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The Adaptive Immune ResponseThe Adaptive Immune Response“Match me perfectly and I’m neutralized”“Match me perfectly and I’m neutralized”

Kathy HuschleKathy Huschle

Northland Community and Technical CollegeNorthland Community and Technical College

Adaptive Immune ResponseAdaptive Immune Response

in contrast to the innate immune response which we are in contrast to the innate immune response which we are basically born with, the adaptive immune response is an basically born with, the adaptive immune response is an ever developing systemever developing system– it continues to mature throughout our lifeit continues to mature throughout our life


– in most cases as each new microbial in most cases as each new microbial invader is encountered, our adaptive invader is encountered, our adaptive immune response initiates a specific immune response initiates a specific attack against the invaderattack against the invader

– generally this invader is remembered generally this invader is remembered and that and that “memory”“memory” is readily available is readily available in the case of a second or subsequent in the case of a second or subsequent attack from the same invaderattack from the same invader


this system is an extremely complex system to this system is an extremely complex system to which we will attempt to gain a basic understandwhich we will attempt to gain a basic understand

immunologists are continually discovering many immunologists are continually discovering many facts about the adaptive immune responsefacts about the adaptive immune response


the adaptive immune response the adaptive immune response – is learned or acquiredis learned or acquired– recognizes specific substances foreign to the recognizes specific substances foreign to the

bodybody– is essential for lifeis essential for life


other terms used for the adaptive immune response other terms used for the adaptive immune response includeinclude– acquired immunityacquired immunity– specific immunityspecific immunity

though at one time thought to function exclusive of the though at one time thought to function exclusive of the innate immune system, research is now discovering a innate immune system, research is now discovering a correlation between the two systemscorrelation between the two systems

regardless of a correlation or not, the regardless of a correlation or not, the failure of our failure of our immune system results in mortalityimmune system results in mortality


adaptive immune response is characterized byadaptive immune response is characterized by– specificityspecificity– memorymemory– learned ability to recognize (acquired) pathogens learned ability to recognize (acquired) pathogens

which allows the body to usually only suffer once which allows the body to usually only suffer once from that particular pathogenfrom that particular pathogen

Components of the Adaptive Immune Components of the Adaptive Immune SystemSystem

antigensantigens

antibodiesantibodies

lymph systemlymph system

lymphocyteslymphocytes– B cellsB cells– T cellsT cells– NK cell (Natural Killer)NK cell (Natural Killer)

Antigen

Antibody

B cell

T cellNK cell

AntigensAntigens

the term antigen derives from the two words the term antigen derives from the two words antiantibody body genegeneratorrator

most antigens are proteins or large polysaccharidesmost antigens are proteins or large polysaccharides

AntigensAntigens

often a component of invading often a component of invading microbes, such as the capsule, microbes, such as the capsule, cell wall, flagella, toxincell wall, flagella, toxin– particular chemical that will particular chemical that will

activate the adaptive activate the adaptive immune responseimmune response

Antigens found in autologous tumor

AntigensAntigens

invading microbes can invading microbes can have many antigens on have many antigens on its surfaceits surface

pathogen

AntigensAntigens

when and antigen elicits an immune response it is when and antigen elicits an immune response it is often referred to as a immunogenoften referred to as a immunogen

epitope is the reactive portion of the antigen that reacts epitope is the reactive portion of the antigen that reacts chemically with an antibody to form the antigen-chemically with an antibody to form the antigen-antibody complex or immune complexantibody complex or immune complex

AntigensAntigens

two essential properties of antigens includetwo essential properties of antigens include– immunogenicityimmunogenicity

the ability to stimulate immune systemthe ability to stimulate immune system

antigen-antibody complex

AntigensAntigens

– specific reactivityspecific reactivity

the ability to react with effector molecules the ability to react with effector molecules (antibody) to form an antigen-antibody complex(antibody) to form an antigen-antibody complex

Antigens in red with green borders

AntibodiesAntibodies

glycoproteins that are also referred to as glycoproteins that are also referred to as immunoglobiulinsimmunoglobiulins

basic structure is a Y shaped molecule with 2 functional basic structure is a Y shaped molecule with 2 functional partsparts– Fab regionFab region– Fc regionFc region

Fab regionFc region


Fab regionFab region– this is the part of the antibody that binds to the this is the part of the antibody that binds to the

antigenantigen

Fc regionFc region– the stem of the antibody that functions as a “red flag”the stem of the antibody that functions as a “red flag”

notifies the rest of the immune system: “here I am, notifies the rest of the immune system: “here I am, come and help”come and help”

Fab regionsFab regions

The Fab portion of IgG binds to epitopes of a capsule. The Fab portion of IgG binds to epitopes of a capsule.

