Last edited: 8/8/2021

T-CELL DEVELOPMENT
Immunology: T-Cell Development Medical Editor: Dr. Sofia Suhada M.Uzir

OUTLINE II) LYMPH NODES

I) LYMPHOID STRUCTURES ● Include external, lymphatic flow and internal structures
II) LYMPH NODES
III) SPLEEN
IV) PEYER’S PATCHES
V) TONSILS
VI) T-CELL DEVELOPMENT
VII) REVIEW QUESTIONS
VIII) REFERENCES

I) LYMPHOID STRUCTURES
● Lymphoid organs with immune function

Figure 2. Lymph node structure [VectorStock]

(A) EXTERNAL STRUCTURE

● Kidney bean shaped
● Has many afferent lymphatic vessels feeding lymph node
● Has very few efferent lymphatic vessels draining lymph
node

(B) LYMPHATIC FLOW

● Afferent lymphatic vessels → subcapsular sinus →
trabecular sinus → medullary sinus → efferent lymphatic
vessel

(C) INTERNAL STRUCTURE

(1) Cortex
● Contains lymphoid follicles filled with B-cells
(i) Primary follicles
Figure 1. The lymphoid organs in adults [NursingTimes]
o This is the inactive follicle
o Contain a dense pack of B-cells that are inactive
(A) PRIMARY LYMPHOID ORGANS  They haven't bound or interacted with any antigen
yet
● Primarily function during younger age of life until early  These inactive B-cells have a dense nucleus
age of adolescence
which gives the primary follicle a dark color
o Atrophies and fibrosed → no longer functional
● Bone marrow (ii) Secondary follicles
o Where immune cells are produced o This is the active follicle with a germinal center at the
 B-cells core and surrounding mantle zone
 T-cells o The core contains B-cells that have interacted or
 Granulocytes bound an antigen and start proliferating and
 Monocytes differentiating into centrocytes & plasma cells and
preparing to make antibodies
● Thymus
 Centrocytes and plasma cells have a less dense
o Where T-cells mature and differentiate
nucleus so they give a pale color to the germinal
(B) SECONDARY LYMPHOID ORGANS center
o Around the core of proliferating B-cells is inactive B-
● Lymph nodes
cells that are densely packed next to each other
● Spleen
 This is known as the mantle zone
● Peyer's patches
 These inactive B-cells have a dense nucleus
● Tonsils
which gives the mantle zone a dark color

T-CELL DEVELOPMENT IMMUNOLOGY: Note #1. 1 of 6

 (iii) Around the follicles
o Other antigen presenting cells called macrophages (D) CLINICAL SIGNIFICANCE
and dendritic cells and collagen type III
 Produced by fibroblasts (1) In Digeorge syndrome

(2) Paracortex ● There is improper development of the 3rd and 4th

pharyngeal pouch of which the 3rd pharyngeal pouch
● This area contains a large number of T-cells that have doesn't give way to the thymus
migrated from the thymus → ↓ T-cell development
● This area is where T-cells interact with APCs and become → ↓ development of the paracortex in lymph node
activated and release cytokines
● There is also a large amount of capillaries in this area (2) When there is inflammation or infections
which allows T-cells and some B-cells to move into the ● ↑ proliferation of T-cells in paracortex
blood o paracortical hyperplasia
(3) Medulla o lymphadenopathy
● This is very common in EBV infections seen with
(i) Medullary cords
infectious mononucleosis
o This area contains a large amount of plasma cells
(3) In Bruton's disease
(ii) Medullary sinus
● There is a deficiency in B-cells which causes
o Drains lymph from trabecular sinus and feeds efferent
o ↓ development of cortex
lymphatic vessels
o ↓antibody production → also known as
agammaglobulinemia

Figure 3. Internal structures of lymph node [NursingTimes]

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 III) SPLEEN

(A) GROSS ANATOMY

● Located in LUQ of abdomen
● Protected by 9th & 11th ribs
● Arterial supply
o Splenic artery of the celiac trunk
● Venous drainage
o Splenic vein which drains into the hepatic portal venous
system
● Innervation
o Sympathetic nervous system
 Celiac plexus
Figure 4. Cross section of spleen [NursingTimes] o Parasympathetic nervous system
 Vagus nerve
(B) MICROSCOPIC ANATOMY

Figure 5. Histology spleen [Indiana University]

