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Immunity and the Mammary Gland Defense System (Leitner

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<strong>Immunity</strong> <strong>and</strong> <strong>the</strong> mammary gl<strong>and</strong><br />

defense system<br />

Dr. Gabriel <strong>Leitner</strong><br />

National Mastitis Laboratory,<br />

Kimron Veterinary Institute,<br />

Israel<br />

leitnerg@moag.gov.il


The Function of <strong>the</strong> Immune <strong>System</strong><br />

1. Protect from pathogens<br />

2. Distinguish between self/non-self<br />

3. Memory<br />

The Immune <strong>System</strong><br />

A) natural/adaptive = innate/acquired<br />

B) cell-mediated/humoral<br />

C) active/passive<br />

D) primary/secondary


The mammary<br />

gl<strong>and</strong> <strong>Immunity</strong><br />

Blood <strong>System</strong><br />

Barrier<br />

Between gl<strong>and</strong>s<br />

Udder Epi<strong>the</strong>lial cells<br />

Barrier<br />

Body- Udder


The mammary<br />

gl<strong>and</strong> <strong>Immunity</strong><br />

Selective transfer<br />

Body Udder<br />

supra-mammary<br />

lymph node<br />

Mucosal lymph system<br />

lymph node<br />

mouth<br />

digestion<br />

anus<br />

respiratory


The implication of <strong>the</strong> body-udder barrier<br />

<strong>and</strong> <strong>the</strong> barrier between <strong>the</strong> two udder-halves:<br />

1. acquired immunity in <strong>the</strong> body is only partial<br />

<strong>and</strong> at a lower level in <strong>the</strong> udder<br />

2. Not all <strong>the</strong> immune responses in <strong>the</strong> mammary<br />

gl<strong>and</strong>s will be recognized by <strong>the</strong> body<br />

supra-mammary<br />

lymph node<br />

<strong>System</strong>ic immunity<br />

Macrophage + bacteria<br />

Local immunity


“Most mammary gl<strong>and</strong>s, most of <strong>the</strong> time are<br />

sterile with no contaminating microorganisms”


Teat canal<br />

The major barrier, protecting penetration<br />

of bacteria into <strong>the</strong> mammary gl<strong>and</strong>s


Infection “cycle” in <strong>the</strong> mammary gl<strong>and</strong><br />

recovery<br />

chronic infection<br />

Bacteria<br />

death<br />

removal<br />

clinical infection


Interaction between <strong>the</strong> intruder <strong>and</strong><br />

<strong>the</strong> mammary gl<strong>and</strong> immunity<br />

innate immunity<br />

mainly PMN from<br />

<strong>the</strong> blood stream<br />

No establishment<br />

of immune memory<br />

removal<br />

recovery<br />

clinical infection<br />

death


Bacteria penetrating <strong>the</strong> teat canal come<br />

across cells from <strong>the</strong> immune system<br />

If <strong>the</strong> encounter is with polymorphonuclear<br />

cells (PMN) or macrophages, <strong>the</strong> event<br />

can end successfully: removal or killing<br />

of <strong>the</strong> intruder with no sign of infection<br />

but more important, without establishment<br />

of immune memory


When <strong>the</strong> intruder is encountered by macrophage<br />

or dendritic cells, it can be presented to B<br />

<strong>and</strong>/or T cells via <strong>the</strong> supra-mammary lymph<br />

node which will lead to systemic response <strong>and</strong>/or<br />

sporadic B (possibly B1) <strong>and</strong> T cells, which will<br />

lead to a local response<br />

chronic infection<br />

Establishment<br />

of immune memory


Y<br />

Y Y<br />

Y<br />

Antibodies<br />

Bacteria<br />

PMN or MØ<br />

Acquired <strong>Immunity</strong><br />

Memory<br />

T lymphocyte<br />

B lymphocyte<br />

Innate <strong>Immunity</strong><br />

No memory<br />

T or B lymphocyte


Why is it important to know <strong>the</strong><br />

mammary gl<strong>and</strong> immunity?<br />

The major income from dairy animals is derived<br />

from <strong>the</strong>ir milk production; <strong>the</strong>refore, factors that<br />

reduce milk quantity <strong>and</strong> quality can cause<br />

overwhelming economic losses to <strong>the</strong> farmers<br />

The increasing public concern on food safety is<br />

focused among o<strong>the</strong>r on milk quality in <strong>the</strong><br />

desire to minimize antibiotic residues in milk on<br />

<strong>the</strong> one h<strong>and</strong>,<strong>and</strong> reducing somatic cell counts<br />

