Because learning changes everything.

Chapter 12
Host Defenses I Overview
and Innate Defenses

Microbiology
FUNDAMENTALS
A Clinical Approach
2024 Release
Marjorie Kelly Cowan, Heidi Smith

© McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.
 Learning Outcomes Section 12.1 1

1. Summarize the three lines of host defenses.

2. Define “marker” and discuss its importance in the second

and third lines of defense.

3. Name the body systems that participate in immunity.

4. Describe the structure and function of the lymphatic

system and its connection with the circulatory system.

© McGraw Hill, LLC 2

 Learning Outcomes Section 12.1 2

5. Name three kinds of blood cells that primarily function in

innate immunity.

6. Connect the mononuclear phagocyte system to innate

immunity.

7. Explain how histiocytes are different from other

macrophages.

8. Summarize the importance of cytokines, and list one pro-

inflammatory and one anti-inflammatory cytokine.

© McGraw Hill, LLC 3

 Flowchart Summarizing Major Components of Host
Defenses

Access the text alternative for slide images.

© McGraw Hill, LLC 4

 Defense Mechanisms of the Host 1

Host defenses are a multilevel network of innate, nonspecific

protections and adaptive, specific protections commonly
referred to as the first, second, and third lines of defense.
First line of defense:
• Any barrier that blocks invasion at the portal of entry
• Limits access to the internal tissues of the body
• Very general in action

© McGraw Hill, LLC 5

 Defense Mechanisms of the Host 2

Second line of defense: Third line of defense:

• Internalized system of • Acquired on an individual
protective cells and fluids basis as each foreign
substance is encountered
• Includes inflammation and
by lymphocytes
phagocytosis
• The reaction with each
• Acts rapidly at both the
different microbe
local and systemic levels produces unique
once the first line of protective substances
defense has been
overcome • Provides long-term
immunity

© McGraw Hill, LLC 6

 Defense Mechanisms of the Host 3

Most defenses overlap and are redundant in some of their

effects.
Immunology:
• The study of all features of the body’s second and third
lines of defense
• Study of the body’s response to infectious agents
• Study of allergies and cancer

© McGraw Hill, LLC 7

 Mandate of the Immune System

A healthy functioning immune

system is responsible for the
following:
• Surveillance of the body

• Recognition of foreign material

• Destruction of entities deemed

to be foreign

Access the text alternative for slide images.

© McGraw Hill, LLC 8

 Immune Function 1

White blood cells constantly move throughout the body,

searching for potential pathogens:
• Recognize body cells (self)
• Differentiate them from any foreign material in the body
(nonself)
• The ability to evaluate macromolecules as self or nonself
is central to the functioning of the immune system
• Many autoimmune disorders are a result of the immune
system mistakenly attacking the body’s own tissues and
organs

© McGraw Hill, LLC 9

 Immune Function 2

The immune system evaluates cells by examining molecules

on cell surfaces called antigens or markers:
• Consist of proteins and/or sugars

• Allow cells of the immune system to identify whether a

newly discovered cell poses a threat and should be
marked for destruction:
• Most common method of destruction is phagocytosis

© McGraw Hill, LLC 10

 P A M Ps and P R Rs

Pathogen-associated molecular patterns (P A M Ps):

• Markers that many different kinds microbes have in
common
Pattern recognition receptors (P R Rs):
• Used by host cells with important roles in the innate
immunity of the second line of defense
• Recognize P A M Ps

Nonself proteins that are not harmful are generally

recognized as such and the immune system is signaled not
to react or to react differently.

© McGraw Hill, LLC 11

 Tissues, Organs, and Cells Participating in Immunity

For effective immune responsiveness, the activities of one

compartment must be communicated to other compartments.
Mononuclear phagocyte system (MPS):

• In direct contact with tissue cells and the extracellular fluid

(ECF)
• Blood and lymphatic capillaries penetrate into these
tissues
• Allows cells and chemicals that originate in the MPS and
ECF to diffuse into the blood and lymphatics

© McGraw Hill, LLC 12

 Circulatory and Lymphatic Systems

Access the text alternative for slide images.

