GENERAL CHARACTERIZATION OF THE IMMUNE SYSTEM

MAJOR TASKMAJOR TASK

MAINTAIN THE BALANCE OF THE HOST’S IMMUNE SYSTEM MAINTAIN THE BALANCE OF THE HOST’S IMMUNE SYSTEM WITH THE ENVIRONMENTWITH THE ENVIRONMENT

Commensal and pathogenic microorganismsCommensal and pathogenic microorganisms

Other environmental effects Other environmental effects

3. FUNCTION

Defense against pathogens

Recognize, prevent spread, clear from the body

Protection of self

2. ACTION – dynamic

Homeostasis – environmental factors

Replacement vs death

Activation vs differentiation

Th

GENERAL FEATURES OF THE IMMUNE SYSTEM

1. STRUCTURE – various cell types, diffuse Cell communication

Partners

Mode – direct

– soluble factors

macrophage

extracellular matrix

AdhesionHoming

Migration

macrophage

pathogenB

Cell – to – cellcommunication

4. SPECIAL FEATURES

Recognition – self - antigen - danger

Signal processing and transduction

Signal storage – learning, memory

SIMILARITIES TO THE NERVOUS SYSTEM

IMMUNE IMMUNE CELLCELL

OTHER OTHER CELL TYPES CELL TYPES

IMMUNE IMMUNE CELLCELL

Direct cellular interactions

Receptor – ligandAdhesion

Signal transduction

Indirect cellular Indirect cellular interactionsinteractions

Soluble moleculesCytokines, chemokines

CELLULAR INTERACTIONS AND COMMUNICATION IN THE CELLULAR INTERACTIONS AND COMMUNICATION IN THE IMMUNE SYSTEMIMMUNE SYSTEM

ENVIRONMENTENVIRONMENT

ENVIRONMENTENVIRONMENT

Neutrophil granulocyte

BacteriaBacteria

neutrophil

Endothelial cell Inflammed tissue

NEUTROPHIL MIGRATION NEUTROPHIL MIGRATION FROM THE BLOOD TO THE FROM THE BLOOD TO THE

INFLAMMED TISSUEINFLAMMED TISSUE

How immune cells communicate?Cell surface molecules mediate cell-cell contact

Expression and level of expression controls cell-cell adhesionActivation can induce expression.

Cell adhesion, migration, antigen specificity, antigen presentation,costimulation, helper function, effector function.

Cell surface molecules influenced by activation include cytokine receptors.

Resting cells Activated cells

INDUCEDINDUCED

UPREGULATEDUPREGULATED

How immune cells communicate?Cell-cell contact

Peripheral lymphoid tissues trap antigen-containing phagocytic cells and concentrate cells together to promote cell-cell contact.

Cell-cell contact occurs at many stages of immune responses.

T

CTL

T

BY

Ab productionAccessory cell activation

Antigenpresentation

Target cell

Killing

InfectionInfection

Phagocyteactivation

How immune cells communicate?Soluble mediators

CYTOKINES & CHEMOKINESDiverse collection of soluble proteins

made by cells that affect the behaviour of other cells. The balance & level of cytokines and chemokines secreted affects the outcome of the

responseINFLAMMATIONEarly events involve endothelial cells and result in the accumulation of fluid, plasma proteins & leucocytes.

Later events involve the activation and maturation of lymphocytes and granulocytes.

INTEGRATION OF METABOLISM AND IMMUNITYINTEGRATION OF METABOLISM AND IMMUNITY

Evolutionary need for survivalEvolutionary need for survivalParallel development of organ systems & signalling pathwaysParallel development of organ systems & signalling pathways

Phagocytosis – nutrition & protection agains harmful materialPhagocytosis – nutrition & protection agains harmful material

Fat body of DrosophilaFat body of DrosophilaLiver, adipose tissue & lymph nodes of mammalsLiver, adipose tissue & lymph nodes of mammals

• Nutrient sensingNutrient sensing• Energy efficiency• Energy storage• Energy surplus• Metabolic syndromeMetabolic syndrome

• Pathogen sensingPathogen sensing• Food deprivation• Defense against pathogens• High energy expenditure• Impaired immune responses• Chronic inflammationChronic inflammation

METABOLIC HOMEOSTASIS – PROPER IMMUNE SYSTEMMETABOLIC HOMEOSTASIS – PROPER IMMUNE SYSTEM

Hotamisligil & Erbay NRI 2008

IMMUNE RESPONSEIMMUNE RESPONSE

ReproductionReproduction ThermoregulationThermoregulation LactationLactation

HIGHEST ENERGY CONSUMING SYSTEMSHIGHEST ENERGY CONSUMING SYSTEMS

Loss of apetite – induction of leptin synthesis

Usage of local energy and nutrient stores

Chronic nutrient deficiency or overnutrition lead to pathological relationshipsChronic nutrient deficiency or overnutrition lead to pathological relationships

Pre-adipocytes – Macrophages – Adipocytes – Dendritic cellsPre-adipocytes – Macrophages – Adipocytes – Dendritic cells

SHARED GENES IN PHYSIOLOGICAL CONDITIONS & METABOLIC SHARED GENES IN PHYSIOLOGICAL CONDITIONS & METABOLIC DISEASE STATES DISEASE STATES

