ACQUIRED IMMUNITY

RECOGNITION

ORGANIZATION OF IMMUNE CELLS UNDER EPITHELIAL SURFACES

DC

Epithelial cells

PERIPHERAL LYMPHOID TISSUES

PERIPHERAL TISSUES

Stroma cells

CELL – TO – CELL COMMUNICATION NETWORKS

Granulocyte

Macrophage

NK cell

NKT cell

Macrophage activation

Cellular killing

Neutrofil granulocyte

B

Ag-specific B-cell

Eosinophil granulocyte

Th17

Th2

Treg CTL

Th1

SENSINGSENSING

RECOGNITIONRECOGNITION

SIGNAL SIGNAL TRANSDUCTIONTRANSDUCTION

RESPONSERESPONSE

INNATE IMMUNITYINNATE IMMUNITY ACQUIRED IMMUNITYACQUIRED IMMUNITY

SENSINGSENSINGRECOGNITIONRECOGNITION

SIGNAL SIGNAL TRANSDUCTIONTRANSDUCTION

RESPONSERESPONSE

CellsCells

ReceptorsReceptors

Signaling Signaling pathwayspathways

Cell-to-cell Cell-to-cell collaborationcollaboration

Effector Effector mechanismsmechanisms

DEFENCE SYSTEMSDEFENCE SYSTEMS

LampreyLamprey

FishesFishes 450 450 mill millonon years years

ADAPTIVE (ACQUIRED) IMMUNITY

Antigen recognizing receptors

B cB cellell

Helper T cell Cytotoxic T cell

LYMPHOCYTES

WHAT IS RECOGNIZED BY INNWHAT IS RECOGNIZED BY INNAATE AND ACQUIRED TE AND ACQUIRED IMMUNITY?IMMUNITY?

HOHOW DO THEY RECOGNIZE PATHOGENS?W DO THEY RECOGNIZE PATHOGENS?

Common pattern of groups of pathogensCommon pattern of groups of pathogensPathogen Associated Molecular PatternPathogen Associated Molecular Pattern

PAMPPAMPRecognition by receptorsRecognition by receptors

Pattern Recognition ReceptorPattern Recognition ReceptorPRRPRR

9-19-133 various various Toll-Toll-rreecceptoreptorssTLR familyTLR family

SSeveral millions antigen everal millions antigen receptorsreceptors

UUnique structural elenique structural elemmentsentsAntigenic determinantAntigenic determinant

Recognition by highly speciRecognition by highly speciffic ic aantigen receptorsntigen receptors

B cell receptorB cell receptor BCR (sIg) BCR (sIg)T cell receptorT cell receptor TCR TCR

RECEPTORS

InInnate immunitynate immunity

AncientAncient 450 450 million yearsmillion years

AAcquired immunitycquired immunity

CELLS

HUMORAL

FACTORS

Phagocytes (monocyte/macrophage, neutrophil, dendritic cell)

Killer cells (NK cell, δ T cell)

B1 lymphocytes (CD5+)

B lymphocytes (B2)

T lymphocytes

helper T cell

cytotoxic T cell

Enzymes (lysozyme,transferrin, lactoferrin, spermin, trypsin)

Antibacterial peptides

Complement system

Cytokines, chemokines

Antibodies

Produced by B-cell derived plasma cells

WHAT CELL TYPES MEDIATE ACQUIRED IMMUNITY

INNATE/NATURAL IMMUNITY

ACQUIRED/ADAPTIVE IMMUNITY

Macfarlane BurnetMacfarlane Burnet (1956 - 1960) (1956 - 1960)

CLONAL SELECTION THEORY Antibodies are natural products that appear on

the cell surface as receptors and selectively react with the antigen

Lymphocyte receptors are variable and carry various antigen-recognizing receptors

‘Non-self’ antigens/pathogens encounter the existing lymphocyte pool (repertoire)

Antigens select their matching receptors from the available lymphocyte pool, induce clonal proliferation of specific clones and these clones differentiate to antibody secreting plasma cells

The clonally distributed antigen-recognizing receptors represent about ~107 – 109 distinct antigenic specificities

Cc. (minimum) 10 mCc. (minimum) 10 milliillion various (10on various (1077) B lymphocyte clones with ) B lymphocyte clones with different different aantigntigeen-recognizing receptorsn-recognizing receptors

CCc. (minimum) 10 – 1000 mc. (minimum) 10 – 1000 milliillion various (10on various (1077 - - 99) ) TT lymphocyte lymphocyte clones with different clones with different aantigntigeen-recognizing receptorsn-recognizing receptors

DIVERSITY OF LYMPHOCYTES

AAssumptionssumption 1 1 AAll lymphocytes ll lymphocytes have have a different a different receptor receptor

AAssumption ssumption 22 TThe receptor can behe receptor can beactivated by many activated by many different different antigensantigens

10101212 l lyymphocytes in our body ( B and T lymphocytes)mphocytes in our body ( B and T lymphocytes)

How many SPECIFICITIES

?

