LYMPH NODES, SPLEEN, TONSILS,MUCOSA ASSOCIATED TISSUES, APPENDIX, PAYERS PATCHES

1. LYMPHOID ORGANS
[SECONDARY LYMPHOID ORGANS]
Dr. R. RENUKA
ASSOCIATE PROFESSOR OF BIOCHEMISTRY
V.V.VANNIAPERUMAL COLLEGE FOR WOMEN
MADURAI KAMARAJ UNIVERSITY, INDIA.

3. SECONDARY OR PERIPHERAL
LYMPHOID ORGANS
While primary lymphoid organs are concerned with production and
maturation of lymphoid cells, the secondary or peripheral lymphoid
organs are sites where the lymphocytes localise, recognise foreign
antigen and mount immune response against it by producing either
antibodies or sensitized cells. Thus, the matured lymphocytes
received from the primary lymphoid organs are made active in
secondary lymphoid organs.

4. SECONDARY OR PERIPHERAL
LYMPHOID ORGANS
Secondary lymphoid organs include lymph nodes, spleen, tonsils,
adenoids, appendix, and clumps of lymphoid tissue in the small
intestine known as Peyer's patches. They trap and concentrate
foreign substances, and they are the main sites of production of
antibodies. Some lymphoid organs are capsulated such as lymph
node and spleen while others are non-capsulated, which include
mostly mucosa-associated lymphoid tissue (MALT).

5. SECONDARY LYMPHOID TISSUES AND ORGANS
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6. 1. LYMPH NODES
 Lymph nodes are well-organized forms of
lymphoid tissue situated at the junction of
lymphatic vessels, and are present in all parts
of the body.
 They are numerous in areas such as neck,
retroperitoneum, media sternum, axilla, groin
and abdominal cavity.
 It is the major site where APC’s present antigen
to activate T cells and where T cells ‘help’ B
cells undergo immunoglobulin class switching.

7. LYMPH NODES
Lymph node appear in the human foetus in the third
month along the course of lymphatic vessels.
Most nodes survive for 60 years or more with only slight
atrophy and retain the capacity to enlarge throughout life

8. STRUCTURE OF LYMPH NODE
 Human lymph nodes are encapsulated bean
or ovoid shaped complex cellular structures
ranging from few millimetre to a centimetre.
 One side is convex and the other side has an indentation, the hilus through
which efferent lymphatic vessels leave the node and blood vessels enter
and leave.
 Afferent lymphatic vessels pierce the convex surface of the capsule and
empty into the tube.

9. STRUCTURE OF LYMPH NODE CONTD…
 The lymph node is covered by a capsule (made
of dense collagenous tissue) which penetrates in
to the lymph node to form septa called
trabeculae.
 Each lymph node is made up of three regions
namely an outer cortex, a middle paracortex
and an inner medulla.
 The cortex contains B cells; the paracortex
contains T cells and the medulla contains both B
and T cells.

10. STRUCTURE OF LYMPH NODE CONTD…
CORTEX:
 A group of lymphoid and non-lymphoid
cells (macrophages, follicular dendritic
cells) is organised in a spherical or ovoid
structure termed as lymphoid follicle or
nodules.

11. STRUCTURE OF LYMPH NODE
CORTEX CONTD…
 Primary follicles consists of tightly packed small naïve (not yet encountered ag)
lymphocytes and follicular dendritic cells.
 After antigenic exposure, primary follicle becomes a larger secondary follicles
which contain a central, pale staining area called germinal centres. These centres
are the sites of rapid multiplication of lymphocytes.
 Follicular dendritic cells which reside in the germinal centres display Ags on their
surface and selectively activate B cells to differentiate into plasma cells and
memory cells.

12. STRUCTURE OF LYMPH NODE
CORTEX CONTD…
 The cortex consists of primary and secondary lymphoid follicles containing B
lymphocytes, macrophages and follicular dendritic cells (FDCs).
 T cell activation occurs in the cortex.
 Activated T cells migrate to primary follicles and activate B cells, converting
the primary follicle into secondary follicle with germinal centres (GCs).
 The GCs are surrounded by densely packed proliferating B cells with the
central thinly populates area consisting of B cells, T cells, macrophages, FDCs,
plasma cells and antibodies.

