Histo HemeOnc Flashcards
Lymphatic system provides what?
immune response to antigens (proteins, carbs, lipids, or nucleic acids)
What are the effector cells of the lymphatic system? What are the three main types?
lymphocytes: B, T, NK
What are the supporting cells of the lymphatic system and what is their role?
- stromal cells - support cells forming loose meshwork creating a good environment for lymphocytes
- monocytes/macrophages, polymorphonuclear leukocytes, and dendritic cells - assist with antigen presentation and regulation of the immune response
What is innate immunity?
- not specific,
- does not require exposure to an antigen
- functional at birth
- natural barriers (physical or chemical)
- phagocytic and NK cells
Adaptive immunity
- specific
- develops after exposure to antigen
- induces resistance against pathogens
- two types
- humoral immunity
- cell-mediated immunity
humoral immunity
- mediated by abs acting on invading agent
- abs produced by B lymphocytes and plasma cells
- best against extracellular bacteria
Cell mediated immunity
- Tc lymphocytes, NK cells, monocytes/macrophages, and polymorphonuclear leukocytes
- attack and destroy virus infected host cells, foreign and tumor cells
- effective v intracellular and extracellular pathogens
What are the two primary lymphatic organs?
bone marrow and thymus
initially, lymphocytes in the primary lymphatic organs are programmed to….
recognize a single antigen in process called antigen-independent proliferation and differentiation
What kind of tissue is bone marrow?
reticular connective tissue, filling the internal spaces of bone
How is bone marrow separated from the bone proper?
endosteum
How does blood get to the bone marrow cavity?
nutrient arteries through bone, into arterioles, into plexus of capillary sinusoids aka venous sinuses
What is the general structure of bone marrow?
- hemopoietic cords of cells supported by reticular fibers surround the venous sinuses;
- cords of cells contain blood cell precursors, mature blood cells, adipocytes, and stromal cells
Composition of bone marrow in young v old
younger people have fewer adipocytes in bone marrow and this is called “red marrow”
adults have more adipocytes in the bone marrow and are called “yellow marrow”
What are the stromal cells in bone marrow and what do they do?
CT cells like fibroblasts and macrophages; important role in secreation of facters to stimulate hemopoiesis like IL-11
Where do B cells become immunocompetent B cells?
bone marrow and MALT
Where do T cells become immunocompetent?
originate in bone marrow and then become immunocopetent in thymus
What does the organ of the thymus look like?
asymmetric, bilobed organ in the superior mediastinum on the posterier side of the manubrium of the sternum
At what point in life is the thymus the largest?
thymus is largest in kids and begins to regress at puberty
What pharyngeal pouches does the thymus originate from?
3rd and 4th pharyngeal pouches
When do CLP cells from the bone marrow invade the epithelium rudiment of the thymus?
about 10th week
What does the stroma of the thymus originate from?
endodermal origin
Where do lymphocytes and macrophages originate from?
mesodermal origin (bone marrow derived)
What is the most abundant cell of the thymus?
T lymphocyte aka thymocyte
How many of the T cells that start the differentiation process undergo apoptosis and are phagocytized?
98%
What cells support lymphocytes and provide framework for developing T cells? What are they like?
epithelioreticular cells
true epithelial cells and connected by occluding junctions and desmosomes forming a cytoreticulum; have basal lamina; DO NOT secrete reticular fibers like the true reticular cells of the LNs
In the thymus, what cells are dispersed among the T cells? What do they do?
Macrophages
responsible for phagocytosis of T cells that do not fulfill thymus education requirements
What is the histological structure of the thymus capsule?
- well-developed CT capsule
- divided into lobes
- CT dives into parenchyma in thin struts, forming trabeculae, dividing the thymus into incomplete lobes
What is the cortex of the thymus like?
- outer, densely cellular portion of each lobule
- densely packed lymphocytes giving a basophilic appearance
- least differentiated lymphocytes found here, then mature and go toward medulla
What is the medulla of the thymus like?
- less cellular part of lobules
- lighter stain than cortex
- has mature, differentiated T cells, macrophages
- Hassal’s corpuscles - concentric structures of epithelioreticular cells
- center can have keratin pearl
What prevents antigens from escaping cortical capillaries into the thymus cortex to avoid contact with developing T cells?
