Blood
Main features
• Blood cells and blood plasma
• Plazma proteins cause blood clotting and
form thrombs.
• Serum does not contain white or red blood
cells nor a clotting factor; it is the blood
plasma with the fibrinogens removed.
• Blood cells are: erythrocytes, leukocytes
and platelets
http://en.wikipedia.org/wiki/Blood
Formed elements
Blood plasma
Blood plasma - 55% of blood volume.
90% - 92% water, 7%-9% proteins, 1% inorganic elements, glucose, hormons,
vitamins, a.o.
Tissue liquid – similar concentration of electrolyte, smaller concentration of
proteīns a.o. organic substances.
Border: basal membrane and wall of blood vessels with Continuous or
Fenestrated endothelium.
Ions
Ions
Concentration (mmol.l−1)
Calcium
Chlorine
Potassium
Sodium
2.1–2.8
95–105
3.6–5.1
135–145
Proteins
Protein
Albumin
Koncentrācija
3.5-5.0 g/dl
%
Function
55%
maintains colloid osmotic pressure; create
oncotic pressure and transport
insoluble molecules
Globulins
2.0-2.5 g/dl
38%
α and β globulins transport metals,
vitamins, a.o., γ tubulin (antibodies)
involved in immune response
Fibrinogen
0.2-0.45 g/dl
7%
Blood clotting
Regulatory
proteins
<1%
Regulate gene expression a.o. cell
functions
Blood clotting
factors
(proteins)
<1%
Transform fibrinogen into fibrine
Complement
Cascade of protein activation, to attach them to antigens and
cause destruction of foreign cells in human body.
http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter22/animation__activation_of_complement.html
Blood clotting
http://www.youtube.com/watch?v=xNZEERMSeyM
Erytrocytes
http://www.pbrc.hawaii.edu/~kunkel/gallery.
Erythrocytes (red), leukocytes (green) un platelets (yellow). (SEM x 9,900).
Erythrocytes can move through capillaries with diameter smaller than
diameter of erythrocyte.
carbohydrates
carbohydrates
Extracellular
matrix
Protein 3
Glycophorin
ß -Spektrin
Actin
Protein 4,1
Cholesterol Phosfolipids
Glicolipids
-Spectrin
-Ankirin
Protein 4,1
Protein 4,2
Tropomiosin
Plsmatic membrane of an erythrocyte
Band 3 protein - Cl-/HCO3 antiporter
Glikophorin – negative charge on membrane surface
• Erythrocytes change their shape during the movement.
• Colour depends on concentration of CO2
• Hemoglobin - 4 polipeptide chains. Functional group – heme, contains
Fe atoms.
• Content: 65% water, 1% organelles, 9% hemoglobine.
Fe
http://en.wikipedia.org/wiki/File:Erytrocyte_deoxy_to_oxy_v0.7.gif
Human blood group system
• Glycolipids A and B (aglutinogens)
• 0-I group, A -II groupa, B-III groupa, AB-IV groupa.
• Plazma contain proteins – aglutins. Can be attached to
aglutinogens.
Sickle cell anemia
Rhesus factor
• 50 aglutinogens
• most important C,D,E aglutinogens
• Cause hemolysis of
fetus if in the blood
of “Rh-” mother
antibodies against Rh
becomes synthesized
after first labour.
Classification of leukocytes
• Granulocytes – contain specifc and
unspecific granules
• Agranulocytes – do not contain granules
Cell structure after staining can be:
eosinophilic (acidophilic), basophilic (stain
with methilene blue) and azurophilic
(purple), light purple (weak staining with
eosin un methilene blue, specific granules)
Leukocyte differencial analysis
•
•
•
•
•
•
Number of leukocytes in addults:
Neutrophilic granulocytes - 2.0–7.0×109/l (40–80%)
Limphocytes - 1.0–3.0×109/l (20–40%)
Monocytes - 0.2–1.0×109/l (2–10%)
Eosinophilic granulocytes - 0.02–0.5×109/l (1–6%)
Basophilic granuloccytes- 0.02–0.1×109/l (< 1–2%)
• Numbers can differ in different populations and in
different laborotories.
