Transcript INNATE (NON-SPECIFIC) IMMUNITY

Ahmad Silmi
Lecturer of Haematology and Immunology
Development of the Immune
System
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Cells of the Immune System
Myeloid cells
lymphoid cells
Granulocytic
Monocytic
T-cells
B-cells
Neutrophils
Basophils
Eosinophils
Macrophages
Langerhans &
Kupffer cells
Dendritic cells?
Helper
Cytotoxic
Suppressor
Plasma
cells
Dendritic
cells?
Components of the Immune
System
Nonspecific
Humoral
complement,
interferon,
TNF etc.
Cellular
macrophages,
neutrophils
Specific
Humoral
antibodies
Cellular
T cells; other
effectors cells
Balance between Infection and
Immunity
infection
immunity
Disease =
Bolus of infection x virulence
immunity
Response to Infection
infection
Innate
immunity
x
disease
no
disease
adaptive
immunity
Significance of the Immune System


Beneficial:

Protection from Invaders

Elimination of Altered Self
Detrimental:

Discomfort (inflammation)

Damage to self (autoimmunity)
Characteristics of Innate and
Adaptive Immunity
Innate Immunity
Adaptive Immunity
Antigen independent
Antigen dependent
No time lag
A lag period
Not antigen specific
Antigen specific
No Immunologic
memory
Development
of memory
Components of Innate and
Adaptive Immunity
Innate Immunity
Adaptive Immunity
physical barriers
skin, gut Villi, lung cilia,etc
none
soluble factors
many protein and
non-protein secretions
cells
phagocytes, NK cell
eosinophils, K cells
Immunoglobulins
(antibody)
T and B lymphocytes
Physical Barriers to Resistance
Effector mechanisms in Innate
Immunity -1
Site
Skin
GI tract
Lung
Component
Functions
squamous cells
sweat
desquamation
flushing, fatty acids
columnar
cells
Peristalsis, low pH
bile salts, fatty acids
tracheal cilia
mucociliary elevator
surfactants
Effector mechanisms in Innate
Immunity -2
Site
Component
Functions
Nasopharynx
and eye
mucus, saliva, tears
flushing, lysozyme
Blood and
Lymphiod
organs
Phagocytes
phagocytosis and
intracellular killing
K, NK & LAK
cells
direct and antibody
dependent cytolysis
Effector mechanisms in Innate
Immunity -3
Site
Serum and
other serous
fluids
Component
Functions
lactoferrin,
transferrin
iron deprivation
interferons,
TNF-
antiviral proteins
phagocyte activation
lysozyme
Fibronectin &
complement
peptidoglycan hydrolysis
opsonization, enhanced
phagocytosis, inflammation
Phagocytes are the Most
Important Cells
George Bernard Shaw wrote:
“There is at bottom only one
genuine treatment for all
diseases,…to
stimulate
Influenced
by the
work of
phagocytes.theDrugs
are a
Eli Metchnikoff,
delusion. …(when) the
phagocytes are stimulated;
they devour the disease…”
Phagocytes:
Macrophages
 phagocytosis,
intracellular and extracellular killing, tissue
repair, antigen
presentation for specific
immune response
 characteristic nucleus
and CD14 membrane
marker.
Characteristics of Neutrophil
Granules
primary granules
secondary granules
azurophilic; characteristic
of young neutrophils;
specific for mature neutrophils
contain cationic proteins,
lysozyme, defensins,
proteases and
myeloperoxidase
contain lysozyme, NADPH
oxidase, lactoferrin and B12binding protein
Phagocyte Response to Infection

The SOS Signals
– N-formyl
methionine
– Clotting system
peptides
– Complement products

Phagocyte response
– Vascular
adherence
– Diapedesis
– Chemotaxis
– Activation
– Phagocytosis and killing
Initiation of Phagocytosis
Attachment via
ScavengerR
IgG FcR
CR
Toll-like R
Respiratory Burst
Oxygen Dependent Myeloperoxidase
Independent Reactions
Glucose +NADP+
G-6-P-dehydrogenase
NADPH + O2
Cytochrome b558
Pentose-P
+ NADPH
+
NADP + O2
-
-
2O2 + 2H+
Superoxide dismutase
-
2O2 + H2O2
H2O2 + 1O2
.OH + OH- + 1O2
Respiratory Burst
Oxygen Dependent Myeloperoxidase
dependent reactions
H2 O2 + Clmyeloperoxidase
-
2OCL + H2O
-
OCl + H2O
1O -+ Cl-+
2
H2O
-
2O2 + 2H+
Superoxide dismutase
2 H2 O2
catalase
H2O2 + O2-
H2O + O2-
Pathways of Intracellular Killing
Intracellular Killing
oxygen-depenedent
myloperoxidase-independent
oxygen-independent
myeloperoxidase-dependent
Mediators of Oxygen Independent
Killing in the Phago-lysosome
Effector Molecule
Function
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 Killing
TNF
TNF
Nitric Oxide
Nitric Oxide
Non-specific Killer Cells
NK and LAK cells
ADCC (K) cell
Activated
macrophages
Eosinophils
They all kill foreign
and altered self
targets
Natural 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-γ to
become LAK cells
Lymphokine Activated Killer
(LAK) cell
kills
kills
transformed
malignant
and
malignant
cells
cells
Regulation of NK Cell Function
MHC I KIR
No Killing
KAR KAL
Killing
K Cells

morphologically undefined

have IgG Fc receptor

recognize antibody coated
targets

could be NK cells (IgG),
macrophages (IgG),
eosinophils (IgE) or other
cells (IgG)