Immunologic Responses

8/7/2019 Immunologic Responses

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The Immune ResponseThe Immune Response

ImmunityImmunity: ³Free from burden´. Ability of : ³Free from burden´. Ability of

an organism to recognize and defend itself an organism to recognize and defend itself againstagainst specificspecific pathogens or antigens.pathogens or antigens.

AntigenAntigen: Molecules from a pathogen or: Molecules from a pathogen orforeign organism that provoke a specificforeign organism that provoke a specific

immune response.immune response.



Antibodies are Proteins that Recognize Specific Antigens



SerumSerum: Fluid that remains after blood has clotted: Fluid that remains after blood has clottedand cells have been removed.and cells have been removed.

AntiserumAntiserum: Serum containing antibodies to a: Serum containing antibodies to a

specific antigen(s). Obtained from injecting anspecific antigen(s). Obtained from injecting an

animal (horse, rabbit, goat) with antigen (snakeanimal (horse, rabbit, goat) with antigen (snake

venom, botulism or diphtheria toxin).venom, botulism or diphtheria toxin).

SerologySerology: The study of reactions between: The study of reactions between

antibodies and antigens.antibodies and antigens.



Line of Defense Against Infection



Innate or Genetic ImmunityInnate or Genetic Immunity: Immunity an: Immunity an

organism is born with.organism is born with.

Genetically determined.Genetically determined.May be due to lack of receptors or otherMay be due to lack of receptors or other

molecules required for infection.molecules required for infection.

Innate human immunity to canine distemper.Innate human immunity to canine distemper.

Immunity of mice to poliovirus.Immunity of mice to poliovirus.

Adaptive (acquired)Adaptive (acquired) ImmunityImmunity:Immunity:Immunity

that an organismthat an organism d evelopsd evelops during lifetime.during lifetime.

Not genetically determined.Not genetically determined.

May be acquired naturally or artificially.May be acquired naturally or artificially.

Development of immunity to measles in response toDevelopment of immunity to measles in response to

infection or vaccination.infection or vaccination.



Components of Human Immune System



Types of Adaptive ImmunityTypes of Adaptive ImmunityI. Naturally Acquired ImmunityI. Naturally Acquired Immunity: Obtained in: Obtained in

the course of daily life.the course of daily life.A. Naturally Acquired Active ImmunityA. Naturally Acquired Active Immunity::

Ant igensAnt igens or pathogens enter body naturally.or pathogens enter body naturally.

Body generates an immune response to antigens.Body generates an immune response to antigens.

Immunity may be lifelong (chickenpox or mumps)Immunity may be lifelong (chickenpox or mumps)or temporary (influenza or intestinal infections).or temporary (influenza or intestinal infections).

B. Naturally Acquired Passive ImmunityB. Naturally Acquired Passive Immunity::

Ant ibod iesAnt ibod ies pass from mother to fetus via placentapass from mother to fetus via placentaor breast feeding (or breast feeding (colostrumcolostrum).).

No immune response to antigens.No immune response to antigens.

Immunity is usuallyImmunity is usually shortshort--livedlived (weeks to months).(weeks to months).

Protection until child¶s immune system develops.Protection until child¶s immune system develops.



Types of Acquired Immunity (Continued)Types of Acquired Immunity (Continued)II. Artificially Acquired ImmunityII. Artificially Acquired Immunity: Obtained by: Obtained by

receiving a vaccine or immune serum.receiving a vaccine or immune serum.1. Artificially Acquired Active Immunity1. Artificially Acquired Active Immunity::

Ant igensAnt igens are introduced in vaccines (are introduced in vaccines (immunizationimmunization).).

Body generates an immune response to antigens.Body generates an immune response to antigens.

Immunity can be lifelong (oral polio vaccine) or temporaryImmunity can be lifelong (oral polio vaccine) or temporary(tetanus(tetanus toxoidtoxoid).).

2. Artificially Acquired Passive Immunity2. Artificially Acquired Passive Immunity::

PreformedPreformed ant ibod iesant ibod ies ((antiserumantiserum) are introduced into body) are introduced into bodyby injection.by injection.

SnakeSnake antivenomantivenom injection from horses or rabbits.injection from horses or rabbits. Immunity is short lived (half life three weeks).Immunity is short lived (half life three weeks).

Host immune system does not respond to antigens.Host immune system does not respond to antigens.



Duality of Immune SystemDuality of Immune System

I.I. HumoralHumoral (Antibody(Antibody--Mediated) ImmunityMediated) Immunity

Involves production of antibodies against foreignInvolves production of antibodies against foreign

antigens.antigens.