• Immature granulocyte (IG)
• Immature granulocytes (IGs) encompass immature cells of
granulocytic lineages, including metamyelocytes, myelocytes,
and promyelocytes, which are easily recognized
morphologically and are reported by automated analyzer as IG
altogether. IG normally absent from peripheral blood.
• Increased IG occurs accompanied by an increase in neutrophils
in the following conditions:[2]
• Bacterial infections
• Acute inflammatory diseases
• Cancer (particularly with marrow metastasis)
• Tissue necrosis
• Acute transplant rejection
• Surgical and orthopedic trauma
• Myeloproliferative diseases
• Steroid use
• Pregnancy (mainly during the third trimester)
• Neutrophil granulocytes — May indicate bacterial infection. May also
be raised in acute viral infections. Because of the segmented
appearance of the nucleus, neutrophils are sometimes referred to as
"segs." The nucleus of less mature neutrophils is not segmented, but
has a band or rod-like shape. Less mature neutrophils — those that
have recently been released from the bone marrow into the
bloodstream — are known as "bands" or "stabs". Stab is a German
term for rod.[3]
• Lymphocytes — Higher with some viral infections such as glandular
fever and. Also raised in chronic lymphocytic leukemia (CLL). Can be
decreased by HIV infection. In adults, lymphocytes are the second
most common WBC type after neutrophils. In young children under
age 8, lymphocytes are more common than neutrophils.[3]
• Monocytes — May be raised in bacterial infection, tuberculosis,
malaria, Rocky Mountain spotted fever, monocytic leukemia, chronic
ulcerative colitis and regional enteritis [3]
• Eosinophil granulocytes — Increased in parasitic infections, asthma, or
allergic reaction.
• Basophil granulocytes — May be increased in bone marrow related
conditions such as leukemia or lymphoma.[3]
Monocytes un macrophages
Cell Name
Location
Adipose tissue macrophages
Adipose tissue
Monocyte
Bone Marrow/Blood
Kupffer cell
Liver
Sinus histiocytes
Lymph node
Alveolar macrophage(dust cell)
Pulmonary alveolus of
Lungs
Tissue macrophage (Histiocyte) leading to Giant
cells
Connective Tissues
Langerhans cell
Skin and Mucosa
Microglia
Central Nervous System
Hofbauer cell
Placenta
Intraglomerular mesangial cell
Kidney
Osteoclasts
Bone
Epithelioid cells
Granulomas
Red Pulp Macrophage (Sinusoidal lining cells)
Red pulp of Spleen
Peritoneal macrophages
Peritoneal cavity
• Monocytes and macrophages are phagocytes.[3]
Macrophages function in both non-specific defense (innate
immunity) as well as help initiate specific defense
mechanisms (adaptive immunity) of vertebrate animals.
• Macrophages have the unique ability to metabolize one
amino acid, arginine, to either a "killer" molecule (Nitric
Oxide) or a "repair" molecule (Ornithine).
• Macrophages predominantly expressing the killer or repair
phenotype are now mainly called M1 or M2 macrophages
because these 2 types of macrophages also stimulate T cell
responses that further activate the killer macrophages or T
cell phenotype (Th1), or stimulate antibody production
(Th2)
Monocytes
• Large number of lysosomes.
Makrophages
• Beta glikans and other signalling molecules
activate macrophages
Macrophages
1. Erithrocytes; 2. – cytoplasm;
3. - nucleus, 4. – bacteria
containing endosomes;
5. - pseudopodia.
Scale bar: 10 μm.