© McGraw Hill, LLC 13

 Functions of the Lymphatic System

• Provide a route for the return of extracellular fluid to the

circulatory system

• Act as a “drain-off” system for the inflammatory response

• Render surveillance, recognition, and protection against

foreign materials through a system of lymphocytes,
phagocytes, and antibodies

© McGraw Hill, LLC 14

 Lymphatic Fluid

• Plasmalike liquid carried by the lymphatic circulation

• Formed when certain blood components move out of

blood vessels into extracellular space and diffuse or
migrate into the lymphatic capillaries

• Transports numerous white blood cells

• Also transports fats, cellular debris, and infectious agents

that have gained access to the tissue spaces

© McGraw Hill, LLC 15

 Lymphatic Vessels

• Similar to thin-walled veins

• Accompany blood capillaries
• Extend into all parts of the body except parts of the central
nervous system and certain organs such as bone,
placenta, and thymus
• Walls are easily permeated by extracellular fluid that has
escaped from the circulatory system
• Found in high numbers in the hands, feet, and around the
areola of the breast
• Lymph flows from the extremities to the heart
• Lymph moves only through the contraction of skeletal
muscles
© McGraw Hill, LLC 16
 Lymphatic Organs

Primary lymphatic organs: sites of immune cell birth and

maturation:
• Red bone marrow
• Thymus

Secondary lymphatic organs: sites of immune cell

activation, residence, and functioning:
• Lymph nodes
• Spleen
• Associated lymphoid tissues

© McGraw Hill, LLC 17

 Red Bone Marrow

An important intersection between the circulatory system,

skeletal system, and lymphatic system

Typically found in flat bones and the ends of long bones and
is the site of blood cell production:
• After B lymphocytes begin to express markers that identify
them as B cells, they complete their maturation in the
bone marrow and then migrate to secondary lymphatic
organs

© McGraw Hill, LLC 18

 Thymus: Site of T-Cell Maturation

• Originates in the embryo as two lobes in the lower neck

region and fuse into a triangular structure

• Naïve T lymphocytes develop specificity and are released

into circulation as mature T cells

• T cells subsequently migrate to, and settle in, the lymph

nodes and spleen

© McGraw Hill, LLC 19

 Lymph Nodes

Small, encapsulated, bean-shaped

organs
Stationed in clusters along lymphatic
channels and large blood vessels of the
thoracic and abdominal cavities
Aggregations of lymph nodes found in:
• Armpit (axillary nodes)

• Groin (inguinal nodes)

• Neck (cervical nodes)

Enlargement of lymph nodes can

provide physicians with important clues
to a patient’s condition
Access the text alternative for slide images.

© McGraw Hill, LLC 20

 Spleen

• Found in the upper-left portion of the abdominal cavity

• Serves as a filter for blood instead of lymph
• Primarily removes worn-out red blood cells
• Also filters pathogens from the blood for phagocytosis by
macrophages
• Adults who have had their spleen removed can live a
relatively normal life, but children who have had their
spleen removed are severely immunocompromised
• Storehouse of blood that can be released in the event of a
hemorrhage

© McGraw Hill, LLC 21

 Associated Lymphoid Tissues 1

• Discrete bundles of lymphocytes at many sites or just

beneath the skin and mucosal surfaces

• Skin-associated lymphoid tissues (S A L T)

• Mucosa-associated lymphoid tissues (M A L T)

© McGraw Hill, LLC 22

 Associated Lymphoid Tissues 2

Tonsils: active source of lymphocytes in the pharynx

Breasts of pregnant and lactating people also become
temporary sites of antibody-producing lymphoid tissues
Gut-associated lymphoid tissue (G A L T):
• Appendix
• Lacteals
• Peyer’s patches: compact aggregations of lymphocytes in
the ileum of the small intestine

© McGraw Hill, LLC 23

 The Blood 1

Whole blood consists of:

• Blood cells: formed elements suspended in plasma
• Plasma: clear, yellowish fluid
• Serum: essentially the same as plasma, except that it is
the clear fluid from clotted blood; used in immune testing
and therapy
Hematopoiesis: production of blood cells

© McGraw Hill, LLC 24

 Blood Cells and Platelets

Access the text alternative for slide images.

