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 Second line of defense Third line of defense

• Intact skin • Phagocytes, such as neutrophils, • Specialized lymphocytes:

• Mucous membranes eosinophils, dendritic cells, and T cells and B cells
and their secretions macrophages • Antibodies
• Normal microbiota • Inflammation
• Fever
• Antimicrobial substances
 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
 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
 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
 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 3 Formation of phagosome

1 CHEMOTAXIS (phagocytic vesicle)
2 INGESTION
and
of microbe by phagocyte
ADHERENCE
of phagocyte to
microbe
4 Fusion of phagosome
with a lysosome
Microbe to form a phagolysosome
or other Lysosome
particle

Details of 5 DIGESTION
PAMP Digestive
adherence (peptidoglycan
enzymes of ingested
in cell wall)
microbes by
Partially
enzymes in the
digested
phagolysosome
microbe

Indigestible
material

TLR 6 Formation of
(Toll-like receptor) the residual body
Plasma membrane containing
indigestible
material

7 DISCHARGE of
waste materials
 Microbial Evasion of Phagocytosis

• Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae

• Kill phagocytes: Leukocidins Staphylococcus aureus

• Lyse phagocytes: Membrane attack Listeria monocytogenes

complex
• Escape phagosome Shigella

• Prevent phagosome-lysosome fusion HIV

• Survive in phagolysosome 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 Vasodilation, increased permeability of blood

vessels
• Kinins Vasodilation, increased permeability of blood
vessels
• Prostaglandins Intensity histamine and kinin effect

• Leukotrienes 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
C3a and C3b. C3

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 C5a receptor
C5a
by coating with C3b Histamine

C5b C5a

4 C5b, C6, C7, and C8 bind

Insert Fig 16.9 Mast cell

together sequentially and C6 C3a receptor C3a

insert into the microbial
plasma membrane, where
they function as a receptor
C7 inflammation
to attract a C9 fragment; C8 Increase of blood vessel
additional C9 fragments are permeability and chemotactic
added to form a channel. attraction of phagocytes
Together, C5b through C8
and the multiple C9
fragments form the C9
membrane attack complex,
resulting in cytolysis.
Microbial
plasma
membrane
Channel

C6 C6
C5b C5b
C7 C7
C8 C8
C9 C9

Formation of membrane Cytolysis

attack complex (MAC)

cytolysis
Bursting of microbe due to inflow of extracellular fluid through
© 2013 Pearson Education, Inc. 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

Histamine-
containing
granule

Insert Fig 16.11

Histamine-
releasing C3a C5a Macrophage
mast cell
C3a receptor
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.
1 Viral RNA from an
infecting virus
enters the cell.
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.

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