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1. Types of leukocytes
2. Production (Leukopoiesis )
3. Functional characteristics of the
different leukocytes
4. Mechanisms: How do they do
what they do?
Lecture topics: characteristics and functions of WBCs*
Leukocytes
• Only formed elements that are complete cells with a nucleus and cytoplasmic organelles.
• On average, there are 4000-10000 WBC/l of blood. Average no.=7000 l of blood
• Remember they account for about 1% of total blood cells.
• Leukocytosis: An increase in no. of WBCs in circulation.
- specific WBC type: lymphocytosis, granulocytosis, neutrophilia.
• Leukopenia: A decrease in no. of circulating WBCs.
Types of leukocytes**
1. Neutrophils………62%
2. Eosinophils………2.3%
3. Basophils…………0.4%
4. Monocytes………..5.3%
5. Lymphocytes……..30%
Polymorphonuclear
Or granulocytes
Note: To remember the order of abundance leukocytes from most
abundant to least abundant: Never Let Monkeys Eat Bananas
**granulocytes and monocytes protect body by ingestion (phogocytosis) of
invading organisms( for example bacteria). They are formed in bone marrow.
** lymphocytes protects body through immune system. They are formed in
lymphogenous tissues (lymph glands, spleen, tonsils, thymus, Peyer‟s patches in
intestinal wall.
agranulocytes
Genesis of WBCs (leukopoiesis)
Pluripotential
stem cell
lymphoblast myeloblast
neutro eosino
baso mono
T
lympho B
lympho Plasma cell
Life span of WBCs*
• Granulocytes stay in blood for 4-8 hours and in the tissues 5 days. When there is serious infection their whole life span is shortened to few hours
• Monocytes stay in the blood for 10-20 hours and then they leave to different tissues where they form tissue macrophages. Tissue macrophages can live for months. If there is infection these macrophages may die earlier.
• Lymphocytes circulate between blood and lymphoid tissues through lymph and they survive for weeks and months
Neutrophils and macrophages
defend against infection
Macrophage : Monocytes in the
blood then in the tissues swell
and increase the diameter and
become
Leukocytes cross capillary wall by
Diapedesis
Diapedesis – Leukocytes able to slip out of the
capillary. They sequeeze themselves through small pore between endothelial cells that form the capillary wall.
– All leucocytes can make this movement between blood and interstitial space.
Note: diapedesis is increased in inflammation. Factors released from inflamed tissues make WBCs to stick to the capillary wall in inflamed tissue (this effect is
called margination). And this increases diapedesis.
Amoeboid motion of Leukocytes
– leukocytes move through the tissue spaces
through this motion.
– They form cytoplasmic extensions that move them along (pseudopods). These pseudopods also help WBC to phogocytize foreign particles.
Movement of WBCs by Chemotaxis towards an
area of tissue damage
• Chemical substances
(chemotactic substance, chemotaxins) found and produced in the tissues or released by other leukocytes that attract WBCs toward these chemicals.
• Chemotaxins include
1. Bacterial or viral toxins
• Degenerative products of inflamed tissues
• Reaction products of „complement complex‟
• Reaction products of plasma clotting
Chemotactic signals effective till 100m
Opsonization
• Plasma factors act on the bacteria to make them
„tasty‟ to the Phagocytes. It enhances the
phagocytic ability of WBCs
• Opsonins which coat the bacteria are IgG and
Complement proteins
• Coated bacteria bind to receptors on the
Neutrophil membrane.
bacteria
Phagocytosis
• Means ingestion of invading agents (bacteria, viruses,
foreign bodies, dead tissues). Done mostly by
macrophages and neutrophils (neutrophils can
phagocytize 3-20 bacteria and macrophages
can phagocytize up to 100 bacteria)
• 1. Selective – Natural structures is protected from
phagocytosis by smooth surface and protective proteins.
While foreign bodies have rough surfaces and no
protective proteins so they are liable to be phagocytized.
• 2. Antibodies adhere to surface of bacteria and make
them susceptible for phagocytosis (opsonization).