Antibodies are produced by a subset of lymphocytesAntibodies are produced by a subset of lymphocytes

calledcalled B cellsB cells..

B cells that are stimulated will actively secreteB cells that are stimulated will actively secreteantibodies and are calledantibodies and are called pl asma cellspl asma cells..

Antibodies are found inAntibodies are found in extracellular fluidsextracellular fluids (blood(blood

plasma, lymph, mucus, etc.) and the surface of B cells.plasma, lymph, mucus, etc.) and the surface of B cells.

Defense against bacteria, bacterial toxins, and virusesDefense against bacteria, bacterial toxins, and virusesthat circulate freely in body fluids,that circulate freely in body fluids, beforebefore they enterthey enter

cells.cells.

Also cause certain reactions against transplantedAlso cause certain reactions against transplanted

tissue.tissue.



Antibodies are Produced by B Lymphocytes



Duality of Immune System (Continued)Duality of Immune System (Continued)

II. Cell Mediated ImmunityII. Cell Mediated Immunity

Involves specialized set of lymphocytes calledInvolves specialized set of lymphocytes called T cellsT cellsthat recognize foreign antigens on the surface of cells,that recognize foreign antigens on the surface of cells,

organisms, or tissues:organisms, or tissues:

Helper T cellsHelper T cells

Cytotoxic T cells

Cytotoxic T cells

T cellsT cells regulateregulate proliferation and activity of other cellsproliferation and activity of other cells

of the immune system: B cells, macrophages,of the immune system: B cells, macrophages,

neutrophils, etc.neutrophils, etc.

Defense against:Defense against: Bacteria and viruses that are inside host cells and areBacteria and viruses that are inside host cells and are

inaccessible to antibodies.inaccessible to antibodies.

Fungi, protozoa, and helminthsFungi, protozoa, and helminths

Cancer cellsCancer cells

Transplanted tissueTransplanted tissue



Cell Mediated Immunity is Carried Out by T Lymphocytes



AntigensAntigens Most areMost are proteinsproteins or largeor large polysaccharidespolysaccharides fromfrom

a foreign organism.a foreign organism.MicrobesMicrobes: Capsules, cell walls, toxins, viral capsids,: Capsules, cell walls, toxins, viral capsids,

flagella, etc.flagella, etc.

NonmicrobesNonmicrobes: Pollen, egg white , red blood cell: Pollen, egg white , red blood cell

surface molecules, serum proteins, and surfacesurface molecules, serum proteins, and surface

molecules from transplanted tissue.molecules from transplanted tissue.

Lipids and nucleic acids are only antigenic whenLipids and nucleic acids are only antigenic when

combinedcombined with proteins or polysaccharides.with proteins or polysaccharides.

Molecular weight of 10,000 or higher.Molecular weight of 10,000 or higher. HaptenHapten: Small foreign molecule that is not antigenic. Must be: Small foreign molecule that is not antigenic. Must be

coupled to acoupled to a carriercarrier molecule to be antigenic. Once antibodiesmolecule to be antigenic. Once antibodiesare formed they will recognize hapten.are formed they will recognize hapten.



AntigensAntigens

EpitopeEpitope::

Small part of an antigen that interactsSmall part of an antigen that interacts

with an antibody.with an antibody.

Any given antigen may have severalAny given antigen may have several

epitopes.epitopes.

Each epitope is recognized by a differentEach epitope is recognized by a different

antibody.antibody.



Epitopes: Antigen Regions that Interact

with Antibodies



AntibodiesAntibodies

ProteinsProteins that recognize and bind to a particularthat recognize and bind to a particularantigen with very highantigen with very high specifici tyspecifici ty..

Made in response to exposure to the antigen.Made in response to exposure to the antigen.

One virus or microbe may have severalOne virus or microbe may have several ant igenic ant igenic

d et ermi nant si t esd et ermi nant si t es, to which different antibodies, to which different antibodiesmay bind.may bind.

Each antibody has at least two identical sitesEach antibody has at least two identical sites

that bind antigen:that bind antigen: Ant igen bi nd i ng si t esAnt igen bi nd i ng si t es..

Valence of an antibodyValence of an antibody: Number of antigen: Number of antigen

binding sites. Most arebinding sites. Most are bivalentbivalent..

Belong to a group of serum proteins calledBelong to a group of serum proteins called

immunoglobulins (Igs).immunoglobulins (Igs).



