Innate Immunity: Nonspecific Defenses of the Host

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 Ms, 

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 

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 


1 st 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% 


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 

Kill phagocytes: 

Leukocidins 

Lyse phagocytes: 

Membrane attack 

complex 

Escape phagosome 

Prevent phagosomelysosome 

fusion 

Survive in 

phagolysosome 

Streptococcus pyogenes, S. 

pneumoniae 

Staphylococcus aureus 

Listeriamonocytogenes 

Shigella 

HIV 

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 


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 


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 

Copyright of © 2006 tissue 

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 body’s thermostat 

• Endotoxin causes phagocytes to release 

interleukin–1 (IL–1). IL-1 is an endogenous 

pyrogen 

• Hypothalamus releases 

prostaglandins that reset the 

thermostat 

• Body reacts to raise the 

temperature. How? 

• When no more IL–1, body 

temperature falls (crisis). 


Beneficial effects of moderate fever: 

Inhibited pathogen growth 

Increased cellular metabolism e.g.: 

• Increased transferrin production 

• Increased IL–1 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. 


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 


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 


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 


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. 


Interferons (IFNs) 

Fig 16.15 


Unnumbered 

Figure 16.1a 

Applications of 

Microbiology: 

Serum Collection

Unnumbered 

Figure 16.1b

Innate Immunity: Nonspecific Defenses of the Host

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