WEEK 1: BLOOD AND HEMATOLOGICAL TISSUES Flashcards
Differentiate between a red and yellow bone marrow.
*Red bone marrow is haematopoietically active
*Yellow bone marrow has abundant fat and adipocytes and less hematopoietic centers
Describe the blood supply and innervation of the bone marrow.
*The bone marrow is perfused by the same arteries that provide nutrients to the surrounding bone -
-nutrient artery and two nutrient veins travel through nutrient canals.
*The nutrient canals – as well as both epiphyseal and metaphyseal foramina – also carry both unmyelinated and myelinated nerve fibers to the bone and the marrow.
*Some of these fibers serve as vasa nervosa – innervating the smooth muscle layer of the blood vessels – as well as the hematopoietic tissue of the marrow.
What is the parental cell type for ALL blood cells?
Where are they (usually) present only?
*Hematopoietic stem cells (HSCs) are the parental cell type for ALL blood cells
and probably also endothelium.
*HSCs are (usually) present only in the bone marrow.
*The HSC is (probably) able to divide indefinitely, or at least a very large number of times
Describe the embryology of the hematopoietic cells.
1.Haematopoietic stem cells arise from mesodermal cells
2.Under stimulation by fibroblast growth factor 2 (FGF2),
mesodermal cells from yolk sac converted into hemangioblast cells.
3.Hemangioblasts are stem cells for both vascular and hematopoietic cells.
4.In the presence of vascular endothelial growth factor (VEGF), hemangioblast cells differentiate into vascular endothelium.
5.The undifferentiated hemangioblasts will subsequently participate in either.
*Angiogenesis, if peripherally
*Hematopoiesis (formation of blood cells), if located
Angiogenesis is the formation of new blood vessels.
Where do blood cells develop in the bone marrow and how do they reach the circulation?
Blood cells develop in the bone marrow CORDS and when finally mature, they pass through endothelium of the sinuses to reach blood and are carried out into general circulation
What do the cords of the bone marrow contain?
Contain immature blood cells and megakaryocytes.
Clusters of mature granulocytes, particularly basophils, neutrophils and eosinophils may accumulate at the margin of the cords and will move into the sinuses when needed, as in response to infection or inflammation.
What are the functions of antigen presenting cells?
they process and present antigens for recognition by certain lymphocytes such as T-cells
State the classical antigen producing cells
*dendritic cells
*macrophages
* B cells
Describe dendritic cells
*They can arise from myeloid and lymphoid stem cells.
*Their role is to phagocytose antigens, process them, and carry them to secondary lymphoid tissue for display to lymphocytes
*They have long membranous cell processes (dendrites) which increase their surface area
State the several types of dendritic antigen presenting cells
*Langerhans cells (epithelial DCs) are found in the skin and transfer antigens to lymph nodes
*Interstitial DCs: are found in interstitial spaces in all organs except the brain. They transfer antigens to lymph nodes or spleen.
*Monocyte derived DCs: arise from monocytes in tissues and can migrate to the blood stream. They display antigens in lymph nodes or spleen.
*Plasmacytoid derived DCs: arise from plasmacytoid cells
dendritic cells are only phagocytic when picking up antigens. They then lose their phagocytic ability, becoming antigen presenting cells
State the 3 types of lymphocytes
*B-lymphocyte
*T-lymphocyte
*Natural killer cells
All tissues have macrophages, which have often been given specific names by histologists. Their exact role and appearance may be different in different tissues.
Name the macrophages found in the liver, bones, kidneys, lungs and the brain
*LIVER macrophages are known as Kupfer cells
*BONE they are osteoclasts, *KIDNEY mesanglial cells, *BRAIN microglial cells.
*LUNGS alveolar macrophages
What activates the macrophages that have engulfed pathogens to make them more effective at killing macrophages?
type 1 helper T-cells
Describe the appearance and lifespan of lymphocytes
*Most mature lymphocytes in the circulation are inactive (dormant). They
are not activated until they encounter a specific antigen which their
specific recognition molecule (antibody or T-cell receptor) recognizes and binds.
*In this dormant form lymphocytes are small cells with large nuclei, taking up most of the cell, surrounded by a thin rim of cytoplasm.
*In this form they are very long lived, and may circulate for months or years.
*Dormant lymphocytes carry a sample of their specific recognition molecule on the cell surface. When they encounter an antigen they recognize they are activated.