Antibody StructureAntibody Structure

MonomerMonomer: A flexible Y: A flexible Y--shaped molecule withshaped molecule withfour protein chains:four protein chains:

2 identical2 identical light light chainschains

2 identical2 identical heavyheavy chainschains

Variable RegionsVariable Regions: Two sections at the end of : Two sections at the end of Y¶s arms. Contain theY¶s arms. Contain the antigen binding sitesantigen binding sites

(Fab)(Fab). Identical on the same antibody, but vary. Identical on the same antibody, but vary

from one antibody to another.from one antibody to another.

Constant RegionsConstant Regions: Stem of monomer and lower: Stem of monomer and lowerparts of Y arms.parts of Y arms.

Fc regionFc region: Stem of monomer only. Important: Stem of monomer only. Important

because they can bind to complement or cells.because they can bind to complement or cells.





Immunoglobulin ClassesImmunoglobulin Classes

I. IgGI. IgG Structure:Structure: MonomerMonomer

Percentage serum antibodies:Percentage serum antibodies: 80%80%

Location:Location: Blood, lymph, intestineBlood, lymph, intestine

Half Half--life in serum:life in serum: 23 days23 days

Complement Fixation:Complement Fixation: YesYes

Placental Transfer:Placental Transfer: YesYes

Known Functions:Known Functions: Enhances phagocytosis,Enhances phagocytosis,

neutralizes toxins and viruses, protects fetus andneutralizes toxins and viruses, protects fetus and

newborn.newborn.




II.II. IgMIgM Structure:Structure: PentamerPentamer

Percentage serum antibodies:Percentage serum antibodies: 55--10%10%

Location:L

ocation:B

lood, lymph,B

cell surface (monomer)B

lood, lymph,B

cell surface (monomer) Half Half--life in serum:life in serum: 5 days5 days

Complement Fixation:Complement Fixation: YesYes

Placental Transfer:Placental Transfer:NoNo

Known Functions:Known Functions: First antibodies producedFirst antibodies produced

during an infection. Effective against microbes andduring an infection. Effective against microbes and

agglutinating antigens.agglutinating antigens.




III.III. IgAIgA Structure:Structure: DimerDimer

Percentage serum antibodies:Percentage serum antibodies: 1010--15%15%

Location:L

ocation: Secretions (tears, saliva, intestine, milk),Secretions (tears, saliva, intestine, milk),blood and lymph.blood and lymph.


Complement Fixation:Complement Fixation: NoNo


Known Functions:Known Functions: Localized protection of Localized protection of mucosal mucosal

surfaces. Provides immunity to infant digestivesurfaces. Provides immunity to infant digestive

tract.tract.




IV. IgDIV. IgD Structure:Structure: MonomerMonomer

Percentage serum antibodies:Percentage serum antibodies: 0.2%0.2%

Location:Location: BB--cell surface, blood, and lymphcell surface, blood, and lymph




Known Functions:Known Functions: In serum function is unknown.In serum function is unknown.

On B cell surface, initiate immune response.On B cell surface, initiate immune response.




V. IgEV. IgE Structure:Structure: MonomerMonomer

Percentage serum antibodies:Percentage serum antibodies: 0.002%0.002%

Location:Location: Bound to mast cells and basophilsBound to mast cells and basophils

throughout body. Blood.throughout body. Blood.




Known Functions:Known Functions: Allergic reactions. PossiblyAllergic reactions. Possibly

lysis of worms.lysis of worms.



How Do B Cells Produce Antibodies?How Do B Cells Produce Antibodies?

B cells develop fromB cells develop from stem cellsstem cells in the bonein the bone

marrow of adults (liver of fetuses).marrow of adults (liver of fetuses).

After maturation B cells migrate to lymphoidAfter maturation B cells migrate to lymphoid

organs (lymph node or spleen).organs (lymph node or spleen).

ClonalClonal SelectionSelection: When a B cell encounters an: When a B cell encounters anantigen it recognizes, it is stimulated and dividesantigen it recognizes, it is stimulated and divides

into many clones calledinto many clones called plasma cellsplasma cells, which, which

actively secrete antibodies.actively secrete antibodies.Each B cell produces antibodies that willEach B cell produces antibodies that will

recognize only one antigenic determinant.recognize only one antigenic determinant.



Clonal Selection of B Cells is Caused

by Antigenic Stimulation



Humoral Immunity (Continued)Humoral Immunity (Continued)

ApoptosisApoptosisProgrammed cell death (³Falling away´).Programmed cell death (³Falling away´).

Human body makes 100 million lymphocytesHuman body makes 100 million lymphocytes

every day. If an equivalent number doesn¶t die,every day. If an equivalent number doesn¶t die,

will develop leukemia.will develop leukemia.

