1 Chapter 14 Talaro The Nature of Host Defenses Nonspecific Defense.

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Chapter 14Talaro

The Nature of Host Defenses

Nonspecific Defense

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Defenses can be classified as either (1) innate & nonspecific or (2) acquired & specific

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• 1st Line of Defense– Physical / anatomical barriers

– Chemical barriers

– Innate /genetic barriers

• 2nd Line of Defense– Phagocytic white blood cells

– Inflammation - Complement proteins

– Fever - Interferon

• 3rd Line of Defense– B cells

• Antibodies

– T cells Specific - acquired• Killer cells

Nonspecific - innate

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Physical or Anatomical Barriers• Outermost layer of skin

– Epithelial cells – Compacted, cemented together & impregnated with keratin– Damaged cells are rapidly replaced

• Sweat glands– Flushing effect

• Mucous membranes– Impedes attachment & entry of bacteria- also keeps membranes moist

• Blinking & tear production –also keeps surfaces moist• Nasal hair traps larger particles• Ciliated epithelial cells in upper respiratory tract – keeps moving

small objects out on a continual basis…. (“ciliated escalator”)

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Chemical Defenses• Sebaceous secretions – sebum and dead cells

– Inhibit attachment of bacteria & fungi to epithelial cells• Antimicrobial peptides• Lysozyme in tears

– Hydrolyzes the cell wall of bacteria• Acidic pH of skin

– High lactic acid & electrolyte concentration in sweat• HCl in stomach• Digestive juices and bile of intestines• Antimicrobial chemicals of semen – high pH

sperm-binding proteins (epididymis), prostasomes, cleavage products of semenogelin I; also lysozyme, phospholipase 2 amd lactoferrin

• Acidic pH of vagina – normal flora like Lactobacillus• Urine – correlated with high concentrations of urea and ammonia

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Physical & Chemical Barriers

General protection mechanisms that attempt to stop pathogens from invading the body.

Evidence for the effectiveness of physical & chemical barriers can be deduced by observing individuals who have lost or never had them.

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Genetic Defenses• Some hosts are genetically

immune to the diseases of other hosts

• Some pathogens have great specificity

• Some pathogens have a narrow host range

“Humans can’t acquire distemper from cats & cats can’t get mumps from humans.” Foundations in Microbiology (5th) Talaro

“Shigella are pathogens of humans and baboons but not chimpanzees.”Todar’s On-Line Textbook of Bacteriology

Why?Possible Explanations- Absence of receptor on host cell- Absence of a particular cell or tissue- Inappropriate temperature for growth- Missing nutritional requirement- Missing target for toxin

Age, sex, stress, diet/malnutrition, trauma or other disease maypredispose the host to infection.Todar’s On-Line Textbook of Bacteriology

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The Second Line of Host Defense

• Second line of defense is much more complex, involves many different types of cells, many levels

• Phagocytosis

• Inflammation – redness and increased blood flow and increase in temperature, edema

• Fever – increase in temperature of body

• Complement proteins

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Immunology: the study of the immune system

• Surveillance of the body• Immune cells constantly move throughout the body

searching for pathogens & infected / damaged cells

• Recognition of foreign material• Self versus non-self• Glycoproteins

• Destruction of foreign entities or infected/damaged cells

• Phagocytosis• Induce apotopsis

• Programmed Cell Death

Immune system is responsible for…

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Epitope

Ab recognize andbind to a specific epitope

Proteins produced by the immune system that specifically binds to an

epitope and initiates its removal of

the antigen from the body

Some moredefinitions

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Specialized WBC “touch” cells as they pass through tissues. The WBC recognize surface glycoproteins to determine what is self and what is not. An immune response is mounted if non-self glycoproteins are recognized.

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Human Body & the Immune SystemNetwork of cells & fluids that permeate every organ & tissueFluid-filled spaces that are interconnected

• Reticuloendothelial System (RES) – Very important part of immune system – consists of monocytes and macrophages– Fibrous support network enmeshing cells –reticular connective tissue– This web connects one cell to another within a tissue or organ and provides

a niche for phagocytic WBC• Reticulum = small net• Endothelium = lining of a blood vessel

• Extracellular fluid (ECF)– Spaces surrounding tissue cells

• Bloodstream• Lymphatic System

– A system of vessels & organs that serve as sites for the development of immune cells

• Spleen, thymus, lymph nodes & gut-associated lymphoid tissue

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Dendritic CellsAn antigen-presenting leukocyte that is found in the skin, mucosa, and lymphoid tissues and that initiates a primary immune response.

