2.

Immune Cells and Organs

 Primary lymphoid organs (thymus & bone marrow) for production of lymphocytes
 Secondary lymphoid organs help antigen to come into contact with lymphocytes expressing appropriate specific
receptors
 Lymphocyte numbers are carefully regulated, and they recirculate
 T cells express CD3, and recognise processed antigen presented by MHC molecules
 B cells express CD19 and CD20, and recognise intact, free antigen
 Important APC are dendritic cells, B cells, and macrophages

1. Name the primary and secondary lymphoid organs and briefly differentiate between their functions.

Primary lymphoid organs: organs where lymphopoeisis occurs, i.e. where lymphocytes are produced, including
the bone morrow and thymus to produce T and B lymphocytes.

Secondary lymphoid organs: where lymphocytes can interact with antigen and with other lymphocytes,
including spleen, lymph nodes, mucosal associated lymphoid tissues (MALT)

2. Draw simple diagrams to illustrate the structure of the thymus, lymph node, spleen, Peyer’s patch
and indicate the changes that occur after stimulation by antigen.

Primary lymphoid Organs:

 Bone Marrow
- Site of haematopoesis, i.e.
generation of blood cells
- In an embryo, this happens in
amniotic sac
- In foetus, occurs in all bones, liver
and spleen. Marrow is also very
cellular
- In adults, this occurs mostly in flat
bones, vertebrae, Iliac bones, Ribs
and the ends of long limbs
 Thymus
- Where maturity of T-cells occurs
- Bi- lobed
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 -
-

- Medulla and cortex regions

- No change during immune response to antigens, continuous development of T cells

- Hassalls’ corpuscle secretes soluble factors, and is important in regulatory T

cells Secondary Lymphoid Organs

 Lymphatic System
- Fluid drained from between tissue cells absorbed into lymph
- 2 to 3 litres of lymph are returned to the blood each day (via superior vena cava)
- In the process of draining, lymph can “capture” pathogens
- Fluid passes through lymph nodes which survey for pathogens
LYMPH NODES
- Kidney shaped organs > 1cm
- During immune response, swell in size
- Fluid enters through AFFERENT vessel
- Fluid leaves via EFFERENT vessel
- Lymph perculates through all lymphocytes before
leaving the node
- Usually a SUMMATIVE junction, i.e. there are many
afferent vessels but one efferent vessel
- Rich blood supply lets lymphocytes into the lymph
nodes via the HIGH ENDOLTHELIAL VENUES
- T-cell zone: parafollicular cortex
- B-cell zone: lymphoid follicle- mostly on the
periphery of the lymph node
- During immune response, there is a massive proliferation of B cells, which leads to the formation of a
GERMINAL CENTRE
- Specific chemokines target their respective lymphocytes to their specific areas, e.g. T-cells to the
parafollicular cortex
- The lymph entering lymph nodes may also contain cells such as dendritic cells and macrophages

 Spleen
- Filter for antigens in the blood
- Large organ in the abdomen
- Separated into
white pulp: lymphoid cells around blood vessels, full
of lymphocytes
red pulp: contains old damaged RBC
- Any diseases involving RBC, i.e. sickle-cell, often
results in an enlargement of the spleen
- T cell area: peri-arteriolar lymphatic sheath (PALS)
- B cell area is located further away from blood vessels
- Not a vital organ: Individuals who do not have a spleen are highly susceptible to infections with encapsulated
bacteria

Mucosal Associated Lymphoid Tissue (MALT)

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 • Epithelium is the first line of defence
• mucosae and skin form a physical barrier
• very large surface area, in large part a single layer of cells
• heavily defended by the immune system in case it breaks

 Gut Associated Lymphoid Tissue

- Many villi, plus smoother regions

- Involved in the mesenteric lymphatic drainage
system to mesenteric lymph nodes, including
intraepithelial lymphocytes
- PEYER’S PATCH: non-capsulated aggregation
of lymphoid tissue- predominantly B
lymphocytes and contain germinal centres
during immune responses

- M-CELLS: sample contents of the intestine,

surveying for pathogens which they can then
deliver to immune cells

 Cutaneous Immune System

- I.e. the skin
- Epidermis contains keratinocytes, Langerhans cells
and intraepidermal lymphocytes
- The dermis heavily guards the epidermis with
immune cells, e.g. macrophages, T lymphocytes etc
- The demis also consists of venules and lymphatic
vessels, providing entry to the blood circulation and
drainage to regional lymph node

3. Outline the recirculation of lymphocytes.

PROBLEM:
There are a very large number of T cells with different
specificities
There are a very large number of B cells with different
specificities
There may only be limited amounts of antigen
How does the body ensure that the antigen
meets lymphocyte with specific receptor?