Specific ekxpresion of proteins CD14, CD40, CD11b, CD64, F4/80 (pele)/EMR1
(cilvēks), lysozyme M, MAC-1/MAC-3 and CD68 by flow cytometry or
immunohistochemical staining.[4]
Macrophages
www.beta-glucan-13d.com/
http://www.life.umd.edu/classroom/bsci422/mosser/macrophage.jpg
Macrophages and cytoskeleton
•
http://www.svi.nl/products/software/fluvr/
• When a monocyte enters damaged tissue through the
endothelium of a blood vessel, a process known as the
leukocyte extravasation, it undergoes a series of changes to
become a macrophage.
• Monocytes are attracted to a damaged site by chemical
substances through chemotaxis, triggered by a range of
stimuli including damaged cells, pathogens and cytokines
released by macrophages already at the site.
• At some sites such as the testis, macrophages have been
shown to populate the organ through proliferation.
• Unlike short-lived neutrophils, macrophages survive
longer in the body up to a maximum of several months.
http://en.wikipedia.org/wiki/Macrophage
•
•
•
•
Role in adaptive immunity
Macrophages are versatile cells that play many roles. As
scavengers, they rid the body of worn-out cells and other
debris.
Along with dendritic cells, they are foremost among the
cells that "present" antigen, a crucial role in initiating an
immune response.
As secretory cells, monocytes and macrophages are vital to
the regulation of immune responses and the development
of inflammation; they produce a wide array of powerful
chemical substances (monokines) including enzymes,
complement proteins, and regulatory factors such as
interleukin-1.
At the same time, they carry receptors for lymphokines
that allow them to be "activated" into single-minded
pursuit of microbes and tumour cells.
http://en.wikipedia.org/wiki/Macrophage
• After digesting a pathogen, a macrophage will present the
antigen (a molecule, most often a protein found on the
surface of the pathogen and used by the immune system
for identification) of the pathogen to the corresponding
helper T cell.
• The presentation is done by integrating it into the cell
membrane and displaying it attached to an MHC class II
molecule, indicating to other white blood cells that the
macrophage is not a pathogen, despite having antigens on
its surface.
• Eventually, the antigen presentation results in the
production of antibodies that attach to the antigens of
pathogens, making them easier for macrophages to adhere
to with their cell membrane and phagocytose. In some
cases, pathogens are very resistant to adhesion by the
macrophages.
http://en.wikipedia.org/wiki/Macrophage
Antigen presentation
• The antigen presentation on the surface of infected macrophages (in the context of
MHC class II) in a lymph node stimulates TH1 (type 1 helper T cells) to
proliferate (mainly due to IL-12 secretion from the macrophage).
• When a B-cell in the lymph node recognizes the same unprocessed surface antigen
on the bacterium with its surface bound antibody, the antigen is endocytosed and
processed.
• The processed antigen is then presented in MHCII on the surface of the B-cell.
• T cells that express the T cell receptor which recognizes the antigen-MHCII
complex (with co-stimulatory factors- CD40 and CD40L) cause the B-cell to
produce antibodies that help opsonisation of the antigen so that the bacteria can be
better cleared by phagocytes.
• Macrophages provide yet another line of defense against tumor cells and somatic
cells infected with fungus or parasites.
• Once a T cell has recognized its particular antigen on the surface of an aberrant
cell, the T cell becomes an activated effector cell, producing chemical mediators
known as lymphokines that stimulate macrophages into a more aggressive form.
http://en.wikipedia.org/wiki/Macrophage
• In spite of a spectrum of ways to activate macrophages, there are
two main groups designated M1 and M2.
• M1 macrophages, as mentioned earlier (previously referred to as
classically or alternatively activated macrophages),[7] M1 "killer"
macrophages are activated by LPS and IFN-gamma, and secrete
high levels of IL-12 and low levels of IL-10.
• In contrast, the M2 "repair" designation broadly refers to
macrophages that function in constructive processes like wound
healing and tissue repair, and those that turn off damaging immune
system activation by producing anti-inflammatory cytokines like
IL-10.