© McGraw Hill, LLC 25

 Cytokines: Critical for Cell Communication 1

Cytokines:
• Hundreds of small active molecules secreted to regulate,
stimulate, suppress, and otherwise control many aspects
of cell development, inflammation, and immunity
• Produced by monocytes, macrophages, lymphocytes,
fibroblasts, mast cells, platelets, and endothelial cells

© McGraw Hill, LLC 26

 Cytokines
Type Examples Source Target

Pro-inflammatory cytokines, that Interleukin-1 Macrophages, B B cells, T cells

encourage specific and nonspecific (IL-1) cells, dendritic cells
immune responses

Tumor necrosis T cells Phagocytes, tumor cells

factor-β (TNF-
β)
Anti-inflammatory cytokines, that Interleukin-10 T cells B cells, macrophages
discourage specific and nonspecific (IL-10)
immune responses

Vasodilators and vasoconstrictors, Serotonin Platelets and Cells in peripheral and

that can change the diameter of intestinal cells central nervous system
blood vessels or vessel permeability

Histamine Mast cells and Blood vessels, sensory

basophils nerves, neutrophils

Growth factor cytokines, that Interleukin-7 Bone marrow cells, Stem cells (stimulates
regulate lymphocyte growth or (IL-7) epithelial cells growth of B and T cells)
activation

Erythropoietin Endothelial cells Stem cells (stimulates

production of red blood
cells)
© McGraw Hill, LLC 27
 Mononuclear Phagocyte System 1

Reticulum:
• A support network of connective
tissue fibers that permeate the
tissues of the body
• Interconnects nearby cells and
meshes with the massive
connective tissue that
surrounds every organ
• Phagocytic cells enmeshed in
this network are collectively
called the mononuclear
phagocyte system (MPS)
Access the text alternative for slide images.

© McGraw Hill, LLC 28

 Mononuclear Phagocyte System 2

Found in:
• Thymus: site of white blood cell maturation
• Lymph nodes
• Tonsils
• Spleen
• Lymphoid tissue of the mucosa of the gut and respiratory
tract
The MPS is loaded with white blood cells called
macrophages and dendritic cells waiting to attack passing
foreign intruders as they arrive in these locations

© McGraw Hill, LLC 29

 Histiocytes

When differentiated
macrophages and dendritic
cells take up permanent
residence in tissues, they are
called histiocytes and include
Kupffer cells in the liver,
alveolar cells in the lungs,
Langerhans cells in the skin,
and microglia in the brain.

Access the text alternative for slide images.

© McGraw Hill, LLC 30

 Concept Check 1

Lymphatic fluid contains all of the following except Blank.

A. white blood cells

B. extracellular fluid
C. red blood cells
D. cellular debris
E. infectious agents

© McGraw Hill, LLC 31

 Learning Outcomes Section 12.2

9. Identify the three components of the first line of defense.

10. Identify the four body systems that participate in the first
line of defense.

11. Describe two examples of how the normal microbiota

contribute to the first line of defense.

© McGraw Hill, LLC 32

 First Line of Defense

• Inborn, nonspecific

• Physical and chemical

barriers that impede the
entry of microbes and
foreign agents, whether
living or not

Access the text alternative for slide images.

© McGraw Hill, LLC 33

 Built-In Defenses of the Skin

© McGraw Hill, LLC 34

 Built-In Defenses of the Mucous Membranes 1

Mucous membranes of the digestive, urinary, and respiratory

tracts and of the eye:

© McGraw Hill, LLC 35

 Built-In Defenses of the Mucous Membranes 2

Respiratory tract

© McGraw Hill, LLC 36

 Ciliary Defense of Respiratory Tree

Cultura Creative Ltd/Alamy Stock Photo (b) epithelial lining

Access the text alternative for slide images.

