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Immunology Immunology (elective)(elective)MLIM-101MLIM-101
Lecture: 1Lecture: 1
Prepared by: Prepared by: Dr. Mohamed S. Abdel-Dr. Mohamed S. Abdel-
LatifLatif
Learning Outcome:
At this time you should know the following:
1. Differences between the non-specific and specific immune functions. 2. Humoral components of the non-specific immune system and their action. 3. Cellular components of the non-specific immune function and their action. 4. Pathways of intracellular killing of bacteria by phagocytes and their characteristic features. 5. Effect of humoral components such as interferon, TNF, IL-2, complement etc. on cellular components of the non-specific immune system.
Development of the Immune SystemDevelopment of the Immune System
ery pl
mye
neu mφ
lym
nk
thy
CD8+
CD4+
CTL
TH2
TH1
Cells of the Immune System
BasophilsNeutrophils
Eosinophils
Granulocytic
Langerhans &Macrophages
Kupffer cellsDendritic cells?
Monocytic
CytotoxicHelper
Suppressor
T-cells
Plasmacells
B-cells Dendriticcells?
lymphoid cellsMyeloid cells
Components of the Immune System
Components of the Immune System
Humoral Cellular Humoral Cellular
SpecificNonspecific
complement, interferon, TNF etc.
macrophages, neutrophils
T cells; other effectors cells
antibodies
Balance between Infection and Immunity
Balance between Infection and Immunity
infection immunity
Bolus of infection x virulenceimmunity
Disease =
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
Innate Immunity Adaptive Immunity
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
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
Site Component Functions
Effector mechanisms in Innate Immunity -1
Effector mechanisms in Innate Immunity -1
Peristalsis, low pHbile salts, fatty acids
columnar cellsGI tract
Skin squamous cellssweat
desquamationflushing, fatty acids
tracheal ciliaLung mucociliary elevator
surfactants
Site Component Functions
Effector mechanisms in Innate Immunity -2
Effector mechanisms in Innate Immunity -2
Nasopharynxand eye
mucus, saliva, tears flushing, lysozyme
PhagocytesBlood andLymphiodorgans
phagocytosis and intracellular killing
K, NK & LAK cells
direct and antibody dependent cytolysis
Site Component Functions
Effector mechanisms in Innate Immunity -3
Effector mechanisms in Innate Immunity -3
Serum and other serous
fluids
lactoferrin, transferrin
iron deprivation
interferons, TNF-
antiviral proteins phagocyte activation
lysozyme peptidoglycan hydrolysis
Fibronectin & complement
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…”
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
Attachment via
IgG FcR
ScavengerR
CR
Toll-like R
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 + O2-2O2
- + 2H+
Superoxide dismutase
H2 O2 + Cl-
myeloperoxidaseOCl- + H2O
H2O + O2-2 H2 O2
catalase
2OCL- + 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
Non-specific Killer CellsNon-specific Killer Cells
NK and LAK cells
ADCC (K) cell
Activated
macrophages
Eosinophils
NK and LAK cells
ADCC (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-γ 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-γ 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)