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
 Cytokines!
TLRs on Ms,
dendritic cells,
epithelial cells 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.

Fig 16.1
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings
 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
Fig 16.3
Lacrimal apparatus
Saliva
Nose hairs
(Muco)-ciliary escalator
Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings
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 Streptococcus pyogenes, S.
protein, capsules pneumoniae
Kill phagocytes:
Staphylococcus aureus
Leukocidins
Lyse phagocytes:
Membrane attack Listeriamonocytogenes
complex
Escape phagosome Shigella
Prevent phagosome-
HIV
lysosome fusion
Survive in
Coxiella burnetti
phagolysosome
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 Compare to
Complement Foundation
System 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 Gram-
negatives prevent MAC formation.
Enzymatic digestion of C5a by Gram-
positives.

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