(SCC) on <strong>the</strong> o<strong>the</strong>r h<strong>and</strong>


High correlation between udder<br />

infection <strong>and</strong> bulk milk tank SCC<br />

Udder infection is <strong>the</strong> most Important<br />

single factor influencing bulk SCC<br />

Udder infection BMTSCC<br />

% <strong>and</strong> type of udder infection in <strong>the</strong> herd


High correlation between bulk milk<br />

tank SCC <strong>and</strong> milk products<br />

Storage time influences <strong>the</strong> quantity<br />

<strong>and</strong> quality of milk products<br />

Low BMTSCC<br />

High BMTSCC<br />

Time of storage


Somatic cells in sheep milk<br />

SCC (1000)<br />

Epi<strong>the</strong>lial<br />

Lymphocytes<br />

Macrophages<br />

PMN<br />

Not infected<br />

>300<br />

30-40%<br />

5-15%<br />

~ 10%<br />

20-40%<br />

Infected (Sub clinic)<br />

500 - > 3,000<br />

< 5%<br />

~ 5%<br />

~ 10%<br />

85%


Fresh curd from uninfected milk (~1x10 5 cells)


Fresh curd from infected milk (~1x10 6 cells)


Cheese from uninfected (left)<br />

or infected (right) milk


The mammary gl<strong>and</strong> immunity functions at a<br />

low level, that mainly involve innate immunity<br />

Not in all chronic infection <strong>the</strong>re are acquired<br />

immunity<br />

Products of <strong>the</strong> acquired immunity in <strong>the</strong> milk<br />

(i.e., antibodies) are lower than that of <strong>the</strong><br />

blood stream (10-25%)


Treatment (during lactation, at dry-off) !!!!!<br />

“Dry-off treatment of Assaf sheep:<br />

efficacy as a management tool for improving<br />

milk quantity <strong>and</strong> quality”<br />

Average milk yield (sheep lactation -1 )<br />

500<br />

480<br />

460<br />

440<br />

420<br />

400<br />

380<br />

2003 2004 2005<br />

Year<br />

55<br />

50<br />

45<br />

40<br />

35<br />

30<br />

25<br />

20<br />

Flock infection (%)<br />

2600<br />

2400<br />

2200<br />

2000<br />

1800<br />

1600<br />

1400<br />

1200<br />

1000<br />

800<br />

Bulk tank somatic cell count (x 1000)


Average milk yield per individual lactation increased<br />

by 19%, from 395 to 487 l over <strong>the</strong> 2 years of <strong>the</strong><br />

study. Over <strong>the</strong> same period <strong>the</strong> bulk tank milk SCC<br />

decreased from about 2,500 × 10 3 in 2003 to less than<br />

1,000 × 10 3 in 2005. The percentage infection level of<br />

<strong>the</strong> flock, as tested 2 weeks PP, decreased from about<br />

60% in 2003 to about 22% in 2005.<br />

It was found that IMI, mainly with CNS, reduced<br />

individual milk yield by 0.189 l d -1 , equivalent to an<br />

overall annual milk loss of 42 L per ewe.


Among <strong>the</strong> IMI-affected ewes, <strong>the</strong> milk yield began to<br />

fall immediately PP, <strong>and</strong> <strong>the</strong> diminution continued<br />

throughout <strong>the</strong> lactation.<br />

Milk (L day -1 )<br />

3.0<br />

2.5<br />

2.0<br />

1.5<br />

1.0<br />

0.5<br />

0.0<br />

0 25 50 75 100 125 150 175 200 225<br />

Days in milk


Vaccination !!!!!!!<br />

MASTIVAC I: a vaccine that protects cows<br />

from Staphylococcus aureus mastitis<br />

<strong>Leitner</strong> G.,et al., Vet. Immunol. Immunopath (2003a,b,c).<br />

93:159-167. 93:31-38 93:153-158

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