• M2 is the phenotype of resident tissue macrophages, and can be
further elevated by IL-4.
• M2 macrophages produce high levels of IL-10, TGF-beta and low
levels of IL-12. Tumor-associated macrophages are mainly of the
M2 phenotype, and seem to actively promote tumor growth.[8]
http://en.wikipedia.org/wiki/Macrophage
Role in muscle regeneration
• The first step to understanding the importance of macrophages in muscle repair,
growth, and regeneration is that there are two “waves” of macrophages with the
onset of damageable muscle use – subpopulations that do and do not directly
have an influence on repairing muscle.
• The initial wave is a phagocytic population that comes along during periods of
increased muscle use that are sufficient to cause muscle membrane lysis and
membrane inflammation, which can enter and degrade the contents of injured
muscle fibers.[9][10][11]
• These early-invading, phagocytic macrophages reach their highest concentration
about 24 hours following the onset of some form of muscle cell injury or
reloading.[12]
• Their concentration rapidly declines after 48 hours.[10]
• The second group is the non-phagocytic types that are distributed near
regenerative fibers. These peak between two and four days and remain elevated
for several days during the hopeful muscle rebuilding.[10]
• The first subpopulation has no direct benefit to repairing muscle, while the
second non-phagocytic group does.
http://en.wikipedia.org/wiki/Macrophage
• It is thought that macrophages release soluble substances that influence the
proliferation, differentiation, growth, repair, and regeneration of muscle, but at this
time the factor that is produced to mediate these effects is unknown.[12]
• It is known that macrophages' involvement in promoting tissue repair is not muscle
specific; they accumulate in numerous tissues during the healing process phase
following injury.[13]
• A study conducted in 2006 showcased macrophage influences on muscle repair of
soleus muscle on mice.[14]
• The first procedural step was to make sure macrophages are present in the muscle
after onset of muscle injury, and then decrease their presence to see what effects
were had on the muscle.
• By using anti-F4/80 to bind to macrophages and render them useless, it was seen
that when the second wave of macrophages were depleted, there were many more
lesions in the muscle cell membrane between the second and fourth day – showing
muscle damage when repairing is supposed to occur.
• After testing for membrane lesions in both the total amount of muscle fibers
present, it was noticed that most of the damage occurred in muscle cells that did
not have the second subpopulation of macrophages present. Macrophages
depletion prevents muscle membrane repair.
http://en.wikipedia.org/wiki/Macrophage
• When examining muscle regeneration, a significant reduction was found in the
amount of myonuclei.
• Depletion of macrophages was found to cause, between the second and fourth
day of repair, much less muscle regeneration compared to muscle with
macrophage population.[14]
• Macrophages promote muscle regeneration between the second and fourth day.
• To determine the influence of macrophages in muscle growth, muscle crosssectional area in macrophage-depleted muscle area was measured against two
muscle sets: muscle that was injured and had macrophage presence and muscle
that was not injured and had macrophage presence.
