Phagocytosis is the process by which cells called phagocytes engulf and digest particles. Professional phagocytes like neutrophils and macrophages recognize, bind to, and ingest bacteria or fungi through receptors on their surface. They destroy the ingested microbes in intracellular vesicles. Acute inflammation is the initial immune response to infection or injury, characterized by redness, swelling, heat and pain. It involves recruitment of phagocytes to sites of damage through adhesion molecules and chemokines, where they eliminate microbes through phagocytosis. Once the threat has been removed, anti-inflammatory mediators resolve inflammation and tissue repair begins.
Types of immune cells
∆Lymphoid cells
-lymphocytes
constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph
continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs
lymphocytes enlarge into 15 µm-diameter blast cells, called lymphoblasts; these cells have a higher cytoplasm : nucleus ratio and more organellar complexity than small lymphocytes.
Lymphoblasts proliferate and eventually differentiate into-
effector cells or into
memory cells.
* B-lymphocytes
*T-lymphocytes
* Natural killer cells
∆mononuclear phagocytes
The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues.
-macrophages
-monocytes
∆granulocytes cells
Granulocytes are at the front lines of attack during an immune response and are considered part of the innate immune system.
Granulocytes are white blood cells (leukocytes) that are classified as neutrophils, basophils, mast cells, or eosinophils on the basis of differences in cellular morphology and the staining of their characteristic cytoplasmic granules
The cytoplasm of all granulocytes is replete with granules that are released in response to contact with pathogens.
These granules contain a variety of proteins with distinct functions:
Some damage pathogens directly;
some regulate trafficking and activity of other white blood cells, including lymphocytes
-neutrophills
-basophils
-eosinophils
-dendritic cells
-mast cells
Inflammation is the reaction of living tissues to all forms of injury.
Inflammation is essentially a protective response intended to destroy invading microorganism inactivate toxins and to achieve healing and repair.
Inflammation is a protective immune vascular response that involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair.
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Types of immune cells
∆Lymphoid cells
-lymphocytes
constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph
continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs
lymphocytes enlarge into 15 µm-diameter blast cells, called lymphoblasts; these cells have a higher cytoplasm : nucleus ratio and more organellar complexity than small lymphocytes.
Lymphoblasts proliferate and eventually differentiate into-
effector cells or into
memory cells.
* B-lymphocytes
*T-lymphocytes
* Natural killer cells
∆mononuclear phagocytes
The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues.
-macrophages
-monocytes
∆granulocytes cells
Granulocytes are at the front lines of attack during an immune response and are considered part of the innate immune system.
Granulocytes are white blood cells (leukocytes) that are classified as neutrophils, basophils, mast cells, or eosinophils on the basis of differences in cellular morphology and the staining of their characteristic cytoplasmic granules
The cytoplasm of all granulocytes is replete with granules that are released in response to contact with pathogens.
These granules contain a variety of proteins with distinct functions:
Some damage pathogens directly;
some regulate trafficking and activity of other white blood cells, including lymphocytes
-neutrophills
-basophils
-eosinophils
-dendritic cells
-mast cells
Inflammation is the reaction of living tissues to all forms of injury.
Inflammation is essentially a protective response intended to destroy invading microorganism inactivate toxins and to achieve healing and repair.
Inflammation is a protective immune vascular response that involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair.
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2. Phagocytosis Definition
•Phagocytosis, or “cell eating”, is the process
by which a cell engulfs a particle and digests
it. The word phagocytosis comes from the
Greek phago-, meaning “devouring”, and -
cyte, meaning “cell”.
•Phagocytosis was first observed by E´ lie
Metchnikoff (1) more than 100 years ago.
Since then, it has been recognized as a
3. critical component of the innate and adaptive
Phagocytosis
• Phagocytosis is a process of ingestion of particles larger than 0.5 µm
in diameter. It begins with membrane receptors binding to the
microbe. phagocytosis involves the recognition and binding of prey by
receptors on the cell surface.
• Foreign bodies such as bacteria or fungi can be cleared from infection
sites by professional phagocytes such as neutrophils, macrophages,
and dendritic cells.