(1) Red pulp
(i) Splenic sinusoids
o Most permeable capillaries
 Capillaries with large intercellular clefts and a
fenestrated basement membrane that prevent
malformed and old RBCs & platelets from
entering venous circulation
o Open circulation: This circulation involves blood
flowing from capillary sheaths into spaces outside
splenic sinusoids called splenic cords. Then some of
the blood in those cords can flow into the splenic
sinusoids via the spaces in the splenic sinusoids
o Closed circulation: This circulation involves blood
flowing from capillary sheaths → splenic sinusoids
(ii) Splenic cords
o A space between the splenic sinusoids formed by a
connective tissue network that filters old & damaged
RBCs
(C) FUNCTION
(1) Red pulp
● Filters old, damaged RBCs and platelets
● Sequesters platelets
● Is involved in erythropoiesis during fetal development
(2) White pulp
(i) Periarteriolar lymphatic sheaths (PALS)
o Dense collection of T-lymphocytes surrounding the
splenic arterioles
(ii) Follicles
o In close proximity to PALS there is a dense
follicular/nodular collection of B-lymphocytes
(iii) Marginal zone
o This structure forms between red pulp and white pulp
and contains Macrophages and B-cells
(2) White pulp
● Immune portion of the spleen
o House for APCs when exposed to a particular antigen
o Splenic macrophages are crucial to removing
encapsulated bacteria of which S.pneumoniae,
N.meningitidis and H.flu are of significant concern.
o Forms memory B cells and plasma cells where antibodies
may be produced in response to antigen exposure.

(D) CLINICAL SIGNIFICANCE

(1) Splenectomy
o White pulp is not present to protect against
encapsulated bacteria of which S.pneumoniae, N.
meningitidis and H. flu are of significant concern.
o This means the individual must be vaccinated against
these organisms if they haven't been already.
(2) Splenic rupture
o Red pulp contains a large portion of platelets and old,
damaged RBCs as well as circulating RBCs and
platelets so with splenic rupture this person would
spill significantly large volumes of RBCs and platelets
into their abdomen

T-CELL DEVELOPMENT IMMUNOLOGY: Note #1. 3 of 6

 IV) PEYER’S PATCHES
(A) STRUCTURE
(B) FUNCTIONS
● Follicles densely packed with lymphocytes, macrophages
● Ingested pathogens will activate these follicles immune
and dendritic cells scattered throughout the GI tract
cells
primarily located in the lamina propria or submucosa of
● Specialized cells in the GI tract called M-cells transport
the ileum.
antigens of pathogen across intestinal lumen
→ macrophages phagocytose those antigens
→ macrophages present antigens to B-cells
→ B-cells then differentiate into plasma cells
→ plasma cells then make IgA type antibodies that are
released into the GIT lumen which will lead to
neutralization and destruction of pathogens

V) TONSILS

Figure 6. The lingual and palatine tonsils [TeachMeAnatomy]

(A) STRUCTURE (B) FUNCTIONS

● These lymphoid structures are located primarily in the ● First line of defense against inhaled or ingested
oropharynx, base of tongue and nasopharynx/nasal pathogens
cavities.
o Pharyngeal tonsils
o Palatine tonsils
o Lingual tonsils
o Tubal tonsils

Figure 7. Four tonsils - Waldeyer's ring [TeachMeAnatomy]

● These lymphoid structures contain follicles densely

packed with:
o Lymphocytes
o Macrophages
o Dendritic cells,
● But most importantly some of them contain crypts (little
pockets) which trap microorganisms in them