• The macrophage-depleted muscle showed less growth after four days, and
injured muscle with macrophages nearly grew back to the level of uninjured
muscle.[14]
http://en.wikipedia.org/wiki/Macrophage
• Role in wound healing
• Macrophages replace Polymorphonuclear neutrophils as the predominant cells in the
wound by two days after injury.[16]
• Attracted to the wound site by growth factors released by platelets and other cells,
monocytes from the bloodstream enter the area through blood vessel walls.[17]
• Numbers of monocytes in the wound peak one to one and a half days after the injury
occurs. Once they are in the wound site, monocytes mature into macrophages. The
spleen contains half the body's monocytes in reserve ready to be deployed to injured
tissue.[18][19]
• The macrophage's main role is to phagocytize bacteria and damaged tissue,[15] and
they also debride damaged tissue by releasing proteases.[20]
• Macrophages secrete a number of factors such as growth factors and other
cytokines, especially during the third and fourth post-wounding days. These factors
attract cells involved in the proliferation stage of healing to the area.[21]
• Macrophages may also restrain the contraction phase.[22] Macrophages are
stimulated by the low oxygen content of their surroundings to produce factors that
induce and speed angiogenesis [23] and they also stimulate cells that reepithelialize
the wound, create granulation tissue, and lay down a new extracellular
matrix.[24][25]
http://en.wikipedia.org/wiki/Macrophage
Neutrophilic granulocytes
11.11.2013
Eozinophilic granulocytes
• Eosinophils also have lobed nuclei (two to four lobes). The number of
granules in an eosinophil can vary because they have a tendency to
degranulate while in the blood stream.[15]
• Eosinophils play a crucial part in the killing of parasites (e.g., enteric
nematodes) because their granules contain a unique, toxic basic protein
and cationic protein (e.g., cathepsin[12]);[16] receptors that bind to
IgE are used to help with this task.[17]
• These cells also have a limited ability to participate in
phagocytosis,[18] they are professional antigen-presenting cells, they
regulate other immune cell functions (e.g., CD4+ T cell, dendritic cell,
B cell, mast cell, neutrophil, and basophil functions),[19] they are
involved in the destruction of tumor cells,[15] and they promote the
repair of damaged tissue.[20] A polypeptide called interleukin-5
interacts with eosinophils and causes them to grow and differentiate;
this polypeptide is produced by basophils.[16]
http://en.wikipedia.org/wiki/Granulocyte
Basophylic granulcytes
• Basophils are one of the least abundant cells in bone
marrow and blood (occurring at less than two percent of all
cells). Like neutrophils and eosinophils, they have lobed
nuclei; however, they have only two lobes, and the
chromatin filaments that connect them are not very visible.
• Basophils have receptors that can bind to IgE, IgG,
complement, and histamine. The cytoplasm of basophils
contains a varied amount of granules; these granules are
usually numerous enough to partially conceal the nucleus.
Granule contents of basophils are abundant with histamine,
heparin, chondroitin sulfate, peroxidase, platelet-activating
factor, and other substances.
http://en.wikipedia.org/wiki/Granulocyte
• When an infection occurs, mature basophils will be released from the
bone marrow and travel to the site of infection.[21] When basophils
are injured, they will release histamine, which contributes to the
inflammatory response that helps fight invading organisms.
• Histamine causes dilation and increased permeability of capillaries
close to the basophil.
• Injured basophils and other leukocytes will release another substance
called prostaglandins that contributes to an increased blood flow to the
site of infection. Both of these mechanisms allow blood-clotting
elements to be delivered to the infected area (this begins the recovery
process and blocks the travel of microbes to other parts of the body).
• Increased permeability of the inflamed tissue also allows for more
phagocyte migration to the site of infection so that they can consume
microbes.[18]
http://en.wikipedia.org/wiki/Granulocyte
Heparinocytes
• Mast are now considered to be part of the immune system.
• Mast cells are very similar to basophil granulocytes (a class of white blood
cells) in blood.
• Both are granulated cells that contain histamine and heparin, an anticoagulant.
Both cells also release histamine upon binding to immunoglobulin E.[3]
• These similarities have led many to speculate that mast cells are basophils that
have "homed in" on tissues. Furthermore they share a common precursor in
bone marrow expressing the CD34 molecule.
• Basophils leave the bone marrow already mature, whereas the mast cell
circulates in an immature form, only maturing once in a tissue site. The site an
immature mast cell settles in probably determines its precise characteristics.[2]
• The first in vitro differentiation and growth of a pure population of mouse mast
cells has been carried out using conditioned medium derived from concanavalin
A-stimulated splenocytes.[6]
• Later, it was discovered that T cell-derived interleukin 3 was the component
present in the conditioned media that was required for mast cell differentiation
and growth.[7]
http://en.wikipedia.org/wiki/Mast_cell
http://en.wikipedia.org/wiki/Mast_cell
Megakariocytes produce thrombocytes
• Megakariocyte in red bone marrow. (left side)
• Megakarioc form thrombocytes. Gimsza
stain. (right side)
Thrombocytes lack major organelles.
