Immunology & Immunotechnology

Immunology & Immunotechnology
(Biot-3111) Lecture -3
1
2.8. Phagocytosis
• The engulfment of a particle or a microorganism by

leukocytes such as macrophages and neutrophils
• Phagocytosis is one types of endocytosis
• Endocytosis
• General term for the uptake by a cell of material from its
environment
• Phagocytosis
• Pinocytosis
2
2.8. Phagocytosis …
• Most phagocytosis is conducted by specialized

cells called Phagocytes
• All phagocytes are types of WBCs or derivatives of
WBCs
• Blood monocytes
• Tissue macrophages
• Neutrophils
• Occasionally eosinophils
3
• Actions of phagocytic cells

• When an infection occurs:
• Both granulocytes (especially neutrophils, but also

eosinophils and dendritic cells) and monocytes migrate to the
infected area
• During this migration, monocytes leave the blood and migrate

into tissues, where they enlarge and develop into actively
phagocytic macrophages
• Some macrophages called fixed macrophages, or histiocytes

4
• Fixed Macrophages (Histiocytes) are found in:

• Liver (Kupffer’s cells)
• Lungs (alveolar macrophages)
• Nervous system (microglial cells)
• Bronchial tubes
• Spleen (splenic macrophages)
• Lymph nodes
• Red bone marrow (Osteoclasts)
• The peritoneal cavity surrounding abdominal organs
(peritoneal macrophages) 5
• Other macrophages are motile and called free

(wandering) macrophages
• Which roam the tissues and gather at sites of infection or

inflammation
• Wandering macrophages
• Originate from monocytes that leave blood and enter

infected tissue, and develop into phagocytic cells
6
• During the course of an infection, a shift occurs in the type of

WBCs that predominates in the bloodstream
• During the initial phase of bacterial infection

• Neutrophils become dominant
• As the infection progresses

• The macrophages becomes dominant; they scavenge and
phagocytize remaining living bacteria and dead or dying bacteria
• Each dominance can be reflected in a differential WBC count

7
• Steps of phagocytosis
1) Chemotaxis and adherence
2) Ingestion/ Engulfment
3) Formation of phagosome
4) Formation of phagolysosome
5) Digestion of ingested microbes
6) Formation of residual body
7) Discharge of waste materials
8
1. Chemotaxis and adherence

• Chemotaxis
• Migration of cells along a concentration gradient of an
attractant
• Phagocytes recruited to site of infection / damage

• Chemical stimuli acts as chemo-attractants
• Products of microbes
• Phospholipids from damaged cells
• C5a 9
• Adherence - Attachment
• Receptors on phagocytes can recognize and bind microbes
directly & indirectly
• Direct binding
• Receptors recognize pathogen associated molecular pattern
(PAMP) on microbes
• Indirect binding
• Particles first is opsonized  Increases phagocytes ability to
attach & engulf
• Opsinization
• Coating of a particle/ a bacterium with antibody and/or a
complement that lead to enhanced phagocytosis 10
2. Ingestion/ Engulfment
• Once phagocytic cells in contact with a particle/microbe
• Pseudopods extend and surround the material being engulfed
• The pseudopods meet and fuse, surrounding the microbe with

a membrane-bound vacuole/sac called a phagosome or
phagocytic vesicle
11
3. Formation of phagosome
• The phagosome pinches off from the plasma membrane
and enters the cytoplasm
• Yet, the microbe does not destroy
12
4. Formation of phagolysosome
• Phagosome transported along cytoskeleton
• Within the cytoplasm
• Phagosome contacts lysosomes that contain digestive

enzymes (lysozyme & proteases) and bactericidal
substances
• The phagosome and lysosome membranes fuse to form a

single, larger sac called a phagolysosome
13
5. Digestion of ingested microbes
• In the phagolysosome
• O2 consumption increases
• Sugars metabolized via aerobic respiration
• Produces toxic oxygen products: superoxide radicals (O2–),

hydrogen peroxide (H2O2), singlet oxygen (1O2−), hydroxyl
radicals (OH), nitric oxide (NO)
• Metabolic pathway will switch to fermentation with production

of lactic acid (lowers pH)
• Kills microbes 14
5. Digestion of ingested microbes …

• Hydrolytic enzyemes (lipases, proteases, ribonuclease and
deoxyribonuclease) of the lysosome:
• Degrade peptidoglycan & other cell components of the
ingested microbes
6. Formation of residual body

