TORTORA FUNKE CASE Microbiology AN INTRODUCTION EIGHTH EDITION
TORTORA • FUNKE • CASE Microbiology AN INTRODUCTION EIGHTH EDITION B. E Pruitt & Jane J. Stein Chapter 16 Nonspecific Defenses of the Host
Nonspecific Defenses of the Host • Susceptibility Lack of resistance to a disease • Resistance Ability to ward off disease • Nonspecific resistance Defenses against any pathogen • Specific resistance Immunity, resistance to a specific pathogen • Native (innate) species specific immunity
Figure 16. 1 An overview of the body’s defenses. Host Defenses First line of defense • Intact skin • Mucous membranes and their secretions • Normal microbiota Second line of defense • Phagocytes, such as neutrophils, eosinophils, dendritic cells, and macrophages • Inflammation • Fever • Antimicrobial substances Third line of defense • Specialized lymphocytes: T cells and B cells • Antibodies
First line of Defense Mechanical Factors Physical barriers to pathogens • Skin • Epidermis consists of tightly packed cells with • Keratin, a protective protein
Mechanical Factors • 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
Lacrimal glands Upper eyelid Lacrimal canal Nasolacrimal duct Nose
Chemical Factors Chemical factors: • Low p. H (3 -5) of skin • Fungistatic fatty acid in sebum • Saltiness from perspirations • Lysozyme in perspiration, tears, saliva, and tissue fluids • Low p. H (1. 2 -3. 0) of gastric juice • Transferrins in blood bind iron • Cerumin – physical and chemical Blocks and low p. H transplant?
Normal Microbiota • Microbial antagonism/competitive exclusion: • Normal microbiota compete with pathogens.
Second line of Defense 1. 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 Table 16. 1
Differential White Cell Count • Percentage of each type of white cell in a sample of 100 white blood cells (Never let monkeys eat bananas) Neutrophils 60 -70% Basophils 0. 5 -1% Eosinophils 2 -4% Monocytes 3 -8% Lymphocytes 20 -25%
White Blood Cells • 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
Phagocytosis • Phago: eat • Cyte: cell • Ingestion of microbes or particles by a cell, performed by phagocytes • Some travel out of blood into tissues: • Margination • Diapedesis
Phagocytosis Figure 16. 8 a
Toll like Receptors and PAMPs
A phagocytic macrophage uses a pseudopod to engulf nearby bacteria. Pseudopods Phagocyte Cytoplasm 1 CHEMOTAXIS and ADHERENCE of phagocyte to microbe 2 INGESTION of microbe by phagocyte Microbe or other particle Details of adherence 3 Formation of phagosome (phagocytic vesicle) 4 Fusion of phagosome with a lysosome to form a phagolysosome Lysosome PAMP (peptidoglycan in cell wall) Digestive enzymes Partially digested microbe 5 DIGESTION of ingested microbes by enzymes in the phagolysosome Indigestible material 6 Formation of the residual body containing indigestible material TLR (Toll-like receptor) Plasma membrane 7 DISCHARGE of waste materials
Microbial Evasion of Phagocytosis • Inhibit adherence: M protein, capsules • Kill phagocytes: Leukocidins Streptococcus pyogenes, S. pneumoniae • Lyse phagocytes: Membrane attack complex • Escape phagosome Listeriamonocytogenes • Prevent phagosome-lysosome fusion • Survive in phagolysosome HIV Staphylococcus aureus Shigella Coxiella burnetti and Mycobacteria spp
Inflammation • Redness • Pain • Heat • Swelling (edema) • Loss of function 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
Chemicals Released by Damaged Cells • Histamine • Kinins • Prostaglandins • Leukotrienes Vasodilation, increased permeability of blood vessels Intensity histamine and kinin effect Increased permeability of blood vessels, phagocytic attachment
Figure 16. 8 a-b The process of inflammation. Inflammation Bacteria entering on knife Epidermis Bacteria Blood vessel Dermis Nerve Subcutaneous tissue (a) Tissue damage 1 Chemicals such as histamine, kinins, prostaglandins, leukotrienes, and cytokines (represented as blue dots) are released by damaged cells. 2 Blood clot forms. 3 Abscess starts to form (orange area). (b) Vasodilation and increased permeability of blood vessels Figure 16. 9 a, b
Inflammation Figure 16. 9 c, d
Fever: Abnormally High Body Temperature • 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)
The Complement System Serum proteins activated in a cascade. Increasing as previous catalyzes the next step Outcomes of Complement system 1. Chemotaxic 2. Opsonization 3. Cell lysis Figure 16. 10
Figure 16. 9 Outcomes of Complement Activation. 1 Inactivated C 3 splits into activated C 3 a and C 3 b. 2 C 3 b binds to microbe, resulting in opsonization. C 3 b C 3 a C 3 b proteins 3 C 3 b also splits C 5 into C 5 a and C 5 b mast cells to release histamine, resulting in inflammation; C 5 a also attracts phagocytes. opsonization C 5 Enhancement of phagocytosis by coating with C 3 b C 5 a C 5 b C 5 a receptor Histamine C 5 a Insert Fig 16. 9 Mast cell 4 C 5 b, C 6, C 7, and C 8 bind together sequentially and insert into the microbial plasma membrane, where they function as a receptor to attract a C 9 fragment; additional C 9 fragments are added to form a channel. Together, C 5 b through C 8 and the multiple C 9 fragments form the membrane attack complex, resulting in cytolysis. 5 C 3 a and C 5 a cause C 6 C 3 a receptor C 3 a inflammation C 7 C 8 Increase of blood vessel permeability and chemotactic attraction of phagocytes C 9 Microbial plasma membrane Channel C 6 C 7 C 5 b C 8 C 9 Formation of membrane attack complex (MAC) C 6 C 5 b C 7 C 8 C 9 Cytolysis cytolysis © 2013 Pearson Education, Inc. Bursting of microbe due to inflow of extracellular fluid through transmembrane channel formed by membrane attack complex
Effects of Complement Activation • Opsonization or immune adherence: enhanced phagocytosis • Membrane attack complex: cytolysis • Attract phagocytes Figure 16. 11
Effects of Complement Activation C 3 B - Opsinozation C 3 a - triggers Mast Cells to release agents of inflammation C 5 a - chemotaxic for phagocytes Figure 16. 12
Figure 16. 11 Inflammation stimulated by complement. C 5 a receptor Histamine Phagocytes Neutrophil Histaminecontaining granule Insert Fig 16. 11 Histaminereleasing mast cell C 3 a receptor C 5 a Macrophage
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 C 5 b - C 9) formation • Enzymatic digestion of C 5 a
Interferons (IFNs) 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) 2 The infecting virus replicates into new viruses. 1 Viral RNA from an infecting virus enters the cell. 5 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. 3 The infecting virus also induces the host cell to produce interferon on RNA (IFN-m. RNA), which is translated into alpha and beta interferons. 4 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. Figure 16. 16
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