Innate Immune Response on line.ppt

Innate Immune Innate Immune ResponseResponse

Kathy HuschleKathy Huschle

Northland Community and Technical CollegeNorthland Community and Technical College

The Human BodyThe Human Body

we are made up of warm, moist, nutrient rich we are made up of warm, moist, nutrient rich substances, an ideal environment for the substances, an ideal environment for the housing of microorganismshousing of microorganisms– every drop of water we drink contains 100’s every drop of water we drink contains 100’s

of bacteriaof bacteria– the air we breath introduces millions of the air we breath introduces millions of

bacteria daily to our lungsbacteria daily to our lungs– every time we brush our teeth we drive every time we brush our teeth we drive

microorganisms into our gumsmicroorganisms into our gums

Bacteria on just brushed teeth

The Human BodyThe Human Body

despite this environment our body is relatively sterile despite this environment our body is relatively sterile (pathogen free)(pathogen free)

in most cases the presence of microorganisms are in most cases the presence of microorganisms are controlled by our defense mechanismscontrolled by our defense mechanisms– innate immunityinnate immunity– adaptive immunityadaptive immunity

these 2 systems interact to keep out microorganisms, these 2 systems interact to keep out microorganisms, remove microorganisms if they get in, and combat them remove microorganisms if they get in, and combat them if they remain insideif they remain inside

ImmunityImmunity

immunity is the ability to ward off diseases through immunity is the ability to ward off diseases through nonspecific and specific defensesnonspecific and specific defenses

our bodies normally have 2 defense mechanisms against our bodies normally have 2 defense mechanisms against pathogenspathogens– innate immunityinnate immunity

nonspecific resistance that refers to all body nonspecific resistance that refers to all body defenses that protect the body against any kind of defenses that protect the body against any kind of pathogenpathogen

– adaptive immunityadaptive immunity

specific resistance that refers to defenses against specific resistance that refers to defenses against specific microorganismsspecific microorganisms

Innate ImmunityInnate Immunity

the protection provided by the innate the protection provided by the innate immune system is one the human body is immune system is one the human body is born withborn with

initially it was thought to be a very initially it was thought to be a very generalized system and was often generalized system and was often referred to as the non-specific immune referred to as the non-specific immune systemsystem

Innate ImmunityInnate Immunity

recent research has determined that though the system recent research has determined that though the system will attack a variety of microbial pathogens, the system will attack a variety of microbial pathogens, the system does rely on recognition of patterns of invading does rely on recognition of patterns of invading pathogenspathogens

innate immunity is supplemented by the adaptive innate immunity is supplemented by the adaptive immune response which will be discussed in the next immune response which will be discussed in the next lecturelecture

Innate Defenses OverviewInnate Defenses Overviewfirst-line defensesfirst-line defenses– physical barriersphysical barriers– antimicrobial substancesantimicrobial substances– normal floranormal flora

sensor systemssensor systems– toll like receptorstoll like receptors– complementcomplement– phagocytesphagocytes

inflammationinflammation

interferonsinterferons

feverfever

First-line Defenses

First Line Defenses: Physical BarriersFirst Line Defenses: Physical Barriers

skin and mucosaskin and mucosa– body’s first line of defensebody’s first line of defense– the function of defense is both the function of defense is both

mechanical and chemicalmechanical and chemical


skin and mucosaskin and mucosa– mechanical function involves physical barriers that mechanical function involves physical barriers that

block entry or processes that remove microbesblock entry or processes that remove microbes– chemical function include substances that the body chemical function include substances that the body

makes that inhibit microbial growth or destroys makes that inhibit microbial growth or destroys microbesmicrobes


This figure is a representation of the human body. The purple represents skin, the pink the mucous membranes. You can easily visualize the complete protection offered our body by intact skin and mucous membranes

First-Line Defenses: SkinFirst-Line Defenses: Skinintact skin physically blocks the entrance intact skin physically blocks the entrance of microorganismsof microorganismsmade up of 2 distinct layersmade up of 2 distinct layers– dermisdermis

thick inner portion made up of tight thick inner portion made up of tight connective tissueconnective tissue