• Indigestible products of microbes packed in a vessicles
called residual body which is ready to be released outside
the phagocytes
15
7. Discharge of waste materials/ Exocytosis
• The residual body with the indigested material fuses with

the plasma membrane
•  Expels material to environment
16
17
Microbial evasion of phagocytosis
• The ability of a pathogen to cause disease is related to its

ability to evade phagocytosis
• Some bacteria have structures that inhibit adherence, such

as the M protein and capsules
• Other microbes may be ingested but not killed
• For example, Staphylococcus produces leukocidins that may

kill phagocytes
18
Microbial evasion of phagocytosis …

• A number of intracellular pathogens secrete pore-forming
toxins that lyse phagocyte cell membranes once inside the
phagocyte
• Still other microbes have the ability to survive inside

phagocytes
• Bacteria that are part of biofilms are much more resistant to

phagocytosis
• Because the phagocytes cannot detach bacteria from the biofilm

prior to phagocytosis 19
2.9. Inflammation
• A complex reaction of the innate immune system to

tissue injury or infection involving accumulation and
activation of leukocytes, plasma proteins and fluid at a
site of damage
• The tissue damage can be caused by:

• Microbial infection
• Physical agents such as:
• Heat, radiant energy, electricity or sharp objects
• Chemical agents such as:
• Acids, bases or gases
20
2.9. Inflammation …
• Inflammation
• Swollen and reddened state
• Usually characterized by four cardinal signs:
• Redness
• Pain
• Heat
• Swelling
• Sometimes loss of function 21
• Function of inflammation:
• To destroy the injurious agent and to remove it and its by-

products from the body if possible
• To limit the effects on the body by confining or walling

off the injurious agent and its by-products if destruction is
not possible
• To repair or replace tissue damaged by the injurious agent

or its by-products 22
• Excess inflammatory responses may lead to

inflammatory disorders such as rheumatoid arthritis
and Crohn’s disease
• Events that initiate the inflammatory response:

• Microbial products
• Microbial cell surfaces
• Tissue damage
23
Microbial products
• LPS, flagellin, bacterial DNA trigger toll-like receptors
of macrophages
• Cause macrophages to produce pro-inflammatory cytokines

(IL-1, IL-6, TNF and interferons)
• TNF-alpha induces liver to synthesize acute-phase

proteins that facilitate phagocytosis & complement
activation
24
Microbial cell surfaces
• Trigger complement cascade
• Produces C3a & C5a  stimulate changes associated with

inflammation
• Also induce mast cells to release pro-inflammatory

cytokines (TNF-alpha), histamine, & others substance
25
Tissue damage
• Results in activation of 2 enzymatic cascades
• Coagulation cascade
• Result in blood clotting
• Other cascade
• Produces molecules like bradykinin – a vasoactive peptide
that is produced as a result of tissue damage and act as an
inflammatory mediator
26
• The process of inflammation has three stages:
1) Vasodilation
• Increased permeability of blood vessels
2) Phagocyte migration and phagocytosis
3) Tissue repair
27
1. Vasodilation
• Immediately following tissue damage:
• Blood vessels dilate in the area of damage and their

permeability increases
• Blood flow to the damaged area increases

• It is responsible for the redness (erythema) and heat associated
with inflammation
• Velocity of blood flow in capillaries decreases

28
1. Vasodilation …
• Permits defensive substances (transferrin, complement,
antibodies) and fluids normally retained in the blood to
pass through the walls of the blood vessels and enter the
injured area
• It is responsible for the edema (accumulation of fluid) of

inflammation
• Direct effect of chemicals and pressure created by fluids

on sensory nerve endings cause pain 29
1. Vasodilation …
• Vasodilation and increase in permeability of blood vessels
are caused by a number of chemicals released by damaged
cells in response to injury, such as:
• Histamine
• A vasoactive amine stored in mast cells, causing dilation of local
blood vessels and smooth muscle contraction
• Kinins
• A polypeptide that causes dilation in blood vessels and contraction
of smooth muscle
30
1. Vasodilation …
• Prostaglandins
• Unsaturated fatty acid which control smooth muscle
contraction, blood pressure, inflammation, and body
temperature
• Cytokines
• Any protein secreted by lymph cells that affects cellular
activity and controls inflammation
31
1. Vasodilation …
• Vasodilation and the increased permeability of blood
vessels also help deliver clotting elements of blood into
the injured area
• The blood clots that form around the site of infection

prevent the microbe (or its toxins) from spreading to other
parts of the body
32
2. Phagocyte migration and phagocytosis
• As flow of blood gradually decreases, phagocytes stick to the inner

surface of the endothelium (lining) of blood vessels
• This sticking process in response to local cytokines is called

margination
• Then the collected phagocytes squeeze between the endothelial cells

of the blood vessel to reach the damaged area
• This migration, which resembles ameboid movement, is called

diapedesis
33
2. Phagocyte migration and phagocytosis …

• Then phagocytes are ready to destroy invading microbes by
phagocytosis
• Certain chemicals attract neutrophils to the site of injury (chemotaxis)
• These include chemicals produced by microbes and even other neutrophils
• Other chemicals are:

• kinins
• Leukotrienes
• Chemokines
• Components of the complement system
34
• Chemokines are cytokines that are chemotactic for

phagocytes and T cells
• They stimulate both the inflammatory response and an

adaptive immune response
35

• As the inflammatory response continues, monocytes
follow into the infected area
• In the tissue monocytes become free microphages
• Granulocytes predominate in the early stages of infection
• Macrophages predominate during a later stage of infection
36

• Macrophages are more phagocytic than granulocytes
• After granulocytes or macrophages engulf large numbers

of microbes and damaged tissue, they themselves
eventually die
• As a result, pus forms = Dead cells + tissue debris
37
3. Tissue repair
• A process by which tissues replace dead or damaged cells
• A tissue is repaired when the stroma (supporting tissue) or

parenchyma (functioning tissue) produces new cells
• The ability of a tissue to regenerate, or repair itself, depends

on the type of tissue:
• Skin has a high capacity for regeneration
• Cardiac muscle tissue does not have a high capacity to

regenerate 38
3. Tissue repair …
• Tissue repair by fibroblasts produces scar tissue by a
process called fibrosis
• Scar can interfere with normal tissue function
39
40
3. Tissue repair …
41

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• The engulfment of a particle or a microorganism by

• Phagocytosis is one types of endocytosis

• Most phagocytosis is conducted by specialized

• Actions of phagocytic cells

• Both granulocytes (especially neutrophils, but also

• During this migration, monocytes leave the blood and migrate

• Some macrophages called fixed macrophages, or histiocytes

• Fixed Macrophages (Histiocytes) are found in:

• Other macrophages are motile and called free

• Which roam the tissues and gather at sites of infection or

• Originate from monocytes that leave blood and enter

• During the course of an infection, a shift occurs in the type of

• During the initial phase of bacterial infection

• As the infection progresses

• Each dominance can be reflected in a differential WBC count

1. Chemotaxis and adherence

• Phagocytes recruited to site of infection / damage

• Once phagocytic cells in contact with a particle/microbe

• Pseudopods extend and surround the material being engulfed

• The pseudopods meet and fuse, surrounding the microbe with

• Yet, the microbe does not destroy

• Within the cytoplasm

• Phagosome contacts lysosomes that contain digestive

• The phagosome and lysosome membranes fuse to form a

5. Digestion of ingested microbes

• Produces toxic oxygen products: superoxide radicals (O2–),

• Metabolic pathway will switch to fermentation with production

5. Digestion of ingested microbes …

6. Formation of residual body

7. Discharge of waste materials/ Exocytosis

• The residual body with the indigested material fuses with

•  Expels material to environment

Microbial evasion of phagocytosis

• The ability of a pathogen to cause disease is related to its

• Some bacteria have structures that inhibit adherence, such

• Other microbes may be ingested but not killed

• For example, Staphylococcus produces leukocidins that may

Microbial evasion of phagocytosis …

• Still other microbes have the ability to survive inside

• Bacteria that are part of biofilms are much more resistant to

• Because the phagocytes cannot detach bacteria from the biofilm

• A complex reaction of the innate immune system to

• The tissue damage can be caused by:

• To destroy the injurious agent and to remove it and its by-

• To limit the effects on the body by confining or walling

• To repair or replace tissue damaged by the injurious agent

• Excess inflammatory responses may lead to

• Events that initiate the inflammatory response:

• Microbial cell surfaces

• Cause macrophages to produce pro-inflammatory cytokines

• TNF-alpha induces liver to synthesize acute-phase

Microbial cell surfaces

• Trigger complement cascade

• Produces C3a & C5a  stimulate changes associated with

• Also induce mast cells to release pro-inflammatory

• The process of inflammation has three stages:

• Increased permeability of blood vessels

2) Phagocyte migration and phagocytosis

• Blood vessels dilate in the area of damage and their

• Blood flow to the damaged area increases

• Velocity of blood flow in capillaries decreases

• It is responsible for the edema (accumulation of fluid) of

• Direct effect of chemicals and pressure created by fluids

Immunology & Immunotechnology - 3

Immunology & Immunotechnology - 3