Date post: | 13-Dec-2015 |
Category: |
Documents |
Upload: | baldwin-price |
View: | 213 times |
Download: | 0 times |
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