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TORTORA • FUNKE
• CASE
Microbiology
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
Chapter 16
Nonspecific Defenses of the Host
Nonspecific Defenses of the Host
• Susceptibility
Lack of resistance to a
disease
• Resistance
Ability to ward off disease
• Nonspecific resistance
Defenses against any
pathogen
• Specific resistance
Immunity, resistance to a
specific pathogen
• Native (innate)
species specific immunity
Figure 16.1 An overview of the body’s defenses.
Host Defenses
First line of defense
• Intact skin
• Mucous membranes
and their secretions
• Normal microbiota
Second line of defense
• Phagocytes, such as neutrophils,
eosinophils, dendritic cells, and
macrophages
• Inflammation
• Fever
• Antimicrobial substances
Third line of defense
• Specialized lymphocytes:
T cells and B cells
• Antibodies
First line of Defense
Mechanical Factors
Physical barriers to pathogens
• Skin
• Epidermis consists of
tightly packed cells with
• Keratin, a protective
protein
Mechanical Factors
• Mucous membranes
• Ciliary escalator: Microbes trapped in mucus are
transported away from the lungs
• Lacrimal apparatus: Washes eye
• Saliva: Washes microbes off
• Urine: Flows out
• Vaginal secretions: Flow out
Lacrimal glands
Upper eyelid
Lacrimal canal
Nasolacrimal
duct
Nose
Chemical Factors
Chemical factors:
• Low pH (3-5) of skin
• Fungistatic fatty acid in sebum
• Saltiness from perspirations
• Lysozyme in perspiration, tears, saliva,
and tissue fluids
• Low pH (1.2-3.0) of gastric juice
• Transferrins in blood bind iron
• Cerumin – physical and chemical
Blocks and low pH
transplant?
Normal Microbiota
• Microbial antagonism/competitive exclusion:
• Normal microbiota compete with pathogens.
Second line of Defense
1. Phagocytosis
2. Inflammation
3. Fever
4. Antimicrobial substances
Formed Elements In Blood (note functions)
•
RBC’s
•
WBC’s
•
•
Agranulocytes
•
Monocytes
•
Lymphocytes
Granulocytes
•
Neutrophils (PMNs)
•
Basophils
•
Eosinophils
Table 16.1
Differential White Cell Count
• Percentage of each type
of white cell in a sample of
100 white blood cells
(Never let monkeys eat
bananas)
Neutrophils
60-70%
Basophils
0.5-1%
Eosinophils
2-4%
Monocytes
3-8%
Lymphocytes
20-25%
White Blood Cells
• Neutrophils: Phagocytic
• Basophils: Produce histamine
• Eosinophils: Toxic to parasites, some phagocytosis
• Monocytes: Phagocytic as mature macrophages
• Fixed macrophages in lungs, liver, bronchi
• Wandering macrophages roam tissues
• Lymphocytes: Involved in specific immunity
Phagocytosis
• Phago: eat
• Cyte: cell
• Ingestion of microbes or particles by a cell,
performed by phagocytes
• Some travel out of blood into tissues:
• Margination
• Diapedesis
Phagocytosis
Figure 16.8a
Toll like Receptors and PAMPs
A phagocytic macrophage
uses a pseudopod to engulf
nearby bacteria.