13. STRUCTURE OF LYMPH NODES
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14. STRUCTURE OF LYMPH NODE CONTD…
PARACORTEX:
 Beneath the cortex is the paracortex , which is populated largely by Th
cells and sparsely by Tcyt cells.
 It also contains many Ag presenting cells such as Langerhans cells,
follicular dendritic cells (FDCs) and interdigitating dendritic cells (IDCs)
which have large quantities of MHC class II antigens on their suface.
These Ag presenting cells transport Ags from the external and internal
surfaces of the body to the lymph nodes where they encounter naïve
T cells particularly Th cells.
 Thus, paracortex region of the lymph node is the site where T-cell
responses to lymph-borne antigen are initiated.

15. STRUCTURE OF LYMPH NODE CONTD…
MEDULLA:
 The medulla is the innermost region of the lymph node and
extends to the hilus.
 It contains both T and B cells in addition to macrophages,
plasma cells and some granulocytes.
 The lymphocytes are arranged along strands of connective
tissue fibres known as medullary cords.
 These medullary cords are separated by large sinuses known
as medullary sinuses which contain plasma cells.

16. PHYSIOLOGY OF LYMPH NODE CONT...
 As lymph carrying Ags percolate through the lymph nodes, they encounter
macrophages, interdigitating dendritic cells which readily phagocytose the
Ags.
 These Ags are then processed and presented together with class II MHC
molecules by these ag-presenting cells to Th cells in the paracortex.
 This sensitized Th cells activates B cells to differentiate into IgM and IgG-
secreting B cells and memory B cells.
 Some of the plasma cells generated in the germinal centre move to the
medulla and leave the node by efferent lymphatics.

17. PHYSIOLOGY OF LYMPH NODE CONT...
 The lymphocytes whether T or B, remain in their characteristic sites for several
hours, and if they do not engage in ab production they migrate to the medulla
and exit via efferent lymphatics.
 The lymphocytes then recirculate and may also enter a lymph node again
through afferent lymphatics.
 If T and B cells become engaged in ab formation in a node, the lymph leaving a
node is enriched with newly synthesized abs or increased conc. of lymphocytes.

18. FUNCTIONS OF LYMPH NODES
 The lymph nodes act as filters and they filter lymph by trapping damaged
cells, microorganisms, foreign substances and tumour cells.
 Macrophages phagocytose some of the above mentioned and lymphocytes
destroy some by immune defence.
 Lymph nodes are also responsible for the initiation and development of
humoral and cell mediated immune responses.
 Recirculation of mature lymphocytes between blood and lymph nodes.

19. 2. SPLEEN
 Spleen is the flat, ovoid, well
organized lymphoid organ
situated at the left upper region
of the abdominal cavity behind
the stomach and close to the
diaphragm.
 It is deep red in colour and has
direct communication with main
arterial circulation.
 Spleen filters blood as the
lymph node filters lymph.

20. SPLEEN cont…
 The spleen drains the blood borne antigens of pathogens and does not
allow systemic infection to occur.
 Actually spleen conducts dual function:
1. It removes the damaged or old RBCs.
2. It serves as a secondary lymphoid organ.
 In the embryo, before the bone marrow starts producing the RBCS (till 5th
month) the spleen is only concerned with the production of RBCs.
 In the adult, when there is a sudden demand for RBCs, for eg. during
recovery from sudden anaemia, the spleen takes over the function of
haematopoiesis temporarily, along with the bone marrow.

21. STRUCTURE OF SPLEEN cont…
 This is the only lymphoid
organ which is not supplied
with lymphatic vessels.
 The spleen is surrounded by a
capsule.
 The capsule penetrates into
the tissues as septa called
trabeculae.

22. STRUCTURE OF SPLEEN
 The spleen is made up of red pulp and white pulp, separated by marginal
zone: 76-79% of a normal spleen is red of pulp.

23. STRUCTURE OF SPLEEN cont…
RED PULP
 Splenic red pulp consists of a reticular network of splenic cords
and large number of blood filled sinusoids containing
macrophages, granulocytes, platelets, lymphocytes, plasma cells
and most importantly red blood cells which imports the red colour
to red pulp.
 This is the site where old or damaged blood cells are destroyed.
 The red pulp is also reserve site for haematopoiesis.

24. STRUCTURE OF SPLEEN cont…
WHITE PULP
 The splenic artery enters the spleen (through hilus) and branches into the white pulp as
arterioles. The arteriole is surrounded by a densely – packed periarteriolar lymphatic
sheath (PALS) of T and B cells with a few DCs and macrophages.
 Enclosed in the sheath are T cells (mainly Th and partly Tc), IDCs, primary lymphoid
follicles containing FDCs and naïve B cells.
 During immune response, these primary follicles develop into germinal centres and
become secondary follicles.
 The whole splenic material enclosed within PALS constitutes the white pulp.
 Several white pulps are scattered in the spleen.