Blood-thymus barrier
What are the three mechanisms of the blood-thymus barrier?
- tight junctions between the endothelial cells of the thymus cortical continuous capillaries
- perivascular CT surrounding caps is loaded with macrophages that phagocytose antigens that manage to get through epithelium
- endothelioreticular cells form occluding junctions around capillaries and together w their basal laminae form the third component of the blood-thymus barrier
Vaguely, what is T cell education?
- see if T cell is good enough to complete mission later
- several steps, characterized by a change in the expression and deletion of certain surface markers
What is the earliest stage in T cell education? Where does this occur?
double negative stage
in outer cortex, close to the capsule of the thymus
What happens during the double-negative stage?
lymphocytes do not have either CD4 or CD8 and only posess CD2 and CD7 on their cell surface
Where does the double-positive stage occur? What is expressed at this time?
occurs in cortex of thymus
T cells expressing TCR, CD3, and both CD4 and CD8 on cell surface
What happens in the double-positive stage?
T cells are presented with both self-MHC and self- and foreign antigens
if they fail to recognize either they are eliminated;
the cells that do recognize those in the process (positive selection) leave the cortex and enter the medulla
What happens after positive selection? Where does this next step take place?
negative selection
in the medulla
What is the process of negative selection?
double positive cells in the medulla that recognize self-antigen presented by self-MHC are eliminated
Surviving cells of negative selection become what? What is this stage called?
What do the cells do now?
either CD8+ Tc or CD4+ T helper
lose the other CD marker so now they are single-positive stage
they are allowed to leave the thymus and enter circulation
What are the secondary lymphatic organs?
MALT, GALT, BALT, tonsils, LNs, and spleen
Where do lymphocytes undergo antigen-dependent activation?
secondary lymphatic organs
What is MALT typically formed of? (3 major manifestations)
diffuse lymphoid tissue
single lymphoid follicles
aggregated lymphoid follicles
What does not have a capsule and consists of loosely arranged immune cells?
diffuse lymphoid tissue
Where is diffuse lymphoid tissue mostly found?
lamina propria of the GIT, respiratory passages and GUT
After contact with antigen in diffuse lymphoid tissue, where do the lymphocytes go?
travel to lymph nodes where they undergo proliferation and differentiation;
progeny of these cells then return to lamina propria as effector B and T lymphocytes
What are lymphoid follicles and where can I find them?
spherical structures scattered throughout the lamina propria of the GIT, respiratory passages, and GUT; also found in LNs, spleen, and tonsils
lacking a capsule
What cells compose lymphoid follicles?
B lymphocytes mostly
follicular dendritic cells express receptors for soluble immunoglobulins
What do follicular dendritic cells do?
express receptors fo soluble immunoglobulins;
bind immunoglobulins, which will bind antigens
cells do not readily endocytose the immunoglobulin receptors and antigens bound to these receptors are stored on the surface of the cells for long time
important in maintenance of memory B cells and in the selection of B cells with very high affinity antibodies
What is the difference between primary and secondary lymphoid follicles?
- primary
- no dividing lymphocytes
- uniformly composed of small lymphocytes
- B cells that have not yet been activated
- secondary
- dividing lymphocytes
- contain activated B cells
- develop after a lymphocyte that has recognized and antigen in the mucosa returns to a primary follicle and undergoes proliferation
- has germinal center and mantle
What does the germinal center of secondary lymphoid follicles contain?
large activated immatrue lymphocytes (lymphoblasts) that are undergoing mitoses
lighter staining than the mature small lymphocytes
follicular dendritic cells are also present
What does the mantle (aka corona) of the secondary lymphoid follcile contain?
- contains small lymphocytes that surround the germinal center creating characteristic bull’s eye appearance
Where are aggregated lymphoid follicles found?
- peyers patches are in the lamina propria of the ileum and consist of numerous lymphoid follicles
- lamina propria of the vermiform appendix is heavily infiltrated w lymphocytes and contains numerous lymphoid follicles
What forms a ring of lymphatic tissue at the entrance of the oropharynx? What are they composed of?
tonsils
aggregates of lymphoid follicles
What are the largest of the three kinds of tonsils? Where are they located?