Pseudopods
Phagocyte
Cytoplasm
1 CHEMOTAXIS
and
ADHERENCE
of phagocyte to
microbe
2 INGESTION
of microbe by phagocyte
4 Fusion of phagosome
with a lysosome
to form a phagolysosome
Microbe
or other
particle
Details of
adherence
3 Formation of phagosome
(phagocytic vesicle)
Lysosome
PAMP
(peptidoglycan
in cell wall)
Digestive
enzymes
Partially
digested
microbe
5 DIGESTION
of ingested
microbes by
enzymes in the
phagolysosome
Indigestible
material
6 Formation of
the residual body
containing
indigestible
material
TLR
(Toll-like receptor)
Plasma membrane
7 DISCHARGE of
waste materials
Microbial Evasion of Phagocytosis
• Inhibit adherence: M protein,
capsules
• Kill phagocytes: Leukocidins
Streptococcus pyogenes, S. pneumoniae
• Lyse phagocytes: Membrane
attack complex
• Escape phagosome
Listeriamonocytogenes
• Prevent phagosome-lysosome
fusion
• Survive in phagolysosome
HIV
Staphylococcus aureus
Shigella
Coxiella burnetti and Mycobacteria spp
Inflammation
•Redness
•Pain
•Heat
•Swelling (edema)
•Loss of function
Acute-phase proteins activated
(complement, cytokine, kinins) chemical messengers
• Vasodilation (histamine, kinins,
prostaglandins, leukotrienes) bring in more help
• Margination and emigration of
WBCs
• Tissue repair
Chemicals Released by Damaged Cells
• Histamine
• Kinins
• Prostaglandins
• Leukotrienes
Vasodilation, increased permeability of blood
vessels
Vasodilation, increased permeability of blood
vessels
Intensity histamine and kinin effect
Increased permeability of blood vessels,
phagocytic attachment
Inflammation
Figure 16.8a-b The process of inflammation.
Bacteria entering
on knife
Bacteria
Epidermis
Blood vessel
Dermis
Nerve
Subcutaneous
tissue
(a) Tissue damage
1 Chemicals such as histamine, kinins,
prostaglandins, leukotrienes, and cytokines
(represented as blue
dots) are released by
damaged cells.
2 Blood clot forms.
3 Abscess starts to form
(orange area).
(b) Vasodilation and increased
permeability of blood vessels
Figure 16.9a, b
Inflammation
Figure 16.9c, d
Fever: Abnormally High Body Temperature
• Hypothalamus normally set at 37°C
• Gram-negative endotoxin cause phagocytes to release
interleukin 1
• Hypothalamus releases prostaglandins that reset the
hypothalamus to a high temperature
• Body increases rate of metabolism and shivering to
raise temperature
• When IL-1 is eliminated, body temperature falls.
(Crisis)
The Complement System
Serum proteins
activated in a
cascade.
Increasing as
previous
catalyzes the next
step
Outcomes of
Complement
system
1. Chemotaxic
2. Opsonization
3. Cell lysis
Figure 16.10
Figure 16.9 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
C5a
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
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
© 2013 Pearson Education, Inc.
Bursting of microbe due to inflow of extracellular fluid through
transmembrane channel formed by membrane attack complex
Effects of Complement Activation
• Opsonization or
immune adherence:
enhanced
phagocytosis
• Membrane attack
complex: cytolysis
• Attract phagocytes
Figure 16.11
Effects of Complement Activation
C3B - Opsinozation
C3a - triggers Mast Cells to release agents of
inflammation
C5a - chemotaxic for phagocytes
Figure 16.12
Figure 16.11 Inflammation stimulated by complement.
C5a
C5a receptor
Histamine
Phagocytes
Neutrophil
Histaminecontaining
granule
Insert Fig 16.11
Histaminereleasing
mast cell
C3a
C3a receptor
C5a
Macrophage
Classical Pathway
Figure 16.13
Alternative Pathway
Figure 16.14
Lectin Pathway
Figure 16.15
Some bacteria evade complement
• Capsules prevent C’ activation
• Surface lipid-carbohydrates prevent MAC (membrane
attack complex C5b - C9) formation
• Enzymatic digestion of C5a
Interferons (IFNs)
Antiviral proteins
• Alpha IFN & Beta IFN: Cause cells to produce antiviral
proteins that inhibit viral replication
• Gamma IFN: Causes neutrophils and macrophages to
phagocytize bacteria
Interferons (IFNs)
2 The infecting
virus replicates
into new
viruses.
5 New viruses released
by the virus-infected
host cell infect
neighboring host
cells.
6 AVPs degrade viral
m-RNA and inhibit
protein synthesis and
thus interfere with
viral replication.
1 Viral RNA from an
infecting virus
enters the cell.
3 The infecting virus also
induces the host cell to
produce interferon on
RNA (IFN-mRNA), which
is translated into alpha
and beta interferons.
4 Interferons released by the virus-infected host cell bind to plasma
membrane or nuclear membrane receptors on uninfected neighboring
host cells, inducing them to synthesize antiviral proteins (AVPs). These
include oligoadenylate synthetase, and protein kinase.
Figure 16.16