25. STRUCTURE OF SPLEEN cont…
RED PULP AND WHITE PULP

26. DEVELOPMENT OF IMMUNE RESPONSE IN SPLEEN
 Cells and Ags carried through the blood enter the white pulp nodule
through the splenic artery.
 The Ags is trapped in the PALS by IDCs present in PALS. They
process and present the ags to T cells in PALS.
 The T cells proliferate and differentiate into CD4+ Th cells and CD8+
Tc cells.
 Activated Th cells enter the B cell zone and provide help for B cell
activation.
 Some of the activated B cells along with the Th cells migrate to
primary follicles in the marginal zone. They form germinal centres
where activated B cells divide rapidly and differentiate.

27. DEVELOPMENT OF IMMUNE RESPONSE IN SPLEEN
cont...
 Active proliferation of B cells, their differentiation in plasma cells,
affinity maturation and isotype switch occurs in germinal centres.
 Plasma cells produce antibodies specific for the ags of the infectious
microbe, recognized by the B cells.
 The activated Tc cells, plasma cells and antibodies leave the spleen
through the splenic vein, and are eventually taken to the site of
infection.

28. 3. MUCOSA ASSOCIATED LYMPHOID TISSUE
 The mucous membranes lining the digestive, respiratory and
urogenital systems represent the main sites for the entry of microbes
into the body through air, food and tissue injury.
 These three systems make up the largest area which needs
protection from foreign invaders.
 It is for this reason that almost 50% of the lymphoid tissue in the
human body is located within the lining of the major tracts, defending
these venerable membrane surfaces against invading microbes.
 These uncapsulated tissues are collectively called as mucosa
associated lymphoid tissues (MALT).

29. MUCOSA ASSOCIATED LYMPHOID TISSUE cont…
 Mucosa Associated Lymphoid Tissues (MALT) include
nasal - associated lymphoid tissues (nasopharynx) (NALT),
gut – associated lymphoid tissues (GALT), bronchus – associated
lymphoid tissues (BALT) and lymphoid tissue associated with the
genitourinary system.
 Lymphoid tissues such as Payer’s patches in the small intestine,
adenoids, appendix and tonsils are well demarcated.

30. NASAL - ASSOCIATED LYMPHOID TISSUES (NALT)
 Nasal – associated lymphoid tissues are found in three
locations and involved in the defence against the Ags
entering through the nasal and oral routes.
 A pair of pharyngeal tonsils (adenoids) at the back of the
nasopharynx
 A pair of palatine tonsils placed at the back of the mouth on
both sides.
 A third pair called lingual tonsils is located at the base of the
tongue.

31. NASAL - ASSOCIATED LYMPHOID TISSUES (NALT) cont…
 These three main kinds of tonsils
constitute an anatomical structure called
Waldeyer’s ring.
 All these lymphoid tissues protect the
mouth and nasal passage from air
borne pathogens.

32.  In humans, the tonsils contain a meshwork of reticular fibres and
cells co-mingled with lymphocytes, granulocytes, macrophages
and mast cells.
 B cells organized into primary follicles and larger secondary
follicles with germinal centres surrounded by the regions of T cell
activity is the hall mark of the secondary lymphoid organs.

33. PAYER’S PATCHES or GALT
 Payer’s patches are diffuse lymphoid tissue, named after the 17th century Swiss anatomist
Johann Conrad Peyer.
 They are aggregations of lymphoid tissue that are usually found in the lowest portion of
the small intestine, the ileum in humans.

34. PAYER’S PATCHES or GALT
 Peyer’s patches are fairly well- organised small nodules of lymphoid tissues.
 They extend from lamina propria to submucosa.
 Nodules of Payer’s patches consist of 30 – 40 lymphoid follicles.
 B cell follicles with germinal centres are predominantly seen in Payer’s patches.
 Germinal centres are surrounded by regions showing T cell activity.
Cross sectional
Diagram of
intestine

35. PAYER’S PATCHES or GALT cont…
Cross section of Payer’s patches

36. PAYER’S PATCHES or GALT cont…
 A cross sectional area of Peyer’s patches shows a dome- like structure
with the mucosal layers lined with columnar epithelial cells.
 This outer mucosal epithelial layer contains Intra epithelial lymphocytes.
 Most of these lymphocytes are Tc cells and express CD8+ on their surface.
 These cells may be involved in immunosurveillance.
 Specialized cells called microfold cells or M cells are situated in between
the mucosal cells.
 Below the epithelial layer is lamina propria which contains loose clusters of
B cells and T cells along with DCs and macrophages. Most of the T cells in
lamina propria are CD4+.
 Beneath the lamina propria is the submucosal layer which contains
secondary follicles with Germinal Centres.

