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University of Tabuk
Faculty of Applied Medical Science
Department of Medical Laboratory Technology
Basic Immunology
Mr.AYMAN.S.YOUSIF
MSc.Medical Microbiology &
Immunology
Academic Year: 1433-1434 (2012-2013)
Innate Immunity
PHAGOCYTOSIS
Lecture 3 : part 1
Mr.AYMAN.S.YOUSIF
17-18/02/2013
Objectives
1
At the end of this lecture, you should be able to:
1. Recognize the significance of the phagocytosis and
inflammation in combating infection and disease.
2. Define the phagocytosis.
3. know the types and characteristics of phagocytic cells.
4. Understanding the mechanism of action of phagocytosis .
5. know the function of inflammation.
6. Explain the different stages of inflammation and
inflammatory response .
Phagocytosis
2
Is process by which particular substances, such as
bacteria, are engulf by a cell and destroyed.
 Phagocytosis is one form of endocytosis (internalise
solid matter).The other form - pinocytosis – is the
internalization of fluids and solutes.
 Phagocytosis requires :
1. Energy generated through glucose metabolism .
2. Synthesis of a new cell membrane.
3. An active cytoplasmic contractile protein system.

Types of phagocytic cells
3
Most cells are capable of phagocytosis.
 The professional phagocytes of the immune
system, including .

Neutrophils .
 Monocytes/Macrophages.

Types of phagocytic cells
4
Neutrophiles/Polymorphonuclear cells (PMNs)
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Are granulocytes that circulate in the blood and
migrate quickly in response to local invasion by
microorganism .
 Cells that have lobed nuclei. They can be identified
by their characteristic nucleus or by an antigen
present on the cell surface called CD66.
 They contain two kinds of granules
 the
contents of which are involved in the
antimicrobial properties of these cells.

Neutrophiles/Polymorphonuclear cells (PMNs)
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1.The primary or azurophilic granules
which are abundant in young newly formed PMNs,
contain :A. Cationic proteins and Defensins that can kill bacteria.
B. Proteolytic Enzymes like



Elastase, and Cathepsin G to break down proteins.
Lysozyme to break down bacterial cell.
Myeloperoxidase, which is involved in the
generation of bactericidal compounds.
Neutrophiles/Polymorphonuclear cells (PMNs)
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2. The second type of granule
Found in more mature PMNs is the secondary or
specific granule. These contain.
A. Lysozyme.
B. NADPH oxidase components, which are involved
in the generation of toxic oxygen products.
C. Lactoferrin and B12-bindin protein.
Monocytes/Macrophages
8
Monocytes also circulate in blood , but in
much lower numbers than neutrophils. They
migrate to the tissue, where they differentiate
into Macrophage, which reside in all body
tissues. For example
 Kupffer cells are macrophage in the liver .
 Histiocytes are macrophage in connective
tissue.

Monocytes/Macrophages
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Macrophages are characteristic kidneyshaped nucleus. They can be identified
morphologically or by the presence of the
CD14 cell surface marker.
 Unlike PMNs they do not contain granules
but they have numerous lysosomes which
have contents similar to the PNM granules.

Movement of phagocytic cells
10
1. Ameboid movement.
Phagocytic cells migrate in and out of blood vessels
and through out the tissue. The process of cellular
emigration from capillaries is called diapedesis .
2. Chemotaxis.
Phagocytes move toward other cells or organisms
by cytoplasmic streaming in response to chemical
agent called chemotaxin .
DIAPEDESIS
11

The movement or passage of blood cells,
especially white blood cells, through intact
capillary walls into surrounding body tissue. Also
called migration.
CHEMOTAXIS.
12
During chemotaxis cells move in response to chemical signals. The
action of neutrophils is just one example of how the body uses
chemotaxis to respond to an infection
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Factors that chemotactic phagocytic cells
Mechanism of Phagocytosis
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Macrophage
Mechanism of Phagocytosis
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Microbes adhere to the phagocyte.
 Pseudopods engulf the particle (antigen) and
creation of phagosome.
 Phagosomes fuse with a lysosome to form a
phagolysosome.
 Invaders in the phagolysosome are digested by
proteolytic enzymes.
 Indigestible and residual material is removed by
exocytosis.