Neutrophil CellAn abundant type of granular white blood cell that is highly destructive of microorganisms.

MacrophageLarge phagocytic cells found in the reticuloendothelial

system

Reticuloendothelial System

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Leukocytes or WBCClassified according to staining reactions:Granulocytes: granules in the cytoplasm & lobed nucleusAgranulocytes: smaller granules & round nucleus

• Neutrophils or polymorphonuclear (PMNs)– Phagocytes in tissue – make up 55 to 90% of circulating leukocytes (25 billion cells) –

live for about 8 days

• Eosinophils – Destroy eukaryotic pathogens such as Helminth worms & fungi – 1-3% of total WBC

• Basophils– Destroy eukaryotic pathogens - < 0.5% of circulating WBC

• Mast Cells– Granules containing histamine & heparin

• Histamine dilates blood vessels and makes their walls permeable

• Heparin inhibits blood clotting

– Mucous membranes & connective tissue

Granulocytes

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Neutrophil Eosinophils

Basophil Mast cell

Polymorphonuclear

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Process in which phagocytes engulf and digest microorganisms and other cellular debris

What is phagocytosis?

Lysozymes fuse and release digestive enzymes and reactive oxygen compounds

An important defense against infection

Bacterial cells

Pseudopodium

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Agranulocytes• Lymphocytes - 20-35% of circ. WBC

– B cells – mature in bone marrow– T cells – mature in thymus– Involved in the specific immune response

• Monocytes –largest of all WBC (3-7%)– Phagocytic– Differentiate into macrophages

• Found in tissue• Consume damaged host cells• Present antigens• Regulation of the immune systems

– Differentiate into dendritic cells• Trap pathogens in the lymphatic tissue• Present antigens• Also important in specific immune response

T cell

Infected cell

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Vasoconstrictionhistamine & heparin

Vasodilation

EdemaInfiltration of neutrophils

Eliminate microbes, particulate matter

& dead or injured cells

Extract antigens

Macrophages &LymphocytesMacrophages = phagocytosisB cells = antibodiesT cell = killer & memory cells

Inflammatory Response

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Tissue Repair• Involves replacement of dead or damaged cells

• Begins during active phase of inflammation

• Extent of regeneration depends on tissue type, requires production of new cells by STROMA (supportive connective tissue) or PARENCHYMA (active part of tissue)

• Parenchymal regeneration restores skin to original form

• Stromal regeneration results in scaring

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Fever• Systemic nonspecific response to infection

• Higher than normal body temperature• Pyrogen

• Exogenous• LPS, pathogens, foreign cells, vaccines

• Endogenous• Interleukin-1 (IL-1) & Tumor necrosis factor (TNF)• Monocytes, neutrophils & macrophages

• Resets hypothalamus (in brain) thermostat to a higher setting• Elevated temperature maintained until pyrogen is eliminated• Low grade fever effective defense against disease

• Intensifies effects of antiviral agents (interferon)• Inhibits microbial growth• Speeds up physiological reactions (tissue repair)

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Complement: C proteinsComplements the Immune Reactions

• Consists of 26 blood proteins that work in concert to destroy bacteria and viruses

• Nonspecific defense that any foreign cell can activate system• Complement proteins are activated by cleavage

– Cascade reaction

• 1) Classical pathway– C proteins bind to receptors on foreign cell membrane

• 2) Alternative pathway- interaction with normal cell surface components

• 3) Lectin Pathway- Direct interaction with polysaccharide that contains sugar called mannan

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Classical Pathway

Two complement components contribute to inflammation - C3a and C5aBoth bind to mast cells, basophils, and platelets - trigger release of histaminesC5a also a potent chemoattractant for phagocytic cells

Collectively they’re called C1

Initiation

Amplification & Cascade Series of cleavage rxns

C5 binds to membrane

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C5b attracts other C proteinsForm a ring that punctures the cell

Polymerization

Membrane attack

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Interferons (INFs)

• Originally described as interfering with viral infections• Produced in response to a viruses & a variety of antigens

• RNA & products of immune cells• Tumor suppressive effects

• Three types of human interferon• lymphocytes & macrophages• fibroblasts & epithelial cells• T cells

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• and produced in infected cells, diffuse to uninfected cells

- Mediates transcription of antiviral protein in uninfected cells

• Allows resistance to infection- α activates “natural killer” cells (NK cells) (related to T

cells but lack specificity for Ag)- β – maturation of B and T lymphocytes and has role in

inflammation• • interferon produced by T cells

- Inhibits cancer cells, activates macrophages, stimulates B cells

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Defenses can be classified as either (1) innate & nonspecific or (2) acquired & specific