37. PAYER’S PATCHES or GALT cont…
 M cells in the mucosal epithelial layer have microfolds on their surface;
hence the name.
 These cells are distinct from epithelial cells and have no microvilli and
mucous on their surface.
 M cells contain deep invagination in the basolateral plasma membrane
which forms pockets filled with B and T cells, macrophages and DCs.
 The antigens enter Peyer’s patches directly from the lumen of the gut
through M cells by forming endocytic vesicles (endocytosis or
transcytosis).

38. PAYER’S PATCHES or GALT cont…
 These vesicles fuse with pocket membrane, delivering Ags to the
clusters of immune cells in the lamina propria or Payer’s patches.
 Antigens, processed and presented by DCs activate Th cells.
 The helper T cells help to activate B cells to mature into ab producing
plasma cells. These immune cells leave the follicles, pass into
mesenteric lymph nodes and enter the lymphatic and blood
circulation.

39. PAYER’S PATCHES or GALT cont…
 Moreover, lymphocytes stimulated in the GALT can migrate to other MALT sites such as
salivary glands, mammary glands, respiratory passages and other parts of the
gastrointestinal tract and protect these surfaces from invasion by pathogens.

40. PAYER’S PATCHES or GALT cont…
 In the nodules of Payer’s patches, the activated Th cells (by the ags
processed and presented by DCs) activates B cells to mature and
differentiate into sedentary, local plasma cells.
 The abs produced in the GALT are mostly IgA type, which enter the
intestinal lumen through the epithelial lining with the help of secretory
piece by the process of transcytosis.
 In the lumen dimeric form of secretory IgA neutralizes viruses, bacteria
and toxins and also blocks the entry of these Ags into circulation by
acting as an antiseptic paint.

41. PAYER’S PATCHES or GALT cont…

42. PAYER’S PATCHES or GALT cont…
 Transport of IgA

43. PAYER’S PATCHES or GALT cont…
 Peyer’s patches thus establish their importance in the immune
surveillance of the intestinal lumen and in facilitating the generation
of the immune response within the mucosa.

44. PAYER’S PATCHES or GALT cont…
In short:

45. BRONCHUS ASSOCIATED LYMPHOID TISSUE
(BALT)
 Bronchial – associated lymphoid tissues are found in all the lobes of the lungs
and are situated along the bronchi and forms an important defensive tissue
protecting the lungs from the entry of pathogens.
 The tissue is not encapsulated and consists of diffuse accumulation of
phagocytic cells, lymphocytes and plasma cells.
 B cells are organized into follicles situated under the epithelium.
 Antigens are captured by the M cells.
 Antigen-presenting cells are transported to underlying lymphoid tissues which
give an appropriate immune response to the invading pathogens.

46. CUTANEOUS – ASSOCIATED LYMPHOID TISSUES
(CALT)
 The skin serves as a protective barrier and sensing buffer between an organism
and the environment.
 The outer layer of the skin, the epidermal layer consists of specialized cells called
keratinocytes. They are rich in keratin as the name suggests.
 These cells secrete pro – inflammatory cytokines such as IL-1,IL-3, IL-6, tumour
necrosis factor and IFN-𝜸.They can be induced to express class II MHC molecules
on their surface by IFN-𝜸 and therefore can act as APS.
 This suggests that keratinocytes may augment local inflammation and lymphocyte
activation.

47.  LANGERHANS CELL
 Langerhans cells constitute only about 1% of the epidermal cells and they cover
almost 25 – 30% of the surface because of their long membranous dendritic
extensions.
 These extensions sense the ag or microbes, pick them up by phagocytosis or
endocytosis. Then they migrate from the epidermis to the nearest lymph nodes
where they differentiate into IDCs.
 These cells express high levels of class II MHC molecules and function as ag –
presenting cells to activate Th cells.
 They activate the Th cells with appropriate TCR and initiate the process of
immune response.
CALT con…

48. CALT con…
 The epidermis also contains intra epidermal lymphocytes.
 These are CD8+ Tc cells and bear 𝛾: 𝛿 T cell receptors (TCRs) which have
limited diversity.
 The dermis also contains CD4+ and CD8+ cells with few macrophages.
 It is believed that intraepidermal T cells, Langerhans cells as well as
CD4+ and CD8+ T cells are the cells that combat ags that enter through
the skin and generate effective immune responses.