FIGHTING DISEASEFIGHTING DISEASE

IntroductionIntroduction

ResistanceResistance: Ability to ward : Ability to ward

off disease.off disease. Nonspecific Resistance:Nonspecific Resistance: Defenses Defenses

that protect against that protect against allall pathogens. pathogens. Specific Resistance:Specific Resistance: Protection Protection

against against specificspecific pathogens. pathogens.

SusceptibilitySusceptibility: Vulnerability : Vulnerability or lack of resistance.or lack of resistance.

Protection Against Invading Protection Against Invading PathogensPathogens

1. First Line of Defense1. First Line of Defense: : Non-specificNon-specific natural barriers which natural barriers which restrictrestrict entryentry of of pathogen. pathogen.

ExamplesExamples: Skin and mucous : Skin and mucous membranes.membranes.

2. Second Line of Defense2. Second Line of Defense: Innate : Innate non-non-specificspecific immune defenses provide rapid immune defenses provide rapid local response to pathogen local response to pathogen afterafter it has it has enteredentered host. host.

ExamplesExamples: Fever, phagocytes : Fever, phagocytes (macrophages and neutrophils), (macrophages and neutrophils), inflammationinflammation, and interferon., and interferon.

Continued…..

3. Third line3. Third line of defense: of defense: AntigenAntigen--specificspecific immune responses, immune responses, specifically target and attack specifically target and attack invaders that get past first two lines invaders that get past first two lines of defense. of defense.

ExamplesExamples: Antibodies and : Antibodies and lymphocytes.lymphocytes.

Three Lines of Defense Against Infection

First Line of Defense:First Line of Defense:Skin and Mucous MembranesSkin and Mucous Membranes

I. Mechanical DefensesI. Mechanical Defenses1. Skin has two Layers:1. Skin has two Layers:

A. EpidermisA. Epidermis: Thin outer layer of : Thin outer layer of epithelialepithelial tissue. tissue.

Contains Langerhans cells, dead cells, and keratin Contains Langerhans cells, dead cells, and keratin (waterproof).(waterproof).

B. DermisB. Dermis: Thick inner layer of : Thick inner layer of connectiveconnective tissue. tissue.

Infections are rare in intact skin. Exceptions:Infections are rare in intact skin. Exceptions: Hookworms can penetrate intact skinHookworms can penetrate intact skin Dermatophytes: “Skin loving” fungiDermatophytes: “Skin loving” fungi

Intact Skin is an Effective Barrier Against Most Pathogens

I. Mechanical Defenses I. Mechanical Defenses

2. Mucous Membranes2. Mucous Membranes: Line gastrointestinal, : Line gastrointestinal, genitourinary, and respiratory tracts.genitourinary, and respiratory tracts.

Two layers: Outer epithelial and inner connective layer.Two layers: Outer epithelial and inner connective layer. Epithelial layer secretes mucus which maintains moist Epithelial layer secretes mucus which maintains moist

surfaces.surfaces. Although they inhibit microbial entry, they offer less Although they inhibit microbial entry, they offer less

protection than skin. protection than skin. Several microorganisms are capable of penetrating Several microorganisms are capable of penetrating

mucous membranes:mucous membranes: PapillomavirusPapillomavirus Treponema pallidumTreponema pallidum EEnteroinvasive nteroinvasive E. coliE. coli Entamoeba histolyticaEntamoeba histolytica

I. Mechanical Defenses I. Mechanical Defenses 3. Lacrimal apparatus3. Lacrimal apparatus: Continual washing and : Continual washing and

blinking prevents microbes from settling on the blinking prevents microbes from settling on the eye surface.eye surface.

4. Saliva4. Saliva: Washes microbes from teeth and mouth : Washes microbes from teeth and mouth mucous membranes.mucous membranes.

5. Mucus5. Mucus: Thick secretion that traps many : Thick secretion that traps many microbes.microbes.

6. Nose Hair6. Nose Hair: Coated with mucus filter dust, pollen, : Coated with mucus filter dust, pollen, and microbes.and microbes.