Thrombocytes of nonmammalian vertebrates have a nucleus and
resemble B lymphocytes. Mammalian thrombocytes are anucleated
cells called platelets which additionally aggregate in response to ADP,
serotonin, and adrenaline.
www.ipfdd.de/research/ res16/a18/a18.html
Trombocīti veido agregātus.
www.explorepub.com/articles/darkfield_charts/ fungus5.html
• If the number of platelets is too low, excessive bleeding can occur.
• However, if the number of platelets is too high, blood clots can form
(thrombosis), which may obstruct blood vessels and result in such
events as a stroke, myocardial infarction, pulmonary embolism or the
blockage of blood vessels to other parts of the body, such as the
extremities of the arms or legs.
• An abnormality or disease of the platelets is called a
thrombocytopathy,[2] which could be either a low number of platelets
(thrombocytopenia), a decrease in function of platelets
(thrombasthenia), or an increase in the number of platelets
(thrombocytosis).
• There are disorders that reduce the number of platelets, such as
heparin-induced thrombocytopenia (HIT) or thrombotic
thrombocytopenic purpura (TTP) that typically cause thromboses, or
clots, instead of bleeding.
http://en.wikipedia.org/wiki/Platelets
• Platelets release a multitude of growth factors including plateletderived growth factor (PDGF), a potent chemotactic agent, and TGF
beta, which stimulates the deposition of extracellular matrix.
• Both of these growth factors have been shown to play a significant role
in the repair and regeneration of connective tissues.
• Other healing-associated growth factors produced by platelets include
basic fibroblast growth factor, insulin-like growth factor 1, plateletderived epidermal growth factor, and vascular endothelial growth
factor.
• Local application of these factors in increased concentrations through
Platelet-rich plasma (PRP) has been used as an adjunct to wound
healing for several decades.
http://en.wikipedia.org/wiki/Platelets
• The physiological range for platelets is (150 – 400) × 103 per mm3.
• Platelets are produced in blood cell formation (thrombopoiesis) in bone
marrow, by budding off from megakaryocytes.
• Megakaryocyte and platelet production is regulated by thrombopoietin,
a hormone usually produced by the liver and kidneys.
• Each megakaryocyte produces between 5,000 and 10,000 platelets.
• Around 1011 platelets are produced each day by an average healthy
adult.
• Reserve platelets are stored in the spleen, and are released when
needed by sympathetically induced splenic contraction.
• The lifespan of circulating platelets is 5 to 9 days.
• Old platelets are destroyed by phagocytosis in the spleen and by
Kupffer cells in the liver.
http://en.wikipedia.org/wiki/Platelets
• The inner surface of blood vessels is lined with a thin layer of
endothelial cells that, in normal hemostasis, acts to inhibit platelet
activation by producing nitric oxide, endothelial-ADPase, and
PGI2. Endothelial-ADPase clears away the platelet activator, ADP.
• Endothelial cells produce a protein called von Willebrand factor
(vWF), a cell adhesion ligand, which helps endothelial cells adhere to
collagen in the basement membrane.
• Under physiological conditions, collagen is not exposed to the
bloodstream.
• vWF is secreted constitutively into the plasma by the endothelial cells,
and is stored in granules within the endothelial cell and in platelets.
http://en.wikipedia.org/wiki/Platelets
• When the endothelial layer is injured, collagen, vWF and tissue factor from the
subendothelium is exposed to the bloodstream.
• When the platelets contact collagen or vWF, they are activated (e.g. to clump
together).
• They are also activated by thrombin (formed with the help of tissue factor).
• They can also be activated by a negatively charged surface, such as glass.