– epidermisepidermisouter layer of skin made up of outer layer of skin made up of many layers of epithelial cellsmany layers of epithelial cellsthe top layer of the epidermis the top layer of the epidermis contains contains dead cellsdead cells embedded in embedded in a protective protein called keratin a protective protein called keratin

– keratinkeratin is a water-repelling is a water-repelling proteinprotein

First-Line Defenses: SkinFirst-Line Defenses: Skin

the presence of dead cells and the presence of dead cells and keratin in the outer layers of keratin in the outer layers of our skin plays a major role in our skin plays a major role in inhibiting any microorganisms inhibiting any microorganisms from gaining a foot holdfrom gaining a foot hold– microorganisms require microorganisms require

water to survive: keratin water to survive: keratin repels waterrepels water

keratin and dead cells on the surface of skin

First-Line Defenses: SkinFirst-Line Defenses: Skin

– viruses require a living host to invade: dead cells viruses require a living host to invade: dead cells are obviously not suitable for viral invasionare obviously not suitable for viral invasion

– the outer layer of cells are periodically shed which the outer layer of cells are periodically shed which helps remove any microbes that may have found a helps remove any microbes that may have found a home on the skin’s surfacehome on the skin’s surface

Dead skin cells

First-Line Defenses: Mucous First-Line Defenses: Mucous MembranesMembranes

mucous membranes line the internal spaces of organs mucous membranes line the internal spaces of organs and tubes that open to the outside, and also line the and tubes that open to the outside, and also line the body cavitiesbody cavities

some examples of the location of mucous membranes

Mucous MembranesMucous Membranes

mucous membranes mucous membranes inhibit the entrance of inhibit the entrance of microorganisms, but offer microorganisms, but offer less protection than intact less protection than intact skinskin

mucous, the sticky fluid mucous, the sticky fluid found in mucous found in mucous membranes, functions to membranes, functions to keep the membranes keep the membranes moistmoist

Mucous secreting cells


– this moist environment enhances the presence of this moist environment enhances the presence of some microorganismssome microorganisms

these microorganisms, if present in a large these microorganisms, if present in a large enough number, are often capable of penetrating enough number, are often capable of penetrating the membranethe membrane

– but on the other hand, the bathing of mucous but on the other hand, the bathing of mucous membranes by mucosa can in some cases wash the membranes by mucosa can in some cases wash the microorganisms from the surfacesmicroorganisms from the surfaces

Esophagus


in the digestive tract, many microorganisms are in the digestive tract, many microorganisms are directed towards elimination by a process called directed towards elimination by a process called peristalsisperistalsis


– peristalsis is the rhythmic peristalsis is the rhythmic contraction of the contraction of the intestinal tract that moves intestinal tract that moves food through the systemfood through the system

– this process also this process also enhances the removal of enhances the removal of microorganismsmicroorganisms

Gastic gland in digestivetract secrete mucous


cilia line the respiratory tractcilia line the respiratory tract– with a constant beating upward by with a constant beating upward by

the cilia, microorganisms are the cilia, microorganisms are propelled away from the lungs to propelled away from the lungs to the throat where they are either the throat where they are either swallowed or coughed awayswallowed or coughed away

Trachial cell withcilia in green andmucousal glands

in yellow

Cilia actions removing debris


more penetrable than skinmore penetrable than skindry conditions thin mucous layer dry conditions thin mucous layer making them even more making them even more penetrablepenetrable– this explains why we are more this explains why we are more

vulnerable to colds and vulnerable to colds and respiratory infections during respiratory infections during dryer wintersdryer winters

cells of the mucous membranes cells of the mucous membranes are aliveare alive– high concentrations of viruses high concentrations of viruses

and pathogens can overwhelm and pathogens can overwhelm themthem

Bacteria in yellow onnasal epithelium in mauve


mechanical methods of microbial mechanical methods of microbial removal from mucous membranesremoval from mucous membranes– respiratory: coughing, sneezing, respiratory: coughing, sneezing,

gagginggagging– gastrointestinal: peristalsis, vomiting, gastrointestinal: peristalsis, vomiting,

defecationdefecation– genitourinary: urinationgenitourinary: urination

First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial

many of the body fluids found in or on the skin or many of the body fluids found in or on the skin or mucous membranes are antimicrobialmucous membranes are antimicrobial– they can effectively limit ability of invading organisms they can effectively limit ability of invading organisms

to infect by to infect by inhibiting growth: bacteriostaticinhibiting growth: bacteriostatickilling: bactericidalkilling: bactericidal