• Neutrophils and macrophages ingest (phagocytose) microbes and
destroy the ingested microbes in intracellular vesicles .
4. The Steps Involved in Phagocytosis
• Step 1: Activation of the Phagocyte
• Resting phagocytes are activated by inflammatory mediators such as
bacterial products (bacterial proteins, capsules, LPS, peptidoglycan,
teichoic acids, etc.), complement proteins, inflammatory cytokines,
and prostaglandins. As a result, the circulating phagocytes produce
surface glycoprotein receptors that increase their ability to adhere to
the inner surface of capillary walls, enabling them to squeeze out of
the capillary and be attracted to the site of infection.
5. Phagocytosis steps
• Step 2:
• In the immune system, chemotaxis may occur. Chemotaxis is the
movement of phagocytes toward a concentration of molecules.
Immune cells pick up chemical signals and migrate toward invading
bacteria or damaged cells.
• Step 3:
• The cell attaches to the particle that it will ingest. Attachment is
necessary for ingestion to occur. Some bacteria can resist attachment,
making it harder for them to be taken into the cell and destroyed.
6. Phagocytosis Steps
• Step 4:
The cell ingests the particle, and the particle is enclosed in a vesicle (a
sphere of cell membrane with fluid in it) called a phagosome. The
phagosome transports the particle into the cell.
• Step 5:
A lysosome fuses with the phagosome and the particle is digested.
Lysosomes are vesicles that contain hydrolytic enzymes that break
down molecules. A phagosome fused with a lysosome is called a
phagolysosome.
7. Phagocytosis Steps
• Step 6:
Cellular waste, such as broken down molecules that the cell cannot
reuse, is discharged from the cell by the process of exocytosis.
Exocytosis is the opposite of endocytosis; it is when cellular waste
products travel in vesicles to the surface of the cell membrane and are
released, thereby exiting the cell.
8. Process of phagocytosis
A cell ingests a particle, breaks it down with the
enzymes in lysosomes, and expels waste
products through exocytosis.
9. Inflammation
• Inflammation is a tissue reaction that delivers mediators of host
defense—circulating cells and proteins—to sites of infection and
tissue damage. Inflammation is the process by which the body deals
with an insult from physical or chemical agents and invasion by
microbes. It is recognized by its cardinal signs, including redness,
heat, swelling, and pain.
• Acute inflammation is generally of short duration,lasting from
minutes to a few days, and is the result of an initial response by cells
of the immune system (primarily PMNs) to remove an infectious
agent.
• Chronic inflammation, which may last months to years, usually
results from the persistence of a microbe in a viable or inert state and
11. Acute Inflammation
• The process of inflammation consists of recruitment of cells and
leakage of plasma proteins through blood vessels and activation of
these cells and proteins in the extravascular tissues. This is often
followed by a local accumulation in the tissue of phagocytes, mainly
neutrophils, in response to cytokines, discussed below. Activated
phagocytes engulf microbes and dead material and destroy these
potentially harmful substances.
• Cytokines and other mediators are produced by macrophages, dendritic
cells, mast cells, and other cells in tissues in response to microbial
products and damaged host cells. These mediators increase the
permeability of blood vessels, leading to the entry of plasma proteins
(e.g., complement proteins) into the tissues and promote the
12. Recruitment of Phagocytes to Sites of
Infection and Tissue Damage
• Neutrophils and monocytes migrate to extravascular sites of
infection or tissue damage by binding to venular endothelial
adhesion molecules and in response to chemoattractants produced
by tissue cells reacting to infection or injury. Leukocyte migration
from the blood into tissues is a multi-step process in which initial
weak adhesive interactions of the leukocytes with endothelial cells are
followed by firm adhesion and then transmigration through the
endothelium .
