histology lecture 3 blood, lymphatics and the immune system … · · 2013-03-25histology lecture...
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HISTOLOGY Lecture 3
Blood, Lymphatics and the
immune system
PCL1 2012
Prof. P. Kyamanywa
DoS-FACMED
NUR
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nur
7: Blood and blood
vessels
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Blood vascular system
Specialized connective tissue
main functions
to transport oxygen, nutrients and hormones
to the tissues
to collect the waste products (carbon dioxide
and waste metabolites) for removal from the
body via the excretory system.
P. Kyamanywa DOS-FACMED nur
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Composition of Blood Vascular system
Heart (muscular pump)
Vessels – arteries and veins
Pulmonary circulation (system of blood vessels to
and from the lungs)
Systemic circulation (system of blood vessels
bringing blood to and from all the other organs of the
body).
P. Kyamanywa DOS-FACMED nur
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Basic structure of circulatory system
3 layers
Inner: Tunica Intima : consists of
Endothelium: single cell layer – Endothelial cells
sub-endothelial layer
inner elastic limiting membrane (elastic lamina,
which after fixation appears undulating).
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Intermediate: muscular – tunica media
circular smooth muscle (or spiral)
concentric elastic lamina (formed by the
smooth muscle cells).
Absent in capillaries; largest in the heart
Outer: connective tissue: tunica adventitia
connective tissue surrounding the vessel
outer elastic limiting membrane (on the border
between the Tunica media and the Adventitia
with vasa vasorum in large vessels
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P. Kyamanywa DOS-FACMED nur
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P. Kyamanywa DOS-FACMED nur
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P. Kyamanywa DOS-FACMED nur
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P. Kyamanywa DOS-FACMED nur
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Arteries
2 groups
Conducting (Elastic Arteries).
very high blood pressure and flow
Aorta, carotid, subclavian, pulmonary
Distributing (Muscular Arteries)
smaller diameter arteries with a slower
blood flow
Main distributing branches
arterioles, capillaries
The capillaries are present in the form of
microcirculation networks (capillary beds) in the
organs and tissues
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Structure of capillary endothelium
Adapted for exchange
3 types of capillary endothelium
Continuous capillaries
Uninterrupted endothelial layer
Most common type
found in those organs that need strict control
on access of the substances from the blood.
E.g. all the organs with a "blood-barrier" such
as the "blood-brain-barrier" of the Central
Nervous System or the "blood-thymus
barrier".
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Fenestrated capillaries
Large pores in endothelium
More permeable that continuous capillaries
In tissues with much molecular exchange e.g.
small intestines, kidneys, endocrine glands
Discontinuous capillaries: only in liver
P. Kyamanywa DOS-FACMED nur
Structure of capillary endothelium cont’d
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P. Kyamanywa DOS-FACMED nur
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Small Vein with valve
P. Kyamanywa DOS-FACMED nur
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nur
Break
In the next 10 minutes
Review :
basic structure of vessels
Types of arteries and their examples
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Blood
Considered a connective tissue because it contains:
cells,
a liquid ground substance (called plasma), and
dissolved protein fibers.
Adult has ~ 5.5 L
Can be broken down into its liquid and cellular components by a machine called a centrifuge.
blood is withdrawn from a vein and collected in a centrifuge tube
tube is placed into the centrifuge, which then spins it in a circular motion for several minutes
rotational movement separates the blood into liquid and cellular components
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21-19
Components of Blood
Erythrocytes (or red blood cells) form the lower layer of the centrifuged blood
typically make up about 44% of a blood sample
Buffy coat makes up the middle layer
thin, slightly gray-white layer composed of cells called leukocytes (or white blood cells) and cell fragments called platelets
forms less than 1% of a blood sample
Plasma straw-colored liquid that rises to the top
generally makes up about 55% of blood
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21-20
Components of Blood
Erythrocytes and the components of the buffy coat are
called the formed elements.
Formed elements and the liquid plasma compose whole
blood.
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Blood Formed elements
Erythrocytes (red
blood cells)
99% of cells
Carry oxygen
Leukocytes (white
blood cells)
Protect against
infection and cancer
Platelets (cell
fragments)
Blood clotting
Plasma
55% of blood volume
Water (90%)
Electrolytes
Plasma proteins
Albumin
Fibrinogen
Globulins
Substances
transported by blood
Nutrients
Waste products
Respiratory gases
Hormones
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Colorized SEM of Red Blood Cells (red), platelets
(green) and White Blood Cells (purple)
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Erythrocyte
3,9-5,5 (4) women, 4-6 (5) men (million
per µL)
Cytopenia = lower than normal
(associated with anemia),
Cytosis = higher than normal (e.g.
polycythemia vera)
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Erythrocyte
~7.5 µm diameter fresh; 7.2 - 7.4 in
stained smears; 0,8 – 2,6 µm thick
Macrocytes > 9 µm,
Microcytes < 6 µm
Anisocytosis = variation in size
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Erythrocyte
Survive 120 days in circulation
Old RBC removed by macrophages in
spleen and bone marrow
Reticulocytes about 1% of total RBC
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Erythrocyte
Biconcave disc shape which provides a
20-30% greater surface area than a
sphere
no nucleus
Surface area is adapted for gas exchange
Flexible; squeeze through capillaries
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Normal RBC Sickled RBC
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Erythrocyte
pathological shapes - poikilocytes:
spherical - spherocytes
with flat surfaces - planicytes
with convex surfaces - stomatocytes
with multiple projections on the cell surface - echinocytes
with small number of projections -acanthocytes
with half disc shape - schistocytes
sickle-shaped - drepanocytes
with the shape of a drop - dacryocytes
resembling a target - codocytes etc..
