Lymphoid organs Flashcards
What are the primary lymphoid organs?
What are their functions?
- Bone marrow: development of all blood cells
- Haematopoiesis
- Maturation of B lymphocytes
- Recognition of non-self and release to the periphery
- T lymphocytes leave the bone marrow as immature thymocytes
- T lymphocytes go to the thymus to mature
- Education about non-self followed by release to periphery
What is the function of secondary lymphoid organs?
They are where mature immune cells meet to communicate and coordinate
State the secondary lymphoid organs
What are their functions?
- Lymph nodes
Distributed around the body
Detect infections in the tissue
- The spleen
In the abdominal cavity
Like a massive lymph node
Detects blood-borne infections
Filters out red blood cells when they have gone past their useable lifespan
Has a ‘white area’ which is where interactins between immune cells happen
- Peyer’s patches
Sample antigens passing through your gut
What do secondary lymphoid organs aim to maximise?
Where do TH cells interact with B cells?
- Specialised tissue designed to maximize cellular encounters
- Distinct regions of individual cell types (e.g. B cell areas, T cell areas)
- First interaction between dendritic cells and T cells in which antigen presentation and recognition occurs and when a TH cell is turned on by a dendritic cell presenting its antigen, some of those helper T cells will move into another area called a germinal center and thats where they interact with B cells to generate antibody responses
What common features do secondary lymphoid organs have?
- High endothelial venules (HEV)→specialised in moving T cells from the blood and into the lymph nodes
- Lymphoid follicles→ where helper T cells and B cells interact with each other
Describe the function of the afferent and efferent lymphatics, arterioles and venules
What is the medullary sinus?
- Afferent lymphatics bring lymph INTO the lymph node
- Efferent lymphatics take lymph OUT of the lymph node
- Arterioles take blood INTO the lymph node
- Venules take blood OUT of the lymph node
- The medullary sinus is a large space in the middle of a lymph node that is full of dendritic cells waiting for T cells that are interested in the antigen that they have to offer
In the lymph nodes, entry routes are functionally important:
How do cells enter?
How do dendritic cells enter?
How to lymphocyytes (B cells and T cells) enter?
- Cells enter via the lymph (dendritic cells) or blood (T cells)
- DC located at the site of infection get the signal to fight, stop sampling and move to the secondary lymphoid organs via the lymph
- Lymphocytes (B cells and T cells) can enter from the blood via the high endothelial venules (HEV)
In the lymph nodes, entry routes are functionally important:
How is antigen carried to lymph nodes?
What happens to opsonized antigen in the lymph?
- Antigen can be carried to the lymph nodes as MHC on DC and presented to naïve T cells in the medullary sinus (the central part of the lymph node)
- Antigens in the tissue may be opsonized by complement or antibodies, which can be carried into the secondary lymphoid organs in the lymph and they bind to specific cells in the germinal center
- Opsonized antigen (complement or antibodies) in the lymph is trapped and held in the lymphoid follicles by follicular dendritic cells to be presented to TH cells and B cells
What do lymph nodes detect?
Lymph nodes detect infections in the tissues
Tissue DCs deliver antigen via the lymph:
Where do DC’s pick up antigen from?
How do they make interactions with B cells and T cells more likely?
- DCs pick up antigen in the periphery, i.e. the site of infection
- Carry antigen on MHC Class I or MHC Class II as appropriate
- DCs migrate to areas of the lymph node surrounding the HEV to make interactions with T cells and B cells more likely
What are High endothelial venules (HEV)?
- HEV are the ‘doors’ that let T cells and B cells enter into the secondary lymphoid organs from the blood
- Most endothelial cells are flattened, overlapping, tightly fitted (less permeable)
- HEV are tall, columnar cells and not tightly fitted (more permeable)
- Lymphocytes squeeze between HEV to exit the circulation
- 10,000 lymphocytes per second pass through HEV to enter secondary lymphoid organs to allow quick and efficient coordination of your adaptive immune response
Lymphoid follicles:
Do all your secondary lymphoid organs contain lymphoid follicles?
