY
• Body’s ability to fight off microorganisms that cause
diseases
• Immunity = Resistance

• Lack of immunity  Susceptibility / Disease

• Toll-like Receptors (TLR)

Innate Immunity
• Non-specific defenses of the body
• Very important barrier against disease
• Present at birth
Innate Immunity
1st Line of Defense
SKIN & MUCOUS MEMBRANE: Physical barrier
Innate Immunity
1st Line of Defense
SKIN & MUCOUS MEMBRANE
• Respiratory system

• Gastrointestinal system
Innate Immunity
1st Line of Defense
SKIN & MUCOUS MEMBRANE: Physical barrier
• Respiratory system
– Ciliated epithelium
– Microorganisms are trapped by mucus secreted by specialized
cells
– Ciliary escalator keeps mucus blanket move upward to the
throat for expectoration
Innate Immunity
1st Line of Defense
SKIN & MUCOUS MEMBRANE: Physical barrier
• Gastrointestinal system
– Peristalsis, defecation and vomiting
– Mass peristalsis of large intestinal contents into the rectum
results in defecation
– Ingested microbial toxins promote vigorous contraction of the
gastrointestinal tract, thus vomiting or diarrhea, a method of
liberating the body from harmful microbes.
Innate Immunity
1st Line of Defense
CHEMICAL FACTORS
• Sebum
– Oily substance produce by sebaceous gland
– Prevents hair from drying & becoming brittle
– Forms protective covering of the skin because of it contains
unsaturated fatty and maintains low pH of skin

• Perspiration
– Produce by sweat glands
– Maintains body temperature & flushes microorganisms on the
skin
– Contains lysozyme that breaks down cell wall of Gram (+)
bacteria
• Physical barrier alone do not account for
– Lysozyme has antimicrobial property
high degree of resistance of skin and
mucous membranes to microbial invasion
Innate Immunity
1st Line of Defense
CHEMICAL FACTORS
• Saliva
– pH of 6.55 – 6.85 inhibits microbial growth
– Contains antibody (immunoglobulin A) that prevents
attachment of microbes

• Gastric juice
– Very acidic environment (pH 1.2 – 3.0) destroys bacteria and
toxins in the stomach, except Clostridium botulinum &
Staphylococcus aureas

• Urine
– Promotes flushing of microbes in the GUT
– Has an acid pH (ave: 6.0) that inhibits bacterial growth
– Also contains lysozyme
Innate Immunity
1st Line of Defense
CHEMICAL FACTORS
• Saliva
– pH of 6.55 – 6.85 inhibits microbial growth
– Contains antibody (immunoglobulin A) that prevents
attachment of microbes

• Gastric juice
– Very acidic environment (pH 1.2 – 3.0) destroys bacteria and
toxins in the stomach, except Clostridium botulinum &
Staphylococcus aureas

• Urine
– Promotes flushing of microbes in the GUT
– Has an acid pH (ave: 6.0) that inhibits bacterial growth
– Also contains lysozyme
Innate Immunity
2nd Line of Defense
• When first line of defense is breached, 2nd line of
defense come into play.

– Phagocytic cells

– Inflammation

– Fever

– Antimicrobial substance
Innate Immunity
2nd Line of Defense
 PLASMA

PLATELETS
BUFFY COAT GRANULOCYTES

WBC
AGRANULOCYTES

PACKED RED CELL

Formed Blood Elements
GRANULOCYTES
• Neutrophils
– Stain pale lilac with mixture of acidic & basic dyes
– Highly phagocytic and motile
– Active in initial stages of inflammation

• Basophils
– Stain blue-purple with basic dye methylene blue
– Release histamine that is important in inflammation and
allergic response
Formed Blood Elements
GRANULOCYTES
• Eosinophils
– Stain red or orange with the acidic dye eosin
– Produce toxic proteins against certain parasites
– Increase in number in certain parasitic infection and
hypersensitivity reactions
Formed Blood Elements
AGRANULOCYTES
• Monocytes
– Not actively phagocytic until they leave circulating blood
– Become MACROPHAGES, capable of phagocytosis when they
enter body tissues

• Dendritic cells
– Derived from monocytes
– Abundantly found in the epidermis of the skin, mucous
membrane, thymus, lymph nodes
– Destroy microbes by phagocytosis and initiate adaptive
immunity response
Formed Blood Elements
AGRANULOCYTES
• Lymphocytes
– Natural Killer Cells
– Found in the blood, spleen, lymph nodes, red bone marrow
– Ability to kill wide variety of infected cells
– Contains:
– Perforin - inserts into plasma membrane of target cells, causing
perforation and eventually cytolysis
– Granzyme – protein-digesting enzyme that induce apoptosis of target
cells
– T cells and B Cells
– Usually not phagocytic but are involve in adaptive immunity
• White Blood Cells respond to certain infections