LIPID SENSING PATHWAYS AND INFLAMMATIONLIPID SENSING PATHWAYS AND INFLAMMATION

Hotamisligil & Erbay NRI 2008

Increased amounts of fatty acidsIncreased amounts of fatty acids

ER stressER stressUPRUPR

ModulationModulationNuclear hormone Nuclear hormone receptorsreceptors

UPRUPR

SENSINGSENSING

RECOGNITIONRECOGNITION

SIGNALINGSIGNALING

RESPONSERESPONSE

INNATE IMMUNITYINNATE IMMUNITY

CellsCells

ReceptorsReceptors

Signaling Signaling pathwayspathways

Cell-Cell Cell-Cell collaborationcollaboration

Effector Effector functionsfunctions

DEFENSE SYSTEMSDEFENSE SYSTEMS

ADAPTIVE IMMUNITYADAPTIVE IMMUNITY

SENSINGSENSING

RECOGNITIONRECOGNITION

SIGNALINGSIGNALING

RESPONSERESPONSE

HOW INNHOW INNAATE AND ACQUIRED IMMUNITYTE AND ACQUIRED IMMUNITYRECOGNIZE PATHOGENS?RECOGNIZE PATHOGENS?

Common patternCommon patternss of pathogen groups of pathogen groupsPathogen Associated Molecular PatternPathogen Associated Molecular Pattern

PAMPPAMPRecognition by receptorsRecognition by receptors

Pattern Recognition ReceptorPattern Recognition ReceptorPRRPRR

Toll-Toll-rreecceptoreptor family (9 - family (9 - 13)13)

Lectin family, scavenger Lectin family, scavenger receptorsreceptors

RECEPTORS

InInnate immunitynate immunity

AncientAncient

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

450 450 million yearsmillion years

AAcquired immunitycquired immunity

SSeveral millions antigen everal millions antigen receptorsreceptors

CELLS

HUMORAL

FACTORS

Phagocytes Neutrophil, monocyte/macrophage, monocyte/macrophage, dendritic celldendritic cellKiller cells (NK cell, δ T cell)B1 lymphocytes (CD5+)

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

Antibacterial peptides

Complement system

Cytokines, chemokines

TWO LINES OF IMMUNE DEFENSE

INNATE/NATURAL IMMUNITY B1 cells:Fast response within 48 hrsT cell independentSurface IgMLong life spanPeritoneal cavity

γδ T-cells:skin, gutslimited diversityBinds pathogen derived organic phosphatesexpress NKG2D

NKT-cells:fast responselipid antigensprompt cytokine release

ACQUIRED/ADAPTIVE IMMUNITY

CELLS

HUMORAL

FACTORS

Phagocytes Neutrophil, monocyte/macrophage, monocyte/macrophage, dendritic celldendritic cellKiller cells (NK cell, δ T cell)B1 lymphocytes (CD5+)

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

Antibacterial peptides

Complement system

Cytokines, chemokines

INNATE/NATURAL IMMUNITY

TWO TYPES IMMUNE RESPONSES

B-lymphocytes (B2)T-lymphocytes helper T-cells cytotoxic T-cells regulatory T-cells

Antibodies

MUTUAL COLLABORATIONMUTUAL COLLABORATION

TWO LINES OF IMMUNE DEFENSE

INNATE/NATURAL IMMUNITY Innate immunity constitutes Innate immunity constitutes

components that protect against components that protect against infection without any requirement for infection without any requirement for prior activation or clonal expansionprior activation or clonal expansion

ACQUIRED/ADAPTIVE IMMUNITYRequires the activation and clonal

expansion of cells to protect against pathogens

First line of defenseInherited

Always present

Induced by antigenResponse is under genetic controlDepends on environmental stimuli

FUNCTIONAL ATTRIBUTES OF INNATE AND ADAPTIVE IMMUNITYFUNCTIONAL ATTRIBUTES OF INNATE AND ADAPTIVE IMMUNITY

• The innate immune response causes inflammation at sites of infection

• The adaptive immune response adds to an ongoing innate immune response

• Potent immune responses require the collaboration of innate and adaptive immune responses

Chapter 1

© Garland Science 2009

Elements of the Immune System and their Roles in Defense

SinusesTracheaLungs

AIRWAY SYSTEM EYEOral cavityEsophagus

StomachAlimentary

tract

GASTROINTESTINAL SYSTEM

Demage

Infection

Mucus

glycoproteins, proteoglycanes, enzymes

KidneyBladderVagina

UROGENITAL SYSTEM

WALDEYER RINGTonsils, adenoidsPalatinal, pharyngeal lingual and tubar tonsils

SKINSKIN

CONTACT SURFACESCONTACT SURFACESPhysical, chemical, biological bordersPhysical, chemical, biological borders

FIRST LINE OF DEFENSE BY INNATE IMMUNITYFIRST LINE OF DEFENSE BY INNATE IMMUNITY

EPITHELIAL CELLS

•Pattern recognition receptors (PRR)

•Cytokine, chemokine secretion

NEUTROPHIL GRANULOCYTES

•Phagocytósis

•Intracellular cytotoxicity

MONOCITE – MACROPHAGE – DENDRITIC CELL NETWORK

•Pattern recognition receptors (PRR)

•Internalizing receptors

•Phagocytosis

NATURAL KILLER CELLS

•Cytoxicity

•Cytokine production

CELLS & MECHANISMS OF INNATE IMMUNITYCELLS & MECHANISMS OF INNATE IMMUNITY

Soluble proteins – Defensins

Enzymes - Complement system - Chemotaxis

Recognition by Pattern Recognition Receptors

Macrophage & dendritic cell subsets

Neutrophils

Pro-inflammatory cytokine secretion

Local effects

Systemic effects

Chemokine receptors & ligands – cell recruitment, other functions

Cytotoxicity – NK cells