– examples includeexamples includesweatsweatlysozymelysozymeacidsacidslactoferrinlactoferrin


sweat has a high salt contentsweat has a high salt content– as it evaporates on our skin, it leaves behind a as it evaporates on our skin, it leaves behind a

residue that is high in saltresidue that is high in salt– a salty environment on the skin is not conducive to a salty environment on the skin is not conducive to

growth for most microorganismsgrowth for most microorganisms

Sweat gland cells


lysozymelysozyme– an enzyme that is found in tears, saliva, an enzyme that is found in tears, saliva,

sweat, and mucussweat, and mucus– lysozyme degrades peptidoglycan lysozyme degrades peptidoglycan

which is found in bacterial cell wallswhich is found in bacterial cell walls

particularly effective against Gram – particularly effective against Gram – cellscells

– the degradation of the cell wall causes the degradation of the cell wall causes the organism to die from osmotic shock: the organism to die from osmotic shock: it no longer has the rigid protection of it no longer has the rigid protection of the cell wallthe cell wall

lysozyme


acidsacids– generally generally

microorganisms require microorganisms require a neutral environmenta neutral environment

– the presence of acid kills the presence of acid kills or prevents the growth of or prevents the growth of most microorganismsmost microorganisms

vaginal tract has a pH vaginal tract has a pH of 4.4 - 4.6of 4.4 - 4.6

digestive tract has a digestive tract has a pH of 1-2pH of 1-2

Endoscopic view of digestive tract


the presence of normal “friendly” microorganisms the presence of normal “friendly” microorganisms on the skin break down the sebum found in the on the skin break down the sebum found in the skinskin

– the break down of sebum releases fatty acids the break down of sebum releases fatty acids which make the skin more acidic, inhibiting the which make the skin more acidic, inhibiting the growth of invading microorganismsgrowth of invading microorganisms

Sebum on skin


blood and body fluids also contain antimicrobial blood and body fluids also contain antimicrobial chemicalschemicals– iron-binding proteinsiron-binding proteins

transferrintransferrin– found in blood and tissue fluidsfound in blood and tissue fluids

lactoferrinlactoferrin– found in saliva, mild and mucusfound in saliva, mild and mucus

Transferrin-HeLa cells Lactoferrin


transferrin and lactoferrintransferrin and lactoferrin– inhibit bacterial growth by reducing the amount of inhibit bacterial growth by reducing the amount of

available ironavailable iron

bind the available iron so the pathogens can’tbind the available iron so the pathogens can’t– the probability of contracting a STD during the probability of contracting a STD during

menstruation is increased due to increased menstruation is increased due to increased amount of blood in the vaginal tract: more iron amount of blood in the vaginal tract: more iron available for the invading microorganismavailable for the invading microorganism

First Line Defenses: Fluid FlowFirst Line Defenses: Fluid Flow

the cleansing action of fluids also assists in the removal the cleansing action of fluids also assists in the removal of microorganisms from mucous membranesof microorganisms from mucous membranes– salivasaliva

dilutes the number of microorganisms and washes dilutes the number of microorganisms and washes them from the surface of the teeth and the mucous them from the surface of the teeth and the mucous membranes of the mouthmembranes of the mouth

bacteria in saliva


– urinary tracturinary tract

the cleansing of the urethra by the flow of urine the cleansing of the urethra by the flow of urine prevents colonization of microorganismsprevents colonization of microorganisms


– eyeeye

production of tears by the lacrimal apparatus production of tears by the lacrimal apparatus continually washes over the eyescontinually washes over the eyes

lacrimal gland secretes tears: tears are drained by the nasalacrimal duct


this continuous washing of the this continuous washing of the eyes with tears prevents eyes with tears prevents microorganisms from settling microorganisms from settling on the surface of the eyeon the surface of the eye