• Leukocyte migration from the blood into tissues is a multi-step process
in which initial weak adhesive interactions of the leukocytes with
endothelial cells are followed by firm adhesion and then
transmigration through the endothelium (
14. At sites of infection, macrophages, dendritic cells, and other cells that have
encountered microbes produce cytokines such as tumor necrosis factor (TNF)
and interleukin-1 (IL-1) that activate the endothelial cells of nearby venules to
express selectins and ligands for integrins and to secrete chemokines. Selectins
mediate weak tethering and rolling of blood neutrophils on the endothelium,
integrins mediate firm adhesion of neutrophils, and chemokines activate the
neutrophils and stimulate their migration through the endothelium to the site of
infection. Blood monocytes and activated T lymphocytes use the same
mechanisms to migrate to sites of infection.
15. • Mast cells, which are distributed throughout the body are central to the
acute inflammatory process in that, on stimulation, they release
histamine and other vasoactive amines that result in the vascular
changes seen in acute inflammation. Proinflammatory substances
released by mast cells include the cytokines IL-1 and TNFα and other
molecules including leukotrienes, PAF, and nitric oxide which cause
blood vessel dilation and edema. These molecules also increase
adhesion of neutrophils and monocytes to endothelium.
• Tissue macrophages also play a role in generation of pro-inflammatory
cytokines via recognition, through their pattern recognition receptors
(PRRs), of PAMPs associated with microbes. Crucial to both
elimination of a microbe and the healing process is the production of
16.
17. Vascular changes
• The inflammatory mediators released by tissues, mast cells, and
macrophages cause dilation of the blood vessels (vasodilation), which
increases blood flow and smooth muscle contraction. Changes in tight
junctions in endothelial and PMNs from the bloodstream to the site of
release of these inflammatory mediators. Vasodilation and increased
blood flow result in the redness and heat, and the edema (fluid
accumulation) results in swelling. Fluid accumulation together with
tissue damage gives rise to pain through pain receptors. This leads to
arrest and flattening of the PMN, which then extravasates by
squeezing between the endothelial cells. The PMN then migrates into
the tissues towards the source of the inflammatory mediators
18.
19. Termination of the response and repair
• Once the offending insult, for example a microbe, has been removed or
controlled, inhibitors dampen inflammation and tissue repair
mechanisms become activated. Inhibitors of the pro-inflammatory
cytokines include their soluble receptors (e.g., receptors for IL-1,
TNFα, IL-6, and IL-12), the anti-inflammatory cytokines (IL-4, IL-10,
and TGFβ), components of the hemostasis and thrombosis system, and
glucocorticoids.
• As the inflammatory phase is neutralized by these anti-inflammatory
molecules, repair of the damage begins. Various cells, including
myofibroblasts and macrophages, both of which make collagen, mend
tissues. Macrophage products, including epidermal growth factor,
platelet-derived growth factor, fibroblast growth factor, and
20. Specific Immunity
• Specific or acquired immunity develops during an individual’s lifetime.
• It distinguishes self from nonself, and responds specifically to different pathogens and foreign molecules.
• Components:
• Lymphocytes are key players in the specific or acquired immune response:
• Lymphocytes represent 20% to 40% of blood leukocytes;
• T lymphocytes (also called T cells), which participate in cell-mediated immunity (60-70%);
• B lymphocytes (also called B cells), which participate in humoral immunity (10-20%);
• Cell-mediated immunity involves the production of cytotoxic T cells, which have the ability to destroy
antigen-bearing cells.
• Humoral immunity is characterized by the transformation of B cells into plasma cells, which secrete
immunoglobulins (antibodies) that have specific activity against the inciting antigen.
21. Properties of adaptive Immune responses
• Specificity is the ability to distinguish between many different
antigens. It implies that the total collection of lymphocyte specificities,
sometimes called the lymphocyte repertoire, is extremely diverse .
The basis for this remarkable specificity and diversity is that
lymphocytes express clonally distributed receptors for antigens,
meaning that the total population of lymphocytes consists of many
different clones .
• The clonal selection hypothesis each antigen elicits an immune
response by selecting and activating the lymphocytes of a specific
clone
• Memory :The adaptive immune system mounts larger and more
effective responses to repeated exposures to the same antigen.
22. Immunologic memory optimizes the ability of the immune system to
• P.p.42-47 (peter lydyard)
• P.p.46-50 (abbul abbas)