Fundamental Immunology IBRO-Fogarty May 2007 · Fundamental Immunology (Introduction to the Immune System) By BByy By ... The scope of the lecture ... that are always present and

FogartyFogartyFogartyFogartyFogartyFogartyFogartyFogarty--------IBRO SchoolIBRO SchoolIBRO SchoolIBRO SchoolIBRO SchoolIBRO SchoolIBRO SchoolIBRO School

NairobiNairobiNairobiNairobiNairobiNairobiNairobiNairobi--------KENYAKENYAKENYAKENYAKENYAKENYAKENYAKENYA

May 22May 22May 22May 22May 22May 22May 22May 22ndndndndndndndnd –––––––– 2525252525252525thththththththth 20072007200720072007200720072007

Fundamental ImmunologyFundamental ImmunologyFundamental ImmunologyFundamental ImmunologyFundamental ImmunologyFundamental ImmunologyFundamental ImmunologyFundamental Immunology

(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)(Introduction to the Immune System)By By By By By By By By

Ahmed ElAhmed ElAhmed ElAhmed ElAhmed ElAhmed ElAhmed ElAhmed El--------Gohary, M.D.Gohary, M.D.Gohary, M.D.Gohary, M.D.Gohary, M.D.Gohary, M.D.Gohary, M.D.Gohary, M.D.

Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,Faculty of Medicine, Suez canal University,

IsmailiaIsmailiaIsmailiaIsmailiaIsmailiaIsmailiaIsmailiaIsmailia –––––––– EGYPTEGYPTEGYPTEGYPTEGYPTEGYPTEGYPTEGYPT

The scope of the lectureThe scope of the lectureThe scope of the lectureThe scope of the lectureThe scope of the lectureThe scope of the lectureThe scope of the lectureThe scope of the lecture

• Introduction to the Immune system

• Innate Immunity

• Antigen Capture and Presentation to

Lymphocytes

• Antigen Recognition in the adaptive Immune

System

The Immune systemThe Immune system

• Immunity is the resistance to diseases,

specifically infectious diseases

• The physiological function of the immune

system is to prevent infections and to

eradicate established infections.

• The impact of immunology goes beyond infectious diseases.

• The immune system recognizes and respond to

tissue grafts,

• Defense against tumors,

• Abnormal immune responses are the causes of

many diseases.

The Immune systemThe Immune system

Introduction to Immune system

Types of Adaptive Types of Adaptive Types of Adaptive Types of Adaptive Types of Adaptive Types of Adaptive Types of Adaptive Types of Adaptive

ImmunityImmunityImmunityImmunityImmunityImmunityImmunityImmunity

Properties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive Immunity

Properties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive ImmunityProperties of Adaptive Immunity

The The The The The The The The ClonalClonalClonalClonalClonalClonalClonalClonal Selection HypothesisSelection HypothesisSelection HypothesisSelection HypothesisSelection HypothesisSelection HypothesisSelection HypothesisSelection Hypothesis

Phases of Immune ResponsesPhases of Immune ResponsesPhases of Immune ResponsesPhases of Immune ResponsesPhases of Immune ResponsesPhases of Immune ResponsesPhases of Immune ResponsesPhases of Immune Responses

The twoThe twoThe twoThe twoThe twoThe twoThe twoThe two--------signal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activationsignal requirement for lymphocyte activation

Principal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune SystemPrincipal cells of the Immune System

Classes of LymphocytesClasses of LymphocytesClasses of LymphocytesClasses of LymphocytesClasses of LymphocytesClasses of LymphocytesClasses of LymphocytesClasses of Lymphocytes

Maturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of Lymphocytes

Stages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of LymphocytesStages in the life History of Lymphocytes

Lymph Node Lymph Node

MorphologyMorphology

T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.T & B Lymphocytes in peripheral L.N.

Recirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T LymphocytesRecirculation of T Lymphocytes

• The physiologic function of the immune system is to protect individuals against infections.

• Innate immunity is the early line of defense, mediated by cells and molecules that are always present and ready to eliminate infectious microbes.

• Adaptive immunity is the form of immunity that is stimulated by microbes, has a fine specificity for foreign substances, and responds more effectively against each successive exposure to a microbe.

