Non-Specific Non-Specific DefensesDefenses

The first line against diseaseThe first line against disease

Nonspecific Defenses of the Nonspecific Defenses of the HostHost

SusceptibilitySusceptibility Lack of resistance Lack of resistance to a to a disease disease

Resistance Resistance Ability to ward off Ability to ward off diseasedisease

Nonspecific resistanceNonspecific resistance Defenses against Defenses against any any pathogenpathogen

Specific resistanceSpecific resistance Immunity, Immunity, resistance resistance to a to a specific pathogenspecific pathogen

Host DefensesHost Defenses

Figure 16.1

SkinSkin Epidermis consists of tightly packed cells with Keratin, a Epidermis consists of tightly packed cells with Keratin, a

protective proteinprotective protein Mucous membranesMucous membranes Ciliary escalatorCiliary escalator

Microbes trapped in mucus are transported away from Microbes trapped in mucus are transported away from the lungsthe lungs

Lacrimal apparatusLacrimal apparatus Washes eyeWashes eye

SalivaSaliva Washes microbes offWashes microbes off

UrineUrine Flows outFlows out

Vaginal secretionsVaginal secretions Flow outFlow out

Mechanical FactorsMechanical Factors

Fungistatic fatty acid in sebumFungistatic fatty acid in sebum Low pH (3-5) of skinLow pH (3-5) of skin Lysozyme in perspiration, tears, saliva, Lysozyme in perspiration, tears, saliva,

and tissue fluidsand tissue fluids Low pH (1.2-3.0) of gastric juiceLow pH (1.2-3.0) of gastric juice Transferrins in blood find ironTransferrins in blood find iron NO inhibits ATP productionNO inhibits ATP production

Chemical FactorsChemical Factors

Microbial antagonism/competitive Microbial antagonism/competitive exclusionexclusion Normal microbiota compete with Normal microbiota compete with

pathogens.pathogens.

Normal MicrobiotaNormal Microbiota

Formed Elements In Formed Elements In BloodBlood

Table 16.1

Percentage of each type of white cell in Percentage of each type of white cell in a sample of 100 white blood cellsa sample of 100 white blood cells

Differential White Cell Differential White Cell CountCount

NeutrophilsNeutrophils 60-70%60-70%BasophilsBasophils 0.5-1%0.5-1%

EosinophilsEosinophils 2-4%2-4%

MonocytesMonocytes 3-8%3-8%

LymphocytesLymphocytes 20-25%20-25%

Neutrophils: PhagocyticNeutrophils: Phagocytic Basophils: Produce histamineBasophils: Produce histamine Eosinophils: Toxic to parasites, some Eosinophils: Toxic to parasites, some

phagocytosisphagocytosis Monocytes: Phagocytic as mature Monocytes: Phagocytic as mature

macrophagesmacrophages Fixed macrophages in lungs, liver, bronchiFixed macrophages in lungs, liver, bronchi Wandering macrophages roam tissuesWandering macrophages roam tissues Lymphocytes: Involved in specific immunityLymphocytes: Involved in specific immunity

White Blood CellsWhite Blood Cells

PhagocytosisPhagocytosis

Figure 16.8a

Microbial Evasion of Microbial Evasion of PhagocytosisPhagocytosis

• • Inhibit adherence: M Inhibit adherence: M protein, capsulesprotein, capsules

Streptococcus pyogenes, S. Streptococcus pyogenes, S. pneumoniaepneumoniae

• • Kill phagocytes: Kill phagocytes: LeukocidinsLeukocidins

Staphylococcus aureusStaphylococcus aureus

• • Lyse phagocytes: Lyse phagocytes: Membrane attack Membrane attack complexcomplex

ListeriamonocytogenesListeriamonocytogenes

• • Escape phagosomeEscape phagosome ShigellaShigella

• • Prevent phagosome-Prevent phagosome-lysosome fusionlysosome fusion

HIVHIV

• • Survive in Survive in phagolysosomephagolysosome

Coxiella burnettiCoxiella burnetti

RednessRedness PainPain HeatHeat Swelling (edema)Swelling (edema) Acute-phase proteins activated Acute-phase proteins activated

(complement, cytokine, kinins)(complement, cytokine, kinins) Vasodilation (histamine, kinins, Vasodilation (histamine, kinins,

prostaglandins, leukotrienes)prostaglandins, leukotrienes) Margination and emigration of WBCsMargination and emigration of WBCs Tissue repairTissue repair

InflammationInflammation

Chemicals Released by Chemicals Released by Damaged CellsDamaged Cells

• • HistamineHistamine Vasodilation, increased Vasodilation, increased permeability of blood vesselspermeability of blood vessels

• • KininsKinins Vasodilation, increased Vasodilation, increased permeability of blood vesselspermeability of blood vessels

• • ProstaglandinsProstaglandins Intensity histamine and kinin Intensity histamine and kinin effecteffect

• • LeukotrienesLeukotrienes Increased permeability of blood Increased permeability of blood vessels, phagocytic attachmentvessels, phagocytic attachment

InflammationInflammation

Figure 16.9a, b

InflammationInflammation

Figure 16.9c, d

Hypothalamus normally set at 37°CHypothalamus normally set at 37°C Gram-negative endotoxin cause Gram-negative endotoxin cause

phagocytes to release interleukin 1phagocytes to release interleukin 1 Hypothalamus releases prostaglandins Hypothalamus releases prostaglandins

that reset the hypothalamus to a high that reset the hypothalamus to a high temperaturetemperature

Body increases rate of metabolism and Body increases rate of metabolism and shivering to raise temperatureshivering to raise temperature

When IL-1 is eliminated, body When IL-1 is eliminated, body temperature falls. (Crisis)temperature falls. (Crisis)

Fever: Abnormally High Fever: Abnormally High Body TemperatureBody Temperature

Serum Serum proteins proteins activated activated in a in a cascade. cascade.

The Complement The Complement SystemSystem

Figure 16.10

Effects of Complement Effects of Complement ActivationActivation

Opsonization or Opsonization or immune immune adherence: adherence: enhanced enhanced phagocytosisphagocytosis

Membrane attack Membrane attack complex: cytolysis complex: cytolysis

Attract phagocytesAttract phagocytes

Figure 16.11

Effects of Complement Effects of Complement ActivationActivation

Figure 16.12

Classical PathwayClassical Pathway

Figure 16.13

Alternative PathwayAlternative Pathway

Figure 16.14

Lectin PathwayLectin Pathway

Figure 16.15

Some bacteria evade Some bacteria evade complementcomplement

Capsules prevent C activationCapsules prevent C activation Surface lipid-carbohydrates prevent Surface lipid-carbohydrates prevent

MAC formationMAC formation Enzymatic digestion of C5aEnzymatic digestion of C5a

Alpha IFN & Beta IFNAlpha IFN & Beta IFN Cause cells to produce antiviral Cause cells to produce antiviral

proteins that inhibit viral replicationproteins that inhibit viral replication Gamma IFNGamma IFN

Causes neutrophils and macrophages Causes neutrophils and macrophages to phagocytize bacteriato phagocytize bacteria

Interferons (IFNs)Interferons (IFNs)

Interferons (IFNs)Interferons (IFNs)

Figure 16.16

1

2

3

4

5

Viral RNA from an infecting virus enters the cell.

The infecting virus replicates into new viruses.

The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons.

Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase.

New viruses released by the virus-infected host cell infect neighboring host cells. 6 AVPs degrade viral

m-RNA and inhibit protein synthesis and thus interfere with viral replication.