Chapter 14

Innate Immunity:
Nonspecific Defenses
of the Host

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Q&A During one year, nosocomial
infections occurred in 74
patients in one hospital. All
74 patients were incubated
and mechanically ventilated.
The infections were caused
by Burkholderia cepacia
transmitted in nonsterile
mouthwash.
Why did these patients
develop infections while
others who used the
mouthwash were not
infected?
 Overview of Immunity
When a human is attacked by foreign invaders, he/she
has two lines of defense:
Non-specific immunity: no memory
Specific immunity: memory

Immune reactions can be used in the laboratory to

identify substances with a high degree of
specificity (blood typing, disease diagnosis,
bacterial classification)
An Overview of the Body’s Defenses

Figure 16.1
The Concept of Immunity

 Host Pattern recognition receptors (PRRs) or Toll-

like receptors (TLRs) attach to
 Pathogen-associated molecular patterns
(PAMPs)
 TLRs induce cytokines that regulate the intensity
and duration of immune responses Detects
flagellin
14.1. Overview of the Innate Defenses

 First-line defenses are barriers blocking entry

 If invaders breach, sensor systems detect
• Send out signals
 Innate defenses work to destroy invaders
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First-line defenses Skin and mucous membranes

Prevent microbial entry

Microbial invasion

Sensor systems Pattern recognition receptors Pattern recognition receptors Complement system
Detect microbial (surfaces, endosomes, and (cytoplasm of many cell types) (blood and tissue fluids)
invasion phagosomes of sentinel cells)

Innate effector actions Inflammatory Inflammatory Interferon Inflammatory response

Destroy invader response response response Opsonization
Membrane attack complexes
Physical Factors

 Skin
 Epidermis
consists of tightly
packed cells with
 Continuous
layering
 Keratin, a
protective protein

 Dry, Low pH
 Antimicrobial
Secretions
Figure 16.2
Physical Factors
 Mucous membranes
 Mucus: Traps
microbes
 Ciliary escalator:
Microbes trapped in
mucus are transported
away from the lungs
Physical Factors

 Lacrimal apparatus: Washes eye

 Saliva: Washes microbes off
 Urine: Flows out
 Vaginal secretions: Flow out
Lacrimal Apparatus

•Lacrimal apparatus: Washes eye

•LYSOZYME IN TEARS
•PRODUCTION OF TEARS
Figure 16.3
Q&A During one year, nosocomial
infections occurred in 74
patients in one hospital. All
74 patients were incubated
and mechanically ventilated.
The infections were caused
by Burkholderia cepacia
transmitted in nonsterile
mouthwash.
Why did these patients
develop infections while
others who used the
mouthwash were not
infected?
14.2. First-Line Defenses_Chemical
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Antimicrobial factors
in saliva (lysozyme,
peroxidase, lactoferrin)

• Salt accumulates from perspiration Lysozyme in tears

and other secretions
• Fungistatic fatty acid in sebum and in phagocytes

Removal of inhaled Normal microbiota

• Low pH (3–5) of skin particles
Mucus, cilia

• Lysozyme in perspiration, tears,

saliva, and urine Physical barrier
of skin, salty

•
residue, fatty acids,
Low pH (1.2–3.0) of gastric juice normal microbiota

• Low pH (3–5) of vaginal

secretions Acid in stomach
(low p H)

• Peroxidase enzymes break down

hydrogen peroxide Rapid pH change Normal
from stomach to microbiota
Upper intestine

• Lactoferrin binds iron

• Defensins form pores in microbial Flushing of
urinary tract
membranes pH and normal
microbiota of vagina
 NORMAL FLORA
and Innate Immunity

 COMPETE WITH DISEASE-CAUSING ORGANISMS

 INHIBIT DISEASE-CAUSING ORGANISMS
 Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens
or alter the environment
 Commensal microbiota: One organism (microbe) benefits and the other (host) is unharmed
 May be opportunistic pathogens
 Components of the Immune
System
1. Blood Components: serum and leukocytes
• SERUM
– ANTIBODIES
– COMPLEMENT
• CELLS (LEUKOCYTES)
– NEUTROPHIL
– EOSINOPHIL
– BASOPHIL
– LYMPHOCYTE
– MONOCYTE
14.3. The Cells of the Immune System
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Hematopoietic stem cell
(in bone marrow)

Self-
renewal

Common Common
myeloid progenitor lymphoid progenitor

Erythroblast Megakaryoblast Putative mast Myeloblast Monoblast Lymphoblasts

cell precursor

Megakaryocyte

EosinophilBasophilNeutrophil Monocyte Natural T cell B cell

killer (NK) cell
Red blood cell Platelets Granulocytes Lymphocytes
(erythrocyte) (thrombocytes)