Palatine tonsils
located on the posterior part of the soft palate between the palatopharyngeal and palatoglossal arches
What is the epithelium of palatine tonsils like?
non-keratinized stratified squamous epithelium, making multiple dips into the tissue of the tonsil forming the tonsillar crypts
What is the epithelium of the tonsillar crypts like?
thinner than on the surface and usually infiltrated with T cell and dendritic cells
Palatine tonsils contain numerous what?
lymphoid follicles containing B-cells;
spaces between the follicles represent the T cell regions and contain high-endothelial venules
Where do lymphocytes exit the lymphoid tissue and join the bloodstream?
high endothelial venules
Do palatine tonsils have a capsule?
partially encapsulated and separated from the underlying tissue by a thick CT capsule
Where are pharyngeal tonsils located? What else are they called?
adenoids are located on the posterior aspect of the nasopharynx
What is the epithelium of pharyngeal tonsils?
pseudostratified columnar epithelium
makes several folds, but does not have crypts
What tonsils are found on the tongue?
lingual tonsils
What tonsils are found inferior to the auditory tube?
tubal tonsils
What are small bean shaped encapsulated lymphatic organs that filter lymph?
lymph nodes
How does the lymph node receive and send out lymph?
concave area of the node contains the hilum, where the efferent lymphatic vessel exits the node and the blood vessels enter it
the convex part of the node receives lymph from the afferent lymphatic vessels
Describe the capsule of lymph nodes
CT capsule
directly beneath is the subcapsular sinus space
the capsule forms projections into the parenchyma called trabeculae
trabeculae contain trabecular (or radial) sinuses within them
The bulk of the tissue of the lymph nodes is formed of what?
reticular tissue rich in reticular (type III collagen) fibers, reticular cells (fibroblasts), lymphocytes, and dendritic cells/macrophages
What is the cortex of lymph nodes like?
covers outer part except for hilum
consists of dense lymphatic tissue supported by a framework of reticular fibers synthesized by the specialized fibroblasts called reticulocytes
What is cell organization in the outer cortex of the lymph node like?
lymphocytes in outer cortex are organized into lymphoid follicles and thus is the B cell region
What is the inner cortex of the lymph nodes organized like?
inner cortex/paracortex are mostly T cells
contains a large number of high endothelial venules to allow emigration of T cells from blood into the lymph node
What is the medulla of the lymph node like?
more loosely arranged cells than the cortex
composed of medullary cords surrounded by medullary sinuses
also supported by network of reticular fibers secreted by reticular cells
medually cords contain
lymphocytes (mostly B cells), plasma cells, macrophages, dendritic cells, adn few T cells
medually sinuses receive
lymph from trabecular sinuses and converge near the hilum, where they drain into the efferent lymphatic vessel
medually B cells can leave the node through the meduallary sinues to travel the body
What do lymphatic sinuses do and contain?
allows for the filtration of lymph and provides channels
contain a meshwork of reticular fibers and macrophage processes that are designed to trap antigens and transformed cells (metastatic or infected) filtering the lymph
What cells present in lymphatic sinuses secrete antibodies?
plasma cells
What is the lymph flow through the lymph node pathway?
- afferent lymphatic vessels from convex area
- to the subcapsular sinus
- trabecular sinuses run through the CT within the cortex, drain lymph from the subcapsular sinus
- to the medullary sinuses among the medullary cords
- to the efferent lymphatic vessel leaving through the hilum
What is blood flow through the lymph looking like?
artery supplying the LN breaks into the capillary bed within the cortex and the postcapillary venules are formed with the inner cortex (paracortex)
What epithelium lines postcapillary venules in LNs? What are these also known as?
cuboidal
high endothelial venules
How does lymph flow into the LNs?
express a high concentration of water channels (aquaporin-1)
allows rapid resorption of interstitial fluid via water channels into blood stream
causing lymph to be drawn into the node via afferent lymphatic vessels d/t solvent drag
How do B and T cells gain entry to the LNs?
specialized endothelial cells of HEVs have receptors that signal both B and T cells to leave the circulation and migrate into the lymph node between endothelial cells
Where do B and T cells once in the LNs?