B cells that do not encounter stimulating antigenB cells that do not encounter stimulating antigen

will self will self--destruct and send signals to phagocytesdestruct and send signals to phagocytes

to dispose of their remains.to dispose of their remains.

Many virus infected cells will undergo apoptosis,Many virus infected cells will undergo apoptosis,

to help prevent spread of the infection.to help prevent spread of the infection.




Clonal Selection

Clonal Selection

Clonal SelectionClonal Selection: B cells (and T cells) that: B cells (and T cells) that

encounter stimulating antigen will proliferate intoencounter stimulating antigen will proliferate into

a large group of cells.a large group of cells.

Why don¶t we produce antibodies against ourWhy don¶t we produce antibodies against ourown antigens? We have developedown antigens? We have developed t oler ancet oler ance toto

them.them.

Clonal DeletionClonal Deletion: B and T cells that react against: B and T cells that react against

self self antigens appear to be destroyed during fetalantigens appear to be destroyed during fetal

development. Process is poorly understood.development. Process is poorly understood.



Consequences of AntigenConsequences of Antigen--Antibody BindingAntibody Binding

AntigenAntigen--AntibodyComplexAntibody Complex: Formed when an: Formed when an

antibody binds to an antigen it recognizes.antibody binds to an antigen it recognizes.AffinityAffinity: A measure of binding strength.: A measure of binding strength.

1. Agglutination:1. Agglutination: Antibodies cause antigensAntibodies cause antigens(microbes) to clump together.(microbes) to clump together.

IgM (decavalent) is more effective that IgG (bivalent).IgM (decavalent) is more effective that IgG (bivalent).

HemagglutinationHemagglutination: Agglutination of red blood cells.: Agglutination of red blood cells.Used to determine ABO blood types and to detectUsed to determine ABO blood types and to detectinfluenza and measles viruses.influenza and measles viruses.

2. Opsonization:2. Opsonization: Antigen (microbe) is covered withAntigen (microbe) is covered withantibodies that enhances its ingestion and lysis byantibodies that enhances its ingestion and lysis byphagocytic cells.phagocytic cells.



Consequences of Antibody Binding




3. Neutralization:3. Neutralization: IgG inactivates viruses byIgG inactivates viruses by

binding to their surface and neutralize toxins bybinding to their surface and neutralize toxins by

blocking their active sites.blocking their active sites.

4. Antibody4. Antibody--dependent celldependent cell--mediated cytotoxicity:mediated cytotoxicity:

Used to destroy large organisms (e.g.: worms).Used to destroy large organisms (e.g.: worms).Target organism is coated with antibodies andTarget organism is coated with antibodies and

bombarded with chemicals from nonspecificbombarded with chemicals from nonspecific

immune cells.immune cells.

5. Complement Activation:5. Complement Activation: Both IgG and IgMBoth IgG and IgMtrigger the complement system which results intrigger the complement system which results in

cell lysis and inflammation.cell lysis and inflammation.





Immunological MemoryImmunological Memory

Antibody Titer:Antibody Titer: The amount of antibody in theThe amount of antibody in theserum.serum.

Pattern of Antibody Levels During InfectionPattern of Antibody Levels During Infection

Primary Response:Primary Response:

AfterAfter i ni t i al i ni t i al exposure to antigen, no antibodies areexposure to antigen, no antibodies arefound in serum for several days.found in serum for several days.

A gradual increase in titer, first of A gradual increase in titer, first of IgMIgM and thenand then

of of IgGIgG is observed.is observed.

Most B cells become plasma cells, but some B cellsMost B cells become plasma cells, but some B cells

become long livingbecome long living memor y cellsmemor y cells..

Gradual decline of antibodies follows.Gradual decline of antibodies follows.



Immunological Memory (Continued)Immunological Memory (Continued)

Secondary Response:Secondary Response:

Subsequent exposure to the same antigen displaysSubsequent exposure to the same antigen displaysa faster and more intense antibody response.a faster and more intense antibody response.

Increased antibody response is due to theIncreased antibody response is due to the

existence of memory cells, which rapidly produceexistence of memory cells, which rapidly produce

plasma cells upon antigen stimulation.plasma cells upon antigen stimulation.



Antibody Response After Exposure to Antigen



T Cells and Cell Mediated ImmunityT Cells and Cell Mediated Immunity

Antigens that stimulate this response are mainlyAntigens that stimulate this response are mainly

i nt r acellul ar i nt r acellul ar ..

Requires constant presence of antigen to remainRequires constant presence of antigen to remain

effective.effective.

