Molecular Cell Biology and Immunology
Lecture 8. Lymphoid organ development and functioning
INDEX
1. Formation of the lymph nodes .................................................................................................................................................................... 1
1.1. Lymphotoxin- α .................................................................................................................................................................................. 1
1.2. Essential cell population for lymphoid organogenesis ......................................................................................................................... 2
1.3. Retinoic Acid: regulator of development............................................................................................................................................. 2
2. Control of self-reactive lymphocytes ........................................................................................................................................................... 4
2.1. Mechanism ......................................................................................................................................................................................... 5
2.2. Mechanism in the lymph nodes .......................................................................................................................................................... 5
3. Why do stromal cells express MHC-II?......................................................................................................................................................... 6
4. Self-antigen expression leads to Treg conversion ........................................................................................................................................ 6
5. Converted Treg preferentially found at B-T boundary ................................................................................................................................. 6
6. Self-antigen restricted to LNSC: conversion into Treg cells .......................................................................................................................... 7
6.1. Conversion mechanism ....................................................................................................................................................................... 7
7. Function of the Treg cells ............................................................................................................................................................................ 7
, Why do we need lymph nodes? To get the adaptive IR started. It started with immature DC, they are through the body, and they
wait for something to activate them. In the lymph node, the DC has matured and presents the antigen to the T cells, they will
recognize, proliferate, and differentiate to leave the lymph nodes and go back to the skin with the homing receptors. → This gives
protection with the adaptative immune response and a memory response, so that next time we don’t get as sick (vaccination is a
way of doing the first encounter).
The lymph nodes are a location where self-reactive T cells are controlled. The control of reactive T-cells is in the thymus, but it is
not perfect. They have to be controlled in the body, one way to control it is via the lymph nodes.
1. FORMATION OF THE LYMPH NODES
In the image we see a mouse lymph node: in green the B cell
follicles, in blue the non-hematopoietic cells that are stromal
cells in the B cell area, the T cell area is darker and in red also
the stromal cells and the T cells are not stained. → We can
see they are divided in domains (there is organization) thanks
to the stromal cells, they regulate it.
- The blue ones are follicular dendritic cells: FDC
- The red ones are fibroblastic reticular cells: FRC or T
zone reticular cells.
- On the edge we have lymphatic endothelial capsule,
that gives some structure.
- Blood endothelial cells are in the T cell area.
- We see a venule with some B cells around the circle.
Stromal cells are not only develop the stromal cell subset, but they are also important for the organization and formation of lymph
nodes. In the mesenchymal stromal subset there are 9 different subsets, they are all different (information on the paper).
In the embryo we can see that in blue there are location where the 1 st beginning of lymph nodes can be found, they are non-
organized clusters of immune and stromal cells. The cluster evolves into a more organized structure with T and B cell areas.
In mice, at the moment of birth the lymph nodes are not
finished: they don’t contain any B and T cells. They have a cluster
of immune and stromal cells. In a week we can see the distinct B
and T cell areas.
In humans, 8 weeks after gestation we see the 1st cluster of
immune and stromal cells. In 9-5 we see more of the cluster. In
13-15 weeks, we see organized T and B cell area.
o When we are born, we have an adaptative immune
system in place and ready to go, a form of protection.
1.1. LYMPHOTOXIN - α
In 1995, a paper came out where they injected Indian ink to make the lymph node
visible because it drains via the lymphatic system to the lymph node, later it is
taken by the macrophages and is present in the lymph node. In the case of the
knocked out genes of lymphotoxin-α (expressed in T cells) they noticed the lymph
nodes were not there and the organization of the lymphoid organs like the spleen,
was gone. → This means there is probably a programmed process in the lymph
node development, organization, and formation.
