Innate Immunity: Nonspecific
Defenses of the Host
Chapter 15
of the Host
The Concept of Immunity
• A pathogen can cause disease only if
– It gains access, by penetrating the surface of the
skin or entering another portal of entry
– Attach itself to host cells
– Evade the body’s defense mechanisms long
enough to produce harmful changes
The Concept of Immunity
• The structures, cells, and chemicals that act
against pathogens are categorized into 3 main
lines of defense
•
– First line defenses
• External physical barriers
– Second line defenses
• Cells, blood chemicals, and processes to kill invaders
•
– Third line of defense
• Responds uniquely to species or strains of pathogens
First Line of Defense: Skin and Mucous
Membranes
Physical Factors
•
• _________consists of tightly packed cells with
– Keratin, a protective protein
– Outer layer is dead
• Slough off bacteria along with dead skin cells
• Dermis
– Difficult to penetrate
Skin continued
• Skin tends to be ______
– Inhibits cell growth
• Microorganisms rarely penetrate skin on their
own
• Most bacteria live in warm moist areas on skin
• Staphylococcus species
– Normally inhabit epidermis (hair follicles and
sweat glands)
– Most likely organisms to cause infections
Physical Factors
• Mucous membranes
– Line gastrointestinal, respiratory, and urinary tracts
– Mucus:
– Ciliary escalator:
Ciliated cells of the respiratory system infected with Bordetella pertussis.
The ciliary escalator.
Trapped
particles
in mucus
Cilia
Ciliated cells
Goblet cells
Insert Fig 16.4
Ciliated cells propel dust and microbes that have been trapped in mucus upward toward
throat.
1-3cm per hour
Cigarette smoke toxic to ciliated cells which impairs function
Physical Factors
• Lacrimal apparatus: washes eye
• Saliva: dilute and wash microbes off of mouth
surfaces
• Urine: flows out
• Vaginal secretions: flow out
• Peristalsis (coordinated contractions of the GI
tract), defecation, and vomiting expel microbes
The lacrimal apparatus.
Lacrimal glands
Upper eyelid
Lacrimal canal
Nasolacrimal
duct
Nose
Chemical Factors
• Skin:
– Fungi and bacteriostatic fatty acid in sebum (oily
substance)
–
• Lysozyme in perspiration, tears, saliva, and urine
–
• Saliva
– Urea and uric acid
• Low pH (1.2–3.0) of gastric juice in Stomach
• Low pH (3–5) of vaginal secretions
• Urine low pH (6)
Normal Microbiota and Innate Immunity
• Competitive exclusion:
Second Line of Defense
• Operates when pathogens penetrate the skin
or mucous membranes
• Second line defenses include cells and
antimicrobial compounds
The Body’s Second Line of Defense
• Defense Components of Blood
– Lactoferrin- iron-binding compounds
• Bind to iron which is an important part of some
enzymes and important for growth
–
– Antibodies (adaptive system)
Figure 15.4 A schematic representation of hematopoiesis
Blood stem cell in bone marrow
Myeloid
stem cell
Erythroid
stem cell
Erythrocyte Platelets
Basophil
Inflammation
Clotting,
inflammation
Gas
transportation
Neutrophil
Lymphoid
stem cell
Eosinophil
Monocyte
Lymphocyte
Phagocytosis
Innate immunity, second line of defense
Leukocytes
Adaptive immunity
The Body’s Second Line of Defense
• Defense Components of Blood
– Granulocytes
• Contain large granules that stain different colors
• Three types
–
» Phagocytize pathogens
» Capable of migrating out of blood vessels into
surrounding tissue
– _______________ can leave the blood releasing
inflammatory chemicals
» Not phagocytic
The Body’s Second Line of Defense
• Defense Components of Blood
– Agranulocytes
• Two types
–
» Most involved in adaptive immunity
–
» Leave the blood and mature into macrophages
» Macrophages are phagocytic cells that devour foreign
objects, including bacteria, fungi, spores, dust, and dead
body cells
The Body’s Second Line of Defense
• Defense Components of Blood
– Lab analysis of leukocytes
• Differential white blood cell count can signal signs of
disease
– Increased eosinophils indicate allergies or parasitic
worm infection
– Bacterial diseases often show increase in leukocytes
and neutrophils
Effects of Complement Activation
•
•
•
Outcomes of Complement Activation.
1 Inactivated C3 splits into activated
C3
C3a and C3b.
