Lecture 8-10 lymphatics Flashcards
___ comprises the vessels and organs that allow the immune system to work
lymphatic system
some components of the lymphatic system are
thymus, lymph nodes and spleen
lymphatic system maintains ___
functional immunity
Primary lymphatic organs
bone marrow
thymus
Secondary lymphatic system
Lymph nodes
spleen
mucosa associated lymphoid tissue (MALT)
Tertiary Lymphatics
small lymphatics organs that show up during some diseases and preform immune functions
Adult cells of lymphatic system
effector B cells
effector T cells
another name for effector B cells
plasma cells
where are lymphatic cells generated and “educated”
primary lymphoid organs
where are lymphatic cells maintained and activated
secondary lymphoid organs
How do lymphatic cells survey an animal
Lymphocyte recirculation
steps of innate immune response
first line of defense
rapid
mediated by non-specific effector cells (macrophages and neutrophils)
steps of adaptive immune response
later, long lived, memory cells
mediated by T-cells and B cells (cellular-(T-cells) and humoral (B-Cells))
highly specific (antigen recognition)
requires initial innate immune response
how does macrophages and neutrophils destroy pathogens
“eats them”
phagocytosis
innate immune response
soluble proteins made by one cell that affect the function of another
cytokines
chemotactic cytokines
chemokines
explain how cytokines work
Macrophage eats pathogen, this triggers the release of cytokines, which will trigger dilation of local small blood vessels
adhesion molecules are expressed on inside of blood vessels.
these, adhesion molecules, attract leukocytes
leukocytes are taken out of the blood vessel and carried to the original infection because they are attracted by “chemokines”
___ attracts more macrophages/neutrophils to help in the inflammatory response
chemokines
what cells are requires for the initiating of adaptive immune response
dendritic cells
explain how dendritic cells work
capture some bacteria
breaks it up and then takes part of antigen and “presents” it on the dendritic cells surface
Then move to nearest lymphatic vessel and then “drains” into the nearest lymphatic organ (lymph node)
this activates T- Lymphocytes
T cells and B cells have ___ on their surface
monoclonal antigen receptors
small piece of pathogen that is recognized by T and B cell antigen receptors
antigen
Each B cell can identify many types of antigens
True or False
False
1 b cell=1 antigen
very specific
Antigen presenting cells are also called ___
dendritic cells
Where do T-cells develop
in the Thymus
T cells can turn into
T-helper cells (CD4)
T-Cytotoxic (CD8)
(single positive SP)
double positive T cells
precursor T cells that have CD4 and CD8
T-helper cells
CD4
producing cytokines and other soluble mediators that HELP other cells of the immune response including macrophages, eosinophils and B cells
T cytotoxic
CD8
finds and kills infected cells
How does T cell “see” antigen
antigen is expressed on surface of dendritic cell
T cell receptor (TCR) sees and binds to this peptide antigen
antigen is presented on specific MHC proteins
MHC are found in what
dendritic cells
explain how pathogen gets expressed by dendritic cells
dentrictic cell eats pathogen
lysomes breaks down pathogen into antigen
MCH proteins are attached to antigen
this is then expressed onto membrane and is “seen” by the T cell receptor of a T cell
steps of T cell
recognition phase
activation phase (clonal expansion)
effector phase
parts of effector phase of T cells
macrophage activation
B cell activation/antibody production
inflammation
memory T cells
T cell mediated Cytolysis
B cells develop in the
bone marrow
Bursa of Fabricius (in chickens)
what do B cells do
make antibodies
make memory cells (respond to second infection)
antigen receptor on surface is the antibody that Bcells will produce
BCR(antibody) only recognize 1 antigen (directly- free floating antigens)
B cells turn into
activated -clonal expassion
memory cell or plasma cell
plasma cells are
B cells that have differentiated into plasma cells that have increased cytoplasm and increased ER that is used to make antibodies
antibody production
what do antibodies do?