Antigen

ACTIVATIONACTIVATIONClonal expansionClonal expansion

Antigen Antigen

Differentiation

Plasma cell

Antibody(immunoglobulin Ig)

secretion

MEMORY B CELLS

BINDING OF ANTIGEN TO THE SELECTED B-LYMPHOCYTES RESULTS IN CLONAL EXPANSION

B cell

B Cell Receptor (BCR)

Ag

Clonal selection induces proliferationand increases effector cell frequency

No. of cell divisions

No. ofcells with

usefulspecificity

Threshold ofprotective effectorfunction

POSSIBLE FATES OF B-LIMPHOCYTE CLONES

ActivationClonal expansion/proliferation

Differentiation

Plasma cellAntibody production

Memory cell

CirculationRestricted life span

HomeostasisApoptosis

Transient, not final differentiation state

Antibody

THE B-CELL ANTIGEN RECOGNIZING RECEPTOR AND ANTIBODIES PRODUCED BY PLASMA CELLS HAVE THE

SAME PROTEIN STRUCTURE = IMMUNOGLOBULIN

Antigen recognizing receptor

BCRImmunoglobulin (Ig)

B CELL

HH HHLL LL

HH HH

LL LL

Secreted IgSecreted IgAntigen-specificAntigen-specificssoluble proteinoluble protein

EFFECTOR MOLECULEEFFECTOR MOLECULE

TWO FORMS OF IMMUNOGLOBULINS

Membrane-bound IgMembrane-bound IgAntigen-specificAntigen-specific

receptorreceptor

signalsignalllinging

B CELLPLASMA CELL

Antigen binding

FVFV= = VHVH+ + VLVLVVHH

VVLL

IMMUNOGLOBULIN IgG

Antigen binding site

Days

Antibody

g/ml serum

Antigen A A antigén

Response to antigen A

Cell interactionsCENTRAL

Effector/executionRegulationEFFECTOR

Primary response

RecognitionActivationAFFERENT

Lag

Secondary response

MEMORYAntigen A

TIME COURSE OF THE ADAPTIVE IMMUNE RESPONSE

Antigen B

Primary Response to

antigen B

WHAT IS RECOGNIZED BY INNWHAT IS RECOGNIZED BY INNAATE AND ACQUIRED TE AND ACQUIRED IMMUNITY?IMMUNITY?

HOHOW DO THEY RECOGNIZE PATHOGENS?W DO THEY RECOGNIZE PATHOGENS?

Common pattern of groups of pathogensCommon pattern of groups of pathogensPathogen Associated Molecular PatternPathogen Associated Molecular Pattern

PAMPPAMPRecognition by receptorsRecognition by receptors

Pattern Recognition ReceptorPattern Recognition ReceptorPRRPRR

9-19-133 various various Toll-Toll-rreecceptoreptorssTLR familyTLR family

SSeveral millions antigen everal millions antigen receptorsreceptors

UUnique structural elenique structural elemmentsentsAntigenic determinantAntigenic determinant

Recognition by highly speciRecognition by highly speciffic ic aantigen receptorsntigen receptors

B cell receptorB cell receptor BCR (sIg) BCR (sIg)T cell receptorT cell receptor TCR TCR

RECEPTORS

InInnate immunitynate immunity

AncientAncient 450 450 million yearsmillion years

AAcquired immunitycquired immunity

NATURAL/INNATE• Rapid, prompt

response (hours)• No variable receptors• Limited number of

specificities• No improvement

during the response• No memory• Not transferable• Can be exhausted,

saturated

CHARACTERISTICS OF INNATE AND ACQUIRED IMMUNITY

ADAPTIVE/ACQUIRED• Time consuming• Variable antigen receptors • Many very selective

specificities• Efficacy is improving

during the response• Memory• Can be transferred• Regulated, limited• Protects self tissues

COMMON EFFECTOR MECHANISMS FOR THE ELIMINATION OF PATHOGENS

TOW LEVELS OF DEFENSE

TWO TYPES OF THE IMMUNE RESPONSE

INNTE/NATURAL IMMUNITY

Protects without prior activation or multiplication against pathogens

AQUIRED/ADAPTIVE IMMUNITY

Protects after activation and clonal expansion against pathogens

First line of defense

Inrerited

Persistant presence

Rapid response

Short term protection

Second line of defense

Acquired

Slow response

Self and non-self specificity

Long term protection (memory)