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Sickle Cell Anemia (arrow = sickle cell)
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Colorized SEM of Sickle Cell RBCs (green)
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Erythrocyte
Cell membrane: integral membrane
proteins & peripheral proteins
(membrane skeleton)
Interior – 33% hemoglobin, glycolytic
and hexose-monophosphate shunt
enzymes
Oxy- (O2), carbamino- (CO2) and
carboxy (CO) hemoglobin
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Hemoglobin in Erythrocytes
Every erythrocyte is filled with approximately 280 million molecules of a red-pigmented protein called hemoglobin.
Transports oxygen and carbon dioxide, and is
responsible for the characteristic bright red color of
arterial blood.
Hemoglobin that contains no oxygen has a deep red
color that is perceived as blue because the blood within
these veins is observed through the layers of the skin
and the subcutaneous tissue.
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Hemoglobin in Erythrocytes
Each hemoglobin molecule consists of four protein building blocks, called globins.
Alpha (a) chains and beta (b) chains.
All globin chains contain a nonprotein (or heme) group that is in the shape of a ring, with an iron (Fe) ion in its center.
Oxygen binds to these iron ions for transport in the blood.
Each hemoglobin molecule has four iron ions and is capable of binding four molecules of oxygen.
Oxygen binding is fairly weak to ensure rapid attachment and detachment of oxygen with hemoglobin.
Oxygen binds to the hemoglobin when the erythrocytes pass through the blood vessels of the lungs.
It leaves the hemoglobin when the erythrocytes pass through the blood vessels of body tissues.
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Antibodies
An antibody interacts with a specific antigen.
The ABO blood group has both anti-A and anti-B
antibodies that react with the surface antigen A and the
surface antigen B, respectively.
The antibodies in your blood plasma do not recognize
the surface antigens on your erythrocytes.
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Leukocytes
on the basis of presence or absence of SPECIFIC
granules leucocytes are divided into 2 major group:
granular leucocytes (or granulocytes) have
specific granules, nuclei of mature or nearly
mature granulocytes are composed of several
segments: they may have two, three or four
segments
nongranular leucocytes (or agranulocytes)
do not have specific granules and possess a
spherical, oval or horseshoe-shaped nucleus;
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Leukocytes 6-10,000 per µL
Granulocytes (polymorphonuclear leukocytes)
neutrophils 60-70%
eosinophils 2-4%
basophils 0.5-1%
Agranulocytes
lymphocytes 20-30%
monocytes 3-8%
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Neutrophils 1 12-15 µm diameter
are spherical in shape
multi-lobed nucleus
human females may have inactivated second X chromosome (Barr corpuscule drumstick)(3%)
half-life 6-7 hrs in circulation;
lifespan 1-4 days in tissue
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Neutrophils 2
in the cytoplasm, in addition to all basic
organelles, there are:
specific (primary and secondary) (0,5 mm)
nonspecific granules;
specific granule content is alkaline or
neutral in pH
pH for nonspecific granules is acidic
few organelle for protein synthesis
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Neutrophils 3
Primary granules–azurophilic granules myeloperoxidase
neutrophil defensins
contribute to the killing and degradation of
engulfeg microorganisms
Secondary granules – smaller Antimicrobial substances
Lysozym
Collagenase
Lactoferrin
Secretory granules
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Neutrophils 4
on the outer surface of neutrophils there
are receptors for complement component,
Fc-receptors for IgG, as well as for many
immunologic mediators and other
biologically active substances
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Neutrophils 5
Diapedesis = cells crossing over the vascular endothelium/wall
play a central role in inflammatory processes
Form H2O2, powerful cytotoxic substance
Lysozyme breaks down bacterial cell wall
Lactoferrin binds Fe (needed by some bacteria) – bactericidal action
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Neutrophils 6 Large numbers invade sites of infection in response to factors (e.g.
cytokines) released by cells which reside at an infection site.
Neutrophils are the first wave of cells invading infection sires.
Receptors in their plama membrane allow them to recognise foreign bodies (e.g. bacteria, and tissue debris) which they begin to phagocytose and destroy.
The phagocytotic activity of neurophils is further stimulated if invading microorganisms are "tagged" with antibodies (or opsonised).
Neutrophils cannot replenish their store of granules (has few organelle for protein synthesis)
The cells die once their supply of granules has been exhausted.