7. Ciliary Escalator7. Ciliary Escalator: Cilia on mucous membranes of : Cilia on mucous membranes of lower respiratory tract move upwards towards lower respiratory tract move upwards towards throat at 1-3 cm/hour. throat at 1-3 cm/hour.

I. Mechanical Defenses I. Mechanical Defenses 8. Coughing and sneezing8. Coughing and sneezing: Expel foreign objects.: Expel foreign objects.

9. Epiglottis9. Epiglottis: Covers larynx during swallowing.: Covers larynx during swallowing.

10. Urination10. Urination: Cleanses urethra.: Cleanses urethra.

11. Vaginal Secretions11. Vaginal Secretions: Remove microbes from : Remove microbes from genital tract.genital tract.

Epiglottis Protects Respiratory System from Infection During Swallowing

B. Chemical Defenses:B. Chemical Defenses: SebumSebum: Oily substance produced by : Oily substance produced by

sebaceous glands that forms a protective layer sebaceous glands that forms a protective layer over skin. Contains unsaturated fatty acids over skin. Contains unsaturated fatty acids which inhibit growth of certain pathogenic which inhibit growth of certain pathogenic bacteria and fungi.bacteria and fungi.

pHpH: Low, skin pH usually between 3 and 5. : Low, skin pH usually between 3 and 5. Caused by lactic acid and fatty acids.Caused by lactic acid and fatty acids.

PerspirationPerspiration: Produced by sweat glands. : Produced by sweat glands. Contains lysozyme and acids.Contains lysozyme and acids.

LysozymeLysozyme: Enzyme that breaks down gram-: Enzyme that breaks down gram-positive cell walls. Found in nasal secretions, positive cell walls. Found in nasal secretions, saliva, and tears.saliva, and tears.

B. Chemical B. Chemical Defenses (Continued)Defenses (Continued) Gastric JuiceGastric Juice: Mixture of hydrochloric acid, : Mixture of hydrochloric acid,

enzymes, and mucus. pH between 1.2 to 3 enzymes, and mucus. pH between 1.2 to 3 kills many microbes and destroys most toxins. kills many microbes and destroys most toxins. Many enteric bacteria are protected by food Many enteric bacteria are protected by food particles. particles.

Helicobacter pyloriHelicobacter pylori neutralizes stomach acid and neutralizes stomach acid and can grow in the stomach, causing gastritis and can grow in the stomach, causing gastritis and ulcers.ulcers.

TransferrinsTransferrins: Iron-binding proteins in blood : Iron-binding proteins in blood which inhibit bacterial growth by reducing which inhibit bacterial growth by reducing available iron.available iron.

Cellular Elements of BloodCellular Elements of BloodCell TypeCell Type # Cells/mm # Cells/mm33 FunctionFunctionErythrocytes (RBC) Erythrocytes (RBC) 4.8-5.4 million4.8-5.4 million Transport OTransport O22 and CO and CO22

Leukocytes (WBC)Leukocytes (WBC) 5000-9000 5000-9000 VariousVarious A. Granulocytes:A. Granulocytes:

1. Neutrophils (70% of WBC)1. Neutrophils (70% of WBC) PhagocytosisPhagocytosis 2. Basophils (1%)2. Basophils (1%) Produce histamineProduce histamine 3. Eosinophils (4%)3. Eosinophils (4%) Toxins against parasites Toxins against parasites

some phagocytosissome phagocytosis

B. Monocytes/Macrophages (5%)B. Monocytes/Macrophages (5%) PhagocytosisPhagocytosis

C. Lymphocytes (20%)C. Lymphocytes (20%) Antibody production (B cells)Antibody production (B cells) Cell mediated immunity (T cells)Cell mediated immunity (T cells)

PlateletsPlatelets 300,000 300,000 Blood clottingBlood clotting

Composition of Human Blood

Platelets Form Blood Clots

II. Second Line of DefenseII. Second Line of Defense1. Phagocytosis1. Phagocytosis: : Derived from the Greek words “Eat and cell”. Derived from the Greek words “Eat and cell”. Phagocytosis is carried out by white blood cells: Phagocytosis is carried out by white blood cells:

macrophages, neutrophils, and occasionally macrophages, neutrophils, and occasionally eosinophils.eosinophils.

