HISTOLOGY Lecture 3 Blood, Lymphatics and the immune system … · · 2013-03-25HISTOLOGY Lecture...

transcript

HISTOLOGY Lecture 3

Blood, Lymphatics and the

immune system

PCL1 2012

Prof. P. Kyamanywa

DoS-FACMED

7: Blood and blood

vessels

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

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).

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).

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

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

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".

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

Structure of capillary endothelium cont’d

Small Vein with valve

In the next 10 minutes

Review :

basic structure of vessels

Types of arteries and their examples

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

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

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.

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

Colorized SEM of Red Blood Cells (red), platelets

(green) and White Blood Cells (purple)

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)

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

Erythrocyte

Survive 120 days in circulation

Old RBC removed by macrophages in

spleen and bone marrow

Reticulocytes about 1% of total RBC

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

Normal RBC Sickled RBC

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..

Sickle Cell Anemia (arrow = sickle cell)

Colorized SEM of Sickle Cell RBCs (green)

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

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.

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.

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.

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;

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%

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

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

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

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

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

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.

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

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

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

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

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.

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

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

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

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

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

T helper cells

‘helps’ other cells to perform their effector

function by secreting a variaty of

mediators = interleukins

Suppressor T cells

Supress immune responsiveness to self

antigen

Possibly switch off the response when

antigen is removed

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

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

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

Platelets

150-400.000/μl

Fragments of megakaryocyte cytoplasm

2-5 µm diameter

Round or oval

Non-nucleated

Life span 10 days in blood

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

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

Platelet by TEM

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

15 minutes Break

Review

In the next 10 minutes

Review :

key functions of blood

cellular components of blood

HISTOLOGY Lecture 3 Blood, Lymphatics and the immune system … · · 2013-03-25HISTOLOGY Lecture...

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