The Fc portion can now attach the capsule to Fc receptors The Fc portion can now attach the capsule to Fc receptors

on phagocytes for enhanced attachment. Once attached to on phagocytes for enhanced attachment. Once attached to

the phagocyte by way of IgG, the encapsulated bacterium the phagocyte by way of IgG, the encapsulated bacterium

can be engulfed more efficiently and placed in a phagosomecan be engulfed more efficiently and placed in a phagosome


protection gained from the formation of antigen-protection gained from the formation of antigen-antibody complexes basically comes down to the antibody complexes basically comes down to the tagging of foreign cells and molecules for destruction tagging of foreign cells and molecules for destruction by phagocytes and complementby phagocytes and complement

Antibodies shown in different stains


the antibody molecule is not the antibody molecule is not damaging to the antigendamaging to the antigen

Melanoma antigens


foreign organisms and toxins foreign organisms and toxins are rendered harmless byare rendered harmless by– neutralizationneutralization– immobilization and immobilization and

prevention of adherenceprevention of adherence– agglutination and agglutination and

precipitationprecipitation– opsonizationopsonization– complement activationcomplement activation– antibody-dependent antibody-dependent

cellular cytosis (ADCC)cellular cytosis (ADCC)Respiratory syncytial virus antigens


neutralizationneutralization– blocks the adhesion of bacteria and blocks the adhesion of bacteria and

viruses by bathing the surface of the viruses by bathing the surface of the cell with antibodycell with antibody

immobilization and prevention of immobilization and prevention of adherenceadherence– antibodies binding to structures such antibodies binding to structures such

as flagella and pili can interfere with as flagella and pili can interfere with mobility and attachmentmobility and attachment

AntibodiesAntibodiesagglutination and precipitationagglutination and precipitation– enhances phagocytosis by enhances phagocytosis by

gathering antigens into clumpsgathering antigens into clumps

opsonizationopsonization– coating an antigen with antibody coating an antigen with antibody

enhances phagocytosisenhances phagocytosis


complement activationcomplement activation– enhances cell destruction by cell enhances cell destruction by cell

lysislysis

antibody-dependent cellular antibody-dependent cellular cytotxicitycytotxicity– antibodies attach to target cells antibodies attach to target cells

causing destruction by non-causing destruction by non-specific immune system cellsspecific immune system cells




there are 5 classes of immunoglobulins there are 5 classes of immunoglobulins – each class plays a different role in the immune each class plays a different role in the immune

responseresponse

IgGIgG

IgMIgM

IgAIgA

IgDIgD

IgEIgE


IgGIgG– enhances phagocytosisenhances phagocytosis– neutralizes toxins and neutralizes toxins and

virusesviruses– protects the fetus and protects the fetus and

newbornnewborn

only immunoglobulin only immunoglobulin that is transferred that is transferred across the placentaacross the placenta


IgGIgG– circulates in the blood, circulates in the blood,

but can easily exit to but can easily exit to the tissuesthe tissues

– most abundant most abundant circulating antibodycirculating antibody

IgG circulating in tissue

IgGIgG

IgG reacts with epitopes on the host cellIgG reacts with epitopes on the host cellmembrane. Phagocytes then bind to the membrane. Phagocytes then bind to the Fc portion of the IgG and discharge theirFc portion of the IgG and discharge theirlysosomes. lysosomes.


IgAIgA– provides localized protection on provides localized protection on

mucosal surfacesmucosal surfaces– found in mucus, tears, saliva, found in mucus, tears, saliva,

sweat, blood, human milksweat, blood, human milk– protects surface tissues and protects surface tissues and

prevents adherence of prevents adherence of microorganismsmicroorganisms

this is important in respiratory, this is important in respiratory, gastrointestinal and gastrointestinal and genitourinary tract infectionsgenitourinary tract infections


IgMIgM– especially effective against especially effective against

microorganisms and microorganisms and clumping antigensclumping antigens

– these are the first these are the first antibodies produced in antibodies produced in response to a mild response to a mild infectioninfection

– are circulating antibodies are circulating antibodies found in the circulatory found in the circulatory system with IgGsystem with IgG

IgMIgM

IgG or IgM reacts with epitopes on the host cell IgG or IgM reacts with epitopes on the host cell membrane and activates the classical complement membrane and activates the classical complement pathway. Membrane attack complex (MAC) then pathway. Membrane attack complex (MAC) then causes lysis of the cell. causes lysis of the cell.