neutralization (block viral binding)
agglutination (clumps together)
precipitation of dissolved antigens
these steps will be identified by macrophages and be eaten
activation of complement system
leads to
cell lysis
antibodies will activate the complement system which leads to
cell lysis
adaptive immunity is mediated by
B cells and T cells
activated B cells make
antibodies (Humoral)
activated T cells make
cytokines/kills cells
(cellular)
unique antigen receptors
B cell receptors
T cell receptors
B cells recognize
“free” antigens
T cells recoginize
processed and MHC-presents antigen
Cytotoxic T cells
CD8
kill infected cells
Helper T cells
CD4
help shape the specific immune response
primary lymphoid organs
where B cells and T cells develop
B cells come from ___ and develop in ___
Fetal liver
bone marrow (pluripotent hematopoietic stem cells)
bone marrow
T cells come from ___ and mature in ____
fetal liver
bone marrow (pluripotent hematopoietic stem cells)
Thymus
Thymus
bilobed, mediastinal location anterior to the heart
stroma (support structure) is epithelial cells
lobes subdivided into lobules and are separated by trabeculae
the stroma of the thymus are
epithelial cells
the lobules of the thymus are separated by
trabeculae
in mature animals the thymus
involutes and shrinks- not completely
humans early 20s
each lobule of the thymus are broken into two regions:
cortex -dark stained
medulla- lighter
thymus is contained in ___
a capsule
what is number 5
trabeculae that separate each lobule of the thymus
what is 3
medulla (inner lighter area) of the thymus
What is 2
Cortex (outer region -darker)
What is 4
capsule of the thymus, which covers the entire thymus
structure in thymus that is surrounded by cell death
hassal’s corpuscle
thymic corpuscle
found in medulla of lobule of thymus
developing T cells are called ___ and are found in ____
thymocytes (double negative (DN) cells CD4- CD8-)
found in cortex (outer darker region of thymus)
___ epithelial cells are found in the cortex of the thymus
cortical
___ epithelial cells are found in the medulla of the thymus
medullary
part of the thymus that are made from mesenchymal cells
capsule, trabeculae/septae containing blood vessels
___ are found in the medulla of the thymus
hassal’s corpuscles
dendritics cells
macrophages
what might Hassal’s Corpuscles do
found in medulla of the thymus
keratinized epithelium, necrotic, possibly site of cell destruction??
Thymocytes learn how to identify self from non self by ___
interacting
positive and negative selection of mature T cells
errors in self recognition of T cells are
autoimmune diseases
subcapsular cortex of thymus
immature T cell precursors (CD4-CD8- double negative cells) interact with cortical EC
begin to differentiate
T Cell receptor (TCR) proteins made and inserted into membrane (CD3+)
Cells obtain surface expression of CD4 and CD8 (double positive (DP) cells)
mid cortex of thymus
TCR (T cell receptors) bind to self MHC on cortial epithelial cells (self recognition test)
thymocytes that recognize MHC get survival signal
Thymocytes that fail die or get eaten
Positive Selection
surviving thymocytes differentiate into CD4+ and CD8+ (single positive cells)
TCR bind to self MHC on cortical epithelial cells
self recognition test
mid cortex of thymus
how to make a T Cell
cell death
apoptosis
steps of T cell development in the thymus
- double negative to double positive thymocytes
- positive selection (single positive cells)
- negative selection (self tolerance)
- exit
if a thymocytes can not see a MHC the cell will
die
happens in mid-cortex
negative selection of T cell development
step 3 happens in the corticomedullary junction
self tolerance test
dendritic cells and macrophages present common self antigens (parts of every part of the body)
self reactive T cells MHC die and get eaten (T cells see itself this is bad should not see itself as antigen)
NEGATIVE SELECTION
Exit phase of T cell development
in the medulla of the thymus
mature T cells leave bis postcapillary venules to reach circulation
migrate to secondary lymph nodes to “meet” antigen
only around 2-5% make it to the end
what % of thymocyes become mature T cells
2-5%
50,000,000 in and 1,000,000 out every day
T cell precursors migrate from the ___ to the ___
bone marrow
thymus
Thymus is a mesh of ___ and ___ epithelial cells
cortical
medullary
Thymocytes differentiate and become ___ and ___
T Helper (CD4)
T Cytoxic (CD)
Two tests that thymocytes undergo while in the thymus
positive (not self) selection
negative (self) selection
B cell development happens in the ___, in neonatal pigs, sheep and cow, B cells can devlop in the ___ of the gut
bone marrow
Peyer’s Patches
Describe B Cell development
happens in bone marrow (mammals)
B cells precursors interact with stromal cells that provide signals and growth factors promoting immunoglobin gene (antibody) rearrangment
self-reacting B cells die (negative selection) and surviving immature cells migrate via circulation to spleen and peripheral lymph nodes to fully mature (antibody class switch)
B cells in birds
bursa of fabricius
round sac like diverticulum in the cloaca