– LEUKOCYTOSIS – increase in WBC count

– Meningitis
– Infectious mononucleosis
– Appendicitis
– Pneumococcal pneumonia

– LEUKOPENIA – decrease in WBC count

– Salmonellosis
– Brucellosis
– Rickettsial infection
– Certain viral infection
Lymphatic system
• Consists of:
– Lymph
– Lymphatic vessels
– Lymphoid tissue
– Contains T cells and B cells
– Red bone marrow
Phagocytosis
• Means ingestion of microorganism or cell debris
• In infection, granulocytes (neutrophils & eosinophils)
and agranulocytes (dendritic cells & monocytes)
migrate to infected sites
• Monocytes  Macrophages (Histiocytes if they fixed in
certain tissues
– Liver: Kupffer’s cells
– Lungs: Alveolar macrophages
– Nervous system: Microglial cells
– Peritoneal cavity: Peritoneal macrophages
Phases of Phagocytosis
How microbes evade phagocytosis?
• M protein
– Eg: Streptococcus pyogenes

• Capsules
– Eg: Streptococcus pneumoniae, Hemophilus influenzae

• Leukocidin and Streptolysin

– Eg: Staphylococcus, Streptococcus

• Membrane attack complex (MAC)

– Eg: Trypanosoma cruzi, Listeria monocytogenes

• Biofilms
– Eg: Peudomonas aeruginosa
Inflammation
• Body’s local defensive response to damaged tissues
• Signs and symptoms:
1. Redness
2. Pain
3. Heat
4. Swelling
5. Loss of function
Inflammation
• Functions:
1. To destroy the injurious agent, if possible, and to remove it
and its by-products from the body

2. If destruction is not possible, to limit the effects on the body

by confining or walling off the injurious agent and its by-
products

3. To repair or replace tissue damaged by the injurious agent or

its by-products
Inflammation
• Stages:
1. Vasodilation and increased permeability of blood vessels

2. Phagocyte migration and phagocytosis

3. Tissue repair
Inflammation
VASODILATION AND INCREASED PERMEABILITY OF
BLOOD VESSELS
• Prostaglandin & Leukotrienes are released from
damaged tissue – involve in chemotaxis of phagocytes
• Pro-inflammatory cytokines (eg: histamine, kinin) are
secreted by activated fixed macrophages promote
vasodilation, thereby increasing blood flow to
damaged area (redness and heat)
• Blood clots are formed to prevent spreading of
infection (abscess formation)
Inflammation
PHAGOCYTE MIGRATION AND PHAGOCYTOSIS
• Margination of phagocytes to vessel endothelium in
response to cytokines
• Diapedesis – migratory process of phagocyte
• Phagocytes start destroying microbes by phagocytosis
Inflammation
TISSUE REPAIR
• Final stage of inflammation, in which new tissues
replace the damaged cells
• Synthesis of stromal and parenchymal cells
• Activated macrophages release cytokines that induce
fibroblast proliferation in the stroma to synthesize
collagen fibers (fibrosis)
Fever
• Systemic response of the body to tissue injury
• Body temperature is controlled by hypothalamus

• How can bacteria on certain area of the body promote

fever?

CYTOKINES
Interleukin-1
TNF-alpha
Antimicrobial Substances
• COMPLEMENT SYSTEM
• Defensive system of the body, produced in the liver
and found in blood circulating
• 3 pathways to Complement Activation:

– Classical Pathway

– Alternative Pathway

– Lectin pathway
The Classic Pathway
The Alternative Pathway
The Lectin Pathway
Complement Deficiency
• Deficiency of C1, C2, C4
– Collagen vascular disorders resulting to anaphylaxis

• Deficiency of C3
– Increased susceptibility to recurrent infections with pyogenic
microbes

• Defects in C5-9 (MAC)

– Increased susceptibility to Neisserial infections

• May play a role in immune responses

– Asthma, SLE, Multiple sclerosis, Inflammatory bowel disease

• May also contribute in neurodegenerative disorders

– Alzheimer’s disease
How microbes evade complement
activation?
• Capsule contain sialic acid
– Discourages opsonization and MAC formation

• Inhibit formation of C3b and C4b by covering C3b

receptor on the phagocyte
• Salmonella lengthens O polysaccharide of their LPS
– Prevents MAC formation

• Gram positive cocci release enzymes that destroy C5a,

diminishing chemotactic property of phagocyte
Interferons
• A cytokine
• Class of similar antiviral proteins produced by
lymphocytes and macrophages after viral stimulation
• 3 principal types:
– Alpha interferon Produced by virus-infected cells
– Beta interferon Synthesize antiviral proteins (AVPs)
– Gamma interferon
– Produced by lymphocyte to induce neutrophils and macrophages to
kill the bacteria
Interferons
Antimicrobial peptides
• Recently discovered as the most important component
of innate immunity
• Synthesis of AMPs is triggered by protein and sugar
molecules found on the surface of microbes
• Mode of action:
– Inhibit cell wall synthesis
– Forming pores in the plasma membrane, resulting in lysis and
destroying nucleic acids

• AMPs produced by humans:

– Dermicin – by sweat glands
– Defensin & Cathelicidin – by neutrophils, macrophages &
epithelium
– Thrombocidin – by platelets
In summary
In summary
In summary