IgDIgD– function of these antibodies is not yet fully definedfunction of these antibodies is not yet fully defined– it’s presence on B cells functions in the initiation of an it’s presence on B cells functions in the initiation of an

immune responseimmune response


IgEIgE– antibodies responsible antibodies responsible

for allergic reactionfor allergic reaction– possibly involved in the possibly involved in the

lysis of parasitic wormslysis of parasitic worms– found in the blood serumfound in the blood serum– plays a role in the plays a role in the

initiation of the initiation of the inflammatory responseinflammatory response

Lymphoid SystemLymphoid System

in regards to the immune in regards to the immune system the lymphatic system the lymphatic system consists of tissues system consists of tissues and organs that are and organs that are designed and located to designed and located to convey the B and T cells convey the B and T cells into contact with all antigens into contact with all antigens that enter the bodythat enter the body


this process is accomplished this process is accomplished with thewith the– lymphatic vesselslymphatic vessels– fluid of the lymphoid fluid of the lymphoid

system called lymphsystem called lymph– secondary lymph organs secondary lymph organs

such as tonsils, spleen, such as tonsils, spleen, lymph nodeslymph nodes


– primary lymph organsprimary lymph organsbone marrow: the location of stem cells bone marrow: the location of stem cells that will eventually become B and T that will eventually become B and T cells, B cells mature in the bone cells, B cells mature in the bone marrowmarrowthymus: maturation of the T cellsthymus: maturation of the T cells

Healthy bone marrow Bone marrow with leukemia

Lymph node


notice how completely our notice how completely our body is covered by the body is covered by the lymphoid system lymphoid system

LymphocytesLymphocytes

critical part of immune system responsible forcritical part of immune system responsible for– detection of foreign antigensdetection of foreign antigens– activate immune systemactivate immune system

B lymphocytesB lymphocytes

T lymphocytesT lymphocytes

natural killer cells (NK cells)natural killer cells (NK cells)

B lymphocytes: B cellsB lymphocytes: B cells

antibody producing cells antibody producing cells that respond to an that respond to an antigen stimulationantigen stimulation

develop from stem cells develop from stem cells located in the red bone located in the red bone marrow of adults and the marrow of adults and the liver of a fetusliver of a fetus

B Cells dividing

B lymphocytes: B cellsB lymphocytes: B cells

following maturation, they following maturation, they migrate to the lymphatic migrate to the lymphatic tissuetissue

B cell in lymph node

B lymphocytes: B cellsB lymphocytes: B cellsonce in place in the lymphoid once in place in the lymphoid organs, the B cells recognize organs, the B cells recognize antigens by means of the antigens by means of the antigen receptors found on their antigen receptors found on their cell surfacescell surfaces

basis for antibody-mediated basis for antibody-mediated immunityimmunity

B indicates a B cell

HIV antigens in yellowB cells in red

B cellsB cells

T lymphocytes: T cellsT lymphocytes: T cells

key cellular component of key cellular component of immunityimmunity

develop from stem cells develop from stem cells found in the bone marrowfound in the bone marrow

precursors to T cells precursors to T cells migrate to the thymus, migrate to the thymus, where they reach maturitywhere they reach maturity

human T cells

T lymphocytes: T cellsT lymphocytes: T cells

following maturity, T cells migrate following maturity, T cells migrate to various lymph organs where to various lymph organs where they await contact with antigensthey await contact with antigens

basis for cell-mediated immunitybasis for cell-mediated immunity

T cells (on left – orange, on right – gray) killingcancer cells (on left- mauve.on right – red)

T cellsT cells

Natural Killer Natural Killer CellsCells

these cells are not immunologically specificthese cells are not immunologically specific– they do not need to be stimulated by an antigenthey do not need to be stimulated by an antigen