Non-physiological flow conditions (especially high values of shear stress)
caused by arterial stenosis or artificial devices (Mechanical Heart Valves,
blood pumps etc.) can also lead to platelet activation.[10]
• Platelet activation further results in the scramblase-mediated transport of
negatively charged phospholipids to the platelet surface.
• These phospholipids provide a catalytic surface (with the charge provided by
phosphatidylserine and phosphatidylethanolamine) for the tenase and
prothrombinase complexes.
• Calcium ions are essential for binding of these coagulation factors.
http://en.wikipedia.org/wiki/Platelets
Granule secretion
• Platelets contain alpha and dense granules.
• Activated platelets excrete the contents of these granules into their
canalicular systems and into surrounding blood.
• There are three types of granules:
1. dense (or delta) granules (containing ADP or ATP, calcium, and
serotonin)
2. lambda granules – similar to lysosomes and contain several
hydrolytic enzymes.
3. Alpha granules (containing P-selectin, platelet factor 4,
transforming growth factor-β1, platelet-derived growth factor,
fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation
factors V and XIII).
• Thromboxane A2 synthesis[edit]
• Platelet activation initiates the arachidonic acid pathway to produce
TXA2. TXA2 is involved in activating other platelets and its
formation is inhibited by COX inhibitors, such as aspirin.
http://en.wikipedia.org/wiki/Platelets
• Platelets aggregate, or clump together, using fibrinogen and von Willebrand
factor (vWF) as a connecting agent.
• The most abundant platelet aggregation receptor is glycoprotein IIb/IIIa
(gpIIb/IIIa); this is a calcium-dependent receptor for fibrinogen, fibronectin,
vitronectin, thrombospondin, and vWF. Other receptors include GPIb-V-IX
complex (vWF) and GPVI (collagen).
• Activated platelets will adhere, via glycoprotein (GP) Ia, to the collagen that is
exposed by endothelial damage.
• Aggregation and adhesion act together to form the platelet plug.
• Myosin and actin filaments in platelets are stimulated to contract during
aggregation, further reinforcing the plug.
• Platelet aggregation is stimulated by ADP, thromboxane, and α2 receptoractivation, but inhibited by other inflammatory products like PGI2 and PGD2.
• Platelet aggregation is enhanced by exogenous administration of anabolic
steroids.
http://en.wikipedia.org/wiki/Platelets
• Wound repair
• Main article: Wound repair
• The blood clot is only a temporary solution to stop bleeding; vessel repair is
therefore needed. The aggregated platelets help this process by secreting chemicals
that promote the invasion of fibroblasts from surrounding connective tissue into
the wounded area to completely heal the wound or form a scar. The obstructing
clot is slowly dissolved by the fibrinolytic enzyme, plasmin, and the platelets are
cleared by phagocytosis.
• ADP (purinergic/P2) receptors
• Human platelets have three types of P2 receptors: P2X(1), P2Y(1) and P2Y(12).
Although abnormalities in all three genes have been documented, but clinical
correlation is available only for P2Y(12).[11] Patients with P2Y(12) defects have a
mild to moderate bleeding diathesis, characterized by mucocutaneous bleeding and
excessive post-surgical and post-traumatic blood loss. A defects in P2Y(12) should
be suspected when ADP, even at concentrations ≥10 micro molar, is unable to
induce full, irreversible platelet aggregation. Confirmation of the diagnosis is with
tests that evaluate the degree of inhibition of adenylyl cyclase by ADP.
• Cytokine signaling
• In addition to being the chief cellular effector of hemostasis, platelets are rapidly
deployed to sites of injury or infection, and potentially modulate inflammatory
processes by interacting with leukocytes and by secreting cytokines, chemokines,
and other inflammatory mediators.[13][14][15][16] Platelets also secrete plateletderived growth factor (PDGF).
