Download a13 Innate Immunity

Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical
Barriers
 Cells and Chemicals in Non-Specific
Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents
and Opsonizers
• The role of fever
Body Defenses
(Innate
Immunity)
(Acquired
Immunity)
Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical Barriers
 Cells and Chemicals in Non-Specific Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and
Opsonizers
• The role of fever
Nonspecific (Innate) Body Defenses
Mechanical, Chemical, and Competitive Barriers
Skin produces acidic sebum
to limit bacterial growth.
Saliva and tears destroy bacteria
because they contain lysozyme.
Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical
Barriers
 Cells and Chemicals in Non-Specific
Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents
and Opsonizers
• The role of fever
Internal Defenses: Cells and Chemicals
 Necessary if microorganisms invade deeper tissues
• Phagocytes
• Natural killer (NK) cells
• Inflammatory response (macrophages, mast
cells, WBCs, and inflammatory chemicals)
• Antimicrobial proteins (interferons and
complement proteins)
• Fever
Defensive Cells in Non-Specific Defense
 Phagocytes
(neutrophils and macrophages)
• Engulf foreign material into
a vacuole
• Enzymes from lysosomes
digest the material
• Free macrophages wander
through tissues; fixed
macrophages are permanent
(e.g liver Kupfer cells,
brain microglia
Events of Phagocytosis
Lysosome
1 Phagocyte
adheres to
pathogens or debris.
Phagosome
(phagocytic
vesicle)
Acid
hydrolase
enzymes
(b) Events of phagocytosis.
2 Phagocyte forms
pseudopods that
eventually engulf the
particles forming a
phagosome.
3 Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome.
4 Lysosomal
enzymes digest the
particles, leaving a
residual body.
5 Exocytosis of the
vesicle removes
indigestible and
residual material.
Figure 21.2b
Mechanism of Phagocytosis
 Destruction of pathogens
• Acidification and digestion by lysosomal
enzymes
• Respiratory burst
o Release of cell-killing free radicals
o Activation of additional enzymes
• Oxidizing chemicals (e.g. H2O2)
• Defensins (in neutrophils)
Natural Killer (NK) Cells
 Large granular
lymphocytes
 Target cells that lack
“self” cell-surface
receptors (MHC
proteins).
 Induce apoptosis in
cancer cells and virusinfected cells
 Secrete potent chemicals
that enhance the
inflammatory response
(Cytotoxic T cells target cells
that have “self” antigens (MHC
I proteins)
Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical
Barriers
 Cells and Chemicals in Non-Specific
Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents
and Opsonizers
• The role of fever
Inflammatory Response
 Triggered whenever body tissues are injured
or infected
 Prevents the spread of damaging agents
 Disposes of cell debris and pathogens
 Sets the stage for repair
Inflammatory Response
 Cardinal signs of acute inflammation:
1. Redness
2. Heat
3. Swelling
4. Pain
(And sometimes 5. Impairment of function)
Inflammatory Response
 Macrophages and epithelial cells of boundary
tissues bear Toll-like receptors (TLRs)
 TLRs recognize specific classes of infecting
microbes
 Activated TLRs trigger the release of
cytokines that promote inflammation
Inflammatory Response
 Inflammatory mediators (“Alert” chemicals)
• Histamine (from mast cells)
• Blood proteins
• Kinins, prostaglandins (PGs), leukotrienes, and
complement
o Released by injured tissue, phagocytes, lymphocytes, basophils,
and mast cells
 Action of inflammatory chemicals
• Dilation of arterioles, resulting in hyperemia
• Increased permeability of local capillaries and edema
(leakage of exudate)
 Exudate moves foreign material into lymphatic vessels,
delivers clotting proteins to form a scaffold for repair and to
isolate the area
Inflammatory Response - Second Line of Defense
1.
Release of histamines, complement, prostaglandins, and kinins from injured cells
2.
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3.
Activation of pain receptors by swollen tissue pressure
4.
Attraction of phagocytes and other lymphocytes to the area through chemotaxis:
leukocytosis, margination, diapedesis
Steps of Attraction of Leukocytes
Innate
defenses
Internal
defenses
Inflammatory
chemicals
diffusing
from the
inflamed site
act as chemotactic
agents.
Capillary wall
Basement
membrane
Endothelium
Leukocytosis.
Neutrophils enter blood
from bone marrow.
1
Figure 21.4, step 1
Steps of Attraction of Leukocytes
Innate
defenses
Internal
defenses
Inflammatory
chemicals
diffusing
from the
inflamed site
act as chemotactic
agents.
Leukocytosis.
Neutrophils enter blood
from bone marrow.
1
Capillary wall
Basement
membrane
Endothelium
Margination.
Neutrophils cling
to capillary wall.
2
Figure 21.4, step 2
Steps of Attraction of Leukocytes
Innate
defenses
Internal
defenses
Inflammatory
chemicals
diffusing
from the
inflamed site
act as chemotactic
agents.
Leukocytosis.
Neutrophils enter blood
from bone marrow.
1
Margination.
Neutrophils cling
to capillary wall.
2
Capillary wall
Basement
membrane
Endothelium
Diapedesis.
Neutrophils flatten and
squeeze out of capillaries.
3
Figure 21.4, step 3
Steps of Attraction of Leukocytes
Innate
defenses
Internal
defenses
Inflammatory
chemicals
diffusing
from the
inflamed site
act as chemotactic
agents.
Leukocytosis.
Neutrophils enter blood
from bone marrow.
1
Margination.
Neutrophils cling
to capillary wall.
2
Chemotaxis.
Neutrophils
follow chemical
trail.
4
Capillary wall
Basement
membrane
Endothelium
Diapedesis.
Neutrophils flatten and
squeeze out of capillaries.
3
Figure 21.4
Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical
Barriers
 Cells and Chemicals in Non-Specific
Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents
and Opsonizers
• The role of fever
Inflammatory Response - Second Line of Defense
1.
Release of histamines, complement, prostaglandins, and kinins from injured cells
2.
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3.
Activation of pain receptors by swollen tissue pressure
4.
5.
Attraction of phagocytes and other lymphocytes to the area through chemotaxis:
leukocytosis, margination, diapedesis
Clotting proteins leaking into the area wall off damaged sections; interferon &
complement may also be released
Antimicrobial Proteins: Inteferon