UnlikeUnlike humoralhumoral immunity, cell mediated immunityimmunity, cell mediated immunityis not transferred to the fetus.is not transferred to the fetus.

Cytokines:Cytokines: Chemical messengers of immune cells.Chemical messengers of immune cells.

Over 100 have been identified.Over 100 have been identified.

Stimulate and/or regulate immune responses.Stimulate and/or regulate immune responses.

Interleukins:Interleukins: Communication between WBCs.Communication between WBCs.

InterferonsInterferons: Protect against viral infections.: Protect against viral infections.

Chemokines

Chemokines: Attract W

BCs to infected areas.: Attract W

BCs to infected areas.




CellularComponents of Immunity:CellularComponents of Immunity:

T cells are key cellular component of immunity.T cells are key cellular component of immunity.

T cells have an antigen receptor that recognizesT cells have an antigen receptor that recognizes

and reacts to a specific antigen (and reacts to a specific antigen (T cell receptorT cell receptor).).

T cell receptor only recognize antigens combinedT cell receptor only recognize antigens combined

withwith majormajor histocompatabilityhistocompatability (MHC) proteins(MHC) proteins onon

thethe surfacesurface of cells.of cells.

MHC Class I: Found on all cells.MHC Class I: Found on all cells.

MHC

C

lass II: Found on phagocytes.MHC

C

lass II: Found on phagocytes.Clonal selection increases number of T cells.Clonal selection increases number of T cells.



T Cells Only Recognize Antigen Associated

with MHC Molecules on Cell Surfaces




Types of T cellsTypes of T cells

1. T Helper (T1. T Helper (THH) Cells:) Cells: Central role in immuneCentral role in immuneresponse.response.

Most are CD4Most are CD4++

Recognize antigen on the surface of antigen presentingRecognize antigen on the surface of antigen presenting

cells (e.g.: macrophage).cells (e.g.: macrophage).

Activate macrophagesActivate macrophages

Induce formation of cytotoxic T cellsInduce formation of cytotoxic T cells

Stimulate B cells to produce antibodies.Stimulate B cells to produce antibodies.



Central Role of Helper T Cells



Types of T cells (Continued)Types of T cells (Continued)2. Cytotoxic T (Tc) Cells:2. Cytotoxic T (Tc) Cells: Destroy target cells.Destroy target cells.

Most are CD4 negative (CD4Most are CD4 negative (CD4 --).).

Recognize antigens on the surface of all cells:Recognize antigens on the surface of all cells:

�� Kill host cells that are infected with viruses or bacteria.Kill host cells that are infected with viruses or bacteria.

�� Recognize and kill cancer cells.Recognize and kill cancer cells.

�� Recognize and destroy transplanted tissue.Recognize and destroy transplanted tissue.

Release protein calledRelease protein called perfori nperfori n which forms a pore inwhich forms a pore in

target cell, causing lysis of infected cells.target cell, causing lysis of infected cells.

UndergoUndergo apoptosisapoptosis when stimulating antigen is gone.when stimulating antigen is gone.



Cytotoxic T Cells Lyse Infected Cells



Types of T cells (Continued)Types of T cells (Continued)3. Delayed Hypersensitivity T (T3. Delayed Hypersensitivity T (TDD) Cells:) Cells: Mostly TMostly T

helper and a few cytotoxic T cells that arehelper and a few cytotoxic T cells that areinvolved in some allergic reactions (poison ivy)involved in some allergic reactions (poison ivy)

and rejection of transplanted tissue.and rejection of transplanted tissue.

4. T Suppressor (Ts) Cells:4. T Suppressor (Ts) Cells: May shut downMay shut down

immune response.immune response.



Nonspecific Cellular ComponentsNonspecific Cellular Components1. Activated Macrophages:1. Activated Macrophages: Stimulated phagocytes.Stimulated phagocytes.

Stimulated by ingestion of antigenStimulated by ingestion of antigen

Larger and more effective phagocytes.Larger and more effective phagocytes.

Enhanced ability to eliminate intracellular bacteria,Enhanced ability to eliminate intracellular bacteria,

virusvirus--infected and cancerous cells.infected and cancerous cells.

2. Natural Killer (NK) Cells:2. Natural Killer (NK) Cells:

Lymphocytes that destroy virus infected and tumorLymphocytes that destroy virus infected and tumor

cells.cells.

Not specific. Don¶t require antigen stimulation.Not specific. Don¶t require antigen stimulation.

Not phagocytic, but must contact cell in order to lyse it.Not phagocytic, but must contact cell in order to lyse it.



Overview of the Immune Response

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Immunologic Responses