Transcript Immunology Review

Principles of Immunology
Prince Agri-Products & Phibro Animal Health
Training Seminar – Atlanta, Georgia
July 17-18, 2006
Immunity: security against a particular disease; nonsusceptibility to
the invasive or pathogenic effects of foreign microorganisms or the
toxic effect of antigenic substances.
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Innate Immune System:
consists of physical, chemical,
enzymatic barriers and activity
of phagocytic cells
(neutrophils) which are
associated w/ a signaling
system
Adaptive (antibodymediated) Immune System:
consists of two components
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Humoral (antibody production
in response to antigen,
medicated by B-lymphocytes)
Cell-mediated (production of
specific killer cells in response
to an antigen, mediated by Tlymphocytes)
Innate Immune Response Neutrophils, first line of defense
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Phagocytes: first to arrive
at the site of infection
Function to contain
infections, provide time
for adaptive system to
develop
200 billion in adult cow,
50% in circulation,
remainder in bone or
attached to vessel walls
Life span of 1-2 days
Contain a protein
component: L-Selectin,
index of innate immunity
Neutrophil recognition of pathogen
Receptors on surface
of neutrophil
Neutrophil
Pathogen
Pathogen-associated molecular
Patterns: PAMPs)
Phagocytosis
Bacterium
Recognition
Production of NETS by neutrophils
Inactive neutrophils
Activated neutrophils with NETs
+ interleukin-8 (IL-8)
Source: Brinkmann et al., 2004
Association of neutrophil “NETs” with bacteria
S. aureus (gram +) Salmonella (gram -)
Shigella (gram -)
Neutrophils: a first line of defense
- tethering via L-selectin (A)
-shedding L-selectin (B)
- Interleukin-1- proinflammatory (C)
-migration toward “signals”
(D)
-phagocytosis (F)
Source: Burton and Erskine, 2003
-pathogens
Example of relationship between stress and
immunity
Cortisol - Adrenal hormone
•
released in response to a
stressful event
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needed by uterus at time
of calving
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aids in intiating milk
secretion by the
mammary gland
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elevated blood Cortisol
cause neutrophils to lose
their ability to migrate
from blood into tissue by
interfering with Lselectin synthesis
Source: Burton and Erskine, 2003
Cortisol Response Relative to Parturition
Cortisol (ug/dL)
TRANSITION COW TRIAL - CORTISOL
16
14
12
10
8
6
4
2
0
Hospital Cows
All Cows
-7 -6 -5 -4 -3 -2 -1 0 1 7 14
Puntenney & French 2003
Effect of stress on neutrophils
Normal
L-selectin and interleukin
Stress
Proliferation and invasion
of pathogens
Take home on neutrophils
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First line of defense against
bacteria and molds
L-selectin (tethering/rolling/
“surveillance”) (A/B)
IL-8 (signal from infection
site) (D)
IL-1β (access infection site/
“diapedesis”) (C)
Free-flowing blood neutrophil
(E)
Killing mechanisms (digestion
and NETs) (F)
Pluripotent hematopoeitic stem cell
(Self-renewing, white blood cell producing)
Common lymphoid
Progenitor
(lymph tissue)
B cells
T cells
NK cells
Common myeloid
Progenitor
(bone marrow)
White blood
cells
Red blood
cells
Megakaryocytes
Platelets
Monocyte Neutrophil Eosinophil Basophil Dendritic cell
-Adaptive
Macrophage
Janeway et al., 2005
-Innate
Phases of an infection
Innate
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Acquired
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1. Entry of pathogen
2. encounter a macrophage/dendritic cell
3. macrophage recruits neutrophils via IL-8
4. macrophage (phagocytic cell) and
dendritic cells (antigen-presenting cells)
migrate to lymph tissue where they
encounter naïve B and T lymphocyte
5. B and T lymphocytes clonally expand
and differentiate and make antibodies
Linkage of innate and adaptive
immunity
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1. Activated macrophages and
dendritic cells with ingested
pathogen present antigen to Tlymphocytes
2. Chemokines, secreted by
macrophages, enhance tissue
permeability and influx of Tlymphocytes into an infection
site (IL-1B)
3. Macrophages and
neutrophils produce
activating molecules (e.g., IL1β and IL-6)
Janeway et al., 2005
Activated neutrophil
IL-1β
+
B and T
lymphocytes
4. Activated T-cells, in turn,
activate macrophages
Review
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Terms
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Pathogen: disease-causing infectious agent
Antigen: any molecule that stimulates the immune
response (pathogen proteins or carbohydrates)
Phagocytes: cells attracted to site of infection to destroy
pathogens (not antigen-specific, part of innate system)
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Neutrophils
Eosinophils
Monocytes/macrophages
Natural Killer Cells (virus-infected and cancer cells)
Review
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Terms
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Leukocytes: white blood cells
Adaptive Immunity: response to repeat infection
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Synthesis of antibody to bind antigen and promote
elimination
T cell killing of virus-infected cells
T cell activation of macrophages to destroy
phagocytosed pathogens that are resistant to
destruction
Review
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Terms
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Innate Immunity: defense system that can recognize
“generic danger” and responds by walling off and
engulfing foreign organisms
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Barriers - skin, mucous membranes
Mechanical – cilia, blinking, sneezing, coughing, vomiting
Chemical – HCl in stomach, digestive enzymes in tears,
mucus
Phagocytes – Neutrophils, eosinophils, macrophages, M
cells, monocytes
Natural Killer Cells – kill virus/cancer cells
Review
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Terms
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Apoptosis: programmed cell death
Macrophages: innate immune cell, binds pathogens,
produce cytokines to attract other phagocytic cells and
make blood vessels leaky, may present antigen to
stimulate T cell activation (adaptive)
Dendritic cells: innate immune cell, may be
phagocytic and may present antigen to simulate T cell
activation (adaptive immune system)
Lymphocytes: antigen-specific white blood cells
responsible for adaptive immunity
Review
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Terms
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Natural Killer (NK) Cells: large lymphocytes that
lack specific antigen receptors but respond to altered
tissue typing in virus-infected and cancer cells
Cytokines: small proteins produced by macrophages
in response to bacterial antigens; signal other white
blood cells; act by binding to specific membrane
receptors to signal the cell to alter its behavior (gene
expression)
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Lymphokine (lymphocytes), monokine (monocytes),
chemokine (chemotactic activity), interleukin (made by one
leukocyte and acting on others)
Review
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Terms
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Antibody: antigen receptor on B cells and is also secreted to
bind and remove antigen from the body
Immunoglobulins: antibodies that are antigen-binding proteins
(IgG, IgM, IgD, IgA, IgE)
Interleukin-1: cytokines produced by macrophages which
activate nearby vascular endothelium to promote leukocyte
movement into the tissue (extravasation)
Interlukin – 8: chemokines which recruit leukocytes and
attract them to site of infection
L-selectin: neutrophil-adhesion molecule that initiates binding
between leukocytes and endothelium