*The cytoplasm proliferates and they clone
ie. they divide rapidly forming a large number of identical daughter lymphocytes.
These activated cells are much bigger and contain active endoplasmic reticulum. They have a life span of 3-4 weeks.
*A few of the daughter cells do not proliferate, but remain in the circulation as dormant lymphocytes. These cells carry immunological ‘memory’.
What is the lifespan of lymphocytes
They have a life span of 3-4 weeks.
In its life span the body will encounter many different foreign molecules. It must be able to mount a defence against any of them. This means that it has to be capable of producing a massive range of different specific recognition molecules.
- The ‘made to measure’ method.
*Antigens could induce the production of a recognition molecule capable of binding to them
2.The ‘chain store’ method.
*The body can have available a vast range of different recognition molecules. An antigen will stimulate the selection of the one which recognises it from this range.
The body in fact uses method 2, usually called the ‘selective ‘ method. The lymphoid system and the lymphatic circulation is the way in which this is carried out.
State the three types of lymphoid tissues and define them
THE PRIMARY LYMPHOID TISSUES
*are where mature lymphocytes are produced
SECONDARY LYMPHOID TISSUES
* Antigens which enter the body are displayed to lymphocytes within the
secondary lymphoid tissues,
*and it is here where the selection of suitable
recognition molecules takes place, and proliferation starts.
TERTIARY LYMPHOID TISSUES
*Some antigen
presentation and lymphocyte activation can take place outside recognised lymphatic tissues.
* These areas are not
normally apparent but can establish in areas of pathogen attack.
Describe the physiology of lymphocyte production IN PRIMARY LYMPHOCYTES
*Lymphoid stem cells leave the stem cell area of the bone marrow and move
to the primary lymphoid tissues. Here they proliferate rapidly, and then start
to mature.
*Mature lymphocytes are capable of producing a single very specific
recognition molecule. The exact structure of this recognition molecule is
determined during the maturation process by random recombination of the
recognition molecule genes. *This process can produce at least 1012 and possibly as many as 1015 different antibodies and T-cell receptors, but each
mature lymphocyte can only produce one.
*Lymphocytes leave the primary lymphoid tissue as mature but dormant cells.
They will only be activated when they meet an antigen which they recognize.
Describe what happens in secondary lymphoid tissues
*These are areas to which antigen presenting cells migrate, and where lymphocytes accumulate.
*Here lymphocytes are brought into contact with antigen presenting cells, and antigens are tested against recognition molecules.
*Any lymphocyte which carries a recognition molecule which recognizes an antigen will be stimulated to proliferate – cloning to produce daughter cells, most of which will be immediately immunologically active.
*There is only one type of truly encapsulated secondary lymphoid organ.
These are the lymph nodes.
*Other secondary lymphoid tissues are simply unencapsulated areas of lymphoid cells within other organs. They include, importantly, the white pulp areas of the spleen, and mucosal associated lymphoid tissues (MALT), such as the tonsils, Peyer’s patches in the intestines, appendix, and bronchial associated lymphoid tissues.
*Lymphocytes are circulated through these areas and all dormant lymphocytes pass through them once or twice per day.
State the examples of primary lymphoid tissues
*T-lymphocytes are produced in the
thymus gland
*B-lymphocytes are produced in an area of the bone
marrow.
Name the only one type of truly encapsulated secondary lymphoid organ.
Lymph nodes.
What is the common feature in all secondary lymphoid organs?
They all contain lymphoid follicles
Describe the main histological parts of a spleen
*Made up of a lymphoid tissue containing loose lymphoid and blood cells called THE WHITE PULP.
*Which is supported by the TRABECULAE
*And surrounded by connective tissue rich in blood called THE RED PULP
Describe the marginal zone
*This region contains mostly reticular cells and antigen-presenting cells, as well as some lymphocytes that may play a role in antigen trapping or processing.