• Lymphocytes are the cells of adaptive immunity, and the only cells with clonally distributed receptors for antigens.

• Adaptive immunity consists of humoral immunity, in which antibodies neutralize and eradicate extracellular microbes and toxins, and cell-mediated immunity, in which T lymphocytes eradicate intracellular microbes.

• Adaptive immune responses consist of sequential phases: antigen recognition by lymphocytes, activation of the lymphocytes to proliferate and to differentiate into effector and memory cells, elimination of the microbes, decline of the immune response, and long-lived memory.

Summary Summary Summary Summary Summary Summary Summary Summary

• B lymphocytes express membrane antibodies that recognize antigens, and effector B cells �� antibodies that neutralize and eliminate the antigen.

• T lymphocytes recognize peptide fragments of protein antigens displayed on other cells. Helper T lymphocytes �� activate phagocytes to destroy ingested microbes and activate B lymphocytes to produce antibodies. Cytolytic(cytotoxic) T lymphocytes kill infected cells harboring microbes in the cytoplasm.

• Antigen-presenting cells capture antigens of microbes that enter throughepithelia, concentrate these antigens in lymphoid organs, and display the antigens for recognition by T cells.

• Lymphocytes and antigen-presenting cells are organized in peripheral lymphoid organs, where immune responses are initiated and develop.

• Naive lymphocytes circulate through the peripheral lymphoid organs searching for foreign antigens. Effector T lymphocytes migrate to peripheral sites of infection, where they function to eliminate infectious microbes. Effector B lymphocytes remain in lymphoid organs and the bone marrow, from where they secrete antibodies that enter the circulation and find and eliminate microbes.

Microbe Microbe RecogRecog..

Slide 21

MSOffice13 , 5/11/2007

Epithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate ImmunityEpithelia in Innate Immunity

Circulating phagocytes:

neutrophils and monocytes

Circulating phagocytes:

neutrophils and monocytes

Migration of blood Migration of blood Migration of blood Migration of blood

leukocytes to sites leukocytes to sites leukocytes to sites leukocytes to sites

of infectionof infectionof infectionof infection

Receptors and responses of phagocytes

MSOffice14

Slide 26

MSOffice14 Neutrophils and macrophages recognize microbes in the blood and extravascular tissues by surface receptors that are specific for microbial products. There are several different types of receptors, specific for different structures or patterns that are frequently found on microbial molecules. Toll-like receptors (TLRs) are homologous to a Drosophila protein called Toll, which is essential for protecting the flies against infections. TLRs are specific for different components of microbes. For instance, TLR-2 is essential for macrophage responses to several bacterial lipoglycans, TLR-4 for bacterial lipopolysaccharide (LPS, or endotoxin), TLR-5 for a component of bacterial flagella called flagellin, and TLR-9 for unmethylated CpG nucleotides also found in bacteria. Signals generated by engagement of TLRs activate a transcription factor called NF-κB (nuclear factor κB), which stimulates production of cytokines, enzymes, and other proteins involved in the anti-microbial functions of activated phagocytes. , 5/23/2007

• Neutrophils and macrophages recognize microbes in the blood and extravascular tissues by surface receptors that are specific for microbial products.

• There are several different types of receptors, specific for different structures or patterns that are frequently found on microbial molecules. – Toll-like receptors (TLRs) are homologous to a Drosophila

protein called Toll, which is essential for protecting the flies against infections. TLRs are specific for different components of microbes. For instance,

• TLR-2 is essential for macrophage responses to several bacterial lipoglycans,

• TLR-4 for bacterial lipopolysaccharide (LPS, or endotoxin),

• TLR-5 for a component of bacterial flagella called flagellin, and

• TLR-9 for unmethylated CpG nucleotides also found in bacteria.

– Signals generated by engagement of TLRs activate a transcription factor called NF-κB (nuclear factor κB), which stimulates production of cytokines, enzymes, and other proteins involved inthe anti-microbial functions of activated phagocytes.

