Lymphoid Organs Flashcards
Primary Lymphoid Organs
bone marrow & thymus
B lymphocytes differentiate in
bone marrow
T lymphocytes differentiate in
bone marrow, then thymus
Secondary Lymphoid Organs
lymph nodes, spleen, MALT, tonsils
basically anything other than the bone marrow or thymus
Common areas where antigens are likely to gain entry into the body
skin, walls of GI tract, respiratory tract, and urogenital tract
What type of cell are lymphocytes derived from?
pluripotential hematopoietic stem cell
Differentiation in primary lymphoid organs is antigen-independent or antigen-dependent?
antigen-independent
Lymphocytes leave primary lymphoid organs as what? and where do they go?
naive lymphocytes
secondary lymphoid organs
T or B cell activation and proliferation is antigen-independent or antigen-dependent?
antigen-dependent
What are examples of antigen-presenting cells (APCs)?
macrophages and interdigitating dendritic cells (IDCs)
What cells help activate B cells?
T helper cells
What is blast transformation?
cell enlarges to become an immunoblast/lymphoblast/large lymphocyte and divides repeatedly
What type of cells do activated lymphocytes differentiate into?
effector cells and memory cells
Name examples of effector cells
plasma cells
cytotoxic t cells
What is the advantage to having memory cells?
subsequent responses against the same antigen are stronger and faster to develop
What type of organ is the thymus considered?
lymphoepithelial organ
When does the thymus begin to develop?
5th week of gestation
What does the thymus develop from?
the endodermal epithelium of the 3rd pharyngeal pouches
How many lobes does the thymus have?
2
What happens after the two thymic primordial fuse?
it migrates into the superior mediastinum of the thorax (just posterior to the sternum)
What is the thymus initially composed of?
thymic epithelial cells (TECs) or epithelioreticular cells (ERCs)
connected by desmosomes
these are considered the stromal cells of the thymus
What are the precursors of T cells called?
prothymocytes
derived from CFU-L
How do prothymocytes enter the thymus?
via blood vessels
Is the thymus fully functional at birth?
yes
What happens to the thymus at puberty?
it begins to involute
What is the capsule of the thymus made of?
thin layer of dense irregular CT w/ collagen type I and reticular fibers (type III)
What are septa (thymus)?
trabecule
divides the thymus into lobules
Are the lobules of the thymus divided completely?
no
Describe the cortex of the thymus.
dark-staining
outer region
relatively more lymphocytes
Describe the medulla of the thymus.
pale inner region (more TECs and macrophages)
continuous throughout whole organ
What is the only lymphoid organ that has an epithelial stroma (made up of epithelial cells)?
thymus
Characteristics of TECs
found in cortex and medulla large pale cells with euchromatic nuclei have tonofibrils composed of cytokeratin tonofilaments poorly phagocytic do NOT produce reticular fibers
Functions of TECs
physical support (stroma) secrete chemokines (attract prothymocytes) and cytokines (induce thymocyte division & differentiation) contribute to blood thymus barrier
Cortical TECs
Type I -line inner surface of capsule -blood-thymus barrier -connected by tight junctions Type II -thymic nurse cells -form nests that surround thymocytes -participate in positive selection Type III -at corticomedullary boundary -connected by tight junctions -participate in positive selection
Medullary TECs
Type IV -at coricomedullary boundary -joined together and with Type III cells by tight junctions Type V -connected by desmosomes -participate in selection processes Type VI -arranged in concentric layers to form Hassall's corpuscles
Hassall’s corpuscles
medulla of thymus
center may become calcified, keratinized or necrotic
express thymic stomal lyphopoietin (TSLP)
What is the function of thymic stromal lymphopoietin (TSLP)?
activates interdigitating dendritic cells (IDCs)
What do IDCs do in the thymus?
induce the differentiation of regulatory T cells (suppress immune responses)
When are T cells called thymocytes?
once they has left the blood vessels and entered into the thymus
Where do the thymic blood vessels travel?
capsule -> septa -> corticomedullary boundary
What is the thymocyte migration path during thymic cell education?
corticomedullary boundary -> outermost cortex (just beneath capsule) -> corticomedullary boundary -> medulla -> leave the thymus
What cell markers do T cells express when they enter the thymus?
CD2 & CD7
considered double negative cells (no CD4/CD8)
Where does positive selection occur?
cortex
In which order do these occur?
become double positive cells and form T cell receptor
- form T cell receptor
2. begin to coexpress CD4 & CD8 as double positive cells
Where do T cells go after surviving positive selection?
bind to Type II or Type III cells
How many cells die in the cortex?
