Genetic factors

Natural resistance associated macrophage

protein (Nramp)
Hormones
Stress
Nutritional factors
Specific chemical factors
Free fatty acids
Antibacterial peptides & proteins

Natural resistance associated macrophage

protein
Nramp gene Nramp 1 protein
Human, mice, sheep, bison , red deer &
cattle
Protein expressed only in macrophages
Macrophage activation early step
More NO sythase, more phagosomelysosome fusion

Stimulation of immunity
thyroxine
steroids (low doses)
estrogen
Immunosuppression
steroids (high doses)
testosterone
progesterone

Immunosuppressive
Steroids production increase
Shipping fever in cattle
Horse Salmonella enteritis

Malnutrition
Negative protein balance
Vaccination after decreasing parasite
burden

Antibacterial molecules
Lysosyme

In tissues & all body fluids

Except in CSF and urine
Absent in bovine neutrophil & tears
High concentration in egg white
Cleaves the bond between NAM and NAG of
peptidoglycans of Gram +ve bacteria
In conjunction with C can act on Gram ve
bacteria

Sites of bacterial invasion & acute

Inflammation Sites
Neutrophils lysozyme present in some
neutrophil granules accumulation of
lysozyme in acute inflammatory areas
Neutrophil lysosomes high conc. of
lysozyme
pH optimum 3 to 6
Inflammatory Site and phagosomes pH
easily achieved
Potent innate opsonin

Can inhibit bacterial growth

Unsaturatted F.As Bactericidal for
Gram+ve
Saturated F.As fungicidal

Mammalian cells & tissues, > 800 identified so

far
Short, cationic peptides (most 29-35 A.As) rich
in lysine & arginine
Interact with microbial PLs, LPS or teichoic acids
(host cell protected)
Has the ability to form amphipathic structures
Hydrophobic region- insert into lipid rich bacterial
memb.
Hydrophillic region form channel-like pores or cover
the memb.
Membrane disrupting and bacterial death

Cathelicidins (12-80 A.As) neutrophil

granules antibact. Activity Eg. Protegrins,
novispirin, ovispirin
Serprocidins antimicobial serine protease
neutrophil primary granules
Granulysins peptides from NK cells
Antibacterial, also chemo-attractants and activate
macrophages

BPI (bactericidal permeability increasing protein)

primary granules of human & rabbit neutrophils
bind LPS & damage their inner memb.

Calprotectin in neutrophils, monocytes &

macropages and epidermal cells forms
about 60% of neutrophil cytoplasmic protein
released in inflammation
Platelets & Immune complexes interaction
release lysin Bacillus anthracis &
Clostridia
Equine leukocytes several cysteine rich
peptides act against bact. Pathogens.

Typical antimicrobial peptides (28 to 42 A.A), produced

constitutively or in response to infection, > 50 in
mammals
Vertebrate defensins , or
defensins: 15% of the total proteins in neutrophil
granules (cattle neutrophils 13 diff. defensins
produced)
defensins expressed in epithelial cells lining the
airways, skin, salivary gland and urinary system
defensins circular peptide found only in primate
neutrophil
Can kill or inactivate some bact., fungi or enveloped
viruses
Some defensins neutralize microbial toxins toxins from
B. anthracis, Corynebacterium diphtheriae, Staph .
aureus

Lectins CH2O binding proteins

CH2O-major components of bacterial cell wall
Lectins - opsonin or activators of other innate
defenses
P-type, S-type and C-type lectins
P-type - Pentraxins 5 protein subunits
arranged in a ring, bind LPS in a Ca 2+ dependent
manner

include C-reactive protein (CRP), serum amyloid P (SAP)

These are called acute-phase proteins (their blood
levels climb greatly during infections or following
trauma)
Activate C, stimulation of leukocytes, augment the
activities of neutrophils, monocytes/macrophages

S-type Galectins
Mediate binding of leukocytes to extracellular matrix
have role in inflammation

C-type require calcium to bind to CH2O

Selectins and Collectins
Selectins involved in leukocytes adherence to blood
vessels
Collectins involved in innate immune system
C-terminal domain bind to bacterial CH2O & N terminal
domain interact with cells and C components
Mammals - Six different collectins conglutinin, MBL,
pulmonary surfactant proteins (SP-A, SP-D), collectin-46,
collectin-43
conglutinin, collectin-46, collectin-43 only in bovidae

A collectin found in serum

Has multiple CH2O binding sites
Bind to N-acetylglucosamine, mannose, glucose,
galactose and N-acetylgalactosamine
Plays important role in activating the C system
Bind to leukocytes, platelets, endothelial cells and
fibroblasts
MBL coated bacteria readily phagocytosed
through interaction with surface receptors
(opsonization)
Collectins are especially important in young animals
Congenital deficiency of MBL in children highly
susceptible to infections

One of the most imp. Innate factor that determine

bacterial invasion - availability of iron
Many pathogenic bacteria require large amounnts
of iron for growth - S. aureus, E. coli, B. anthracis,
Pasteurella multocida, M. tuberculosis
Host also require iron to survive - Microbe & host
compete for iron
Body iron found in association with iron binding
proteins
Transferrin, Lactoferrin, Haptoglobin, Ferritin & Siderocalin

Bact. Invasion - Iron absorption ceases

M IL-1 hepatocytes secrete transferrin
& haptoglobin - incorporation of iron
(Liver)
Mammary Gland bact. Invasion milk
neutrophils release of stores of lactoferrin
Sequestration of iron
Hemolytic anemia serum iron level more susceptible to bact. Infection

Potent Iron binding proteins (M.

tuberculosis, E.coli and B. anthracis)
Siderophores - withdraw iron from serum
proteins
Mycobacteria caroboxymycobactin
(siderophore)- remove iron from ferritin
E. coli enterochelin (siderophore)
Mammals liver, spleen, macrophage
synthesis Lipocalin 2 (siderocalin) binds
enterochelin with very high affinity