Phagocytosis Phagocytosis Phagocytosis Phagocytosis Phagocytosis Phagocytosis Phagocytosis Phagocytosis

and and and and and and and and

intracellular intracellular intracellular intracellular intracellular intracellular intracellular intracellular

killing of killing of killing of killing of killing of killing of killing of killing of

microbesmicrobesmicrobesmicrobesmicrobesmicrobesmicrobesmicrobes

Functions of activated Functions of activated Functions of activated Functions of activated Functions of activated Functions of activated Functions of activated Functions of activated

macrophages.macrophages.macrophages.macrophages.macrophages.macrophages.macrophages.macrophages.

Natural Killer CellsNatural Killer CellsNatural Killer CellsNatural Killer CellsNatural Killer CellsNatural Killer CellsNatural Killer CellsNatural Killer Cells

The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells The Function of Inhibitory Receptors of NK Cells

The Complement System The Complement System The Complement System The Complement System The Complement System The Complement System The Complement System The Complement System

Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity Cytokines of Innate Immunity

Cytokines of innate immunityCytokines of innate immunityCytokines of innate immunityCytokines of innate immunityCytokines of innate immunityCytokines of innate immunityCytokines of innate immunityCytokines of innate immunity

Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes Evasion of Innate Immunity by Microbes

The role The role The role The role The role The role The role The role

of innate of innate of innate of innate of innate of innate of innate of innate

immunity in immunity in immunity in immunity in immunity in immunity in immunity in immunity in

stimulating stimulating stimulating stimulating stimulating stimulating stimulating stimulating

adaptive adaptive adaptive adaptive adaptive adaptive adaptive adaptive

immune immune immune immune immune immune immune immune

responsesresponsesresponsesresponsesresponsesresponsesresponsesresponses

• All All All All multicellularmulticellularmulticellularmulticellular organisms contain intrinsic mechanisms of defense organisms contain intrinsic mechanisms of defense organisms contain intrinsic mechanisms of defense organisms contain intrinsic mechanisms of defense against infections, which constitute innate immunity.against infections, which constitute innate immunity.against infections, which constitute innate immunity.against infections, which constitute innate immunity.

• The mechanisms of innate immunity respond to microbes and not The mechanisms of innate immunity respond to microbes and not The mechanisms of innate immunity respond to microbes and not The mechanisms of innate immunity respond to microbes and not to to to to nonmicrobialnonmicrobialnonmicrobialnonmicrobial substances, are specific for structures present on substances, are specific for structures present on substances, are specific for structures present on substances, are specific for structures present on various classes of microbes, are mediated by receptors encoded ivarious classes of microbes, are mediated by receptors encoded ivarious classes of microbes, are mediated by receptors encoded ivarious classes of microbes, are mediated by receptors encoded in n n n the the the the germlinegermlinegermlinegermline, and are not enhanced by repeat exposures to , and are not enhanced by repeat exposures to , and are not enhanced by repeat exposures to , and are not enhanced by repeat exposures to microbes. microbes. microbes. microbes.

• The principal components of innate immunity are epithelia, The principal components of innate immunity are epithelia, The principal components of innate immunity are epithelia, The principal components of innate immunity are epithelia, phagocytes and natural killer (NK) cells, cytokines, and plasma phagocytes and natural killer (NK) cells, cytokines, and plasma phagocytes and natural killer (NK) cells, cytokines, and plasma phagocytes and natural killer (NK) cells, cytokines, and plasma proteins, including the proteins of the complement system. proteins, including the proteins of the complement system. proteins, including the proteins of the complement system. proteins, including the proteins of the complement system.

• Epithelia provide physical barriers against microbes, produce Epithelia provide physical barriers against microbes, produce Epithelia provide physical barriers against microbes, produce Epithelia provide physical barriers against microbes, produce antibiotics, and contain lymphocytes that may prevent infectionsantibiotics, and contain lymphocytes that may prevent infectionsantibiotics, and contain lymphocytes that may prevent infectionsantibiotics, and contain lymphocytes that may prevent infections....