~95-99%
How do apoptotic bodies stain?
dark
What are macrophages that contain apoptotic bodies called?
tingible body macrophages
Does negative selection take place before or after positive selection?
after
Where does negative selection occur?
medulla of thymus
What cells present self-antigens during negative selection?
medullary TECs
Interdigitating dendritic cells (IDCs)
possibly macrophages
Which has more antigens the cortex or the medulla of the thymus?
medulla
blood-thymus barrier - tight in cortex, leaky in medulla
What are the mechanisms to protect the cortical thymocytes from antigen?
double layer of Type III and Type IV TECs at the corticomedullary boundary
Type I TECs line the inner surface of the capsule and trabeculae
Can proteins that are expressed in other organs by found in the thymus?
yes, medulla
“promiscuous” or “ectopic” antigen expression
When is the size of the thymus the largest?
at birth
What size does the thymus go from during age involution?
~30g at puberty to ~3g in elderly
What happens during involution of the thymus?
cortex becomes discontinuous (cortical “caps”)
adipose tissue fills
What causes accidental involution
**steroid hormones/corticosteroids severe infections chronic illness ionizing radiation aka severe stress
Is the thymus essential for life?
In adults, no
secondary lymphoid organs have enough T cells to live for years
What happens if a neonatal thymectomy is done?
increased susceptibility to infections
cell-mediated immunity is deficient
humoral immunity is suboptimal (no helper T cells)
paracortex (LN) & PALS (spleen) underdeveloped
DiGeorge Syndrome
malformation of 3rd & 4 pharyngeal pouches thymus underdeveloped or absent may die young of infections transplantation sometimes successful congenital heart defects too
Where are lymph nodes located?
along lymphatic vessels
What is the function of the lymph node?
to filter antigens, particles and cell debris delivered by afferent lymphatics
initiate immune responses
What is the normal size of the lymph node?
~1mm to ~2cm
What is lymphadenopathy?
abnormal enlargement of the lymph node
caused by normal immune reactions
-retention of activated lymphocytes
What is the capsule of the lymph node composed of?
dense irregular CT
also have trabeculae
What is the stoma of a lymph node composed of?
reticular CT cells and reticular fibers (type III)
Afferent lymphatic vessels
penetrate the capsule at many points
What is the hilus/hilum?
where blood vessels enter and leave the lymph node
also efferent lymphatic vessels leave
Are lymph nodes separated into a cortex and medulla?
yes
cortex has outer and deep or paracortex
What does the outer cortex of the lymph node contain?
lymphoid nodules
internodular cortex
What cells do the lymphoid nodules contain?
many B cells
macrophages
follicular dendritic cells (FDCs)
few T helper cells
What cell type does the internodular cortex contain?
mainly T cells
Paracortex of LN
contains mainly T cells
thymus-dependent region
contains high endothelium venules (HEVs)
Medulla of LN
mixed population of T/B cells, plasma cells, macrophages and IDCs
organized into medullary cords
lots of medullary sinuses
NO nodules
Is there a cortex or paracortex at the hilus?
No
medulla is underneath capsule
flow of lymphatic sinuses
lymphatics _> subcapsular sinus -> trabecular sinuses -> medullary sinuses -> efferent lymphatic vessel
What are the other names for trabecular sinuses?
intermediate or cortical sinuses
Can a lymph node have more than 1 hillus and efferent lymphatic?
yes
Do lymph sinuses have valves?
no
Where do lymph sinuses have continuous endothelium?
where they are in direct contact with the CT of the capsule or trabeculae
Where is the stroma present in LN?
lumen of sinuses
except lumen of afferent or efferent lymphatics
What adhere to the stroma in the lymph sinus lumens?
macrophages
What form can the antigen arrive to a node?
free antigen
part of antigen-antibody complex
bound to an APC
What is the purpose of interdigitating dendritic cells (IDCs)?
activating T cells
What are IDCs derived from?
Langerhans cells of the epidermis
change into veiled cells in lymphatic vessels
What number of lymphocytes enter the LN through blood vessels?
~90%
How do lymphocytes enter into the LN?
high endothelium venules (HEVs) in paracortex
diapedesis
Lymphocyte homing?
chemokines attract T & B cells to their appropriate regions of the lymph node
Where are T cells located in the LN? B cells?
T cells - paracortex & internodular cortex
B cells - lymphoid nodules
Antigen-presenting cells (APCs)
macrophages
IDCs
B cells
Where do immune responses in the LN begin?
paracortex (activate naïve T cells)
What is the main cell type in germinal centers of secondary nodules?
memory B cells & plasmablasts
Plasmablasts
antigen-producing cells
migrate to medullary cords where become plasma cells
Memory B cells
become small lymphocytes
become part of mantle/cap of nodule, migrate to medullary cords or leave the node in efferent lymphatics
Parts of the secondary nodule
mantle/cap -small lymphocytes -stains dark germinal center -light-staining -activated B cells are large w/ pale cytoplasm and euchromatic nuclei
Part of the germinal center
Dark zone
-near paracortex
-B cells are called centroblasts
Light zone
-centrocytes
-rate of mitosis decreases
-interact w/ follicular dendritic cells (FDCs)
-selection process = many macrophages ("starry sky")Follicular Dendritic Cells (FDCs)
form stroma of primary and secondary nodules
long cytoplasmic processes with beaded appearance
NOT true antigen-presenting
bind immune complexes
What are the functions of FDCs?
prevent apoptosis of immunoblasts/stimulate mitosis
promote:
-somatic hypermutation
-affinity maturation of antibody
-class switching
-regulation of # of plasma cells vs memory B cells
Do lymph nodes enlarge slowly or quickly in microbial infection? primary malignancies (lymphoma)?