First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers

on a cellular basis, our body is made up of 90% on a cellular basis, our body is made up of 90% microbial cells and only 10% “human”microbial cells and only 10% “human”– most of the bacterial cells found in our body are most of the bacterial cells found in our body are

associated with the gastrointestinal tractassociated with the gastrointestinal tract– S. aureusS. aureus is prevalent on skin is prevalent on skin– LactobacilliLactobacilli are prevalent in the vaginal tract are prevalent in the vaginal tract

S. aureus


this large number of microbial cells are indigenous this large number of microbial cells are indigenous (naturally occurring) and are referred to as normal (naturally occurring) and are referred to as normal microbita or normal floramicrobita or normal flora

microbial barriers play a key role in our immune system microbial barriers play a key role in our immune system by inhabiting specific body surfacesby inhabiting specific body surfaces


many of the normal flora found in various parts of the human body


normal flora are nonpathogenicnormal flora are nonpathogenic– colonize body tissues thus preempting other colonize body tissues thus preempting other

microorganisms from colonizingmicroorganisms from colonizing– they are capable of producing antimicrobial they are capable of producing antimicrobial

substances that interfere with the growth of other substances that interfere with the growth of other microorganismsmicroorganisms

– they reduce the availability of oxygenthey reduce the availability of oxygen– they compete for nutrientsthey compete for nutrients


the normal flora found in our body are a balanced the normal flora found in our body are a balanced complexcomplex– but an imbalance can lead to diseasebut an imbalance can lead to disease

nonpathogenic normal flora are opportunistic nonpathogenic normal flora are opportunistic and will take advantage of any opportunity to and will take advantage of any opportunity to invade which can lead to diseaseinvade which can lead to disease

opportunities that can lead to an imbalance can opportunities that can lead to an imbalance can be injury or a depressed or non-functioning be injury or a depressed or non-functioning immune systemimmune system


the process of acquisition of our normal flora begins the process of acquisition of our normal flora begins during birthduring birth– the human fetus is sterile and through a successional the human fetus is sterile and through a successional

process occurring in stages, acquires the microbiota process occurring in stages, acquires the microbiota necessary for survivalnecessary for survival

– the first step of acquiring the normal flora for some the first step of acquiring the normal flora for some newborns is the transfer of microorganisms from newborns is the transfer of microorganisms from mother’s milkmother’s milk

Cells of the Immune SystemCells of the Immune Systemcells are capable of moving around the body through the cells are capable of moving around the body through the circulatory systemcirculatory system

cells of the immune system are found in normal bloodcells of the immune system are found in normal blood– develop in the bone marrowdevelop in the bone marrow– increase in amounts during infectionincrease in amounts during infection– leukocytes: white blood cellsleukocytes: white blood cells

granulocytesgranulocytes

mononuclear phagocytesmononuclear phagocytes

lymphocyteslymphocytes

stem cellstem cell is the common ancestor to all blood cells: red, is the common ancestor to all blood cells: red, white, and plateletswhite, and platelets

GranulocytesGranulocytes

presence of large granules presence of large granules in their cytoplasm filled in their cytoplasm filled with biologically active with biologically active chemicals critical to their chemicals critical to their functionfunctiongranulocytes differentiate granulocytes differentiate into three types of cellsinto three types of cells– neutrophilsneutrophils– basophilsbasophils– eosinophils eosinophils

granulocytesgranulocytes

NeutrophilsNeutrophils

neutrophilsneutrophils– professional phagocytes – 50% of the professional phagocytes – 50% of the

leukocytes found in the body are leukocytes found in the body are neutrophilsneutrophils

these numbers increase during the these numbers increase during the presence of a bacterial infectionpresence of a bacterial infection


– chemical found in their granules assists in the chemical found in their granules assists in the degradation of engulfed materialdegradation of engulfed material

– often referred to as polymorphonuclear neutrophilic often referred to as polymorphonuclear neutrophilic leukocyte or poymorphs (PMN)leukocyte or poymorphs (PMN)