many folds that have lymphoid follicles lined with pseudostratified columnar epithelium
cortex and medulla
anibody gene rearrangment/ conversion occurs in the cortex and negative selection leads to loss of self reactive B cells (lighter medulla)
where and what is the bursa of fabricius
in birds need cloaca
where B cells develop
Bursa of fabricius
NAME THE STRUCTURES
B cells develop in the ___ of mammals and in some neonates in the ____
bone marrow
peyer’s patch
B cells develop in the ___ in birds
bursa of fabricius
self reactive B cells are ___
deleted, killed eaten
examples of secondary lymphoid organs
lymph nodes (periphery)
spleen (blood)
Mucosa-associated lymphoid tissue (MALT)
Hemal Nodes (Ruminants)
similarites of secondary lymphoid organs
discreet organs
segregated areas (zones)
B Cells in follicles
Germinal centers form in follicles when B cells activate/proliferate
T-cell area contains APCs(i.e. DCs)
lymphocytes (most) enter via blood
differences in secondary lymphoid organs
architecture/structural components
mechanism of lymphocytes entry from blood
mechanism of antigen entry (from blood, lymphatics, via epithelium)
secondary lymphoid organs are divided into two spaces
diffuse (T cells)
nodal (B Cells)
T cells and ___ go to the same area of secondary lymphoid organs
dendritic cells (APCs)
diffuse lymphatic tissue is where ___ go in secondary lymphoid organs
T cells and APCs (dendritic cells)
nodular(follicles) areas of secondary lymphoid organs is where ___ go
B cells
What do lymph nodes do
strategically placed to collect antigen from Tissues to be presented to lymphocytes
Antigens enter via lymphatic vessels (dendritic cells/fluid from tissues)
Most lymphocytes enter from blood-some T cells enter via lymphatics
fluid homeostatis
Do avians have lymph nodes
NO
diffuse lymphatic tissue
lymphatic follicles/nodules
explain lymphatic vessels
carry “lymph” from peripheral tissue to lymph nodes
blind ended one way vessels that begin in the interstitial space in tissues
what is lymph
fluid inside lymphatic system that contains fluid, white blood cells (some T cells and dendritic cells) and antigens (free floating)
lymph comes from everywhere and drains through one way valves into lymph nodes
lymphatic circulation
lymphatic capillary, lymphatic vessel, lymph node, lymphatic vessel, thoracic duct, subclavian vein….blood circulation
describe lymphatic vessels
thin layer of endothelial cells
slow moving, not pumped
moved by negative intraluminal hydrostatic pressure that draws in fluid from the interstitial space of tissues (also SMC contractions/chemotaxis)
Describe Lymph nodes
soft, pale tan oval- kidney shaped
buried in fat
swell when immune response ongoing
encased in a fibrous capsule with an internal framework of fibrous trabeculae/septae
interior is a mesh of reticular cells (stroma) and fibers containing highly segregated areas
identify
lymph node
T cell and dendritic cell areas of lymph node
paracortex (out part of lymph node) outside of follicles
3b
What cells are found in the follicle of the lymph node
B cells
antigens in dendritic cells (DCs) and fluid and some lymphcytes (<5%) enter via ___
afferent lymphatics
Afferent lymphatic penetrate the capsule of the lymph node and drain into the
subcapsular sinus
Lymph percolates through ___ to ___ then exits via ___ to throacic duct and back to blood circulation
paratrabecular sinuses(conduits) (cords)
medullary sinus
efferent lymphatics
___ and ___ in sinuses of lymph node ___ antigen in lymph fuild
macrophages and DCs
phagocytose (eat)
lymph in ____, lymph out ___
antigen rich
lymphocyte-rich
paracortex of the lymph node has
T cells and dendritic cells
B cell area of a lymphnode ___,has an inner area called ___ and outer area called ___
nodule
germinal center (primary, secondary, senescent)
corona
FRCs
Fibroblastic Peticular Cells
attract T and DC cells
FDCs
Follicular Dendritic cells
attract B cells
FRCs and FDCs direct “zoning” by expressing
chemokines
Fibroblastic Reticular Cells -CCL19,CCL21
T cells and DC cells
Follicular Dendritic Cells- CXCL13
B Cells
Fibroblastic Reticular Cells -
chemokine CCL19,CCL21
Chemokitic for T cells and Dendritic cells
(will bring T cells and DC together)
Follicular Dendritic Cells
chemokine CXCL13
B cells are attracted to CXCL13
Follicular Dendritic Cells are found in ___
follicles/nodules in lymph nodes (spleen and MALT)
Explain Follicular Dendritic Cells
found in germinal centers(light zones) of the follicles/nodule of lymph nodes
Can see naked antigen or antibody with antigen attached and will capture it
Will release cytokine CXCL13 which will attract Bcell
BCell with the correct binding site will attach and will become
Plasma cell that makes antibodies
or
Memory B cell
specialized post capillary venules in the paracortex through which lymphocytes (95%) and macrophages enter the lymph nodes
high endothelial venules
why are HEV named that
High endothelial venules
the unusual plump and cuboidal morphology of the endothelial cells
__ express lymphocyte-specific adhesion molecules
HEC
After leaving via HEV, lymphocytes segregate into zones by following ___
chemokine gradients
HEV are in the ___ of the lymph node
cortex
lymph node what is the arrow?