What are they crucial for?
- All your secondary lymphoid organs contain lymphoid follicles
- These are crucial for adaptive immune responses
- They are islands of follicular dendritic cells (FDC’s which are not actual dendritic cells) in a sea of B cells
Follicular dendritic cells (FDC):
What are they derived from?
When were they discovered?
- Not actually dendritic cells (not derived from haematopoietic stem cells); they just look similar to DC under the microscope
- Discovered in 1965, so a relatively poorly understood type of immune cell
- A type of mesenchymal cell
- Only found in the follicles on the edge (cortex) of lymphatic tissue
What do FDC do early on in an infection?
- Early on in an infection, complement activation opsonizes antigen
- Opsonized antigen enters the secondary lymphoid organ via blood or lymph
- FDC have complement receptors so they can capture opsonized antigen
- They keep hold of the antigen and so become decorated with antigen from the site of infection
What do FDC do later on in an infection?
- Later on in an infection, B cell activation results in antibody production and opsonization with antibodies
- FDC have receptors for antibodies (FcR) too, so they can capture and display immune complexes (composed of antigen and immunoglobulins)
- By holding large numbers of antigen close together, FDC crosslink the BCR, which activates the B cell
- Activated B cells proliferate and form a secondary lymphoid follicle (germinal centre)
Draw or describe the Germinal centre structure
- It is in the cortex (edge) of the lymph nodes
- There can be multiple germinal centers in a single lymph node
- swollen lymph nodes= germinal centers expanding
- Within the germinal center there is a light zone and a dark zone
Dark zone:
- Called dark zone because it is packed with cells
- Where B cells are going through clonal expansion to make many copies of themselves
- Where B cells go through somatic hypermutaion to refine the affinity of their antibody molecule
Light zone:
- Where FDC/T cell/B cell interactions take place
- This leads to the foramtion of plasma cells which will be antibody factories and memory B cells that will migrate to a different zone of the lymph node and wait for a reucurring infection or B cells can go through apopotosis because they failed in affinnity maturation
B cells test their antibodies all the time via which process?
via somatic hypermutation
B cells test their antibodies all the time via somatic hypermutation:
What are the three possible consequences?
- BCR affinity decreases
- BCR affinity stays the same
- BCR affinity increases
- Options 1 and 2 – B cells die by apoptosis and are eaten by macrophages in the germinal centre
- Option 3 – B cells are rescued- only select for the ones that are better at recognising antigen
- BCR cross-linked by antigen on FDC
- co-stimulation by TH in the light zone (CD40-CD40L interactions)
Where does class switching take place?
Class switching (IgD and IgM to IgA, IgE, and IgG) takes place in the light zone (with T cell help)
What is the function of Mucosa-associated lymphoid tissue (MALT)?
Function as a secondary lymphoid organs at mucosal surfaces (areas of the body exposed to the outside world)
Mucosa-associated lymphoid tissue (MALT:
Subdivided into specific mucosal areas:
- BALT (bronchial)
- NALT (nasal)
- GALT (gut) → Peyer’s patches
- Tonsils and appendix can also be included
Describe the basic features of a Peyer’s patch
- M cell captures antigens from the gut (takes the place of the dendritic cell)
- The antigen is coming to the secondary lymphoid organ through the gut
- There is a lymphod follicle so you get interactions between FDC, B cells and T cells to generate the immune response
- T cells and B cells move through Peyer’s patch through HEV
What is antigen collected by M cells is carried in?
What can opsonized antigen be captured by?
How do T cells and B cells get in?
- In lymph to underlying lymph nodes (NO afferent lymphatics)
- Opsonised antigen can be captured by FDC
- T cells and B cells still get in via HEV
- Interactions occur in the same areas
What makes Peyer’s patches different to lymph nodes?
It’s the route of entry of antigen that makes Peyer’s patches different