NeutrophilSEM pictogram of neutrophil

Neutrophil in collagen


– have the ability to leave the blood, enter an have the ability to leave the blood, enter an infected tissue and destroy microbes and foreign infected tissue and destroy microbes and foreign particlesparticles

– always present for protection and surveillancealways present for protection and surveillance

BasophilsBasophils

the role of basophils is not particularly well the role of basophils is not particularly well understoodunderstood– they are involved in allergic reactions and they are involved in allergic reactions and

inflammationinflammation

EosinophilsEosinophils

important defense against parasitesimportant defense against parasites– capable of leaving the blood and infiltrating tissuecapable of leaving the blood and infiltrating tissue– major function is to produce toxic proteins against major function is to produce toxic proteins against

parasitesparasites

physically too small to ingest parasites, eosinophils are physically too small to ingest parasites, eosinophils are able to attach to the outer surface of a parasite and able to attach to the outer surface of a parasite and discharge a toxin that destroys themdischarge a toxin that destroys them

Mononuclear PhagocytesMononuclear Phagocytes

2 types of phagocytic cells arise from monocytes2 types of phagocytic cells arise from monocytes

monocytes circulate in the blood after leaving the monocytes circulate in the blood after leaving the bone marrowbone marrow


monocytes migrate to tissue and monocytes migrate to tissue and form:form:– macrophagesmacrophages

also considered to be also considered to be professional phagocytesprofessional phagocytes

abundant in spleen, liver, abundant in spleen, liver, lymph nodes, lungs, lymph nodes, lungs, peritoneal cavityperitoneal cavity

macrophagemacrophage


– dendritic cellsdendritic cells

scout phagocytes; highly mobile cellsscout phagocytes; highly mobile cells

more involved with adaptive immune more involved with adaptive immune system which will be discussed latersystem which will be discussed later

Leukocyte InvasionLeukocyte Invasion

LymphocytesLymphocytes

cells that are players in the adaptive immune cells that are players in the adaptive immune systemsystem– these cells are not phagocytesthese cells are not phagocytes– occur in the lymphoid tissue of the lymphatic occur in the lymphoid tissue of the lymphatic

system; tonsils, spleen, red bone barrow, system; tonsils, spleen, red bone barrow, lymph nodeslymph nodes

LymphocytesLymphocytes

B cellsB cells– produce antibodiesproduce antibodies

T cellsT cells– destroy infected/abnormal destroy infected/abnormal

cells and coordinate the cells and coordinate the immune responseimmune response

Natural Killer cells (NK)Natural Killer cells (NK)– kill cells kill cells – are capable of recognizing a are capable of recognizing a

target and then destroying target and then destroying that cellthat cell

B cell with bacteria

T cell

NK cells attacking

Cell CommunicationCell Communication

the function of the immunes system relies on the function of the immunes system relies on cooperation between many factorscooperation between many factors– this cooperation relies on a method of communication this cooperation relies on a method of communication

between the playersbetween the players

receive signals from environmentreceive signals from environment

send messagessend messages

direct contactdirect contact

Cell CommunicationCell Communicationsurface receptorssurface receptors– proteins that bind signal molecules or specific chemical proteins that bind signal molecules or specific chemical

messengersmessengers– connect outside of the cell to the insideconnect outside of the cell to the inside

eyes and ears of the celleyes and ears of the cell– allows cell to respond to what’s happening outside it’s allows cell to respond to what’s happening outside it’s

cell wallcell wall– the response that is made is called chemotaxisthe response that is made is called chemotaxis

movement made in response to a chemicalmovement made in response to a chemical


cytokinescytokines– proteins that bind to certain surface receptorsproteins that bind to certain surface receptors– chemical messengers of the immune systemchemical messengers of the immune system– there are numerous types of cytokines that have there are numerous types of cytokines that have

various affects on the behavior of cellsvarious affects on the behavior of cells– please view the table 15-3 on page 380 in your please view the table 15-3 on page 380 in your

textbook for examples of the many kinds of cytokinestextbook for examples of the many kinds of cytokines

Interleukin L in red, human cells in green


adhesion moleculesadhesion molecules– ““grab” other cells as they grab” other cells as they

pass such as phagocytic pass such as phagocytic cellscells

– allow cells to make direct allow cells to make direct contact enabling delivery of contact enabling delivery of cytokines to a cell cytokines to a cell