NeutrophilsNeutrophils predominate early in infection. predominate early in infection. Wandering macrophagesWandering macrophages: Originate from : Originate from

monocytesmonocytes that leave blood and enter infected that leave blood and enter infected tissue, and develop into phagocytic cells.tissue, and develop into phagocytic cells.

Fixed Macrophages (Histiocytes):Fixed Macrophages (Histiocytes): Located in Located in liver, nervous system, lungs, lymph nodes, bone liver, nervous system, lungs, lymph nodes, bone marrow, and several other tissues.marrow, and several other tissues.

Phagocytic Cells: Macrophages (Monocytes), Neutrophils, and Eosinophils

(Macrophages)

Stages of PhagocytosisStages of Phagocytosis1. Chemotaxis1. Chemotaxis: Phagocytes are chemically : Phagocytes are chemically

attracted to site of infection.attracted to site of infection.

2. Adherence:2. Adherence: Phagocyte plasma membrane Phagocyte plasma membrane attaches to surface of pathogen or foreign attaches to surface of pathogen or foreign material. material.

Adherence can be inhibited by capsules (Adherence can be inhibited by capsules (S. S.

pneumoniaepneumoniae) or M protein () or M protein (S. pyogenesS. pyogenes).).

OpsonizationOpsonization: Coating process with opsonins that : Coating process with opsonins that

facilitates attachment. facilitates attachment.

• OpsoninsOpsonins include antibodies and complement proteins. include antibodies and complement proteins.

Phagocytes are Attracted to Site of Infection by Chemotaxis

Stages of Phagocytosis (Continued)Stages of Phagocytosis (Continued)

3. Ingestion3. Ingestion: Plasma membrane of phagocytes : Plasma membrane of phagocytes extends projections (pseudopods) which engulf the extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called microbe. Microbe is enclosed in a sac called phagosomephagosome..

Stages of Phagocytosis (Continued)Stages of Phagocytosis (Continued)

4. Digestion4. Digestion: Inside the cell, phagosome fuses : Inside the cell, phagosome fuses with lysosome to form a with lysosome to form a phagolysosomephagolysosome. .

Lysosomal enzymes kill most bacteria within Lysosomal enzymes kill most bacteria within 30 minutes and include:30 minutes and include:

Lysozyme: Destroys cell wall peptidoglycanLysozyme: Destroys cell wall peptidoglycan Lipases and ProteasesLipases and Proteases RNAses and DNAsesRNAses and DNAses

After digestion, After digestion, residual bodyresidual body with with undigestable material is discharged.undigestable material is discharged.

Process of Phagocytosis

Inflammation Inflammation Triggered by tissue damage due to infection, heat, Triggered by tissue damage due to infection, heat,

wound, etc. wound, etc.

Four Major Symptoms of Inflammation:Four Major Symptoms of Inflammation:

1. Redness1. Redness

2. Pain2. Pain

3. Heat3. Heat

4. Swelling4. Swelling

May also observe:May also observe:

5. Loss of function5. Loss of function

Functions of Inflammation Functions of Inflammation 1. Destroy and remove pathogens1. Destroy and remove pathogens

2. If destruction is not possible, to limit 2. If destruction is not possible, to limit effects by confining the pathogen and its effects by confining the pathogen and its products.products.

3. Repair and replace tissue damaged by 3. Repair and replace tissue damaged by pathogen and its products.pathogen and its products.

Stages of InflammationStages of Inflammation1. Vasodilation1. Vasodilation: Increase in diameter of blood : Increase in diameter of blood

vessels. vessels.

Triggered by chemicals released by damaged cells: Triggered by chemicals released by damaged cells: histamine, kinins, prostaglandins, and histamine, kinins, prostaglandins, and leukotrienes.leukotrienes.