Dead neutrophils and tissue debris are the major components of pus.
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Eosinophils 1
12-15 µm diameter,
bi-lobed nucleus
are spherical in shape
Circulate in the blood for about 8-12 hrs
Survive in tissue for several days
Is easy to recognise by its large specific granules, which stain bright orange/red
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Eosinophils 2
The most characteristic ultrastructural feature is a large ovoid specific granule which contains an elongated crystalloid
Specific granules contain 4 major proteins: major basic protein (MBP) → in crystalloid,
eosinophil cationic protein(ECP),
eosinophil peroxidase(EPO), → in granule matrix
eosinophil-derived neurotoxin(EDN),
Also hydrolytic enzymes (histaminase), collagenase , cathepsins
Azurophilic granules - lysosomes
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Eosinophils 3
Kill parasites, especially helminthic parasites
Are associated with allergic reactions
Phagocytose ag-ab complexes formed in allergy
Implicated in chronic inflammation
Corticosteroids decrease eosinophils in blood
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Basophils 1
Less than 0.5% of total leukocytes, hard to
find in smears
12-15 µm diameter,
Lobed nucleus, obscured by basophilic
granules
Many blue (basophilic) specific granules
with heparin and histamine
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Basophils 2
2 types of granules:
Specific granules – heparin, histamine, SRSA
→ dilatation of blood vessels
Azurophilic granules - lysosomes
The function is related to that of mast cells
May supplement mast cell function –
immediate hypersensitivity reaction.
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Lymphocytes 1
The most common agranulocytes
6-8 µm diameter
Round, dark, heterochromatic nucleus
Thin layer of basophilic, non-granular
cytoplasm
B, T and NK
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B Cells 1
They were first recognised as a
separate population in the bursa of
Fabricius in birds
Have variable life spans
Are involved in production of antibodies
Constantly patrol the body, circulating in
the blood, lymph and other extracellular
fluids and pausing in the lymphoid
tissues
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B Cells 2
Are involved in humoral immunity via
immunoglobulins
Primary immune response – antigen is
encountered for the first time
Secondary immune response – occurs
much rapidly, is of a much greater
magnitude and produces IgG rather
than IgM
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T Cells
Are so named because they undergo
differentiation in the thymus
Have a long life span
Are involved in cell-mediated immunity
• T helper cells,
• T suppressor cells,
• cytotoxic T cells
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T Cells
Immature T cells migrate from marrow to
the thymus where they develop into
mature lymphocyte
The maturation process includes
proliferation, rearrangement of TCR genes
and acquisition of surface receptors and
accesory molecules
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T helper cells
‘helps’ other cells to perform their effector
function by secreting a variaty of
mediators = interleukins
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Suppressor T cells
Supress immune responsiveness to self
antigen
Possibly switch off the response when
antigen is removed
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Cytotoxic T cells
Are able to kill virus-infected and some
cancer cells
They require interaction with Th cells to
become activated and proliferate to form
clones of effector cells
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Monocytes
12-20 µm dia;
Circulate for 3-4 days before emigrating into
tissues and organs
differentiate into macrophages
do not re-enter circulation
oval or kidney shaped nucleus, eccentric
Lighter stained and larger nucleus than
lymphocytes
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Monocytes
They respond by chemotaxis to the
presence of factors from damaged tissue,
microorganism and inflammation by
migration into the tissues and differentiation
into macrophages
Phagocyte bacteria, others cells and tissue
debris
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Platelets
150-400.000/μl
Fragments of megakaryocyte cytoplasm
2-5 µm diameter
Round or oval
Non-nucleated
Life span 10 days in blood
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Platelets
Light blue cytoplasm, dark blue/purple granules
Contains a well-developed cytoskeleton
At the periphery is a marginal band of microtubules which depolymerise at the onset of platelet aggregation
The cytoplasm is rich in the contractile proteins actin and myosin which are involved in the function of clot retraction and extrusion of granule contents as part of degranulation
Plasma membrane expresses cell adhesion molecules involved platelets interactions , adhesion to extracellular matrix or binding coagulation factors
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Platelets - TEM
Peripheral zone: - plasma membrane
- coagulation factors
Structural zone: - microtubule, actin and myosin
filaments,
Organelle zone: - mitochondria, peroxisomes,
glycogen particules, granules: Alpha granules (300-500nm) fibrinogen, platelet derived
growth factor and other proteins
Lambda granules (175-250nm) lysosomal enzymes
Delta granules (Dense bodies) (250-300nm) calcium,
pyrophosphate, serotonin
Membrane zone: - system of interconnected
canalicular system
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Platelet by TEM
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Platelets Function
1)They form plugs to occlude sites of vascular
damage by adhering to the collagenous tissue at
the margin of the wound
Later the platelet plug is reinforced by fibrin
2)They promote clot formation by providing a
surface for the assembly of coagulation protein
complex
3)Secrete factors that modulate coagulation and
vascular repair
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nur
15 minutes Break
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nur
Review
In the next 10 minutes
Review :
key functions of blood
cellular components of blood