T cells remain in the paracortex
B cells migrate to the outer cortex
How do lymphocytes leave LNs?
most lymphocytes leave the LN by entering lymphatic sinuses from which they flow to an efferent lymphatic vessel
What is the function of LNs?
important site for phagocytosis and initiation of immune response
Increased concentration of antigens in the LN enhances what? What does this cause?
enhances the presentation to lymphocytes
leads to activation and differentiation of B cells into antibody producing plasma cells and memory B cells
What do plasma cells do within LNs?
migrate to medullary cords where they synthesize and release specific antibodies into the lymph flowing through the sinuses
What do memory B cells do upon leaving the LNs?
circulate to various regions throughout the body, proliferate in response to subsequent exposure to their specific antigen
exit of the lymphocytes into the blood from lymphatic tissue goes through what?
cuboidal epithelium, high endothelial venules
The majority of lymphocytes in the blood are….
T cells
Where are HEVs usually found?
T cell regions of lymphoid tissues
What is a B cell’s pathway to get out of the lymphoid tissue?
leaving through HEV, have to migrate through the T cell region, during which time they become activated, to reach the B cell region of the lymphoid tissue
What does the spleen do?
filters blood and reacts immunologically to blood-borne antigens
What does the capsule of the spleen contain? Why is this important?
dense CT capsule contains regular fibroblasts and myofibroblasts, allowing for the organ to contract, squeezing the blood out of it
trabeculae from the capsule dive into the parenchyma
What does the spleen parenchyma contain?
white pulp - large number of WBCs
red pulp - high concentration of RBCs
What are the two major components of white pulp?
periarterial lymphatic sheath (PALS) - mainly T cells surrounding central artery
lymphoid follicles - consist mainly of B cells, attached to the PALS
What does the red pulp contain?
RBCs, splenic sinuses (dilated sinusoidal capillaries), splenic cords (cords of Billroth)
circulation within the red pulp allows macrophages to screen antigens in the blood
What are splenic cords like?
resemble meduallary cords in having a dense meshwork of reticular fibers secreted by reticular cells
RBCs, macrophages, lymphocytes, plasma cells, and granulocytes reside within the meshwork
Where are damaged RBCs phagocytized?
splenic macrophages
iron is recycled
splenic sinuses receive blood from where?
blood that has been filtered through the cords
How does blood get into the spleen? What surrounds these arteries?
splenic artery brings blood in and upon entering the capsule breaks into trabecular arteries, which are running through the CT trabeculae and are NOT surrounded by lymphocytes
After exiting from the trabeculae the arteries develop…
a layer of T cells around them called the periarterial lymphatic sheath (PALS)
artery at this point is called central artery as it is located in the center of PALS
What pulp is the central artery in?
white pulp, where PALS has a greater role
As the central artery loses PALS, it enters
the red pulp and branches into several short straight vessels called penicillar arterioles
Penicillar arterioles continue as small arterial capillaries which are surrounded by a sheath of
macrophages, and are thus called sheathed capillaries
sheathed capillaries dump the blood…
this type of circulation is considered…
directly into the splenic cords
open circulation
after ‘percolating’ through the cords, blood filters into…
splenic sinuses, which are dilated venous sinusoidal capillaries
What is the endothelium lining sinuses in the spleen like?
endothelial cells are rod-shaped and contain gaps between individual cells allowing for RBCs to squeeze through the walls
do NOT have continuous basal lamina
blood from the splenic sinuses is collected into the
pulp veins
pulp veins deliver blood to the larger
trabecular veins located within the CT trabeculae
trabecular veins eventually merge to form the
splenic vein, which exits organ via hilum
What are the immune functions of the spleen?
antigen presentation by antigen-presenting cells and initiation of immune response
activation and proliferation of B and T lymphocytes
producation of antibodies against antigens present in circulating blood
removal of macromolecular antigens from the blood
What are the blood maintenance/hemopoiesis functions of the spleen?
removal and destruction of senescent/damaged and abnormal RBCs and platelets (macrophages of red pulp)
retrieval of iron from RBC hgb
formation of RBC during early fetal life
How is iron stored once retrieved by the spleen?
ferritin/hemosiderin
Heme is broken into what by the spleen?
bilirubin