Produced by most leukocytes and lymphocytes

Function

•
Reduce inflammation, active macrophages, activate
macrophages and mobilize NK cells
•
Hinder microorganisms’ ability to reproduce
1.
Viral-infected cells secrete IFNs
2.
IFNs enter neighboring cells
3.
Neighboring cells produce antiviral proteins that block viral
reproduction
Genetically engineered IFNs for hepatitis, herpes, MS
How Interferon Activates the Production of Antivirals
Innate defenses
Virus
Viral nucleic acid
1 Virus
Internal defenses
New viruses
enters cell.
5 Antiviral
proteins block
viral
reproduction.
2 Interferon
genes switch on.
DNA
Nucleus
mRNA
4 Interferon
3 Cell produces
interferon
molecules.
Host cell 1
Infected by virus;
makes interferon;
is killed by virus
Interferon
Host cell 2
Binds interferon
from cell 1; interferon
induces synthesis of
protective proteins
binding
stimulates cell to
turn on genes for
antiviral proteins.
Figure 21.5, step 5
Antimicrobial Proteins: Complement
 What they are
• About 20 blood proteins that circulate in an inactive
form
• Include C1–C9, factors B, D, and P, and regulatory
proteins
 Function
• Major mechanism for destroying foreign substances
• Amplifies all aspects of the inflammatory response
• Kills bacteria and certain other cell types by cell lysis
• Enhances both nonspecific and specific defenses
Complement Activation
 Two pathways
1. Classical pathway
o Antibodies bind to invading organisms
o C1 binds to the antigen-antibody
complexes (complement fixation)
2. Alternative pathway
o Triggered when activated C3, B, D, and P
interact on the surface of microorganisms
Complement is Activated in Two Ways
Classical pathway
Antigen-antibody complex
+
complex
Opsonization:
coats pathogen
surfaces, which
enhances phagocytosis
Insertion of MAC and cell lysis
(holes in target cell’s membrane)
Alternative pathway
Spontaneous activation
+
Stabilizing factors (B, D, and P)
+
No inhibitors on pathogen
surface
Enhances inflammation:
stimulates histamine release,
increases blood vessel
permeability, attracts
phagocytes by chemotaxis,
etc.
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
Transmembrane channel (membrane attack complex) causing lysis
Figure 21.6
Inflammatory Response - Second Line of Defense
1.
Release of histamines, complement, prostaglandins, and kinins from injured cells
2.
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3.
Activation of pain receptors by swollen tissue pressure
4.
5.
6.
7.
Attraction of phagocytes and other lymphocytes to the area through chemotaxis:
leukocytosis, margination, diapedesis
Clotting proteins leaking into the area wall off damaged sections; interferon & complement
may also be released
Increased local metabolic rate raises the local temperature to increase rate of repair processes
Production of a fever (stimuated by pyogenic compounds)
.
8. Dead or dying neutrophils, dead cells, and pathogens may form, walling off a sac of pus to
form an abscess
.
Innate defenses
Tissue injury
Internal defenses
Release of chemical mediators
(histamine, complement,
kinins, prostaglandins, etc.)
Release of leukocytosisinducing factor
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Initial stimulus
Vasodilation
of arterioles
Increased capillary
permeability
Local hyperemia
(increased blood
flow to area)
Capillaries
leak fluid
(exudate formation)
Attract neutrophils,
monocytes, and
lymphocytes to
area (chemotaxis)
Leukocytes migrate to
injured area
Margination
(leukocytes cling to
capillary walls)
Physiological response
Signs of inflammation
Leaked protein-rich
fluid in tissue spaces
Result
Heat
Redness
Locally increased
temperature increases
metabolic rate of cells
Pain
Swelling
Possible temporary
limitation of
joint movement
Leaked clotting
proteins form interstitial
clots that wall off area
to prevent injury to
surrounding tissue
Temporary fibrin
patch forms
scaffolding for repair
Diapedesis
(leukocytes pass through
capillary walls)
Phagocytosis of pathogens
and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Pus may form
Area cleared of debris
Healing
Figure 21.3
Fever
 Abnormally high body temperature
 Hypothalmus heat regulation can be reset by
pyrogens (secreted by white blood cells)
 High temperatures inhibit the release of iron
and zinc from liver and spleen needed by
bacteria
 Fever also increases the speed of tissue repair
by increasing metabolic rate
Innate (Non-Specific) Immunity
 Divisions of the Immune System
 Mechanical, Chemical, and Physical Barriers
 Cells and Chemicals in Non-Specific Immunity
 Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and
Opsonizers
• The role of fever