SOLUTION:

 Lymphocyte recirculation
- Pathogen on mucosal surface
- Naive lymphocytes leave BM and Thymus and enter the bloodstream
- Recirculate through peripheral lymphoid tissue
- Recognition of antigen- massive B cell proliferation in secondary lymphoid tissue (lymphocyte activation)
- Otherwise the lympcytes die

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 Extravasion of naive T cells into the lymph nodes (occurs during immune response)
- The naive T cell “rolls” along
the epithelium

- These are then stopped and

activated by specific chemokines at
a particular place on the
epithelium. This “right place” is

determined by SELECTINS 10

- INTEGRINS then increase adhesion of the T cell to the epithelium, leading to arrest of the cell
- Transendothelial migration of the T cell from the bloodstream into the lymph node then occurs
- Antigens also enter the lymph nodes via the draining lymphatics
- Naive lymphocytes recirculate approx once per day -- enter lymph node—high endothelial venue –
lymphocyte is activated by antigen – stops recirculatng – massive proliferation of B lymphocytes –
reenter the blood via the superior vena cava (via the efferent vessel) – target invading
microbes/pathogens

 Anatomical structure of the immune system

4. Explain the use of CD (cluster of differentiation) markers for discrimination between lymphocytes.

Lymphocytes
• Small cells with agranular cytoplasm and a large nucleus
• Can be subdivided into 2 groups depending on where they were produced
- B lymphocytes (Bone Marrow)
- T lymphocytes (Thymus)
• These express different CD molecules, which are recognised by different antibodies

CD Markers
• an internationally recognised systematic nomenclature for cell surface molecules
• used to discriminate between cells of the haematopoietic system
• more than 300 CD markers
• clinical importance e.g. CD4 in HIV

5. Compare and contrast phenotypic characteristics of B and T cells.

Relative Quantities
T cells B cells
7.5 x 109 in the blood

Blood contains 2% of the total pool, therefore ~ 1012, but mostly in the gut
50 x 7.5 x 109 = 3.75 x 1011

T Lymphocytes

• all express CD3- antigen specific receptor (TCR)

•  TCR, about 10% in blood
•  TCR, about 90% in blood: ~2/3 express CD4, ~1/3 express CD8. All mature T cells express one or the other
 CD4+ = T helper cells, regulatory T cells- Secrete cytokines
 CD8+ = cytotoxic T cells- Lyse infected cells, secrete cytokines
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 • Thymic output of naive T cells declines with age, and the thymus atrophies. Therefore older people have a
reduced ability to respond to new infections. However the total number of T cells does not change, there are
just more memory cells.
ANTIGEN RECOGNITION
• only recognise processed antigen presented at the surface of another cell using T cell receptor
• antigen is presented by an MHC molecule

B lymphocytes

• Produced by and develop in bone marrow

• Surface antigen receptor (B cell receptor) : immunoglobulin like molecule
• Express CD markers CD19 & CD20 (not CD3, CD4 or CD8)
• Express MHC Class II (can present antigen to helper T cells)
• Effector function is to produce antibodies
ANTIGEN RECOGNITION

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 • recognise intact antigen free in body fluids (so
not presented by another molecule)
• Use B cell receptor, a membrane anchored
form of antibody linked to signalling subunits

6. Give examples of antigen presenting cells (APCs)

and their locations.

Antigen presenting cells (APC)

cells that can present processed antigen (peptides) to T

lymphocytes to initiate an acquired (adaptive) immune response:

 Dendritic cells (DC)

- Location: Widely spread e.g. Skin & mucosal tissue
- Presents to T cells

 B lymphocytes
- Location: lymphoid tissue
- Presents to T cells

 Macrophages (activated)
- Location: lymphoid tissue
- Presents to T cells

 Follicular dendritic cells

- Location: lymph node follicles
- Presents whole antigens to B cells
MCD Immunology Alexandra Burke-Smith

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MCD Immunology Alexandra Burke-Smith

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