Macrophage (A) usingpseudopodia (B) tograb bacteria (C)

Sensor SystemsSensor Systems

responsible for detecting signs of tissue damage or responsible for detecting signs of tissue damage or microbial invasion within the blood or tissuemicrobial invasion within the blood or tissue

recognize and respond to patterns associated with recognize and respond to patterns associated with “danger”“danger”– toll-like receptorstoll-like receptors– complement systemcomplement system

Macrophage roams and monitors lung tissue

Toll-Like ReceptorsToll-Like Receptors

a very recent discovery in the microbial worlda very recent discovery in the microbial world

10 different toll-like receptors have been discovered so 10 different toll-like receptors have been discovered so far, each recognizing a specific or group of specific far, each recognizing a specific or group of specific compounds associated with “danger” for the cellcompounds associated with “danger” for the cell

surface receptor proteins that are surface receptor proteins that are capable of recognizing microbial capable of recognizing microbial particles and activating immune particles and activating immune cells against the source of these cells against the source of these microbial particlesmicrobial particles

ComplementComplement

glycoproteins found in glycoproteins found in blood that are responsible blood that are responsible forfor– removal of invading removal of invading

pathogenspathogens– preventing and limiting preventing and limiting

bacterial infectionsbacterial infections– assisting in other assisting in other

defenses that protectdefenses that protect

Glycoprotein E

Complement CytolysisComplement Cytolysis

complement system destroys complement system destroys microbes by cytolysis, microbes by cytolysis, inflammation or phagocytosisinflammation or phagocytosis


complement proteins act complement proteins act in a cascade; one in a cascade; one reaction triggers another, reaction triggers another, triggers another, etctriggers another, etc– this amplifies the effect this amplifies the effect

as the reaction as the reaction continuescontinues


complement is activated by complement is activated by – classical pathway: antibody/antigen complex classical pathway: antibody/antigen complex – alternative pathwayalternative pathway– lectin pathwaylectin pathway


classical pathwayclassical pathway– is initiated by an antigen-antibody reactionis initiated by an antigen-antibody reaction– this complex activates complement which this complex activates complement which

ultimately initiates cytolysis, inflammation or ultimately initiates cytolysis, inflammation or opsonizationopsonization


alternative pathwayalternative pathway– complement is activated by the contact between complement is activated by the contact between

specific complement proteins and a pathogenspecific complement proteins and a pathogen– can be stopped by regulatory proteins which are can be stopped by regulatory proteins which are

found in host cells found in host cells but are not associated with but are not associated with microbial surfacesmicrobial surfaces


lectin pathwaylectin pathway– requires mannan-binding lectins (MBL) requires mannan-binding lectins (MBL)

mannan is a substance that is found on microbial mannan is a substance that is found on microbial cells and not mammalian cellscells and not mammalian cells

as a result of binding, the MBL acts as an opsonin as a result of binding, the MBL acts as an opsonin (serum protein) to enhance phagocytosis(serum protein) to enhance phagocytosis


activation of complement generally leads toactivation of complement generally leads to– inflammationinflammation: contributes to vascular permeability: contributes to vascular permeability– lysislysis of foreign cells of foreign cells

assembles a membrane attack complex (MAC)assembles a membrane attack complex (MAC)– creates pores in the cell, disrupting cell integritycreates pores in the cell, disrupting cell integrity– most effective against Gram – cells because of most effective against Gram – cells because of

the outer membrane of the Grams – cellthe outer membrane of the Grams – cell– opsonizaion:opsonizaion: the coating of microorganisms with the coating of microorganisms with

serum particles to make them more susceptible to serum particles to make them more susceptible to phagocytosisphagocytosis

PhagocytosisPhagocytosis

phagocytes are cells that engulf and digestphagocytes are cells that engulf and digest

they are capable of pattern recognition which is they are capable of pattern recognition which is critical in the determination between self and non-critical in the determination between self and non-self cellsself cells

