IMMUNOLOGY BASICS
Lactation Biology
Animal Science 337
Leo Timms
Iowa State University
MEANS OF AQUIRING IMMUNITY
1. ACTIVE: make own antibody
chance encounter w/Ag
a) natural
pregnancy
vaccination
b) artificial
introduce Ag via trt.
MEANS OF AQUIRING IMMUNITY
2. PASSIVE: transfer preformed antibody
a) natural : mother to fetus
(6 mo protection)
placental vs. colostral
b) artificial: immune therapy
Type of immune response
• Innate
• defense we are
born with
– phagocytic
cells
– complement
proteins
– anatomical *
– physiological *
• Adaptive/acquired
• defense that
develops with
exposure/time
– serum
antibodies
– T cells (CMI)
* 1st line of defense!!!
Mechanisms of immunity:
• Cellular
• Humoral
– cells responsible
– antibodies (in
for protection
serum) are
responsible for
– lymphocytes
protection
– phagocytes
Two Arms of The Immune System
Innate Immunity
Adaptive Immunity
Phagocytes
Lymphocytes
Neutrophils
Macrophages
T lymphocytes
B lymphocytes
pathogens
pathogens
Antigen
presentation
TH1 Cytokines
chemokines
Antigen
presentation
TH1 Cytokines
TH1 or TH2 Cytokines
Cytotoxicity
Antibodies
© Jeanne L. Burton, Michigan State University
Cells of the Immune System
Myeloid-lineage cells of the innate immune system
PMN
M
Tissue macrophage
B
B cell
Circulating neutrophil
TH
Helper T cell (TH)
TC
Cytotoxic T cell (TC )
Lymphoid-lineage cells of the adaptive immune system
© Jeanne L. Burton, Michigan State University
• large cell (10-25 um dia)
• main purpose: phagocytosis / kill
• act non specifically
• “chemotactic” capability
• potent phagocytosis when activated
by T lymphocytes (lymphokines)
• Express Ag on surface to T / B cells
• multilobulated nucleus
• lysosomal granules
• phagocytosis and kill
• 1st white blood cell to infection site
• die and release contents
• irritate surrounding tissue / recruit cells
• Phago. improved by opsonization with Ig
Macrophages and neutrophils are needed to kill extracellular bacteria,
such as those the infect the mammary glands of dairy cows
Tissue
macrophage
Blood
IL-1, IL-6,
IL-8,TNF-a
M
PMN
TNF-a
IFN-g
Circulating
neutrophil
PMN
No memory
M or
PMN cells
develop
Infected
Gland
Extracellular bacteria
Inflammatory
neutrophil
© Jeanne L. Burton, Michigan State University
Inflammation: part of innate immunity
• poor at phagocytosis
• granules contain histamine / serotonin
• vasodilators / permeability factors
• requires binding of 2 IgE for release
lymphocytes
• small (5 – 15 um)
• No lysosomes : all “brain” until activated
• distinguish self from non self
• specific : recognize specific antigens
• MEMORY**
• need presentation of Ag by macrophage
• interactions
- antigen
- macrophage
- T cell (Th)
- B cell
- cytokines
cytokines
• interactions
- antigen
- macrophage
- T cell (Th)
- cytokines
T helper (Th)
T suppressor
T killer
others
CYTOKINES / LYMPHOKINES
•
1.
2.
3.
4.
Small polypeptide messengers
• very powerful in low doses
• multiple uses
• hormones
Interleukins
Interferon: viral
Colony Stimulating factors: GCFS
Tumor Necrosis Factor (TNF)
inflammation / cell movement / traffic
OTHER IMMUNE FACTORS
• Complement: 9 specific serum proteins
- interaction of components provide
numerous biological events
• Lactoferrin: Iron binding protein
*** competes with bacteria for iron
• Lactoperoxidase ( LP/ SCN- / H2o2 syst.)
** antioxidant / oxygen radicals
HUMORAL IMMUNITY (Ab or AMI)
• Antigen + Macrophage + T cell + B cell
cytokines
• Antibodies or Immunoglobulins
• SPECIFICITY!
• MEMORY
• (immunity: short, long, or no term)
Antibodies are produced by antigen-activated B
lymphocytes and, in cattle, come in six isotypes
Fab = antigen binding = Fab
variable region
IgM (m)
IgG1 (g1)
IgG2 (g2)
IgG3 (g3)
IgA (a)
IgE (e)
L
L
Fc = biological
function
constant region
(Fc-m)
H H
© Jeanne L. Burton, Michigan State University
L = light chain
H + heavy chain
Functions
• Variable region (Fab) bind
specifically-neutralize, ppt
or agglutinate
**** antigen binding region
• Constant region (Fc) –
- activate effector cells or
complement
- opsonin end
Antibody Isotypes-5
IgG:
IgG1
IgG2
• Principle Ab in serum
• 14 – 18 mg / ml
• IgG1: 11 mg/ml
• IgG2: 7 mg/ml
• fixes complement
• late response to Ag
IgG1
• selective transfer (colostrum)
• fetal / neonatal defense
• toxin inactivation
• principal milk / colostrum Ig
(farm species)
IgG2
10 opsonin
for
phagocytosis
Opsonization
• Free IgG binds Fc
receptors with low
affinity
• IgG bound to Ag,
binds to Fc receptors
with high affinity
• Cross-linking
receptors sends
signal
IgM
IgE
• largest Ig
• pentamer
• serum (1-3 mg/ml)
• fixes complement
• 1st Ig produced
to Ag challenge!
• Binds to mast cells
basophils
• ACTIVATION
• RELEASE OF
- histamine - serotonin
The various Fc portions of antibody molecules have very different
biological functions, including pathogen blocking, complement
fixation, toxin neutralization, and opsonization of bacteria for
enhanced phagocytosis by neutrophils and macrophages
IgM = blocking &
complement
fixation
IgG1 = endotoxin
IgG2 = opsonization
neutralization &
& neutrophil
complement fixation
phagocytosis
serum
complement
© Jeanne L. Burton, Michigan State University
• 3 different forms in serum
• different form in secretion ( secretory piece)
• serum: 1-3 mg/ ml
• activates complement: serum (yes) milk (no)
IgA
Secretory piece
• local immunity and secretions
• prevents bacterial adherence
• maternal milk: very important
• primary Ig in colostrum (humans)!