*This transition zone between white pulp and red pulp function as a primary site of antigen presentation in the spleen
Outline the features of a spleen white pulp
1.central arteriole
2. Periarteriolar Lymphoid Sheath( PALS)
SPLENIC FOLLICLES
*Primarily B cells
1.CENTRAL ARTERIOLE
*NOT centrally located in follicles
*surrounded by a layer primarily T-cells
GERMINAL CENTER
*Has activated B-cells
surrounded by MANTLE ZONE
*Darker
*More dense
*B-cells and macrophages
surrounded by MARGINAL ZONE
*Not densely packed
*thicker ring
*B- cells, macrophages and dendritic cells
Describe the red pulp
*eosinophilic because of large amount of RBC
*70% is parenchyma
30% is VENOUS SINUSES/ SINUSOIDS
*BROAD INTERCONNECTED VASCULAR SPACES
*LINED WITH SPECIALISED ENDOTHELIAL CELLS
.filter the blood
.defective or abnormally shaped RBC wont pass between the endothelial cells
.large round basophilic nuclei
.reticular fibers surround the
sinusoids
*EVENTUALLY JOIN WITH ONE ANOTHER AND DRAIN INTO THE SPLENIC VEIN
PARENCHYMA- called cords of Billroth
*macrophages
*lymphocytes
*loose connective tissue
*arterioles
*RBC
has sinusoid and arteriole which branches from the central arteriole of the white pulp
Describe the roles of the thymus
*primary organ for maturation of lymphocytes
*it plays a role in developing self tolerance
Describe the histology of the thymus
There are three sub types of epithelial cells in the cortex:
*SQUAMOUS THYMIC EPITHELIAL CELLS are important in the formation of the thymus blood barrier.
*STELLATE THYMIC EPITHELIAL CELLS that form the cytoreticulum.
*OTHER THYMIC EPITHELIAL CELLS that form the corticomedullary barrier.
There are three sub-types of epithelial cells in the medulla:
*THE SQUAMOUS THYMIC AND STELLATE THYMIC CELLS of the medulla have similar functions to their counterparts in the cortex.
*Hassall corpuscles.
Other non-thymic, non-lymphoid cells include:
*MYELOID CELLS include monocytes, macrophages, and dendritic cells,
*FIBROBLASTS facilitate the production of collagenous material,
*The rarely observed myoid cells are believed to facilitate migration of lymphoid tissues across the thymus.
Why is the thymic medulla lighter than the cortex?
With their dark staining nuclei and little cytoplasm, the abundant T lymphocytes in the cortex give the thymus a dark color. The thymic medulla has far fewer lymphocytes in it and so stains much lighter.
Describe the histology of lymph nodes
- has two parts, cortex and medulla
*Consists fibrous connective tissue , containing many lymphocytes and other immune cells through which the lymph flows
*In the cortex, lymphocytes are gathered into lymph nodules, also called lymphoid particles
*At the center of each nodule is a germinal center where lymphocytes proliferation - The medulla appears less visibly organized.An efferent lymph vessel drain the lymph node from the hilus, in the region of the medulla.
- A lymph vessel also received the blood in through the hilus and passing through high endothelial venules, specialized for interacting
Outline the sites for red bone marrow in adults
*sternum ( breast bone)
*Ribs
*Pelvis
*Upper ends of the long limb bones
These are the sites where bone marrow is extracted for examination or for use in bone marrow transplants
Describe how the 3 lymphocytes work?
B-lymphocytes: produce antibodies, thy mature in the bone marrow
*They form about 15 – 25% of circulating lymphocytes.
T-lymphocytes: secrete recognition molecules T-receptor, which remain at
*T-cells form
about 65 – 80 % of circulating lymphocytes.
Natural killer cells: they kill malignant cells (cancer cells) and some virus infected cells.
*form 5 – 15% of circulating lymphocytes
Describe the characteristics of macrophages
*They remove and digest the by-products of both foreign particles and normal growth and degeneration
*Are mobile (ameboid movement) over a short distance within a local region of connective tissue
*They are formed when monocytes circulating in the blood differentiate when they enter the connective tissue
*Macrophages which have engulfed pathogens can be activated by the type 1 helper T-cells, making them more effective at killing pathogens
They enter the blood as immature monocytes, which remain in the blood for only a few hours before entering the tissues and maturing into macrophages. Mature macrophages are 5 – 10 times larger than monocytes, and contain more organelles. They have a life span of several months in their tissue location.
Where is the MALT found?
In the lamina propria of most mucosal organs , GIT
Have lymph nodules or lymphoid follicles which are a spot where lymphocytes congregate and a germinal center at the center of each nodule where the lymphocytes proliferate
Describe Peyer’s patch
- Each patch is made up of a cluster of lymph nodes which buldge toward the lumen
*It is located in the mucosa of ileum
