innate 1
TRANSCRIPT
Abdul GhaffarMicrobiology and Immunology
H um oral C ellular
N onspecific
H um ora l C ellular
Specific
macrophages, neutrophils
complement, interferon, TNF etc.
T cells; other effectors cells
antibodies
Components of the Immune System
Components of the Immune System
Balance between Infection and Immunity
Balance between Infection and Immunity
infection immunity
Response to InfectionResponse to Infection
infection
x
disease
Innate immunity no disease
recove
ry
adaptive immunity
re-infectio
n no disease
x
Beneficial:
Protection from Invaders Elimination of Altered Self
Detrimental:
Discomfort (inflammation) Damage to self (autoimmunity)
Beneficial:
Protection from Invaders Elimination of Altered Self
Detrimental:
Discomfort (inflammation) Damage to self (autoimmunity)
Significance of the Immune SystemSignificance of the Immune System
Characteristics of Innate and Adaptive Immunity
Characteristics of Innate and Adaptive Immunity
No Immunologic
memory
Antigen independent
No time lag
Not antigen specific
Antigen dependent
A lag period
Antigen specific
Development
of memory
Innate Immunity Adaptive Immunity
Components of Innate and Adaptive Immunity
Components of Innate and Adaptive Immunity
Innate Immunity Adaptive Immunity
skin, gut Villi, lung cilia,etc
many protein andnon-protein secretions
phagocytes, NK cell eosinophils, K cells
physical barriers
soluble factors
cells
none
Immunoglobulins(antibody)
T and B lymphocytes
Effector mechanisms in Innate Immunity -1
Effector mechanisms in Innate Immunity -1
Peristalsis, low pHbile salts, fatty acids
columnar cellsGI tract
Site Component Functions
Skin squamous cellssweat
desquamationflushing, fatty acids
tracheal ciliaLung mucociliary elevator
surfactants
Effector mechanisms in Innate Immunity -2
Effector mechanisms in Innate Immunity -2
Site Component Functions
Nasopharynxand eye
mucus, saliva, tears flushing, lysozyme
Phagocytes,
K, NK &LAK cells
Blood andLymphiodorgans
phagocytosis and intracellular killing
direct and antibody dependent cytolysis
Effector mechanisms in Innate Immunity -3
Effector mechanisms in Innate Immunity -3
Site Component s Functions
Serum and other serous fluids
lactoferrin,transferrin
iron deprivation
interferons,TNF-
antiviral proteins phagocyte activation
lysozyme peptidoglycan hydrolysis
fibronectincomplement
opsonization, enhanced phagocytosis, inflammation
Phagocytes are the Most Important Cells
Phagocytes are the Most Important Cells
Influenced bythe work of
Eli Metchnikoff,
George Bernard Shaw wrote:
“There is at bottom only one
genuine treatment for all
diseases,…to stimulate the
phagocytes. Drugs are a
delusion. …(when) the
phagocytes are stimulated;
they devour the disease…”
All phagocyteseat, digest
and extrude
Phagocytes:MacrophagesPhagocytes:
Macrophages
phagocytosis, intracellular and extra-cellular killing, tissue repair, antigen presentation for specific immune response
characteristic nucleus and CD14 membrane marker.
Characteristics of Neutrophil Granules
Characteristics of Neutrophil Granules
primary granules
contain cationic proteins, lysozyme, defensins, proteases and myeloperoxidase
secondary granules
contain lysozyme, NADPH oxidase, lactoferrin and B12-binding protein
azurophilic; characteristic of young neutrophils;
specific for mature neutrophils
Phagocyte Response to InfectionPhagocyte Response to Infection
The SOS Signals– N-formyl methionine– Clotting system
peptides– Complement products
Phagocyte response– Vascular adherence– Diapedesis– Chemotaxis– Activation– Phagocytosis and killing
The SOS Signals– N-formyl methionine– Clotting system
peptides– Complement products
Phagocyte response– Vascular adherence– Diapedesis– Chemotaxis– Activation– Phagocytosis and killing
Initiation of PhagocytosisInitiation of Phagocytosis
IgG FcR
ScavengerR
CR
Attachment via
Respiratory BurstOxygen Dependent Myeloperoxidase
Independent Reactions
2O2
- + H2O2
.OH + OH- + 1O2
Glucose +NADP+
G-6-P-dehydrogenase
Pentose-P
+ NADPH
NADPH + O2
Cytochrome b558
NADP++ O2
-
2O2
- + 2H+
Superoxide dismutase
H2O2 + 1O2
Respiratory BurstRespiratory Burst
Oxygen Dependent Myeloperoxidase dependent reactions
H2O2 + 1O22O2
- + 2H+
Superoxide dismutase
H2 O2 + Cl-
myeloperoxidaseOCl- + H2O
H2O + O22 H2 O2
catalase
OCL- + H2O1O2 + Cl- + H2O
Pathways of Intracellular KillingPathways of Intracellular Killing
m yloperoxidase-independent m yeloperoxidase-dependent
oxygen-depenedent oxygen-independent
In trace llu la r K illing
m yloperoxidase-independent m yeloperoxidase-dependent
oxygen-depenedent oxygen-independent
In trace llu la r K illing
Effector Molecule Function
Mediators of Oxygen Independent Killing in the Phago-lysosome
Mediators of Oxygen Independent Killing in the Phago-lysosome
Cationic proteins (cathepsin) Damage to microbial membranes
Lysozyme Hydrolyses mucopeptides in the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms
Nitric Oxide Dependent KillingNitric Oxide Dependent KillingIFN
TNF
TNF
Nitric Oxide
Non-specific Killer CellsNon-specific Killer Cells
NK and LAK cells
K cell
Activated
macrophages
Eosinophils
NK and LAK cells
K cell
Activated
macrophages
Eosinophils
They all kill foreign
and altered self
targets
They all kill foreign
and altered self
targets
Natural Killer (NK) cellsNatural Killer (NK) cells
also known as large granular
lymphocytes (LGL)
kill infected and malignant
cells
are identified by the presence
of CD56 & CD16 and
absence of CD3 activated by IL2 and IFN- to
become LAK cells
also known as large granular
lymphocytes (LGL)
kill infected and malignant
cells
are identified by the presence
of CD56 & CD16 and
absence of CD3 activated by IL2 and IFN- to
become LAK cells
Lymphokine Activated Killer (LAK) cell
Lymphokine Activated Killer (LAK) cell
IL2
IFNIFN
IL2
kills malignant
cells
kills transformed
and malignant cells
Regulation of NK Cell FunctionRegulation of NK Cell Function
M HC I K IR KAR KAL
No K illing K illing
K CellsK Cells
morphologically undefined
have IgG Fc receptor
recognize antibody coated
targets
could be NK cells (IgG),
macrophages (IgG),
eosinophils (IgE) or other
cells (IgG)
morphologically undefined
have IgG Fc receptor
recognize antibody coated
targets
could be NK cells (IgG),
macrophages (IgG),
eosinophils (IgE) or other
cells (IgG)