Phagocytosis by neutrophils and
macrophages • Phagocytized particles digested by intracellular
enzymes
• Neutrophils and Macrophages have proteolytic enzymes.
• Macrophages (but not neutrophils) have
lipases which can digest lipid membrane surrounding some bacteria (Tuberculosis bacilli)
• Macrophages are more powerful phagocytes than neutrophils. They can engulf large particles and digest them and extrude the residual products of digestion so they survive after so many phogocytosis process.
Phagocytosis process • The WBC sends pseudopods around foreign particle and making a
enclosed chamber that contains the particle forming phagocytic vesicle (called phagosome).
• Lysosomes containing digestive enzymes fuse with phagosome which is called now digestive vesicle. The particle is digested and residual products are thrown outside WBC.
Phagocytosis (cont.)
• Neutrophils and Macrophages produce
Oxidizing agents which are bactericidal (killing
bacteria) e.g. Super oxide(O2-), Hydrogen
peroxide(H2O2), hydroxyl ions
• Myeloperoxidase is lysosomal enzyme which
can convert chloride to form hypochlorite which
is very strong bactericidal agent.
Note: O2- and H2O2 are Oxidants and Bactericidal
Reticuloendothelial system RES:
Monocytes, Mobile macrophage,
fixed macrophage, spleen, lymph
nodes and specialized endothelial
cells in the bone marrow (all
originated from monocytic stem
cells)
RES is used in medical terms than
monocyte macrophages system as
they are synonymous
Special macrophages are present
in :
1. Skin, subcutaneous tissues
2. Lymph nodes
3. Alveolar macrophages in the
lungs
4. Macrophages (Kupffer cells) in
the liver
5. Macrophages in the spleen and
bone marrow
Eosinophils
• About 2% of all leukocytes
• Ineffective protection against usual types of infection.
• Contain large granules that stain red.
• About the same size as neutrophils but weaker phagocytes
• nucleus has 2 lobes
Eosinophils (cont.) • Eosinophils no. is increased in
people with parasite infection (like worms)
– Release the enzymes (hydrolytic enzymes, highly reactive form of oxygen, major basic protein) from their cytoplasmic granules onto the parasite‟s surface, killing the parasites .
• Eosinophils are attracted by chemotactic factor released by basophils and mast cells toward allergic tissues.
• They detoxify the substances that released during allergic reaction. Also they engulf antibodies-antigens complexes so they help in reducing spread of allergic reaction
Basophils
• Large histamine-containing granules
– Affinity for basic dyes so they stain purplish black (baso = basic).
• Similar in function to mast cells. Mast cells are found in the tissues.
• Both mast cells and basophils liberate histamin and heparin, small quantities of bradykinins and serotonin.
Basophils
• Basophils and mast cells play important role in allergic
reactions.
• IgE attached to surface of basophils and when antigen bind
with IgE on the surface, degranulation follows this binding
and release of histamine, bradykinin, serotonin, Slow
Reactive Substance of Anaphylaxis, heparin and other
lysosomal enzymes
antigen
Agranulocytes
• Lack visible cytoplasmic granules
• Include lymphocytes and monocytes
B lymphoctes
– Attack bacteria, viruses and toxins and converted into
a. Plasma cells that produce antibodies (Ig = immunoglobulin)
b. Memory cells
• Keep a “record” of pathogens
monocyte
T Lymphocytes
• T cells
– Acting directly against
virus-infected cells and
tumor cells
1. CD 4
• T helper cells
2. CD 8
• T cytotoxic cells
3. suppressor T cells
1. T Helper cells : (AIDS) The most
numerous type of T cells. They help in
the function of immune system ,
forming protein mediators called
lymphokinase
which cause:
a. Stimulation of growth and
proliferation of cytotoxic and
suppressor T cells
b. Stimulation of B cells growth and
form plasma cells and antibodies.
c. Activation of macrophage
system.
d. Feedback stimulatory effect
on the T helper cells (positive
feedback effect
2. Cytotoxic cells : Killer cells,
direct attack
3. Suppressor cells: Limiting the
ability of immune system to
attack a person‟s own body
tissues (Immune tolerance)
Monocytes
• They have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is distinctively U or kidney shaped
• Migrate from blood into tissues where they enlarge and become macrophages (which are phagocytic).