HEV
high endothelial venules
Medulla of the lymph node
inner part of lymph node (macrophages and plasma cells)
medullary sinus
medullary cords
medullary sinus is lyphatic vessels separated by
medullary cords (reticular fibers)
medullary sinus contains ___ that phagocytose debris/ microorganisms
macrophages
Medullary cords contain ___ and __ that have migrated from germinal centers
macrophages
plasma cells
Plasma cells make antibodies that exit the lymph node via ___ and enter circulation
efferent lymphatics
Medullary sinus has ____
Medullary cord has ____
macrophages and reticular cells
packed with plasma cells
The spleen
removed antigen directly from the blood to encounter B and T cells
removes and destroys aging red cells and other hematopoietic cells
during fetal development spleen can make blood cells, declines in adults but can reoccur in extreme anemia - extramedullary haematopoesis
___ antigen and __ lymphocyte enter from the blood in the spleen
ALL and ALL
during anemia or systemic infections, spleen can make lymphoid or red blood cells this is called
extramedullary haematopoesis
parts of the spleen
white pulp- lymphocyte come here (antigen, T cells, B cells- where antigen recognition happens)
red pulp- where red blood cells go
sunuses
arterioles- found in
red pulp of spleen
less cells/ red cell rich
site of. red cell destruction
network of splenic sinusoids
white pulp of spleen
dense structures
contains lymphocytes
PALS of spleen
periarteriolar lymphoid sheath
contain T cell Zone
area around the central arteriole
Follicle of Spleen
Contains B cells (5% T helper)
marginal zone of spleen
border of Red pulp and white pulp
contains M phages, DCs and B cells
spleen
blood circulation in the spleen
all antigens and lymphocytes enter from the blood
supplied only by arterial blood vis the trabecular artery
blood flows through central arteriole, the marginal sinus, arterioles, splenic sinuses, venules then to trabecular vein (closed circulation)
Lymphocytes and antigen also enter form terminal arterioles (Open circulation) into the red pulp
some arterioles/capillaries are sheathed in reticular fibers/macrophages (ellipsoids)
marginal zone
lymphocytes migrate from blood to PALS (T cells) or the follicles (B cells)- driven by chemokines
antigens are eaten by macrophages, DCs and Marginal zone B cells in the “marginal zone”
macrophages, DCs and Marginal zone B cells carry antigen to T cells in PALS/Follicle that become activated and “help” B cells
antigen “presented” by Follicular Dendritic Cells to B cells in Follicles
in the marginal zone of the spleen what eats antigens
macrophages, DCs and Marginal zone B cells
MALT
mucosa-associated lymphoid tissue
collect antigen in mucosal surface:
respiratory tract
skin
intestinal tract
urogenital tract
mammary glands
GALT
gut associated lymphoid tissue
NALT
nasal associated lymphoid tissue
MALT
unorganized
T cells (little dots) are scattered throughout the surface epithelial laters (inter-epithelial lymphocytes)
diffuse lymphatic tissue- not encapsulated
organized MALT
tonsils in oral pharynx (lingual, tubal,palatine)
adenoids in nasal cavity
appendix in gut
Peyer’s patch in gut
crypts are found in the palatine tonsil of ___
horses
no crypts in carnivores
Horse Palatine Tonsil
Where are peyer’s patches located
lower portion of the small intestine (distal jejunum and throughout the ileum)
in pigs and ruminants what are the two types of peyer’s patches
jejunal patches: remain throughout life to protect intestine
ileocecal patches: early B cell development then regress (at 6 months)
what is the largest collection of mucosal lymphoid tissue
peyer’s patch
Dog Peyers Patch
peyers patch provides ___ for gut
immune protection
M Cells
multifold cells
help peyer’s patches in gut
highly specialized epithelial cells
sample antigens as they pass by (engulf antigens)
then bring the antigens into the prior patch
how does salmonella get into body
uses M cells (multifold cells) to get into body
found in gut wall
antigen in lumen is collected in specialized epithelial cells names Multifold cells that are within an area of ____
FAEs
follicle-associated epithelial cells
antigens are brought from the gut, through the M cells, into the peyers patch by
transcytose
lymphocytes enter peyers patch via
High Endothelial Venules (HEV) located in the T cell zones
lymphocytes leave the peyers patch vis the
blood circulation
Dendritic cells exit the peyers patch by
draining lymphatics- will migrate to mesenteric lymph nodes