© McGraw Hill, LLC 37

 Built-In Defenses of the Mucous Membranes 3

Genitourinary tract

© McGraw Hill, LLC 38

 Human Microbiome

• Crohn’s disease and ulcerative colitis may be the result of

attempts to free our environment of microbes and
overtreatment with antibiotics, resulting in an ill-trained gut

© McGraw Hill, LLC 39

 Nonspecific Chemical Defenses

• Sebaceous secretions • High lactic acid and

electrolyte concentration
• Specialized glands of the
• Acidic pH and fatty acid
eyelids
• Hydrochloric acid
• Lysozyme • Digestive juices and bile
• Antimicrobial chemicals
• Protective pH in the vagina

© McGraw Hill, LLC 40

 Effect of Barrier Loss

© McGraw Hill, LLC 41

 Concept Check 2

For each of the barriers below, state whether it is a physical

or chemical barrier.

A. Hydrochloric acid of the stomach

B. Sloughing of skin
C. Lysozyme in saliva and tears
D. Ciliary escalator

© McGraw Hill, LLC 42

 Learning Outcomes Section 12.3

12. List the four major categories of the second line of

defense.
13. Outline the steps of phagocytosis.
14. Outline the steps of inflammation.
15. Discuss the mechanism of fever and how it helps defend
the body.
16. Name four types of antimicrobial host-derived products.
17. Compose one good overview sentence about the
purpose and the mode of action of the complement
system, and another about the purpose and mode of
action of interferon.

© McGraw Hill, LLC 43

 Second Line of Defense

Generalized and nonspecific defenses that support and

interact with specific immune responses:
• Phagocytosis

• Inflammation

• Fever

• Antimicrobial proteins

© McGraw Hill, LLC 44

 Phagocytosis: Cornerstone of Inflammation and Specific
Immunity

General activities of phagocytes:

• Survey the tissue compartments and discover microbes,
particulate matter, and injured or dead cells
• Ingest and eliminate these materials
• To read immunogenic information (antigens)

Types of phagocytes:
• Neutrophils
• Monocytes
• Macrophages

© McGraw Hill, LLC 45

 Neutrophils

• General-purpose phagocytes

• React early in the inflammatory response to bacteria and

other foreign materials and to damaged tissue

• High neutrophil count in the blood is a common sign of

bacterial infection

• Primary component of pus

© McGraw Hill, LLC 46

 Monocytes Lead to Macrophages and Dendritic Cells

Monocytes are transformed into macrophages after they

migrate out of the bloodstream and into the tissues

Histiocytes: live in a certain tissue and remain there during

their life span
• Alveolar (lung) macrophages
• Knupffer cells in the liver
• Dendritic cells in the skin
• Macrophages in the spleen, lymph nodes, bone marrow,
kidney, bone, and brain

Other macrophages drift nomadically throughout the MPS

© McGraw Hill, LLC 47

 Mechanisms of Phagocytic Recognition, Engulfment,
and Killing 2
Phagocytosis
Chemotaxis Phagocytes migrate into a region of inflammation with a deliberate sense
of direction, attracted by a gradient of stimulant products from the parasite
and host tissue at the site of injury.
Adhesion Phagocytes use their PRRs to recognize PAMPs on foreign cells. This
receptor interaction causes the two to “stick” together.
Engulfment and Once the phagocyte has made contact with its prey, it extends
Phagosome pseudopods that enclose the cells or particles in a pocket and internalize
Formation them in a vacuole called a phagosome. It also secretes more cytokines to
further amplify the innate response.
Phagolysosome In a short time, lysosomes migrate to the scene of the phagosome and
Formation and fuse with it to form a phagolysosome. Granules containing antimicrobial
Killing chemicals are released into the phagolysosome, forming a toxic brew
designed to poison and then dismantle the ingested material.
Destruction Two separate systems of destructive chemicals await the microbes in the
phagolysosome. 1. The oxygen-dependent system (known as the
respiratory burst, or oxidative burst) involves several toxic oxygen
substances. 2. Destructive enzymes such as myeloperoxidase, complete
the job.
Elimination The small bits of undigestible debris are released from the macrophage by
exocytosis.

© McGraw Hill, LLC 48

 Phagocytosis

Access the text alternative for slide images.