Natural Killer CellsNatural Killer Cells

capable of destroying other cells, particularly capable of destroying other cells, particularly viruses-infected cells and tumor cellsviruses-infected cells and tumor cells

also can attack large parasitesalso can attack large parasites

Clonal Selection of LymphocytesClonal Selection of Lymphocytes

speaks to the ability of B cells and T cells to speaks to the ability of B cells and T cells to differentiate to a population of cells capable of differentiate to a population of cells capable of recognizing an infinite number of antigensrecognizing an infinite number of antigens– it is estimated that the human body has it is estimated that the human body has

approximately 1 billion B cells, yet each individual approximately 1 billion B cells, yet each individual cell is only capable of recognizing and responding cell is only capable of recognizing and responding to one antigento one antigen

B cell differentiation


terms used to define various stages of clonal terms used to define various stages of clonal selection includeselection include– immatureimmature– naïvenaïve– activatedactivated– effectoreffector– memorymemory


immature lymphocytesimmature lymphocytes– have not fully developed their antigen-specific have not fully developed their antigen-specific

receptorreceptor

naïve lymphocytesnaïve lymphocytes– have an antigen receptor, but have not have an antigen receptor, but have not

encountered the antigenencountered the antigen

immature lymphocyte


activated lymphocytesactivated lymphocytes– have received confirmation of the danger of the have received confirmation of the danger of the

antigen and are able to proliferate more antigen and are able to proliferate more lymphocytes specific for that antigenlymphocytes specific for that antigen

effector lymphocyteseffector lymphocytes– descendents of activated lymphocytesdescendents of activated lymphocytes

Activated lymphocyte


memory lymphocytesmemory lymphocytes– long-lived descendents of activated lymphocyteslong-lived descendents of activated lymphocytes– can revert back to activated lymphocytes with can revert back to activated lymphocytes with

stimulation from the same antigenstimulation from the same antigen

Antibody-Mediated ImmunityAntibody-Mediated Immunity

humoral or antibody-mediated immunity involves humoral or antibody-mediated immunity involves antibodies that are produced by B cellsantibodies that are produced by B cells– the term humoral is derived from the word “humors”, the term humoral is derived from the word “humors”,

which is Latin for fluidwhich is Latin for fluid

in response to foreign antigens, the B cell is activated to in response to foreign antigens, the B cell is activated to produce a clone of plasma cells and memory cellsproduce a clone of plasma cells and memory cells– plasma cells secrete antibodiesplasma cells secrete antibodies– memory cells recognize pathogens from previous memory cells recognize pathogens from previous

encountersencounters

B memory cells are long lived and are ready to B memory cells are long lived and are ready to mount an attack the next time that specific antigen mount an attack the next time that specific antigen presents itselfpresents itself

Primary & Secondary ResponsePrimary & Secondary Response

The body can make low levels of soluble antibody about one week after exposure to antigen. However, a second exposure to antigen produces a much faster response, and several orders of magnitude higher levels of antibody. The ability of antibody to bind antigen also increases in the secondary response. The memory of antigen and stimulated response is the basis for vaccination


the antigen-antibody the antigen-antibody complexes that are formed as a complexes that are formed as a result of antibodies produce by result of antibodies produce by B plasma cells attract B plasma cells attract phagocytesphagocytes

Bacteria in green


phagocytosis destroys the pathogen and control of phagocytosis destroys the pathogen and control of the disease is accomplishedthe disease is accomplished

Bacteria

Cell-Mediated ImmunityCell-Mediated Immunity

cell-mediated immunity involves specialized cell-mediated immunity involves specialized lymphocytes that respond to intracellular antigenslymphocytes that respond to intracellular antigens

T cells are responsible for managing cell-mediated T cells are responsible for managing cell-mediated immunityimmunity– after maturation in the thymus, T cells after maturation in the thymus, T cells

differentiate into 2 groupsdifferentiate into 2 groups

T-cytotoxic cells and T helper cellsT-cytotoxic cells and T helper cells

Cytotoxic T cells Helper T cell


recognizes modified host cells recognizes modified host cells (abnormal cells)(abnormal cells)– cell-mediated immunity is critical cell-mediated immunity is critical

to controlling infections where to controlling infections where pathogens reproduce in human pathogens reproduce in human cellcell

viruses, bacteria (rickettes), viruses, bacteria (rickettes), protozoaprotozoa

important role in recognizing important role in recognizing and destroying abnormal and destroying abnormal cells, such as tumor cellscells, such as tumor cells

