Functional Lymphoid Anatomy Flashcards
What is the difference between central and peripheral lymphoid tissue in respect to B and T cells?
Central lymphoid tissue (bone marrow, thymus) generates B and T cells (lymphopoiesis) and is responsible for central tolerance
Peripheral lymphoid tissue (LN, spleen, MALT) primes the mixture of B and T cells into effector cells and is responsible for peripheral tolerance
What are the mechanisms in central lymphoid tissue to protect against self-reactive lymphocytes?
Positive and negative selection
What directs cells where to go?
Chemokines and their receptors!
What is the difference between lymph nodes and the spleen?
Lymph nodes process antigen from tissue, where the spleen processes blood borne pathogen
What does MALT do?
protects entryways against pathogenic intruders, and also maintains homeostasis in regards to commensal organisms or benign food particles
What originates in the bone marrow? From what?
B and T lymphocytes, from hematopoietic precursors
Where to B cells mature?
The bone marrow
Does B cell development decline as we age?
No - B cells are continuously produced from the bone marrow, even as we age
What do BM stromal cells do?
Produce signals that direct the development of progenitor and eventually B cells –> in the bone marrow
What is central tolerance?
immarure B cells are checked against self-antigen in the bone marrow and are eliminated if auto-reactive
Where does the final stage of development of immature B cells into mature B cells occur?
in the peripheral lymphoid organs
Where do immature B cells that are not auto-reactive go first?
They are carried via the venous blood to the spleen
describe the general process of T cell development
Progenitor cells migrate to the thymus during embryonic development, become thymoctyes, and mature into T cells
Does the production of T cells decline as we age?
yes!
How are T cell populations maintained?
Long lived T cells and devision of mature T cells in the periphery
What is the thymic cortex, and what is found there?
The outer cortical region
Contains immature thymocytes and scattered macrophages
Most T cell development occurs here
What is the corticomedullary junction, what is found here?
Where T cell progenitors enter
What is the medulla, and what is found there?
Inner region
More mature single positive T cells, along with dendritic cells and macrophages
What is the thymic cortical stroma, and what is found there?
Network of epithelia where T cell precursors reside
Provides environment for T cell development
has epithelial cells that express both MHCI and MHCII on their surface
What is the first step in T cell development?
progenitors enter at the corticomedullary junction and migrate to the outer cortex
What is the receptor status of thymocytes proliferating in the outer cortex?
they are double negative
What does double negative mean?
They lack both the CD3+ T cell receptor complex and CD4+/CD8+ co-receptor
What happens when thymocytes leave the outer cortex?
They migrate further into the cortex and undergo receptor rearrangement to become CD3+ and CD4+CD8+ double positive thymocytes
What happens if a thymocyte can’t recognize self peptide/self MHC?
They die by apoptosis
what amount of T cells develop in the thymus also undergo apoptosis in the thymus?
~98%
What is positive selection?
If a T cell can recognize self-peptide:self-MHC, it will drop one of it’s co-receptors and become single positive (either CD3+CD4+ or CD3+CD8+) thymocytes, then migrate to the medulla
If it can’t recognize self-peptide:self-MHC, it will die by apoptosis
What happens in the medulla?
Negative selection
What is negative selection?
If a T cell recognizes self-peptide:self-MHC too strongly, it will undergo apoptosis, if not, it will be exported to the periphery
What are circulating through secondary lymphoid tissues?
Mature, naive lymphocytes, interacting with pathogen that are being delivered to these tissues
What is considered secondary lymphoid tissue?
lymph nodes, spleen, MALT
What is the general function of secondary lymphoid tissue?
trap APC and antigen, allowing them to be presented to circulating lymphocytes
induce adaptive immune response
provide sustaining signals to lymphocytes that do not encounter their Ag so they survive and continue to circulate
What mediates homing of lymphocytes?
chemokines
What converges at the lymph nodes?
Blood and lymph
How do naive lymphocytes get into the LN?
via high endothelial vessels (HEVs), located in paracortical areas
Where are B cells located in the LN?
lymph node follicles
What are found in the cortex?
Follicles
What are found in the paracortical areas?
T cells and free Ag that get trapped on resident dendritic cells and macrophages, and where migrating DCs bring their Ag
What are germinal centers?
Where B cells undergo intense proliferation and differentiation into plasma cells with the help of Thelper cells
Is the spleen directly connected to the lymphatic system?
No!
What is the spleen involved in?
immune response to blood borne pathogen
What is another function of the spleen?
disposal of old RBCs
describe the path of lymphocytes through the spleen
enter via blood via marginal sinus, migrate to white pulp, leave via red pulp
what is the red pulp of the spleen?
largest part of spleen, where RBC get recycled - macrophages can engulf RBC and present anything it finds
what is the white pulp of the spleen?
lymphocytes surrounding arterioles running through the spleen
What is a splenic periarteriole lymphoid sheath (PALS) and what is found there?
sheath of lylmphocytes surrounding a central arteriole, mainly find T cells there
Where are splenic follicles, and what is found there?
adjacent to PALS, find B cells there, may become marginal centers
What is the marginal zone of the spleen and what is found there?
surrounds follicle, contains macrophages and resident B cells
What are different types of MALT?
GALT (gut-associated), BALT (bronchiole-associated), urogenital mucosa, lacrimal & salivary glands, mammary tissue
What is BALT?
Bronchus/respiratory mucosa (sinus, trachea, lungs)
What is specialized tissue of BALT?
tonsils, adenoids
What does BALT respond to?
inhaled particles
What is secreted outside of the BALT epithelial barrier?
IgG, IgM, IgA
What is the function of ciliated epithelial cells of BALT?
production of mucus and defensins that neutralize pathogen and move them out of the respiratory area
What are some specialized anatomy of GALT?
Tonsils, appendix, peyer’s patches, lamina propria, isolated lymphoid follicles
What do peyer’s patches contain, and what do they do?
Microfold (M) cells: directly collects Ag from lumen
Follicle: Central dome of B cells (secrete IgA) surrounded by T cells
Resident DCs that present Ag to T cells
What do Paneth cells do?
Defensin production
What’s the difference between stroma and parenchyma?
Stroma are non-leukocytes
Parenchyma are leukocytes
What happens if you don’t have a thymus?
can produce lymphoid progenitors, but cannot develop T cells
What do developing thymocytes rely upon for survival, and what do they release?
Thymic epithelial cells, release IL-7, etc.
What cells mediate positive and negative selection?
Cortical medullary cells, dendritic cells, macrophages
How do circulating lymphocytes get from the blood to the paracortical areas?
Chemokines!
How can B cells in a follicle get exposed to free floating Ag?
Macrophages in the cortical sinus or resident medullary dendritic cells can deliver Ag to follicular B cells, or free floating Ag can reach follicles via conduits
What T cells are allowed in the follicle?
Tfh
What kind of infection is the spleen particularly good at clearing?
encapsulated bacteria - pneumococcal, meningococcal
What is peripheral tolerance?
In the absence of infection, B and T cells that encounter strong interactions in peripheral lymphoid organs will undergo clonal deletion or anergy