© McGraw Hill, LLC 49

 Signal Molecules on Microbe Surfaces

Pathogen-associated molecular patterns (PAMPs):

• Signal molecules found on microbial surfaces recognized
by phagocytes and other defensive cells
• Molecules shared by many organisms, but not present in
mammals
• Bacterial PAMPs
• Viral PAMPs

© McGraw Hill, LLC 50

 Receptors in the Host

Pattern recognition receptors (PRRs):

• Found on phagocytes, dendritic cells, endothelial cells, and
lymphocytes
• Cells possess PRRs – when?
Inflammasomes:
• PRRs found within the cytoplasm of phagocytic cells of the
innate immune system
• Recognize P A M Ps once they have been phagocytosed
• Recognition leads to the release of signals that initiate and
regulate inflammation

© McGraw Hill, LLC 51

 Inflammatory Response: A Complex Reaction to Injury 1

Easily identifiable by a classic series of signs and symptoms:

• Rubor: redness caused by increased circulation and
vasodilation in the injured tissue
• Calor: warmth caused by the heat given off by the
increased flow of blood
• Tumor: swelling caused by fluid escaping into the tissues
• Dolor: pain caused by the stimulation of nerve endings
• Loss of function

© McGraw Hill, LLC 52

 Inflammatory Response

Inflammation can be local or systemic, acute or chronic

Some chronic diseases, such as cardiovascular disease, are
caused by chronic inflammation.
Some researchers believe that aging is a consequence of
increasing inflammation in multiple body systems
Factors that elicit inflammation:
• Trauma from infection
• Tissue injury or necrosis due to physical or chemical
agents
• Adaptive immune reactions
© McGraw Hill, LLC 53
 Inflammation 1
Stage
Injury and • Following an injury, early changes occur in the vasculature
Immediate (arterioles, capillaries, venules) in the vicinity of the damaged tissue.
Reactions • Changes are controlled by nervous stimulation, chemical
mediators, and cytokines released by blood cells, tissue cells, and
platelets in the injured area.
• Some mediators are vasoactive (affect the endothelial cells and
smooth muscle cells of blood vessels), others are chemotactic
factors, also called chemokines, that affect white blood cells.

Access the text alternative for slide images.

© McGraw Hill, LLC 54

 Inflammation 2
Stage
Vascular • The blood vessels in the vicinity of injury dilate, constrict, then dilate again.
Reactions • The wide-narrow-wide sequence is thought to first flush irritants like bacteria
away from the area, then the narrowing stems blood leaving the blood
vessels, followed by dilation to bring helpful blood components to the site.
• The overall effect of vasodilation is to increase bloodflow into the area (rubor
and calor), which facilitates the influx of immune components
• Some substances cause the endothelial cells in the walls of postcapillary
venules to contract and form gaps through which blood-borne components
exude into the extracellular spaces. The fluid part that escapes is called the
exudate.

Access the text alternative for slide images.

© McGraw Hill, LLC 55

 Inflammation 3
Stage
Edema and • Accumulation of exudate in the tissues gives rise to local swelling and
Pus hardness, called edema.
Formation • The fluid contains varying amounts of plasma proteins, such as globulins,
albumin, the clotting protein fibrinogen, blood cells, and cellular debris.
• Depending on its content, the fluid may be clear (called serous), or it may
contain red blood cells or pus, composed mainly of white blood cells and
the debris generated by phagocytosis.
• In some types of edema, the fibrinogen is converted to fibrin threads that
enmesh the injury site.
• Within an hour, multitudes of neutrophils responding chemotactically to
special signaling molecules converge on the injured site.

Access the text alternative for slide images.

© McGraw Hill, LLC 56

 Inflammation 4
Stage
Resolution • Repair is the last step and results either in complete resolution to
and Scar healthy tissue or in formation of scar tissue, depending on the
Formation tissue type and the extent of the damage.
• Note here that macrophages are pictured leaving the blood
vessels in a process called diapedesis (dye″-ah-puh-dee′-sis).
• Meanwhile, differentiated stem cells in the area begin to divide and
repopulate the damaged site with new cells to replace those that
were damaged.

Access the text alternative for slide images.

© McGraw Hill, LLC 57

 Diapedesis and Chemotaxis 2

Steve Kunkel (b)

Access the text alternative for slide images.

