Host Defenses I: Overview

and Nonspecific Defenses

Chapter 14

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Learning Objectives

• Define first and second line of host defense

• Describe the role of skin and mucous membranes in innate immunity.

• Differentiate physical from chemical protective barriers, give examples of each

• Describe parts of the immune system and the role they play in the innate non-specific immunity

• List and describe the stages in inflammation and phagocytosis

• Describe three complement activation pathways, explain the consequences of complement activation

3

Overview of Host Defenses

4

Overview of Host Defenses

Innate Defenses

• Constitutive defenses

• Always on guard, but do not improve with repeated exposures

• Physical defenses

• Chemical defenses

• Phagocytic defenses

• Inflammatory defenses

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UrinationDefecation

MucusMucus

Intestinal enzymesIntestinal enzymes

Stomach acidStomach acid

MucusMucus

Low pH

Wax

Sweat

Intactskin

Cilia

Saliva(lysozyme)

Mucus

Tears(lysozyme)

Sebaceousglands

Skin as a Protective Barrier

• First line of defense

• Epidermis consists of tightly packed cells with

• Keratin, a protective protein

• Surface area of about 2 m2

• Dead cells

• Secretions

• Shed Cells

Mucous Membranes

• Lack keratin• Ciliary escalator• Mucous production and cell

turn-over• Sneezing and coughing• Normal biota• Washing microbes out:• Lacrimal apparatus• Saliva• Urine• Vaginal secretions

Chemical Factors

• Fungistatic fatty acid in sebum.

• Low pH (3-5) of skin.

• Lysozyme in perspiration, tears, saliva, and tissue fluids.

• Low pH (1.2-3.0) of gastric juice.

• Iron chelators.

Noxious Molecules

• Hydrochloric acid (stomach)

• Bile acids (gall bladder)

• Fatty acids (sebum)

• Sodium chloride (sweat)

Enzymes

• Lysozyme and lysostaphin in tears and secretions

• DNase and RNase on skin

• Proteases

• Typsin, chymotrypsin, etc. in digestive tract

Chelators

• Limit availability of essential metals like iron.

• There are three main types in our body

• Hemoglobin - RBC

• Lactoferrin - Secretions

• Transferrin – Serum

Starved for iron, many microbes cannot grow

Genetic Defenses

• Host specificity

• Genetic mutations

Immune System: Second

and Third Line of

Defense

1. Surveillance

2. Recognition

3. Destruction

Immune Defense Systems

• Reticuloendothelial system (RES)

Connective tissue network

Provides passageway for immune system cells and fluids

• Extracellular fluid

• Bloodstream

• Lymphatic system

Lymphatic System

• System of vessels, cells and organs, which

• Render surveillance, recognition and protection against foreign material

Lymphatic System Organs

• Thymus: site of T-cell maturation

• Lymph nodes: filter out materials from lymph, provide cells and sites for immune reactions.

• Spleen: filters out dead RBS, filters out infectious agents, site of phagosytosis

• GALT: immunity against intestinal pathogens

• Appendix

• Peyer’s patches

Hematopoiesis and Differentiation of Blood Cells

•Yolk sack •Liver and lymphatic organs•Bone marrow

Blood Cells

Signs of Inflammation

• Rubor – Redness

• Tumor – Swelling

• Dolor – Pain

• Calor – Heat

• Functio laesa

• Loss of Function

Causes of Inflammation

• Increased blood flow

• Erythema

• Increased vascular permeability

• Influx of phagocytes and serum proteins to the region of infection

• Exudate

InflammationCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

1 2

3 4

Macrophage

Lymphocytes

Scar

Resolution/Scar FormationNewly healedtissue

Edema due tocollected fluid

Rubor(inflammation)

Edema and Pus Formation

Vascular ReactionsInjury/Immediate Reactions

Bacteria in wound

Mast cells releasechemical mediators

Vasoconstriction

Clot

Vasodilation

Seepage ofplasma andmigration ofWBC out ofblood vessels

NeutrophilBacteria

Scab

Neutrophils

Pus

Fibrous exudate

Stages in Inflammation• Immediate reactions• Chemical mediators and cytokines (histamines,

kinines, prostaglandines) released• Vasoconstriction

• Vascular reactions• Contraction of endothelial cells, vasodilation• Leakage of blood components into the damaged site.

• Edema and pus formation• Influx of fluid• Accumulation of neutrophils, cell debris and bacteria• Pyogenic bacteria

• Resolution• Clearance of pus by macrophages

Chemotaxis

• Diapedesis (transmigration)

• Chemotaxis

Toll-Like Receptors

• Surface receptors

• Bind to molecular patterns

• TLR4 LPS

• Signal sent to nucleus

• Cytokine production is induced

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Foreign molecule

Nucleus

Toll-like receptor

CytokinesInterleukins

Inflammatory mediators

Macrophage

Types of Phagocytic Cells

• Professional Phagocytes

• Neutrophils - 70% of WBC

• Monocytes

• Macrophage - tissues

• Non-Professional Phagocytes

• Epithelial Cells

1. Chemotaxis by phagocyte

Bacterial cells

PAMPs 2. Adhesion of bacteria

Pattern recognitionreceptor on host cell

3. Engulfmentinto phagocyticvacuole

Lysosomes

4. Phagosome

5. Phagolysosomeformation

Nucleus

7. Release ofresidual debris

6. Killing and destructionof bacterial cells

Phagocytosis

Mechanisms of Killing

• Enzymatic Hydrolysis

• Lysozyme, Lipases, Proteases, Nucleases

• Oxidative Burst

• NADPH oxidase and cytochrome B – produce superoxide anion

• Superoxide dismutase – hydrogen peroxide

• Myeloperoxidase – hypochlorite (bleach)

Effects of Complement Activation

• Opsonization or immune adherence: enhanced phagocytosis.

• Membrane attack complex: cytolysis.

• Chemotaxis: attract phagocytes.

Classical Pathway

Figure 16.12

Alternative Pathway

Figure 16.13

Lectin Pathway

Figure 16.14

Fever

Advantages

• Limits iron availability

• Inhibits bacterial growth

• Interferes with viral replication

• Increases effectiveness of some immune molecules

Disadvantages

• Tachycardia

• Acidosis

• Dehydration

•Fever (elevated host body temperature)•Caused by interleukin 1 or exogenous pyrogens

Antiviral Defense Molecules

• Interferons

• Produced during viral infection

• Antiviral protein production

Blocks virusreplication

Synthesis of antiviral proteins

Nearby cell

Signalsactivation of genes

Infected cell

IFNgene

Virusinfection

Viralnucleic acid

Assemblyof viruses

Virusrelease

Attachment of IFNto special receptor

Degrades virusnucleic acid

Synthesisof IFN