16

Innate
Immunity:
Nonspecific
Defenses
of the Host

SLOs
Differentiate between innate and adaptive immunity.
Define toll-like receptors.
Differentiate physical from chemical factors, and list examples of
each.
Describe the role of normal microbiota in innate resistance.
Classify phagocytic cells, and describe the roles of granulocytes and
monocytes.
Define and explain phagocyte and phagocytosis.
Explain the different stages of inflammation.
Describe the cause and effects of fever.
Describe two of the three pathways of activating complement and
describe the 3 outcomes.
Compare and contrast the actions of -IFN and -IFN with -IFN.
Describe
the role of transferrins and antimicrobial peptides in innate
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

TLRs on M s,
dendritic cells,
epithelial cells

Cytokines!

PAMPs recognition

Horseshoe structure of TLR3, showing attached sugars

(spheres) and internal structures

Fig. 16.7

The Concept of Immunity

Susceptibility: Lack of resistance to a disease.
Immunity: Ability to ward off disease.
Innate immunity: Defenses against any pathogen.
Adaptive immunity: Immunity, resistance to a specific
pathogen.

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Fig 16.1

First Line of Defense:

Skin and Mucous Membranes
Physical Factors
Epidermis: consists of tightly packed cells with
keratin, a protective protein
Two other protective physical factors of skin?
Mucus of mucous membranes
Lacrimal apparatus
Saliva
Nose hairs
(Muco)-ciliary escalator
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Fig 16.3

Chemical Factors

Fungistatic fatty acids in sebum

Low pH (3-5) of skin
Lysozyme in _______________________
Low pH (?) of gastric juice
Transferrins in blood
Also important: Antagonism and
competitive exclusion of normal microbiota
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

1st Line
Defense in
Human

ANIMATION Host
Defenses: The Big Picture

Second Line of Defense: Formed Elements

in Blood
Compare to Table 16.1

60-70%
2-4%
0.5-1%%

3-8%

20-25%
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Process of Phagocytosis
Phagocytes engulf and kill microorganisms
Steps of phagocytosis:

Chemotaxis

Recognition and attachment

Engulfment and creation of phagosome

Fusion of phagosome with lysosome

Destruction and digestion

Residual body Exocytosis

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Fig 16.7

Phagocytosis

Foundation Fig
16.7

Microbial Evasion of Phagocytosis

Inhibit adherence: M
protein, capsules

Streptococcus pyogenes, S.
pneumoniae

Kill phagocytes:
Leukocidins

Staphylococcus aureus

Lyse phagocytes:
Membrane attack
complex

Listeriamonocytogenes

Escape phagosome

Shigella

Prevent phagosomelysosome fusion

HIV

Survive in
phagolysosome

Coxiella burnetti

Phagocytosis and Evasion of Phagocytosis

ANIMATION Phagocytosis: Overview
ANIMATION Phagocytosis: Mechanism

ANIMATION Virulence Factors: Hiding From Host Defenses

ANIMATION Virulence Factors: Inactivating Host Defenses
ANIMATION Phagocytosis: Microbes That Evade It
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Inflammation
Tissue damage leads to inflammatory response
Purpose:
Destroy pathogen
limit spread of infection
pave way for tissue repair
4 cardinal signs:?
Acute-phase proteins (Chemical mediators)
activated:
Complement proteins
Cytokines
Specialized proteins such as fibrinogen and
bradykinin
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

The Three Stages of Inflammation

1. Vasodilation and increased vessel permeability
due to histamine (and other cytokine) release
edema
2. Phagocyte migration and phagocytosis
Margination and diapedesis (emigration)
Chemotaxis(due to various cytokines and
components of complement system)
Pus formation
Factors challenging effectiveness of
phagocytosis
3. Tissue repair and regeneration depends on type
of tissue
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Inflammatory Process

Margination

Diapedesis
Compare to Fig 16.8

Treatment of abscess?

Fever: Abnormally High Body Temperature

Hypothalamus acts as bodys thermostat
Endotoxin causes phagocytes to release
interleukin1 (IL1). IL-1 is an endogenous
pyrogen

Hypothalamus releases
prostaglandins that reset the
thermostat
Body reacts to raise the
temperature. How?
When no more IL1, body
temperature falls (crisis).

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Beneficial effects of moderate fever:

Inhibited pathogen growth
Increased cellular metabolism e.g.:
Increased transferrin production
Increased IL1 activity T cell production
Faster repair mechanisms

Problematic effects of high fever:

> 40.7C (105F) can be dangerous (Tachycardia,
acidosis, dehydration)
Death at temp. > 44 - 46C

Antimicrobial Substances

1. The complement system

2. Interferons
3. Transferrins: bind serum iron
4. Antimicrobial peptides: cause bacterial
cell lysis. Produced by mucous
membrane cells and phagocytes.

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

The
Complement
System

Compare to
Foundation
Fig 16.9

Complement System Summary

Series of 30 plasma (serum) proteins,
activated in a cascade
Three effects of complement system:
1. Enhances inflammatory response, e.g.:
attracts phagocytes
2. Increases phagocytosis through
opsonization or immune adherence
3. Creates Membrane Attack Complexes (MACs)
Cytolysis
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Opsonins (complement proteins or

antibodies) coat bacteria and promote
attachment of micro-organism to phagocyte
Opsonization

Classical Pathway

Fig 16.12

Alternative Pathway

Does not require a

specific antibody to
get started

Fig 16.13
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Some Bacteria Evade Complement

Capsules prevent Complement activation.
Surface lipid-carbohydrates of some Gramnegatives prevent MAC formation.
Enzymatic digestion of C5a by Grampositives.
ANIMATION Complement System: Overview
ANIMATION Complement System: Activation

ANIMATION Complement System: Results

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Interferons (IFNs)
Family of glycoproteins
Host-cell-specific but not virus-specific
-IFN and -IFN: Produced by virus infected cells.
Mode of action is to induce uninfected cells to produce
antiviral proteins (AVPs) that inhibit viral replication.

-IFN: Produced by lymphocytes. Causes

neutrophils and macrophages to phagocytize
bacteria. Also involved in tumor immunology.
Recombinant interferons have been produced. However
short-acting and many side-effects. No effect on already
infected cells.
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Interferons (IFNs)

Fig 16.15
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Unnumbered
Figure 16.1a

Applications of
Microbiology:
Serum Collection

Unnumbered
Figure 16.1b