Most powerful phagocyte
They can phagocytize whole
RBC, malarial parasites and
dead neutrophils
They are very important in
starting immune responses
They can be called different
names when they stay in
different tissues.
•Skin…..histiocytes
•Lungs...alveolar macrophage
•Liver….Kupffer cells
Plasma cell
A type of immune cell that
makes large amounts of a
specific antibody. They are
develop in the bone marrow
from B cells that have been
activated.They are transported
by plasma and lymphatic
system
Mast cell: Originate from bone marrow
(Monocyte or lymphocytes??),
very similar to basophil.
Found widely in the body
particularly in connective tissues.
They produce histamine, Heparin,
serotonin,
Dopamine and also involve in the
immunological, allergic and
inflammatory conditions.
Leukocytosis: An increase in no. of WBCs in circulation.
- specific WBC type: lymphocytosis, granulocytosis, neutrophilia.
Leukopenia: A decrease in no. of circulating WBCs. Irradiation, Xray or gamma rays. Drugs, chloramphenicol, thiouracil , borbiturate hypnotics
Leukemia :
Uncontrolled production of WBC
1.Lymphocytic (Lymph nodes)
2. Myelogenous (Bone marrow)
Effects of leukemia:
Infection, Sever anemia,
Bleeding tendency, Excessive
use of metabolic substrate by
cancerous cells cause deblitate
of other tissues.
Role of macrophage and
neutrophils in inflammation
• When bacteria get access to certain tissue, the first line of defense is macrophages which are already in that tissue.
• Within hour or so, the no. of neutrophils starts to increase in the area. Neutrophils form the second line of defense.. These neutrophils come from blood due to liberation of chemotactic substances.
Role of macrophage and
neutrophils in inflammation (cont.)
• In severe infection the no. of neutrophils
(neutrophilia) in the blood increases
dramatically 3rd. Products of inflammation
stimulate bone marrow to release the
stored neutrophils there in bone marrow
4th.
( remember that bone marrow stores of
WBCs is more that no. of WBCs in the
blood).
Role of macrophage and
neutrophils in inflammation (cont.)
• Monocytes from blood enter the site of
inflammation and become active
macrophages in few days.
• Factors (Substances) released from
activated macrophages stimulate bone
marrow to produce new monocytes and
neutrophils.
Role of macrophage and
neutrophils in inflammation (cont.) • Monocytes from blood
enter the site of inflammation and become active macrophages in few days.
• Factors (Substances) released from activated macrophages stimulate bone marrow to produce new monocytes and neutrophils.
Activated
macrophage
Releasing
1.TNF (tumor necrosis factor
2. GM-CSF (granulocyte monocyte colony stimulating
factor
3. M-CSF (monocyte colony stimulating factor
4. G-CSF (granulocyte colony stimulating factor
Granulocytes, monocytes
Role of macrophages in activation of
lymphocytes
• When macrophage phagocytize invading microorganisms and digest them, the antigenic products liberated into macrophage cytoplasm. Macrophages pass these antigens directly to lymphocytes leading to activation of specific lymphocytes that can make proper immune reaction against invading microorganism.
• Also macrophages produce substance (interleukin-1) that stimulates growth and reproduction of specific lymphocytes.
macrophage lymphocyte
bacteria
Character of inflammation
•Vasodilatation, permeability, interst fluid
clotting, increase no of granulocyte and
monocyte, swelling of the tissue.
•Tissue product: Histamine, bradykinin,
serotonin, prostaglandin.
•(Walling off) effect of inflamation.
Feedback control of neutro and
macro
TNF, Interleukin 1(IL-1), GM-CSF, M-CSF,
G-CSF
These factors are formed by activated
macrophages in the inflamed tissues
Formation of pus
Neut and Macro engulf bacteria
and necrotic tissues then Neut
and macro die and cavity
formed in the inflamed tissue.
This cavity contains necrotic
tissue, dead Neut, dead Macro
and tissue fluid. This mixture
known as pus
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