Limphocytes
http://www.vet.uga.edu/IVCVM/1998/latimer1/latimer1.htm
Limphocytes
http://www.vet.uga.edu/IVCVM/1998/latimer1/latimer1.htm
Limphocytes
http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Blood/Blood.htm#Leukocytes
• Lymphocytes can be divided into large
lymphocytes and small lymphocytes. Large
granular lymphocytes include natural killer
cells (NK cells). Small lymphocytes consist
of T cells and B cells.
http://en.wikipedia.org/wiki/Lymphocyte
T and B cells
• T cells (thymus cells) and B cells (bursa-derived cells[2]) are the major cellular
components of the adaptive immune response.
• T cells are involved in cell-mediated immunity, whereas B cells are primarily
responsible for humoral immunity (relating to antibodies).
• The function of T cells and B cells is to recognize specific “non-self” antigens,
during a process known as antigen presentation. Once they have identified an
invader, the cells generate specific responses that are tailored to maximally
eliminate specific pathogens or pathogen-infected cells.
• B cells respond to pathogens by producing large quantities of antibodies which
then neutralize foreign objects like bacteria and viruses.
• In response to pathogens some T cells, called T helper cells, produce cytokines
that direct the immune response, while other T cells, called cytotoxic T cells,
produce toxic granules that contain powerful enzymes which induce the death of
pathogen-infected cells.
• Following activation, B cells and T cells leave a lasting legacy of the antigens they
have encountered, in the form of memory cells.
• Throughout the lifetime of an animal these memory cells will “remember” each
specific pathogen encountered, and are able to mount a strong and rapid response
if the pathogen is detected again.
Natural killer cell
• NK cells are a part of the innate immune system and play a major role
in defending the host from both tumors and virally infected cells.
• NK cells distinguish infected cells and tumors from normal and
uninfected cells by recognizing changes of a surface molecule called
MHC (major histocompatibility complex) class I.
• NK cells are activated in response to a family of cytokines called
interferons.
• Activated NK cells release cytotoxic (cell-killing) granules which then
destroy the altered cells.[3]
• They were named "natural killer cells" because of the initial notion that
they do not require prior activation in order to kill cells which are
missing MHC class I.
• Microscopically, in a Wright's stained peripheral blood smear, a normal
lymphocyte has a large, dark-staining nucleus with little to no eosinophilic
cytoplasm.
• The coarse, dense nucleus of a lymphocyte is approximately the size of a red blood
cell (about 7 micrometres in diameter).[4]
• Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or
could exhibit a small clear zone to one side of the nucleus.
• Polyribosomes are a prominent feature in the lymphocytes and can be viewed with
an electron microscope.[4] The ribosomes are involved in protein synthesis,
allowing the generation of large quantities of cytokines and immunoglobulins by
these cells.
• It is impossible to distinguish between T cells and B cells in a peripheral blood
smear.[4]
• Normally, flow cytometry testing is used for specific lymphocyte population
counts.
• This can be used to specifically determine the percentage of lymphocytes that
contain a particular combination of specific cell surface proteins, such as
immunoglobulins or cluster of differentiation (CD) markers or that produce
particular proteins (for example, cytokines using intracellular cytokine staining
(ICCS)).
Typical recognition markers for lymphocytes[6]
CLASS
FUNCTION
PROPO
RTION
PHENOTYPIC
MARKER(S)
NK cells
Lysis of virally infected cells and tumour cells
7% (213%)
CD16 CD56 but not
CD3
Helper T
cells
Release cytokines and growth factors that
regulate other immune cells
46% (28- TCRαβ, CD3 and
59%)
CD4
Cytotoxic
T cells
Lysis of virally infected cells, tumour cells and
allografts
19% (13- TCRαβ, CD3 and
32%)
CD8
γδ T cells
Immunoregulation and cytotoxicity
5% (2%TCRγδ and CD3
8%)
B cells
Secretion of antibodies
23% (18- MHC class II, CD19
47%)
and CD21