T cells attacking cancer


– T cells do not recognize free T cells do not recognize free antigens, the antigen must be antigens, the antigen must be presented by a modified host cellpresented by a modified host cell

augments antibody-mediated augments antibody-mediated immunityimmunity– eliminates cells infected with eliminates cells infected with

virusesviruses– antibodies can’t penetrate a virus antibodies can’t penetrate a virus

within a host cellwithin a host cell

T cells


response to intracellular agents response to intracellular agents includesincludes– antigen presentation antigen presentation

the antigen must be processed the antigen must be processed (degraded) and then individual (degraded) and then individual peptides are displayed on the peptides are displayed on the surface of a glycoprotein called surface of a glycoprotein called a major histocompatibility a major histocompatibility complex (MHC) moleculecomplex (MHC) molecule

this antigen processing is done this antigen processing is done by antigen presenting cell by antigen presenting cell (APC)(APC)


cytotoxic T cellscytotoxic T cells recognize the non-self cell and recognize the non-self cell and induce apoptosis (cell self death) in the viral infected induce apoptosis (cell self death) in the viral infected or other microbial infected cellor other microbial infected cell– this process also recognizes cancer cells and this process also recognizes cancer cells and

destroys themdestroys them– unfortunately this process also recognizes and unfortunately this process also recognizes and

destroys non-self tissue or organ transplantsdestroys non-self tissue or organ transplants


T-helper cells, often referred T-helper cells, often referred to as CD4 cells, are to as CD4 cells, are responsible for the “second responsible for the “second opinion” in immunityopinion” in immunity– T-helper cells judge the T-helper cells judge the

significance of the significance of the antigen presented by the antigen presented by the antigen-presenting cells antigen-presenting cells (APC)(APC)

Cell-Mediated Cell-Mediated ImmunityImmunity

– after binding to an APC, T- helper after binding to an APC, T- helper cells secrete cytokines that cells secrete cytokines that activate other T cells and B cellsactivate other T cells and B cells

interleukin-2interleukin-2

macrophage chemotactic macrophage chemotactic factorfactor

migration inhibition factormigration inhibition factor

macrophage activating factormacrophage activating factor

macrophage colony macrophage colony stimulating factorstimulating factor


interleukin-2interleukin-2– stimulates the production of stimulates the production of

more T cellsmore T cells

macrophage chemotactic factor macrophage chemotactic factor (MCF)(MCF)– attracts macrophages attracts macrophages

(phagocytes) to the site of (phagocytes) to the site of infection or abnormalityinfection or abnormality

migration inhibition factor (MIF)migration inhibition factor (MIF)– once at the infection site, MIF once at the infection site, MIF

inhibits the macrophages from inhibits the macrophages from migrating elsewhere in the bodymigrating elsewhere in the body

T cell (yellow) attractingMacrophage (blue)


macrophage activating factor (MAF)macrophage activating factor (MAF)– once at the infection site, MAF alters the function once at the infection site, MAF alters the function

of the macrophagesof the macrophages– increases their lysosomal activitiesincreases their lysosomal activities

increases their ability to killincreases their ability to kill

Macrophage usingpseudopodia to grabpathogen

Macrophage ingesting bacteria


macrophage colony stimulating factor (CSF)macrophage colony stimulating factor (CSF)– regulates the production of macrophages at the regulates the production of macrophages at the

sitesite

Macrophage and T cell

Macrophage & E.coli

T helper cells also play a role in T helper cells also play a role in activating Bactivating B cellscells in antibody-mediated immunity in antibody-mediated immunity

T-Helper CellsT-Helper Cells

Helper T cellsHelper T cells

Click icon to learn more about T-cell dependent antigens

Overview of Antibody-Mediated Overview of Antibody-Mediated ImmunityImmunity

initial response (bacteria with antigens enters the body)initial response (bacteria with antigens enters the body)

B cells recognizeB cells recognize

differentiate into plasma and memory cellsdifferentiate into plasma and memory cells

memory: recurring exposuresmemory: recurring exposures

plasma produce antibodiesplasma produce antibodies

antigen/antibody complex formsantigen/antibody complex forms

phagocytosisphagocytosis

control of diseasecontrol of disease

Overview of Cell-MediatedOverview of Cell-Mediated

modified host cell arrivesmodified host cell arrives

T cells activatedT cells activated

secrete cytokinessecrete cytokines

increase of T cell reproductionincrease of T cell reproduction

attraction of macrophages (MCF)attraction of macrophages (MCF)

inhibit migration (MIF)inhibit migration (MIF)

activate phagocytosis (MAF)activate phagocytosis (MAF)

control of diseasecontrol of disease

Overview of ImmunityOverview of Immunity

SummarySummary