SummarySummarySummarySummarySummarySummarySummarySummary

• The principal phagocytes, PMN and The principal phagocytes, PMN and The principal phagocytes, PMN and The principal phagocytes, PMN and monocytesmonocytesmonocytesmonocytes/macrophages, are /macrophages, are /macrophages, are /macrophages, are blood cells recruited to sites of infection, where they recognizblood cells recruited to sites of infection, where they recognizblood cells recruited to sites of infection, where they recognizblood cells recruited to sites of infection, where they recognize e e e microbes by several receptors. microbes by several receptors. microbes by several receptors. microbes by several receptors. NeutrophilsNeutrophilsNeutrophilsNeutrophils and macrophages ingest and macrophages ingest and macrophages ingest and macrophages ingest microbes for intracellular destruction, secrete cytokines, and microbes for intracellular destruction, secrete cytokines, and microbes for intracellular destruction, secrete cytokines, and microbes for intracellular destruction, secrete cytokines, and respond in other ways that contribute to elimination of microbesrespond in other ways that contribute to elimination of microbesrespond in other ways that contribute to elimination of microbesrespond in other ways that contribute to elimination of microbesand repair of infected tissues.and repair of infected tissues.and repair of infected tissues.and repair of infected tissues.

• Natural killer cells kill host cells infected by intracellular mNatural killer cells kill host cells infected by intracellular mNatural killer cells kill host cells infected by intracellular mNatural killer cells kill host cells infected by intracellular microbes icrobes icrobes icrobes and produce the cytokine IFNand produce the cytokine IFNand produce the cytokine IFNand produce the cytokine IFN----γγγγ, which activates macrophages to , which activates macrophages to , which activates macrophages to , which activates macrophages to kill phagocytosed microbes. kill phagocytosed microbes. kill phagocytosed microbes. kill phagocytosed microbes.

• The complement system activated sequentially on encounter with The complement system activated sequentially on encounter with The complement system activated sequentially on encounter with The complement system activated sequentially on encounter with some microbes and by antibodies (in the humoral arm of some microbes and by antibodies (in the humoral arm of some microbes and by antibodies (in the humoral arm of some microbes and by antibodies (in the humoral arm of adaptive immunity). Complement proteins coat (adaptive immunity). Complement proteins coat (adaptive immunity). Complement proteins coat (adaptive immunity). Complement proteins coat (opsonizeopsonizeopsonizeopsonize) ) ) ) microbes for microbes for microbes for microbes for phagocytosisphagocytosisphagocytosisphagocytosis, stimulate inflammation, and , stimulate inflammation, and , stimulate inflammation, and , stimulate inflammation, and lyselyselyselysemicrobes. microbes. microbes. microbes.

• Cytokines of innate immunity (TNF, ILCytokines of innate immunity (TNF, ILCytokines of innate immunity (TNF, ILCytokines of innate immunity (TNF, IL----1, 1, 1, 1, chemokineschemokineschemokineschemokines) ) ) )

function to stimulate inflammation, activate NK cells (ILfunction to stimulate inflammation, activate NK cells (ILfunction to stimulate inflammation, activate NK cells (ILfunction to stimulate inflammation, activate NK cells (IL----

12), activate macrophages (IFN12), activate macrophages (IFN12), activate macrophages (IFN12), activate macrophages (IFN----γγγγ), and prevent viral ), and prevent viral ), and prevent viral ), and prevent viral

infections (type I IFN). infections (type I IFN). infections (type I IFN). infections (type I IFN).

• Innate immune responses provide "second signals" for Innate immune responses provide "second signals" for Innate immune responses provide "second signals" for Innate immune responses provide "second signals" for

the activation of B and T lymphocytes. The requirement the activation of B and T lymphocytes. The requirement the activation of B and T lymphocytes. The requirement the activation of B and T lymphocytes. The requirement

for these second signals ensures that adaptive immunity for these second signals ensures that adaptive immunity for these second signals ensures that adaptive immunity for these second signals ensures that adaptive immunity

is elicited by microbes (the natural inducers of innate is elicited by microbes (the natural inducers of innate is elicited by microbes (the natural inducers of innate is elicited by microbes (the natural inducers of innate

immune reactions) and not by immune reactions) and not by immune reactions) and not by immune reactions) and not by nonmicrobialnonmicrobialnonmicrobialnonmicrobial substance.substance.substance.substance.

Antigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to LymphocytesAntigen Capture and Presentation to Lymphocytes

T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a T cell receptor (TCR) recognizes a complex of a

peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major peptide antigen displayed by a major histocompatibilityhistocompatibilityhistocompatibilityhistocompatibilityhistocompatibilityhistocompatibilityhistocompatibilityhistocompatibility

(MHC) molecule(MHC) molecule(MHC) molecule(MHC) molecule(MHC) molecule(MHC) molecule(MHC) molecule(MHC) molecule

Capture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by AntigenCapture of Protein Antigens by Antigen--------Presenting Cells Presenting Cells Presenting Cells Presenting Cells Presenting Cells Presenting Cells Presenting Cells Presenting Cells

Dendritic cellsDendritic cellsDendritic cellsDendritic cellsDendritic cellsDendritic cellsDendritic cellsDendritic cells

The capture and The capture and The capture and The capture and The capture and The capture and The capture and The capture and

presentation of protein presentation of protein presentation of protein presentation of protein presentation of protein presentation of protein presentation of protein presentation of protein

antigens by dendritic antigens by dendritic antigens by dendritic antigens by dendritic antigens by dendritic antigens by dendritic antigens by dendritic antigens by dendritic

cellscellscellscellscellscellscellscells

CrossCrossCrossCrossCrossCrossCrossCross--------presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by presentation of microbial antigens from infected cells by

professional professional professional professional professional professional professional professional APCsAPCsAPCsAPCsAPCsAPCsAPCsAPCs

The Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC MoleculesThe Structure and Function of MHC Molecules

Properties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genesProperties of MHC molecules and genes

Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein Pathways of Intracellular processing of Protein AgsAgsAgsAgsAgsAgsAgsAgs

MHCMHCMHCMHC----associated antigen presentation in the recognition of associated antigen presentation in the recognition of associated antigen presentation in the recognition of associated antigen presentation in the recognition of

microbes by CD4+ and CD8+ T cellsmicrobes by CD4+ and CD8+ T cellsmicrobes by CD4+ and CD8+ T cellsmicrobes by CD4+ and CD8+ T cells


• The induction of immune responses to the protein antigens of microbes is

dependent on a specialized system for capturing and displaying these

antigens for recognition by the rare naive T cells specific for any antigen.

Microbes and microbial antigens that enter the body through epithelia are

captured by professional antigen-presenting cells (APCs), mainly dendritic

cells, located in the epithelia and transported to regional lymph nodes, or are

captured by APCs resident in lymph nodes and spleen. The protein antigens of

the microbes are displayed by the APCs to naive T lymphocytes that

recirculate through the lymphoid organs.

• The function of displaying peptides derived from protein antigens is performed

by molecules encoded in the major histocompatibility complex (MHC).


• Proteins that are ingested by APCs from the extracellular environment are

proteolytically degraded within the vesicles of the APCs, and the peptides

that are generated bind to the clefts of newly synthesized class II MHC

molecules. Class II MHC molecules are recognized by CD4, because of

which CD4+ helper T cells are specific for class II MHC-associated peptides

that are derived mainly from extracellular proteins.

• Proteins that are produced by microbes living in the cytoplasm of infected

cells, or enter the cytoplasm from phagocytosed microbes, are degraded by

cytosolic proteases and bind to the clefts of newly synthesized class I MHC

molecules. Class I MHC molecules are recognized by CD8, because of which

CD8+ cytolytic T lymphocytes are specific for class I MHC-associated

peptides derived from cytosolic proteins.


• The role of MHC molecules in antigen display ensures that T

cells only see cell-associated protein antigens, and the correct

type of T cell (helper or cytolytic cell) responds to the type of

microbe that T cell is best able to combat.

• Microbes activate APCs to express membrane proteins

(costimulators) and to secrete cytokines that provide signals

that function in concert with antigens to stimulate specific T

cells. The requirement for these second signals ensures that T

cells respond to microbial antigens and not to harmless,

nonmicrobial substances.


• B lymphocytes recognize proteins as well as

nonprotein antigens, even in their native

conformations. It is not known if a

specialized system of antigen display is

essential for the induction of B cell

responses. Follicular dendritic cells (FDCs)

display antigens to germinal center B cells

and select the high-affinity B cells during

humoral immune responses.

Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes Antigen Receptors of Lymphocytes

AntibodiesAntibodies

AntibodiesAntibodies

Features of Features of Features of Features of Features of Features of Features of Features of

the major the major the major the major the major the major the major the major

isotypesisotypesisotypesisotypesisotypesisotypesisotypesisotypes

(classes) of (classes) of (classes) of (classes) of (classes) of (classes) of (classes) of (classes) of

antibodiesantibodiesantibodiesantibodiesantibodiesantibodiesantibodiesantibodies

The structure of the T cell antigen receptor (TCR)The structure of the T cell antigen receptor (TCR)The structure of the T cell antigen receptor (TCR)The structure of the T cell antigen receptor (TCR)

Antigen recognition by antibodies and T cell antigen receptorsAntigen recognition by antibodies and T cell antigen receptorsAntigen recognition by antibodies and T cell antigen receptorsAntigen recognition by antibodies and T cell antigen receptors

Maturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of LymphocytesMaturation of Lymphocytes

maturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytesmaturation and selection of B lymphocytes

Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes Maturation and Selection of T Lymphocytes

SUMMARY SUMMARY SUMMARY SUMMARY SUMMARY SUMMARY SUMMARY SUMMARY

•• In the adaptive immune system, the molecules responsible for speIn the adaptive immune system, the molecules responsible for specific cific

recognition of antigens are antibodies and T cell antigen receptrecognition of antigens are antibodies and T cell antigen receptors. ors.

•• Antibodies may be produced as membrane receptors of B lymphocyteAntibodies may be produced as membrane receptors of B lymphocytes s

and as proteins secreted by antigenand as proteins secreted by antigen--stimulated B cells that have stimulated B cells that have

differentiated into antibodydifferentiated into antibody--secreting cells. Secreted antibodies secreting cells. Secreted antibodies ��

capable of neutralizing microbes and microbial toxins and elimincapable of neutralizing microbes and microbial toxins and eliminating ating

them by activating various them by activating various effectoreffector mechanisms. mechanisms.

•• T cell antigen receptors (TCRs) are membrane receptors and are nT cell antigen receptors (TCRs) are membrane receptors and are not ot

secreted. secreted.


• The core structure of antibodies consists of two heavy chains and

two light chains forming a disulfide-linked complex. Each chain

consists of a variable (V) region, which is the portion that recognizes

antigen, and a constant (C) region, which provides structural stability

and, in heavy chains, performs the effector functions of antibodies.

• T cell receptors consist of an αααα chain and a ββββ chain. Each chain

contains one V region and one C region, and both chains participate

in the recognition of antigens, which for most T cells are peptides

displayed by MHC molecules.


• The V regions of Ig and TCR molecules contain hypervariable

segments, also called complementarity-determining regions, which

are the regions of contact with antigens.

• The genes that encode antigen receptors consist of multiple

segments that are separate in the germline and are brought together

during the maturation of lymphocytes. In B cells, the Ig gene

segments undergo recombination as the cells mature in the bone

marrow, and in T cells the TCR gene segments undergo

recombination during maturation in the thymus.


• Receptors of different specificities are generated in part by different

combinations of V, D, and J gene segments. The process of

recombination introduces variability in the nucleotide sequences at the

sites of recombination by adding or removing nucleotides from the

junctions. The result of this introduced variability is the development

of a diverse repertoire of lymphocytes, in which clones of cells with

different antigen specificities express receptors that differ in sequence

and recognition, and most of the differences are concentrated at the

regions of gene recombination.


• During their maturation, lymphocytes undergo alternating cycles of

proliferation and antigen receptor expression and traverse several

checkpoints at which they are selected such that only cells with

complete functional antigen receptors are preserved and expanded. T

lymphocytes are positively selected to recognize peptide antigens

displayed by self MHC molecules.

• Immature lymphocytes that strongly recognize self antigens are

negatively selected and prevented from completing their maturation ��

eliminating cells with the potential of reacting in harmful ways against

self tissues.

Thank YouThank You

Documents

Fundamental Immunology IBRO-Fogarty May 2007 · Fundamental Immunology (Introduction to the Immune System) By BByy By ... The scope of the lecture ... that are always present and