Microbiology B.E Pruitt & Jane J. Stein AN INTRODUCTION EIGHTH EDITION TORTORA FUNKE CASE Chapter 16 Nonspecific Defenses of the Host

SusceptibilityLack of resistance to a disease Resistance Ability to ward off disease Nonspecific resistanceDefenses against any pathogen Specific resistanceImmunity, resistance to a specific pathogen Native (innate)species specific immunity

Host Defenses Figure 16.1

Mechanical Factors Physical barriers to pathogens Skin –Epidermis consists of tightly packed cells with –Keratin, a protective protein First line of Defense

Mucous membranes Ciliary escalator: Microbes trapped in mucus are transported away from the lungs Lacrimal apparatus: Washes eye Saliva: Washes microbes off Urine: Flows out Vaginal secretions: Flow out Mechanical Factors

Fungistatic fatty acid in sebum Low pH (3-5) of skin Lysozyme in perspiration, tears, saliva, and tissue fluids Low pH ( ) of gastric juice Transferrins in blood find iron NO inhibits ATP production Chemical Factors

Microbial antagonism/competitive exclusion: –Normal microbiota compete with pathogens. Normal Microbiota

Second line of Defense Table Phagocytosis 2.Inflammation 3.Fever 4.Antimicrobial substances Formed Elements In Blood (note functions) RBC’s WBC’s Agranulocytes Monocytes Lymphocytes Granulocytes Neutrophils (PMNs) Basophils Eosinophils

Percentage of each type of white cell in a sample of 100 white blood cells Differential White Cell Count Neutrophils60-70% Basophils0.5-1% Eosinophils2-4% Monocytes3-8% Lymphocytes20-25%

Neutrophils: Phagocytic Basophils: Produce histamine Eosinophils: Toxic to parasites, some phagocytosis Monocytes: Phagocytic as mature macrophages –Fixed macrophages in lungs, liver, bronchi –Wandering macrophages roam tissues Lymphocytes: Involved in specific immunity White Blood Cells

Phago: eat Cyte: cell Ingestion of microbes or particles by a cell, performed by phagocytes Phagocytosis

Figure 16.8a

Microbial Evasion of Phagocytosis Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae Kill phagocytes: LeukocidinsStaphylococcus aureus Lyse phagocytes: Membrane attack complex Listeriamonocytogenes Escape phagosomeShigella Prevent phagosome-lysosome fusion HIV Survive in phagolysosomeCoxiella burnetti and Mycobacteria spp

Redness Pain Heat Swelling (edema) Acute-phase proteins activated (complement, cytokine, kinins) - chemical messengers Vasodilation (histamine, kinins, prostaglandins, leukotrienes) - bring in more help Margination and emigration of WBCs Tissue repair Inflammation

Chemicals Released by Damaged Cells HistamineVasodilation, increased permeability of blood vessels KininsVasodilation, increased permeability of blood vessels ProstaglandinsIntensity histamine and kinin effect LeukotrienesIncreased permeability of blood vessels, phagocytic attachment

Inflammation Figure 16.9a, b

Inflammation Figure 16.9c, d

Hypothalamus normally set at 37°C Gram-negative endotoxin cause phagocytes to release interleukin 1 Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature Body increases rate of metabolism and shivering to raise temperature When IL-1 is eliminated, body temperature falls. (Crisis) Fever: Abnormally High Body Temperature

Serum proteins activated in a cascade. Increasing as previous catalyzes the next step Outcomes of Complement system 1.Opsonization 2.Chemotaxic 3.Cell lysis The Complement System Figure 16.10

Effects of Complement Activation Opsonization or immune adherence: enhanced phagocytosis Membrane attack complex: cytolysis Attract phagocytes Figure 16.11

Effects of Complement Activation Figure 16.12

Classical Pathway Figure 16.13

Alternative Pathway Figure 16.14

Lectin Pathway Figure 16.15

Some bacteria evade complement Capsules prevent C’ activation Surface lipid-carbohydrates prevent MAC (membrane attack complex C5b - C9) formation Enzymatic digestion of C5a

Antiviral proteins Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria Interferons (IFNs)

Figure 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.