Macrophage attacking self


there are six general steps in the there are six general steps in the process of phagocytosis which includeprocess of phagocytosis which include

– chemotaxischemotaxis– recognition and attachmentrecognition and attachment– engulfmentengulfment– fusion of phagosomefusion of phagosome– destruction and digestiondestruction and digestion– exocytosisexocytosis

Macrophage ingesting M. pneumoniae

PhagocytosisPhagocytosischemotaxischemotaxis– presence of a chemical stimuli from presence of a chemical stimuli from

microorganisms, damaged mammalian tissue and microorganisms, damaged mammalian tissue and complementcomplement

– chemical stimuli recruits phagocytes to the sitechemical stimuli recruits phagocytes to the site


recognition and attachmentrecognition and attachment– direct binding occurs with surface receptorsdirect binding occurs with surface receptors– indirect binding occurs when a particle has been indirect binding occurs when a particle has been

opsonizedopsonized


engulfmentengulfment– engulfment of the particle forms a membrane-engulfment of the particle forms a membrane-

bound vacuole called a phagosomebound vacuole called a phagosome– this does not destroy the microorganismthis does not destroy the microorganism


fusion with lysosomefusion with lysosome– within the phagocyte within the phagocyte

the phagosome fuses the phagosome fuses with a lysosome, which with a lysosome, which is vesicle filled with is vesicle filled with digestive enzymesdigestive enzymes

– this fusion results in this fusion results in the formation of a the formation of a phagolysosomephagolysosome

Walking macrophage in lungridding it of debris


destruction and digestiondestruction and digestion– within the within the

phagolysosome the phagolysosome the microorganism is broken microorganism is broken down with the aid of down with the aid of enzymesenzymes

– this process generally this process generally takes 10-30 minutes to takes 10-30 minutes to kill most types of kill most types of bacteriabacteria


exocytosisexocytosis– the vesicle containing the digested material joins with the vesicle containing the digested material joins with

the plasma membrane the plasma membrane – the vesicle is then expelled to the external the vesicle is then expelled to the external

environmentenvironment


types of phagocytestypes of phagocytes– macrophagesmacrophages

scavengers and sentries of the systemscavengers and sentries of the system

long lived: weeks to monthslong lived: weeks to months

are able to maintain their killing power by are able to maintain their killing power by regenerating their lysosomesregenerating their lysosomes

Macrophage in lung tissueingesting bacteria


– neutrophilsneutrophils

rapid response team: quickly move to an area rapid response team: quickly move to an area when neededwhen needed

extremely effective in the early stages of infectionextremely effective in the early stages of infection

short life span:1-2 daysshort life span:1-2 days

have more killing power than the larger have more killing power than the larger macrophages but do not last as longmacrophages but do not last as long

both are replaceableboth are replaceable

Stages in neutrophil development


Inflammatory ResponseInflammatory Response

generalized, coordinated response togeneralized, coordinated response to– localize invading microorganisms (penetration of localize invading microorganisms (penetration of

skin)skin)– production of toxic compoundsproduction of toxic compounds

the inflammatory responses role is tothe inflammatory responses role is to– arrest the spread of infectionarrest the spread of infection– localize the responselocalize the response– restore tissue functionrestore tissue function


initiation of inflammatory initiation of inflammatory responseresponse– microbial products microbial products

such as LPS , flagella, such as LPS , flagella, bacterial DNA triggerbacterial DNA trigger

– microbial surfaces can microbial surfaces can trigger the trigger the complement cascade complement cascade which can trigger the which can trigger the inflammatory responseinflammatory response

– tissue damage can tissue damage can triggertrigger

Inflammation response in miceNotice swelling and reddnessin mouse on the right


symptoms of inflammation includessymptoms of inflammation includes– swellingswelling– pain pain – reddeningreddening– elevated tempelevated temp

all of the above symptoms of inflammation are a result of all of the above symptoms of inflammation are a result of the process of inflammation, which begins with the process of inflammation, which begins with – the dilation of blood vessels at the site of damagethe dilation of blood vessels at the site of damage– leakage of fluid from those vessels allowing for the leakage of fluid from those vessels allowing for the

migration of leukocytes to the sitemigration of leukocytes to the site

Inflammation ResponseInflammation Response

redness is due to capillary dilationredness is due to capillary dilation

elevated temp is due to capillary dilation which brings elevated temp is due to capillary dilation which brings heat to the siteheat to the site

swelling is due to increased capillary permeabilityswelling is due to increased capillary permeability

pain is due to lysis of the blood cellspain is due to lysis of the blood cells

dilation of blood vesselsdilation of blood vessels– increases circulationincreases circulation– increase phagocytesincrease phagocytes