Mastcell Macrophage Dendritic cell

White blood cells (leukocytes)
Formed Elements in Blood

Monocytes Phagocytosis

Dendritic cells Phagocytosis

Natural killer cells Destroy target cells

Differential White Cell Count

 Percentage of each type of white cell in a sample of

100 white blood cells

Neutrophils 60–70%
Basophils 0.5–1%

Eosinophils 2–4%

Monocytes 3–8%

Lymphocytes 20–25%
14.3. The Cells of the Immune System
14.4. Cell Communication
 Cytokines Cytokines are “voices” of cell
 Induce changes; growth, movement
 Chemokines: chemotaxis of immune cells
 Colony-stimulating factors (CSFs): multiplication and
differentiation of leukocytes
 Interferons (IFNs): control of viral infections, regulation of
inflammatory response
 Interleukins (ILs): produced by leukocytes; important in
innate and adaptive immunity
 Tumor necrosis factor (TNF): inflammation, apoptosis
Phagocytosis

 Phago: From
Greek, meaning eat
 Cyte: From Greek,
meaning cell
 Ingestion of
microbes
or particles by a
cell, performed by
phagocytes

Figure 16.6
PHAGOCYTOSIS
Neutrophils
Fixed macrophages
Wandering macrophages
•INGESTION AND DESTRUCTION OF
MICROBES

Macrophage phagocytosing Candida

Phagocytosis

phagocytosis
Microbial Evasion of Phagocytosis

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

capsules
Kill phagocytes: Leukocidins Staphylococcus aureus

Lyse phagocytes: Membrane Listeria monocytogenes

attack complex
Escape phagosome Shigella, Rickettsia

Prevent phagosome-lysosome HIV, Mycobacterium tuberculosis

fusion
Survive in phagolysosome Coxiella burnettii
INFLAMMATION
WHAT IS IT?

 MAJOR PROTECTIVE MECHANISM

 RESPONSE TO INJURY OR INFECTION
 ACTIVATED IN MULTIPLE WAYS
 Inflammation
 Damage to the body’s tissues triggers inflammation
 Characterized by four symptoms
1. Redness
2. Pain
3. Heat
4. Swelling (edema)
 Three stages
1. Vasodilation
2. Phagocyte migration and phagocytosis
3. Tissue repair
Vasodilation

Figure 16.8a, b
Phagocyte Migration and Phagocytosis

[Insert Animation Inflammation: Overview, Steps.]

Figure 16.8c
Tissue Repair

Figure 16.8d
14.8. The Inflammatory Response
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Pro-
inflammatory
chemicals
Bacteria

Inflammatory Phagocytic
mediators are cells destroy Neutrophil
Resident released in and remove
macrophage response to invaders.
Blood vessel Recruited
microbial Neutrophil
components macrophage
and tissue
damage.
Monocyte

Normal blood flow in the tissues Neutrophils are the first phagocytes As the infection is brought under
as the injury occurs. recruited to the site. control, macrophages ingest dead
cells and debris.
(a)

Tighter Diapedesis
Loose adherence; adherence
cells tumble to a halt.

Inflammatory mediators cause small blood vessels to dilate. The phagocytic cells
tumble to a halt and then squeeze between the endothelial cells and enter the tissues.
(b)
FEVER

 PROTECTIVE MECHANISM
 INHIBITS GROWTH OF BACTERIA AND
VIRUSES
 ENHANCES IMMUNE RESPONSE
Fever

 Abnormally high body temperature

 Hypothalamus normally set at 37°C
 Gram-negative endotoxin cause phagocytes to
release interleukin–1 (IL–1)
 Hypothalamus releases prostaglandins that reset
the hypothalamus to a high temperature
 Body increases rate of metabolism and shivering
which raise temperature (chill)
 Vasodilation and sweating: Body temperature falls
(crisis)
Fever

 Advantages  Disadvantages
 Increases transferrins  Tachycardia
 Increases IL–1 activity  Acidosis
 Produces Interferon  Dehydration
 44–46°C fatal
The Complement System

 Serum proteins activated in a cascade

 Activated by
 Antigen-antibody reaction
 C3b causes opsonization
 C3a + C5a cause inflammation
 C5b + C6 + C7 + C8 + C9 cause cell lysis

ANIMATION Complement System: Overview

The Complement System

Figure 16.9
 Effects of Complement
Activation
 Opsonization or immune cytolysis
adherence: enhanced
phagocytosis

 Membrane attack
complex: cytolysis

 Attract phagocytes

Figure 16.11
Inflammation Stimulated by
Complement

Figure 16.11
Interferons (IFNs)

 IFN- and IFN-: Cause cells to produce antiviral

proteins that inhibit viral replication
 Gamma IFN: Causes neutrophils and macrophages

to phagocytize bacteria
Antiviral Actions of Interferons (IFNs)

Figure 16.15