Microbial - quickly
Lymphoma - slowly
Follicular Hyperplasia
antibody production predominates
large numbers of secondary nodules
ex. rheumatoid arthritis
Paracortical hyperplasia
cell-mediated response predominates
few secondary nodules
ex. viral infections
Circulation of lymphocytes
leave LN via efferent lymphatics
enter large veins at root of neck
pass through heart and carried through body
What are the functions of the spleen?
filter antigens from blood & initiates immune responses (white pulp)
destroys old or damaged erythrocytes (red pulp)
Does spleen have a hilus? afferent lymphatics?
yes
no
Capsule of spleen
thick dense irregular CT some contractile myofibroblasts covered in mesothelium has trabeculae
Stroma of spleen
reticular fibers and reticular cells
found in white and red pulp
provide support and produce chemokines to attract lymphocytes to spleen
Does the spleen have a cortex or medulla?
no
Is white pulp continuous?
no
Where is white pulp organized around?
central artery
What are the two components of white pulp?
periarteriolar lymphatic sheath (PALS) -cylindrical sheath of lymphocytes around central artery -mainly T cells (thymus-dependent region) -dendritic cells help activate T cells lymphoid nodules -embedded in PALs -B cell regions -contain FDCs
What are the two components of red pulp?
splenic sinuses (venous sinuses or sinusoids)
splenic cords (Bilroth’s cords)
-where old erythrocytes are destroyed
-where hematopoiesis occurs during embryogenesis
-has erythrocytes, T/B/plasma cells, granulocytes, dendritic cells, and macrophages
What is the marginal zone?
surrounds white pulp, separating it from red pulp
supplied by side branches of central arteries
where immune response initiated
What is special about the B cells in the MZ?
do not recirculate
can be activated without T cell help
specific for viral or bacterial antigens
shuttle back and forth from MZ and lymphoid nodules
What type of circulation is the human spleen considered?
open circulation
Blood flow through spleen
Splenic artery -> capsular arteries -> trabecular arteries -> central artery (WP/MZ) -> penicillar arterioles (splenic cord) -> sheathed capillaries (by macrophages) -> splenic sinuses (open) -> pulp veins -> trabecular veins ->capsular veins -> splenic vein
Structure of splenic sinuses
endothelial cells are long and fusiform (spindle-shaped)
basement membrane is discontinuous
hoop-like strands encircle sinus
reticular cells attach to outer surface and secrete reticular fibers
What cells can pas through gaps in sinus walls?
old or defective red blood cells
(should be leukocytes and young RBCs, old and defective can’t so they’re phagocytized by macrophages in splenic cords)
they are phagocytized by macrophages
How do macrophages recognize old red blood cells?
have modified band 3 protein in membrane
phosphatidylserine (PS) found on outer leaflet (usually inner)
How is hemoglobin recycled?
Heme -> biliverdin & Fe
biliverdin -> bilirubin + albumin -> liver -> bile
Fe + transferrin -> bone marrow
What is splenomegaly and its causes?
enlarged spleen
excessive destruction of RBC - congestion of splenic cords by defective RBCs
certain lysosomal storage diseases
Is spleen essential for life?
no
will be more susceptible to infections
Why would someone remove the spleen?
traumatic injury
some hemolytic anemias
some autoimmune conditions
What is lymphoid tissue?
loose cellular CT with lymphocytes as the major cell type
Is lymphoid tissue limited to lymphoid organs?
no
Intraepithelial lymphocytes
located between epithelial cells
secrete cytokines that kill infected cells
Diffuse lymphoid tissue
large # of closely pack lymphocytes
no lymphoid nodules
no capsule
present in lamina propria of respiratory, digestive and urinary tracts
Isolated lymphoid nodules (lymphoid follicles)
presence of primary or secondary nodules
temporary
secondary = humoral immune reaction
Aggregated lymphatic nodules
large groups of primary or secondary nodules
wall of appendix and ileum
Mucosa-Associated Lymphoid Tissue (MALT)
collective name for all lymphoid tisse found in mucosa of hollow organs
also have GALT (gut), BALT (brochus), and NALT (nasal)
What factors increase the efficiency of the immune system?
secondary lymphoid organs -bring together everything need to initiate immune response in one place lymphatic vessels -carries antigens to lymph nodes -recirculates lymphocytes
