Lesson 2: Innate Immunity
I. External Defense System
A. Physical barriers
B. Mechanical barriers
C. Biological barriers
D. Biochemical barriers
II. Internal Defense System
A. Leukocytes
B. Soluble mediators
Physical barriers
Skin
• epidermis is made up of different layers of squamous epithelial cells
• the cells are keratinized making it impermeable to most infectious agents
• constantly sheds off removing microbes on the surface
• dermis is composed of connective tissue with sweat glands, sebaceous glands, blood
vessels, hair follicles, macrophages, dendritic cells & mast cells
Mucous membranes
• lines all of the body cavities that comes into contact with the environment
• secretes mucus that traps inhaled or ingested microbes & other particles
Respiratory tract- Cilia
• hair-like projections of the epithelial cells that move debris out by coughing or sneezing
Urinary tract
• urination helps inhibit movement of microbes from the environment up into the bladder &
kidneys
Biological barriers
• Presence of normal flora
Biochemical barriers
1. pH- lactic acid, HCl
2. Lysozyme- breaks down peptidoglycan
3. Sebum
4. α-defensins, β-defensins- antimicrobial peptides secreted by various cells in the skin
5. Dnases, Rnases- enzymes in the skin that act on DNA & RNA
6. Sweat contains salts that inhibit growth of many bacteria
Internal Defense System
Table 1. Leukocytes & Function
Leukocyte Location Function
Neutrophil • 50%-70% of circulating • Phagocytosis
WBC • Contains primary & secondary
• Marginating pool granules with antimicrobial
• Tissues properties
Eosinophil • 1%-3% of circulating • Antihelminthic activity
WBC • *Phagocytosis
• Allergic response, asthma
• Modulate inflammatory
reactions of mast cells &
basophils
Basophil • <1% of circulating WBC • Inducing & maintaining allergic
reactions
• Contains histamine, heparin
• Stimulate B cells to produce
IgE
Monocyte • 3%-11% of circulating • Phagocytosis, scavengers
WBC • Antigen presenting cells
• Granules are digestive &
antimicrobial
Macrophage • Tissues throughout the • Phagocytosis
body • Antigen presenting cells
Dendritic cells • Skin, lung, GI, other • Posses branchlike cytoplasmic
tissues projections
• Phagocytosis
• Antigen presenting cells
Mast cells • Skin, connective tissues, • Allergic reactions
mucosal epithelium of the • Enhance & modulate adaptive
respiratory, GI, & immunity
genitourinary tracts
Macrophage:
Kupffer cells- liver
Langerhans cells- skin
Microglial cells- CNS
Histiocyte- connective tissue
Osteoclasts- bone
Hofbauer cells- placenta
Mesangial cells- kidneys
Alveolar macrophage/dust cells- lungs
• How are the phagocytes able to recognize microbes?
• pattern-associated molecular patterns (PAMPs) are structures only found in microbes
but not in humans
• ex. lipopolysaccharide, peptidoglycan, flagellin, zymosan
Pattern recognition receptors (PRRs)
• found on surfaces of phagocytes, mast cells, epithelial cells, T cells
• encoded by host’s genomic DNA
• act as sensors for extracellular infection
1. Toll-like receptors (TLRs)
mediate recognition of diverse pathogens
after binding to PAMPs, it activates the release of cytokines & molecules involved in
antimicrobial activity
10 TLRs identified in humans
o TLR 1, 2, 4, 5, 6 are on cell surface- for bacteria, fungi
o TLR 3, 7, 8, 9, 10 are on endosomes- viruses
2. Scavenger receptors
• involved in binding of modified low density lipoproteins, some polysaccharides & some
nucleic acids
• involved in the internalization of bacteria & in the phagocytosis of host cells undergoing
apoptosis
3. Opsonins
• molecules that when attached to the surface of microbes make them more attractive to
phagocytic cells thus facilitating destruction
• receptors for opsonins are found on phagocytes
Soluble Defense Mechanisms
1. Acute phase reactants
normal serum/plasma constituents that increase rapidly because of infection, injury or
trauma to the tissues
many act by binding & promoting adherence
others limit destruction caused by WBC proteolytic enzymes
produced primarily by the liver within 12-24 hours
CRP, fibrinogen AAT, haptoglobin, ceruloplasmin, serum amyloid A, complement
2. Cytokines
• secreted by leukocytes & other cells involved in innate immunity, adaptive & inflammation
• some promote inflammation, proliferation of leukocytes, secrete chemokines, promote
chemotaxis (chemical-induced migration of leukocytes)
Inflammation
• defined as the body’s overall reaction to injury or invasion of microbes
• cardinal signs:
• redness (rubor)- erythema
• edema (tumor)- swelling
• heat (calor)
• pain (dolor)
• loss of function (functio laesa)
• Increased blood supply- dilation of blood vessels caused by the release of histamine
• Increased capillary permeability allows for the influx of fluid & cells from the plasma to the
tissues resulting in swelling
• Migration of phagocytes to the surrounding tissue called diapedesis
Phagocytosis
Steps:
1. Adherence-
recognition & attachment aided by TLRs, opsonins, complement receptors
2. Engulfment
ingestion by extensions of the cytoplasm & cell membrane called pseudopodia
3. Formation of phagosomes
phagocytic vacuoles surround the microbes
4. Granule contact
• lysosomal granules contact & fuse with phagosome
5. Formation of phagolysosomes
• contents of lysosome are emptied into this membrane
6. Digestion of microbes
• hydrolytic enzymes
• oxygen radicals (superoxide radicals, hypochlorite, hydrogen peroxide, hydroxyl radicals)-
oxidative burst
• nitrous oxide
• decreased pH
7. Excretion, secretion