Lymphotoxin-α3 is a trimer that signals to TNF receptors. Lymphotoxin-α1β2
signals via the LTβR. → TNF family members is a very important family of
receptors and molecules for the immune system. When they developed the
Lymphotoxin-α knockout mice, they didn’t know it was this important for lymph
1
Lecture 8. Lymphoid organ development and functioning
INDEX
1. Formation of the lymph nodes .................................................................................................................................................................... 1
1.1. Lymphotoxin- α .................................................................................................................................................................................. 1
1.2. Essential cell population for lymphoid organogenesis ......................................................................................................................... 2
1.3. Retinoic Acid: regulator of development............................................................................................................................................. 2
2. Control of self-reactive lymphocytes ........................................................................................................................................................... 4
2.1. Mechanism ......................................................................................................................................................................................... 5
2.2. Mechanism in the lymph nodes .......................................................................................................................................................... 5
3. Why do stromal cells express MHC-II?......................................................................................................................................................... 6
4. Self-antigen expression leads to Treg conversion ........................................................................................................................................ 6
5. Converted Treg preferentially found at B-T boundary ................................................................................................................................. 6
6. Self-antigen restricted to LNSC: conversion into Treg cells .......................................................................................................................... 7
6.1. Conversion mechanism ....................................................................................................................................................................... 7
7. Function of the Treg cells ............................................................................................................................................................................ 7
, Why do we need lymph nodes? To get the adaptive IR started. It started with immature DC, they are through the body, and they
wait for something to activate them. In the lymph node, the DC has matured and presents the antigen to the T cells, they will
recognize, proliferate, and differentiate to leave the lymph nodes and go back to the skin with the homing receptors. → This gives
protection with the adaptative immune response and a memory response, so that next time we don’t get as sick (vaccination is a
way of doing the first encounter).
The lymph nodes are a location where self-reactive T cells are controlled. The control of reactive T-cells is in the thymus, but it is
not perfect. They have to be controlled in the body, one way to control it is via the lymph nodes.
1. FORMATION OF THE LYMPH NODES
In the image we see a mouse lymph node: in green the B cell
follicles, in blue the non-hematopoietic cells that are stromal
cells in the B cell area, the T cell area is darker and in red also
the stromal cells and the T cells are not stained. → We can
see they are divided in domains (there is organization) thanks
to the stromal cells, they regulate it.
- The blue ones are follicular dendritic cells: FDC
- The red ones are fibroblastic reticular cells: FRC or T
zone reticular cells.
- On the edge we have lymphatic endothelial capsule,
that gives some structure.
- Blood endothelial cells are in the T cell area.
- We see a venule with some B cells around the circle.
Stromal cells are not only develop the stromal cell subset, but they are also important for the organization and formation of lymph
nodes. In the mesenchymal stromal subset there are 9 different subsets, they are all different (information on the paper).
In the embryo we can see that in blue there are location where the 1 st beginning of lymph nodes can be found, they are non-
organized clusters of immune and stromal cells. The cluster evolves into a more organized structure with T and B cell areas.
In mice, at the moment of birth the lymph nodes are not
finished: they don’t contain any B and T cells. They have a cluster
of immune and stromal cells. In a week we can see the distinct B
and T cell areas.
In humans, 8 weeks after gestation we see the 1st cluster of
immune and stromal cells. In 9-5 we see more of the cluster. In
13-15 weeks, we see organized T and B cell area.
o When we are born, we have an adaptative immune
system in place and ready to go, a form of protection.
1.1. LYMPHOTOXIN - α
In 1995, a paper came out where they injected Indian ink to make the lymph node
visible because it drains via the lymphatic system to the lymph node, later it is
taken by the macrophages and is present in the lymph node. In the case of the
knocked out genes of lymphotoxin-α (expressed in T cells) they noticed the lymph
nodes were not there and the organization of the lymphoid organs like the spleen,
was gone. → This means there is probably a programmed process in the lymph
node development, organization, and formation.
Lymphotoxin-α3 is a trimer that signals to TNF receptors. Lymphotoxin-α1β2
signals via the LTβR. → TNF family members is a very important family of
receptors and molecules for the immune system. When they developed the
Lymphotoxin-α knockout mice, they didn’t know it was this important for lymph
1