2 C3b binds to microbe, resulting
in opsonization.
C3b
C3a
C3b
proteins
3 C3b also splits C5
into C5a and C5b
5 C3a and C5a cause
mast cells to release
histamine, resulting
in inflammation;
C5a also attracts
phagocytes.
opsonization
C5
Enhancement of phagocytosis
by coating with C3b
C5b
Histamine
C5a
Insert Fig 16.9
Mast cell
4 C5b, C6, C7, and C8 bind
together sequentially and
insert into the microbial
plasma membrane, where
they function as a receptor
to attract a C9 fragment;
additional C9 fragments are
added to form a channel.
Together, C5b through C8
and the multiple C9
fragments form the
membrane attack complex,
resulting in cytolysis.
C5a receptor
C5a
C6
C3a receptor
C3a
inflammation
C7
C8
Increase of blood vessel
permeability and chemotactic
attraction of phagocytes
C9
Microbial
plasma
membrane
Channel
C6
C7
C5b
C8
C9
Formation of membrane
attack complex (MAC)
C6
C5b
C7
C8
C9
Cytolysis
cytolysis
Bursting of microbe due to inflow of extracellular fluid through
transmembrane channel formed by membrane attack complex
Interferons (IFNs)
– Interferons
•
• Cause many symptoms associated with viral infections
– alpha and beta
» Cause cells to produce antiviral proteins that inhibit
viral replication
Figure 15.7 The actions of alpha and beta interferons
Virus infects cell.
Virus
Doublestranded
RNA
Viral replication
in cell triggers
transcription and
translation of
IFN- or IFN-,
depending on
type of host cell.
IFN
gene
Time
passes
Meanwhile, the
infected cell dies,
releasing viruses.
Nucleus
mRNA
IFN
Infected cell
Infected cell
at a later time
Interferon is released,
diffuses to neighboring
uninfected cells, and
binds to receptors.
Interferon receptor
When the second
cell becomes infected
with viruses, doublestranded RNA of the
virus activates AVP.
Inactive AVP
Binding triggers
transcription
and translation of
inactive antiviral
proteins (AVPs).
AVP
gene
Doublestranded
viral RNA
Active AVPs
Time
passes
Ribosome
mRNA
mRNA
Inactive AVPs
Uninfected
neighboring cell
Same
neighboring
cell now protected
at the later time
Active AVPs degrade mRNA
and bind to ribosomes,
which stops protein
synthesis and viral
replication.
Phagocytosis
• Ingestion of microbes or particles by a cell,
performed by phagocytes
Macrophage
Bacterium
Pseudopods
Phagocytosis
• Neutrophils and Eosinophils
• Macrophages- specialize in phagocytosismature monocytes
Blood stem cell in bone marrow
Myeloid
stem cell
Neutrophil Eosinophil Monocyte
Phagocytosis
Phagocytosis
• Phagocytosis
– Cells capable of phagocytosis are called phagocytes
– Can be divided into 6 steps
•
•
•
•
•
•
Figure 15.6 The events in phagocytosis
Chemotaxis of
phagocyte
Neisseria
to microbes
(microbes)
Adherence
Pseudopodia move
(chemotaxis)
Ingestion of microbes
by phagocytes
Fusion of a
series of vesicles,
including lysosomes
Phagosome
TEM
1m
Killing of
microbes by
enzymes and
other chemicals
Golgi body
Lysosome
Nucleus
Phagolysosome
Residual
body
Pseudopod
Phagocyte
Elimination
(exocytosis)
Inflammation
•
– Sun burn, cuts, chemicals, abrasions
• Acute inflammation
–
– Is typically beneficial
– Elimination of whatever condition precipitated it
• Chronic inflammation
–
– Causes damage to tissue resulting in disease
Signs of Inflammation
•
•
•
•
Redness
Swelling (edema)
Pain
Heat
Inflammation process
• Dilation and increased permeability of the
blood vessels
• Migration of phagocytes into infected
tissue
• Tissue Repair
Fever
• Pyrogens trigger the hypothalamus to increase
the body’s core temperature
• Hypothalamus is normally set at 37°C
• Body increases rate of metabolism, and shivering
occurs, which raise temperature
• Various types of pyrogens
•
•
•
Fever
• Advantages
– Produces interferon
– Thought to enhance
perfomance of
phagocytes
– Increases temperature
above optimal for the
microorganism
• Disadvantages
– Dehydration
– 44–46°C fatal