I.	Colostrum

	1.	Initial Products of Lactogenesis (Colostrogenesis)
	2.	Contains Antibodies (Igs) and Bioactive Factors
		A.	Provide young animal with good start
			a.	Passive Immunity
			b.	Growth and Development
			c.	Digestive Maturation Factors

II.	The Neonate

	1.	Mother's colostrum and milk provide everything except air
	2.	The neonate changes rapidly, both structurally and physiologically
		A.	Neonate structural and physiological limitations
			a.	Limited fat stores
			b.	Fat stores that they have not readily available for metabolism
			c.	Use up limited glycogen supplies rapidly
			d.	Poor gluconeogenic capacity
			e.	Agammaglobulinemia
			f.	Low iron stores
			g.	Structurally and physiologically immature intestine
				i.	Low activity of pancreatic enzymes
				ii.	Low activity of stomach pepsin
				iii.	Low activity of may intestinal enzymes
				iv.	Immature stomach acid generating mechanism
		B.	Adaptions for milk digestion
			a.	High rennin activity
				I.	Precipitation of casein, curd formation in the stomach
			b.	High lactase
				i.	Breakdown of lactose
			c.	High salivary lipase activity
				i.	Breakdown of milk triglycerides
	3.	Colostrum and milk  provides nutrients, water and immunity

III.	Immunoglobulin Transport in the Mammary Gland

	1.	Most neonatal mammals do not have an effective immune system
	2.	Humoral immune protection is supplied 
		by passive immunity transfer
		A.	From maternal serum IgG
			a.	In utero
			b.	via colostrum
		B.	May modulate development of neonate immune system
		C.	Lack colostrum intake after birth can lead to 100% mortality 
			in many mammals
			a.	Primates get most of passive immunity via placenta
				i.	Need for colostrum not as important
			b.	Most domestic animals don't have much immunity transfer 
				in utero
	3.	Colostrum Immunoglobulins
		A.	IgG
			a.	IgG1 is the major immunoglobulin transported by the 					mammary gland 
			b.	IgG2 is increases some too
			c.	IgGs are preformed antibodies from blood
		B.	IgA and IgM
			a.	Also transported by mammary gland cell
			b.	Synthesized in mammary gland by plasma cells 
				(B-lymphocytes) to colostrum
	4.	Immunoglobulin Transport
		A.	Igs bind to receptors on basal side of cell
			a.	IgGs have different receptors than IgA/IgM
			b.	Receptor for IgA/IgM remains bound to IgA during transport
				--Called secretory component (receptor) or secretory-IgA
				--Found in as secretory-IgA in colostrum and milk
		B.	Transport vesicles carry Igs to Apical surface
			a.	Formed by endocytosis mechanism upon receptor binding
			a.	Released via exocytosis

	4.	Immunoglobulin Secretion
		A..	Dairy cow can secrete as much as 2 kg of IgG during 
			the first 5 milkings
		B.	Concentrations decline rapidly over first 24 hours post-partum
		C.	Parity
			a.	Ig levels increase in colostrum with parity
				i.	1st calf ½ of 3rd and 4th calf cows

IV.	Intestinal Absorption of Immunoglobulins

	1.	Generally you think of proteins, like Igs being degraded in the intestine
	2.	Neonates have the ability to absorb macromolecules intact for a certain 		period of time after parturition
		A.	Immunoglobulins are the most important
	3.	Mechanism
		A.	Non-receptor mediated pathway
		B.	Macromolecules are taken up by enterocytes (crypt cells or intestinal 			absorptive cells) by formation of tubules at the base of apical 				microvilli
		C.	Tubules pinch off to form vesicles
		D.	Vesicles transported to basal membrane
		E.	Released into extracellular space and absorbed into blood
		F.	Macromolecule absorption only occurs in jejunum
			a.	Tubule formation and uptake occurs in ileum, but 				macromolecules are degraded by lysosomes within the cells
			b.	Best absorption in calf, piglet, and puppy
			c.	Human infants, guinea pigs, and rabbits absorb little
			d.	Rats have receptor mediated IgG transport for 20 days
	4.	Closure
		A.	The halt of absorption of Igs and other macromolecules
		B.	Timing
			a.	24 hr postpartum in calf
			b.	36 to 48 hr in piglet	

