Lymphoid organs Flashcards

1
Q

What are the primary lymphoid organs?

What are their functions?

A
  • 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
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2
Q

What is the function of secondary lymphoid organs?

A

They are where mature immune cells meet to communicate and coordinate

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3
Q

State the secondary lymphoid organs

What are their functions?

A
  • 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

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4
Q

What do secondary lymphoid organs aim to maximise?

Where do TH cells interact with B cells?

A
  • 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
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5
Q

What common features do secondary lymphoid organs have?

A
  • 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
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6
Q

Describe the function of the afferent and efferent lymphatics, arterioles and venules

What is the medullary sinus?

A
  • 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
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7
Q

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?

A
  • 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)
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8
Q

In the lymph nodes, entry routes are functionally important:

How is antigen carried to lymph nodes?

What happens to opsonized antigen in the lymph?

A
  • 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
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9
Q

What do lymph nodes detect?

A

Lymph nodes detect infections in the tissues

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10
Q

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?

A
  • 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
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11
Q

What are High endothelial venules (HEV)?

A
  • 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
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12
Q

Lymphoid follicles:

Do all your secondary lymphoid organs contain lymphoid follicles?

What are they crucial for?

A
  • 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
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13
Q

Follicular dendritic cells (FDC):

What are they derived from?

When were they discovered?

A
  • 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
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14
Q

What do FDC do early on in an infection?

A
  • 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
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15
Q

What do FDC do later on in an infection?

A
  • 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)
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16
Q

Draw or describe the Germinal centre structure

A
  • 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
17
Q

B cells test their antibodies all the time via which process?

A

via somatic hypermutation

18
Q

B cells test their antibodies all the time via somatic hypermutation:

What are the three possible consequences?

A
  1. BCR affinity decreases
  2. BCR affinity stays the same
  3. 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)
19
Q

Where does class switching take place?

A

Class switching (IgD and IgM to IgA, IgE, and IgG) takes place in the light zone (with T cell help)

20
Q

What is the function of Mucosa-associated lymphoid tissue (MALT)?

A

Function as a secondary lymphoid organs at mucosal surfaces (areas of the body exposed to the outside world)

21
Q

Mucosa-associated lymphoid tissue (MALT:

Subdivided into specific mucosal areas:

A
  • BALT (bronchial)
  • NALT (nasal)
  • GALT (gut) → Peyer’s patches
  • Tonsils and appendix can also be included
22
Q

Describe the basic features of a Peyer’s patch

A
  • 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
23
Q

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?

A
  • 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
24
Q

What makes Peyer’s patches different to lymph nodes?

A

It’s the route of entry of antigen that makes Peyer’s patches different

25
Q

Sampling:

Where do lymph nodes sample antigen from?

Where does the Peyer’s patches sample antigens from?

Where does the spleen sample antigen from?

A
  • Lymph nodes sample antigen from the tissue
  • Peyer’s patches sample antigens from the intestine
  • The spleen samples antigens from the blood
26
Q

Label the spleen and explain its properties

A
  • It is just supplied by blood vessels
  • The B cells and T cells come into the spleen through an artery
  • Only place in the body where B cells and T cells exit via arteries rather than veins because the arteries have a low enough pressure
  • T cell area forms a periarterial lymphatic sheath (PALS) around blood vessels so as soon as antigen, T cells and B cells enter that area, interactions can occur
27
Q

TRUE or FALSE:

The spleen has lymphatic supply

A

False

The spleen has no lymphatic supply

28
Q

What is the function of the spleen?

A
  • Similar structures to lymph nodes
  • Naïve lymphocytes enter the spleen in the blood through arterioles rather than venules (very unusual)
  • They’ll hang around in their particular area
  • If the TH sees its antigen in an APC in the periarterial lymphatic sheath

→activation, migration to lymphoid follicle, help for B cells that have seen their cognate antigen

  • But whilst lymph nodes sample antigen from the lymph, the spleen has no lymphatic supply and it samples antigens from the blood
29
Q

Explain how secondary lymphoid organs preselect cells

A
  • Secondary lymphoid organs have segregated areas for T and B cells, but the cells can move about to interact
  • There’s more chance of an adaptive immune response if the cells are directed towards their partner
  • Secondary lymphoid organs have a pre-selection step
  • T cells entering are only chosen (activated) if they see their cognate antigen in an APC, all the others have to leave
  • The lucky T cells can proliferate and go to help B cells
  • Same for B cells: only B cells that find their cognate antigen on FDC are allowed to stay

•By only keeping useful cells in the secondary lymphoid organ, the chances of the activated B cell meeting its activated T cell are maximized and the tissue doesn’t get filled up with useless cells

30
Q

Pre-selection is a good idea but:

Which cells have the answer?

A
  • TH cells stuck in the germinal centre run out of petrol
  • Activated B cells need help
  • TH have to interact (via CD40L binding CD40) to provide the help
  • So we need TH in the germinal centre
  • Engaged CD40L is internalised so the TH runs out of CD40L
  • To get more CD40L, the TH need to be restimulated by an APC
  • But the APC is back in the T cell area (far away!)

B cells have the answer→activated B cells can act as APC and help the help the TH cell produce more CD40L on its surface

31
Q

Give a summary of the lymphoid organs

A
  • Primary lymphoid organs (bone marrow & thymus) are the site of lymphocyte development & maturation
  • Secondary lymphoid organs (throughout the body) are where adaptive immunity is coordinated
  • Lymph – antigens from tissue
  • MALT – mucosal antigens
  • Spleen – blood-borne antigens

•Lymphoid tissue is organized into distinct areas to maximize cell contact

32
Q

How do T cells enter the lymph nodes?

How do dendritic cells enter the lymph nodes?

A
  • T cells come in through the high endothelial venule
  • Dendritic cells come in through the afferent lymphatics
33
Q

What cells are involved in germinal B cell formation?

A

Once helper T cells are activated by dendritic cells they move to secondary B cell follicles and form a germinal center