InflammationInflammationincreased blood flowincreased blood flow– brings more phagocytic cells to the sitebrings more phagocytic cells to the site– area of inflammation is walled off due to fibrin area of inflammation is walled off due to fibrin

which is more prevalent due to vasodilatationwhich is more prevalent due to vasodilatation– the blood clots formed around the area prevent the the blood clots formed around the area prevent the

microbe and/or its toxin from spreadingmicrobe and/or its toxin from spreadingas a result, there may be a localized collection as a result, there may be a localized collection of inflammatory exudate or pusof inflammatory exudate or pus

– dead microorganismsdead microorganisms– dead phagocytic cellsdead phagocytic cells– debrisdebris– body fluidsbody fluids

final stage of inflammation is final stage of inflammation is repairrepair of affected tissue of affected tissue

InflammationInflammation

Following infection or injury, mast cells release Following infection or injury, mast cells release vasodilators that increase capillary permeability vasodilators that increase capillary permeability allowing plasma and leukocytes to leave the allowing plasma and leukocytes to leave the bloodstream and enter the tissue. bloodstream and enter the tissue.


Step One Step Two

Inflammatory ResponseInflammatory ResponseStep Three

Step Four

Steps of Phagocytosis in the Steps of Phagocytosis in the Inflammatory ResponseInflammatory Response

InterferonsInterferons

a class of antiviral proteins produced a class of antiviral proteins produced by certain animal cells after viral by certain animal cells after viral stimulationstimulation

principal function of interferons is to principal function of interferons is to block replication of viral genetic block replication of viral genetic materialmaterial– blocks translation of viral mRNAblocks translation of viral mRNA– interferons do not block entry interferons do not block entry

InterferonsInterferonsnon-specific protection against viral infectionnon-specific protection against viral infection– response of interferons to one virus offers response of interferons to one virus offers

protection against other virusesprotection against other viruses– it only works with limited quantities: neighboring it only works with limited quantities: neighboring

cells are protected, but not cells throughout the cells are protected, but not cells throughout the bodybody

Inhibition of SARS virus with interferons

InterferonsInterferons

interferons play a major role in the short-term acute interferons play a major role in the short-term acute infections such as the common cold and influenzainfections such as the common cold and influenza

the commercial production of interferons is being the commercial production of interferons is being exploredexplored– not only for their antiviral properties but also as not only for their antiviral properties but also as

potential anticancer agentspotential anticancer agents

FeverFeverhomoeothermic animals maintain a constant body homoeothermic animals maintain a constant body temperaturetemperature

fever is a:fever is a:– systemic responsesystemic response– abnormal increase in tempabnormal increase in temp– strong indication of infectious disease, particularly strong indication of infectious disease, particularly

those of bacterial originthose of bacterial origin

Kevorkian painting entitled “Fever”. This is one of an original series of paintings (now lost) concerning various medical signs and symptoms. It depicts the great discomfort of intense bodily heat.

FeverFever

feverfever– enhances natural defensesenhances natural defenses

stimulates phagocytosisstimulates phagocytosis

increases rate of enzyme increases rate of enzyme reactions which enhancesreactions which enhances

– degradation of microorganismdegradation of microorganism– tissue repairtissue repair

– intensifies the action of interferonsintensifies the action of interferons– reduces the blood iron concentrationreduces the blood iron concentration

FeverFever

up to a up to a certain pointcertain point, fever is considered a defense , fever is considered a defense against diseaseagainst disease– for this reason, one should consult a physician before for this reason, one should consult a physician before

taking drugs to reduce a fevertaking drugs to reduce a fever

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Innate Immune Response on line.ppt