V.	Intestinal Protective Factors
	
	1.	Several Factors in milk may function the neonates digestive tract to 		minimize the potential for enteric disease
		A.	Immunoglobulins
			a.	Protect against enteric disease even after closure
			b.	IgA especially 
		B.	Lactoferrin
			a.	Iron-binding protein
			b.	Bacteriostatic and Bacteriocidal
			c.	High in human milk, low in cow milk
		C.	Lysozyme
			a.	Degrades bacterial walls
			b.	High in human milk, very low in cows
			c.	Works with IgA, lactoperoxidase, and ascorbate
		D.	Lactoperoxidase
			a.	Halogenates bioactive proteins
				i.	Inactivates
			b.	Peroxidation of substances
				i.	Helps digestion
			c.	High in cow, low in human
				i.	Infants secrete lactoperoxidase in saliva
		E.	Milk Cells
			a.	Leukocytes are phagocytotic
			b.	Work to some extent in gut	
	2.	Gut Flora
		A.	Establishment of proper microbial flora is best protection 
			against disease
		B.	Bifidus factor
			a.	Also called carbohydrate growth factor
			b.	Characterized in human milk
			c.	Stimulates growth of Lactobacillus Bifidus
				i.	High lactose, low protein, low bulk, and low buffering 					capacity also stimulate
		C.	Other Gut Flora Growth Factors
			a.	Probably exist but have not been characterized
			
VI.	Bioactive Factors in Colostrum and Milk

	1.	Nutrient Sources

		A.	Milk Fat Globule
			a.	Fat soluble vitamins
				i.	A, D
			b.	Steroid hormones (see below)
		B.	Proteins
			a.	Casomorphins
				I.	Proteolytic product of B-casein
				ii.	May regulate development of the intestinal mucosal 					immune system
			b.	Proteolytic products of b-LG and a-LA may also have 					immunomodulatory activity
	2.	Enzymes
		A.	High in cow milk , low in human
			a.	Lactoperoxidase
			b.	Xanthine oxidase
			c.	Ribonuclease
			d.	Alkaline phosphatase
		B.	High in human milk, low in cow
			a.	Lipase activity
			b.	Lysozyme
			c.	Protease activity
		C.	Found in both
			a.	Plasmin/plasminogen activity
			b.	Trypsin inhibitor activity
				I.	High in colostrum and during mastitis
				ii.	Low in milk
	3.	Carrier Proteins
		A.	Vitamin-binding proteins
			a.	Folate
			b.	Vit. B12
		B.	Mineral-binding proteins
			a.	Fe--Lactoferrin and Transferrin
			b.	Ca--Casein and a-LA
			c.	Cu--Lactoferrin
		C.	Lipid-binding proteins
			a.	b-LG binds FAs and Retinol?
			b.	Serum albumin binds FAs
		D.	Hormone-binding proteins
			a.	Corticosteroid-binding globulin
			b.	IGF-binding proteins
	4.	Growth Factors
		A.	IGF-I and IGF-II
		B.	EGF
			a.	Major growth factor activity in milk
			b.	Stimulates enterocyte proliferation
		C.	TGF-alpha
		D.	NGF
	5.	Hormones
		A.	Steroid hormones
			a.	Found in fat globule
			b.	Most peak in colostrum and then decrease
			c.	Progesterone
			d.	Estrogens
				i.	Estradiol
				ii.	Estrone
			e.	Corticosteroids
			f.	Androgens
		B.	Peptide hormones
			a.	PRL
			b.	ST
			c.	GHRH
			d.	LH
			e.	GnRH
			f.	ACTH
			g.	TRH
			h.	Thyroid hormones
			I.	Insulin
			g.	Melatonin