Download GENERAL CHARACTERIZATION OF THE

GENERAL CHARACTERIZATION OF THE IMMUNE
SYSTEM
MAJOR TASK
MAINTAIN THE BALANCE OF THE HOST’S IMMUNE SYSTEM
WITH THE ENVIRONMENT
Commensal and pathogenic microorganisms
Other environmental effects
GENERAL FEATURES OF THE IMMUNE SYSTEM
1. STRUCTURE – various cell types, diffuse
Cell communication
Th
Partners
Mode
macrophage
– direct
pathogen
– soluble factors
B
extracellular matrix
macrophage
Cell – to – cell
communication
2. ACTION – dynamic
Homeostasis – environmental factors
Adhesion
Homing
Migration
Replacement vs death
Activation vs differentiation
3. FUNCTION
4. SPECIAL FEATURES
Recognition – self - antigen - danger
Defense against pathogens
Recognize, prevent spread, clear from the body
Signal processing and transduction
Signal storage – learning, memory
Protection of self
SIMILARITIES TO THE NERVOUS SYSTEM
CELLULAR INTERACTIONS AND COMMUNICATION IN THE
IMMUNE SYSTEM
ENVIRONMENT
IMMUNE
CELL
Indirect cellular
interactions
Soluble molecules
Cytokines, chemokines
IMMUNE
CELL
OTHER
CELL TYPES
Direct cellular
interactions
Receptor – ligand
Adhesion
Signal transduction
ENVIRONMENT
NEUTROPHIL MIGRATION
FROM THE BLOOD TO THE
INFLAMMED TISSUE
neutrophil
Endothelial cell
Neutrophil granulocyte
Bacteria
Inflammed
tissue
How immune cells communicate?
Cell surface molecules mediate cell-cell contact
Resting cells
Activated cells
INDUCED
UPREGULATED
Expression and level of expression controls cell-cell adhesion
Activation can induce expression.
Cell adhesion, migration, antigen specificity, antigen presentation,
costimulation, helper function, effector function.
Cell surface molecules influenced by activation include cytokine receptors.
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.
Killing
CTL
Target cell
T
Y
Antigen
presentation
B
T
Ab production
Accessory cell activation
How immune cells communicate?
Soluble mediators
Infection
CYTOKINES & CHEMOKINES
Phagocyte
activation
INFLAMMATION
Diverse 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
response
Early 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 IMMUNITY
Evolutionary need for survival
Parallel development of organ systems & signalling pathways
Phagocytosis – nutrition & protection agains harmful material
Fat body of Drosophila
Liver, adipose tissue & lymph nodes of mammals
•
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•
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Nutrient sensing
Energy efficiency
Energy storage
Energy surplus
Metabolic syndrome
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•
•
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•
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Pathogen sensing
Food deprivation
Defense against pathogens
High energy expenditure
Impaired immune responses
Chronic inflammation
METABOLIC HOMEOSTASIS – PROPER IMMUNE SYSTEM
Hotamisligil & Erbay NRI 2008
HIGHEST ENERGY CONSUMING SYSTEMS
Reproduction
Thermoregulation
Lactation
IMMUNE RESPONSE
Loss of apetite – induction of leptin synthesis
Usage of local energy and nutrient stores
Chronic nutrient deficiency or overnutrition lead to pathological relationships
Pre-adipocytes – Macrophages – Adipocytes – Dendritic cells
SHARED GENES IN PHYSIOLOGICAL CONDITIONS & METABOLIC
DISEASE STATES
LIPID SENSING PATHWAYS AND INFLAMMATION
Increased amounts of fatty acids
UPR
ER stress
UPR
Nuclear hormone
receptors
Modulation
Hotamisligil & Erbay NRI 2008
DEFENSE SYSTEMS
ADAPTIVE IMMUNITY
INNATE IMMUNITY
SENSING
Cells
SENSING
RECOGNITION
Receptors
RECOGNITION
SIGNALING
Signaling
pathways
SIGNALING
Cell-Cell
collaboration
RESPONSE
Effector
functions
RESPONSE
HOW INNATE AND ACQUIRED IMMUNITY
RECOGNIZE PATHOGENS?
RECEPTORS
Common patterns of pathogen groups
Pathogen Associated Molecular Pattern
PAMP
Recognition by receptors
Pattern Recognition Receptor
PRR
Toll-receptor family (9 - 13)
Lectin family, scavenger receptors
Innate immunity
Ancient
Unique structural elements
Antigenic determinant
Recognition by highly specific
antigen receptors
B cell receptor BCR (sIg)
T cell receptor TCR
Several millions antigen receptors
Acquired immunity
450 million years
TWO LINES OF IMMUNE DEFENSE
INNATE/NATURAL IMMUNITY
Phagocytes
Neutrophil,
monocyte/macrophage,
dendritic cell
Killer cells (NK cell, δ T cell)
B1 lymphocytes (CD5+)
CELLS
Enzymes
(lysozyme,transferrin,
lactoferrin, spermin, trypsin)
Antibacterial peptides
HUMORAL
Complement system
FACTORS
Cytokines, chemokines
B1 cells:
Fast response within 48 hrs
T cell independent
Surface IgM
Long life span
Peritoneal cavity
γδ T-cells:
skin, guts
limited diversity
Binds pathogen derived
organic phosphates
express NKG2D
NKT-cells:
fast response
lipid antigens
prompt cytokine release
TWO TYPES IMMUNE RESPONSES
INNATE/NATURAL IMMUNITY
Phagocytes
Neutrophil,
monocyte/macrophage,
dendritic cell
Killer cells (NK cell, δ T cell)
B1 lymphocytes (CD5+)
ACQUIRED/ADAPTIVE
IMMUNITY
CELLS
B-lymphocytes (B2)
T-lymphocytes
helper T-cells
cytotoxic T-cells
regulatory T-cells
Enzymes
(lysozyme,transferrin,
lactoferrin, spermin, trypsin)
Antibacterial peptides
HUMORAL
Complement system
FACTORS
Antibodies
Cytokines, chemokines
MUTUAL COLLABORATION
TWO LINES OF IMMUNE DEFENSE
INNATE/NATURAL IMMUNITY
Innate immunity constitutes
components that protect against
infection without any requirement for
prior activation or clonal expansion
First line of defense
Inherited
Always present
ACQUIRED/ADAPTIVE IMMUNITY
Requires the activation and clonal
expansion of cells to protect against
pathogens
Induced by antigen
Response is under genetic control
Depends on environmental stimuli
FUNCTIONAL ATTRIBUTES OF INNATE AND ADAPTIVE IMMUNITY
Chapter 1
Elements of the Immune System and their Roles in Defense
• 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
© Garland Science 2009
CONTACT SURFACES
GASTROINTESTINAL
SYSTEM
Physical, chemical, biological borders
EYE
AIRWAY SYSTEM
Sinuses
Trachea
Lungs
Oral cavity
Esophagus
Stomach
Alimentary
tract
UROGENITAL SYSTEM
SKIN
Kidney
Bladder
Vagina
WALDEYER RING
Tonsils, adenoids
Palatinal, pharyngeal
lingual and tubar tonsils
Demage
Mucus
Infection
glycoproteins, proteoglycanes,
enzymes
FIRST 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 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