© McGraw Hill, LLC 58

 Benefits of Edema and Leaky Vessels

• Influx of fluid dilutes toxic substances

• Fibrin clot can trap microbes to prevent further spread

• Neutrophils aggregated at the inflamed site are involved in

phagocytosing and destroying bacteria, dead tissues, and
particulate matter
• Pus: the accumulation of a white, gooey mass of cells,
liquefied cellular debris, and bacteria
• Bacteria such as streptococci, staphylococci, gonococci,
and meningococci are known as pyogenic because of
their ability to attract neutrophils and stimulate the
formation of pus
© McGraw Hill, LLC 59
 Fever

Abnormally elevated body temperature:

• Nearly universal symptom of infection
• Associated with certain allergies, cancers, and other
organic illnesses
• If cause is unknown, it’s called a fever of unknown origin
(FUO)
Body temperature is maintained around 37°C (98.6°F) by the
hypothalamus:
• Low-grade fever: 37.7 to 38.3°C or 100 to 101°F
• High-grade fever: 40.0 to 41.4°C or 104 to 106°F
© McGraw Hill, LLC 60
 Pyrogens

Substances that reset the hypothalamic thermostat to a

higher setting:
• Exogenous pyrogens: products of infectious agents such
as viruses, bacteria, protozoans, fungi, endotoxin, blood,
blood products, vaccines, or injectable solutions coming
from outside the body
• Endogenous pyrogens: liberated by monocytes,
neutrophils, and macrophages during phagocytosis such
as interleukin-1 and tumor necrosis factor

© McGraw Hill, LLC 61

 Benefits of Fever

Inhibits multiplication of temperature-sensitive

microorganisms such as the poliovirus, cold viruses, herpes
zoster virus, and systemic and subcutaneous fungal
pathogens
Interferes with the nutrition of bacteria by reducing the
availability of iron
Increases metabolism and stimulates immune reactions and
naturally protective physiological processes:
• Speeds up hematopoiesis, phagocytosis, and specific
immune reactions

© McGraw Hill, LLC 62

 Antimicrobial Products: Interferon 1

• Small proteins produced naturally by certain white blood

and tissue cells

• Originally thought to be directed against viruses, but is

involved in defenses against microbes and immune
regulation and intercommunication

• Interferons alpha and beta: produced by lymphocytes,

fibroblasts, and macrophages

• Interferon gamma: produced by T cells

© McGraw Hill, LLC 63

 Antimicrobial Products: Interferon 2

Biological activities of interferon:

• Bind to cell surfaces and induce changes in genetic

expression; exact results vary

• All three IFNs can inhibit the expression of cancer genes

and have tumor suppressor effects

• IFN alpha and beta stimulate phagocytes

• IFN gamma is the immune regulator of macrophages and

T and B cells

© McGraw Hill, LLC 64

 Antiviral Activity of Interferons

Access the text alternative for slide images.

© McGraw Hill, LLC 65

 Steps in the Complement Pathway at a Single Site

Sucharit Bhakdi (micrograph)

Access the text alternative for slide images.

© McGraw Hill, LLC 66

© McGraw Hill, LLC 67
 Antimicrobial Products: Antimicrobial Peptides

Short proteins of 12 to 50 amino acids:

• Defensins and others

Also have an effect on other actions of nonspecific and

specific immunity
Researchers are looking for ways to turn these antimicrobial
peptides into therapeutic drugs

© McGraw Hill, LLC 68

 Antimicrobial Peptides

Access the text alternative for slide images.

© McGraw Hill, LLC 69

 Concept Check 3

Put the steps of phagocytosis in the correct order:

1: engulfment
2: killing and destruction of bacterial cells
3: phagosome formation
4: adhesion of bacteria
5: release of residual debris
6: chemotaxis by phagocyte
7: phagolysosome formation
A. 7, 5, 3, 1, 2, 4, 6
B. 6, 3, 5, 2, 1, 7, 4
C. 2, 4, 6, 7, 5, 3, 1
D. 6, 4, 1, 3, 7, 2, 5
E. 3, 6, 1, 7, 4, 5, 2

© McGraw Hill, LLC 70

 End of Main Content

Because learning changes everything. ®

www.mheducation.com

© McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.