Endocytosis is the movement of a substance into a cell by a vesicle. while
the movement of a substance by a vesicle tot eh outside of a cell is called
exocytosis
Initiation of Phagocytosis
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


Phagocytic cells have a variety of receptors on their
cell membranes through which infectious agents bind
to the cells. These include:
Fc receptors. Bacteria with IgG antibody on their
surface have the Fc region exposed and this part of the
Ig molecule can bind to the receptor on phagocytes .
Complement receptors – Phagocytic cells have a
receptor for the 3rd component of complement, C3b.
Binding of C3b-coated bacteria to this receptor also
results in enhanced phagocytosis and stimulation of
the respiratory burst.
Phagocytic cells receptors
17
Complement receptors
Fc receptors
Initiation of Phagocytosis
18


Scavenger receptors – Scavenger receptors bind a wide
variety of polyanions on bacterial surfaces resulting in
phagocytosis of bacteria.
Toll-like receptors – Phagocytes have a variety of Tolllike receptors (Pattern Recognition Receptors or PRRs)
which recognize broad molecular patterns called
PAMPs (pathogen associated molecular patterns) on
infectious agents. Binding of infectious agents via Tolllike receptors results in phagocytosis and the release of
inflammatory cytokines (IL-1, TNF-á and IL-6) by the
phagocytes. (InterLeukin 1-6 & Tumor Necrosis Factor)
Phagocytic cells receptors
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Toll-like receptors
Intracellular Killing by phagocytosis
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1. Oxygen-dependent intracellular




When a phagocyte ingests bacteria (or any material), its
oxygen consumption increases.
The increase in oxygen consumption, called a respiratory
burst, produces reactive oxygen-containing molecules that
are anti-microbial.
The oxygen compounds are toxic to both the invader and the
cell itself, so they are kept in compartments inside the cell.
This method of killing invading microbes by using the
reactive oxygen-containing molecules is referred to as
oxygen-dependent intracellular killing.
Intracellular Killing by phagocytosis
21
2. Oxygen-independent intracellular
 Phagocytes can also kill microbes by oxygen-independent methods,
but these are not as effective as the oxygen-dependent ones. There are
four main types.
 The first uses electrically charged proteins which damage the
bacterium's membrane.
 The second type uses lysozymes; these enzymes break down the
bacterial cell wall.
 The third type uses lactoferrins, which are present in neutrophil
granules and remove essential iron from bacteria.
 The fourth type uses proteases and hydrolytic enzymes; these
enzymes are used to digest the proteins of destroyed bacteria.
Innate Immunity
Inflammation
Part 2
Mr.AYMAN.S.YOUSIF
17-18/02/2013
Inflammation
21
 The function of inflammation is to localize tissue damage,
localize responses, Prevents spread of agents and then to
restore tissue function (tissue repair).
 The action of localized leukocytes is augmented via the
attraction of neutrophils and monocytes normally found in
circulation.
 Microbial materials such as LPS, flagellin (making up
bacterial flagella), activated complement, and even bacterial
DNA serve as indicators of infection which in turn activates
the production of pro-inflammatory cytokines (immunesystem activating chemicals).
 In addition to the cell-to-cell interactions underlying
inflammation, the inflammatory response involves localized
increases in blood flow, leakage of blood vessels, and
attraction of leukocytes from the blood.
The Three Stages of Inflammation
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1. Vasodilatation and increased vessel permeability
Due to histamine (and other cytokine) release  edema
2. Phagocyte migration and phagocytosis.
 Margination and diapedesis (emigration)
 Chemotaxis(due to various cytokines and
components of complement system)
 Pus formation.
 Factors challenging effectiveness of phagocytosis
3. Tissue repair and regeneration depends on type of tissue
Hallmarks of Inflammation
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Redness – erythema & hyperemia
 Heat – due to dilated BVs
 Swelling – exudates/edema
 Dilutes
 O2 and nutrients for repair
 Clotting proteins enter
 Pain – pressure on localized nerve endings

24
Inflammatory Response
Histamine &
prostaglandins
released
Capillaries dilate
Clotting begins
Chemotactic
factors attract
phagocytic cells
Phagocytes
consume
pathogens &
cell debris
Inflammation
25
Margination
Diapedesis
Inflammation
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27
Figure 21.3
Thank You