Innate Immune Innate Immune Response Response Kathy Huschle Kathy Huschle Northland Community and Technical Northland Community and Technical College College
Jun 19, 2015
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
First Line Defenses: Physical BarriersFirst Line Defenses: Physical Barriers
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
First Line Defenses: Physical BarriersFirst Line Defenses: Physical Barriers
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
Mucous MembranesMucous Membranes
– 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
Mucous MembranesMucous Membranes
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
Mucous MembranesMucous Membranes
– 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
Mucous MembranesMucous Membranes
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
Mucous MembranesMucous Membranes
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
Mucous MembranesMucous Membranes
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: AntimicrobialFirst Line Defenses: Antimicrobial
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
First Line Defenses: Fluid FlowFirst Line Defenses: Fluid Flow
– 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
First Line Defenses: Fluid FlowFirst Line Defenses: Fluid Flow
– 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
First Line Defenses: Fluid FlowFirst Line Defenses: Fluid Flow
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
First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers
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
First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers
many of the normal flora found in various parts of the human body
First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers
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
First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers
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
First Line Defenses: Microbial BarriersFirst Line Defenses: Microbial Barriers
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
NeutrophilsNeutrophils
– 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
NeutrophilsNeutrophils
– 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
Mononuclear PhagocytesMononuclear Phagocytes
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
Mononuclear PhagocytesMononuclear Phagocytes
– 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
Cell CommunicationCell Communication
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
Cell CommunicationCell Communication
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
ComplementComplement
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
ComplementComplement
complement is activated by complement is activated by – classical pathway: antibody/antigen complex classical pathway: antibody/antigen complex – alternative pathwayalternative pathway– lectin pathwaylectin pathway
ComplementComplement
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
ComplementComplement
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
ComplementComplement
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
ComplementComplement
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
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
PhagocytosisPhagocytosis
– 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
PhagocytosisPhagocytosis
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
Inflammatory ResponseInflammatory Response
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
Inflammatory ResponseInflammatory Response
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.
Inflammatory ResponseInflammatory Response
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