2. Phagocyte Migration and Margination2. Phagocyte Migration and Margination: : MarginationMargination is the process in which phagocytes is the process in which phagocytes stick to lining of blood vessels.stick to lining of blood vessels.

Diapedesis (Emigration)Diapedesis (Emigration): Phagocytes squeeze : Phagocytes squeeze between endothelial cells of blood vessels and between endothelial cells of blood vessels and enter surrounding tissue.enter surrounding tissue.

Process of Inflammation

Stages of Inflammation (Continued)Stages of Inflammation (Continued)

Phagocytes are attracted to site of infection Phagocytes are attracted to site of infection through chemotaxis.through chemotaxis.

Phagocytes destroy microbes, as well as dead and Phagocytes destroy microbes, as well as dead and damaged host cells.damaged host cells.

3. Tissue Repair3. Tissue Repair: Dead and damaged cells are : Dead and damaged cells are replaced. replaced.

The Lymphatic system

A complex network of organs that A complex network of organs that

work to rid the body of infectionwork to rid the body of infection Lymph, a transparent fluid that contains white Lymph, a transparent fluid that contains white

blood cells (blood cells (leukocytesleukocytes), circulates through us ), circulates through us It filters out and engulfs foreign bodies (ex. It filters out and engulfs foreign bodies (ex.

bacteria, viruses)bacteria, viruses)

Macrophages:Macrophages: white blood cells that seek and white blood cells that seek and destroy foreign cells destroy foreign cells

When injury happens:

Neutrophils (inflammatory) are the Neutrophils (inflammatory) are the first cells to respond to injuryfirst cells to respond to injury

Macrophages clean up debrisMacrophages clean up debris Mast cells induce swelling, warmth, Mast cells induce swelling, warmth,

and rednessand redness All 3 types of cells summon more All 3 types of cells summon more

immune system cellsimmune system cells

Adaptive/ Acquired Immunity Stronger than innate immunityStronger than innate immunity

Our immune systems have an “immulogical memory”Our immune systems have an “immulogical memory” The basis of vaccinations!The basis of vaccinations!

Pathogens are remembered based on their specific Pathogens are remembered based on their specific structures: antigensstructures: antigens antigens: antigens: antianti-body -body gengen-erators-erators

Adaptive immunity involves T cells Adaptive immunity involves T cells and B cellsand B cells T-cells seek out and kill invadersT-cells seek out and kill invaders B-cell produce antibodies towards antigensB-cell produce antibodies towards antigens Both produce memory cells that will allow the Both produce memory cells that will allow the

immune system to react FASTER and immune system to react FASTER and STRONGER next time, (hopefully) preventing STRONGER next time, (hopefully) preventing spread of infectionspread of infection

Active immunity

- body itself manufactures antibodies through fighting off a disease

-provides lasting protection

Passive immunity

- antibodies are introduced into bloodstream of an individual, given from mother to child during pregnancy and breast-feeding

-short-term protection

Passive versus Active Immunity

II. Interferons: II. Interferons: Antiviral proteins that interfere with Antiviral proteins that interfere with viral multiplication. viral multiplication.

Small proteins (15,000 to 30,000 kDa)Small proteins (15,000 to 30,000 kDa) Heat stable and resistant to low pHHeat stable and resistant to low pH Important in acute and short term infections.Important in acute and short term infections. Have no effect on infected cells.Have no effect on infected cells. Host specific, but not virus specificHost specific, but not virus specific..

Interferon alpha and beta: Interferon alpha and beta: Produced by virus infected Produced by virus infected cells and diffuse to neighboring cells. Cause cells and diffuse to neighboring cells. Cause uninfected cells to produce antiviral proteins (AVPs).uninfected cells to produce antiviral proteins (AVPs).

Interferon gamma: Interferon gamma: Produced by lymphocytes. Causes Produced by lymphocytes. Causes neutrophils to kill bacteria.neutrophils to kill bacteria.