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 VI) T-CELL DEVELOPMENT
(A) SITES
● T-cells are made in the red bone marrow yet are
immature → they then migrate to the thymus to mature
into specific types of T-cells
● The thymus which sits on the heart and is most functional
during childhood produces cytokines which cause the
immature T-cells from the bone marrow to migrate to the
thymus
● The cytokines produced include:
o Thymosin
o Thymopoietin
o Thymotaxin
(B) PHASES OF DEVELOPMENT
● The immature T-cells from the bone marrow have no CD4
& CD8 (double negative) or functional T-cell receptor
(TCR) it's actually a Pre-TCR
● T-cells once in the thymus are again acted on by
thymosin, thymopoietin & thymic factors (IL-2 & IL-7)
o Activate expression of RAG-1 and RAG-2 enzymes
which cause shuffling (recombination) of the DNA and
lead to the expression of T-cell TCRs that vary from
T-cell to T-cell
o These differences in the TCR’s are what allow T-cells
to recognize different antigens
● The T-cell also begins to proliferate and also expresses
CD4 & CD8 (double positive) along with the functional
TCR
(1) Positive selection:
● The function of this phase is to make sure the T-cells are
functional
● Thymic cells in the cortex of the thymus express two
proteins on their surface:
o MHC-I
o MHC-II
● The Double positive (CD4 and CD8) T-cells with a
functional TCR have to interact with the MHC-I and MHC-
II complexes not too strong or too weak but just the right
amount of affinity
(i) It will survive
o If the CD4 protein of the double positive T-cell
interacts properly with the MHC-II on thymic cell
o If the CD8 protein of the double positive T-cell
interacts properly with the MHC-I on thymic cell
(ii) Apoptosis
o If there is a really strong or really weak interaction
between the CD4 or CD8 with the respective MHC
complexes
 The thymus cells release Fas which triggers
apoptosis
T-CELL DEVELOPMENT
(2) Negative Selection
● The function of this phase is to make sure the T-cells are
not going to react with our own tissues (self-reaction)
● The T-cells that survived positive selection still are double
positive (CD4 and CD8) and still contain a TCR
● Thymic cells in the medulla of the thymus express self-
antigens on MHC complexes on their surface
(i) Mechanism
o The mechanism behind this self-antigen presentation
is mediated through a gene called autoimmune
regulator (AIRE)
 When AIRE is active
• it expresses these self-antigens to be placed
on MHC complexes
 Defects in this gene increase susceptibility of
diseases such as
• Adrenal insufficiency
• Chronic candidiasis
• Hypoparathyroidism
(ii) Apoptosis
o If the TCR of a double positive (CD4 and CD8) T-cell
binds a self-antigen on MHC complexes
 It receives an apoptotic signal via Fas release
o There are a few of these T-cells that do not undergo
apoptosis → become T-regulatory cells
(iii) It will survive
o If the TCR of a double positive (CD4 and CD8) T-cell
does not bind with self-antigen on MHC complexes
 It survives
● It's important to note that when the Double positive (CD4
and CD8) T-cells interact with the thymic cells MHC
complexes it can trigger differentiation of these Double
positive T cell to single positive T-cells
o If there is greater affinity between CD4 of the T-cell
and MHC-II of thymic cell
 Triggers downregulation of the CD8 protein on this
double positive T-cell → converting it into a single
positive (CD4) T-cell
 CD4 cells will become T-helper cells
o If there is greater affinity between CD8 of the T-cell
and MHC-I of thymic cell
 Triggers downregulation of the CD4 protein on this
double positive T-cell → converting it into a single
positive (CD8) T-cell
 CD8 cells will become Cytotoxic T-cells
(C) DESTINATION OF MATURE T-CELLS
● Secondary lymphoid organs such as
o Lymph nodes
 Deep part of the cortex
o Spleen
 White pulp/periarteriolar lymphatic sheaths
o MALT
o Thymus gland
 Hassall’s corpuscle
● As well as circulate in the blood
IMMUNOLOGY: Note #1. 5 of 6
 VII) REVIEW QUESTIONS The lymphoid tissues are responsible for creating,
storing, and processing lymphocytes, which are
All of the followings are considered a tonsil except essentially the effector cells of the immune system.
a. Palatine Which of the following is a lymphoid structure that
b. Pharyngeal is also responsible for recycling old red blood
c. Thymus cells?
d. Tubal a. Liver
b. Appendix
Which of the following is true concerning the c. Spleen
function of Peyer’s patches d. Thymus
a. Helps in hemolysis of RBC e. BM
b. Helps in neutralization and destruction of pathogens
c. Responsible in releasing T-lymphocytes CHECK YOUR ANSWERS
d. Regulates T-lymphocytes development
VIII) REFERENCES
The cytokines produced by T-cell include all of the ● Steve Ford. 2020. [Digital photo]
The lymphatic system 2: structure and function of the lymphoid organs
following except
https://www.nursingtimes.net/clinical-archive/immunology/the-
a. Thymosin lymphatic-system-2-structure-and-function-of-the-lymphoid-organs-26-
b. Thymopoietin 10-2020/
c. Thymotaxin ● Vector Shock Lymph node structure medical educational vector
image. [Digital photo ] https://www.vectorstock.com/royalty-free-
d. Thymoperitin vector/lymph-node-structure-medical-educational-vector-8377264
● Indiana University. Histology of Spleen [Digital image]
https://vmicro.iusm.iu.edu/hs_vm/docs/lab7_6.htm
Apoptosis occurs when ● Teach Me Anatomy. Tonsils [Digital Image]
a. The TCR of a double positive (CD4 and CD8) T-cell https://teachmeanatomy.info/neck/misc/tonsils-and-adenoids/
● Varsity Tutors. MCAT Biology [Quiz]
binds a self-antigen on MHC complexes
https://www.varsitytutors.com/mcat_biology-help/lymphoid-organs
b. The CD4 protein of the double positive T-cell ● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the
interacts properly with the MHC-II on thymic cell 3 USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017
c. The CD8 protein of the double positive T-cell ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
interacts properly with the MHC-I on thymic cell ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
d. The TCR of a double positive (CD4 and CD8) T-cell ● Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB, Campbell
does not bind with self-antigen on MHC complexes NA. Campbell Biology. New York, NY: Pearson; 2020.
● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo
J. Harrison's Principles of Internal Medicine. New York etc.: McGraw-Hill
All of the following are the destination of mature Education; 2018.
T-cell except ● lberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P .
Molecular Biology of the Cell. New York, NY: Garland Science; 2002
a. Lymph nodes ● Murphy K, Weaver C. Janeway's Immunobiology. Garland Science;
b. Spleen 2016
c. MALT ● Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology.
Lippincott Williams & Wilkins; 2012
d. Bone marrow ● Levinson W. Review of Medical Microbiology and Immunology.
Lange; 2012
The following are the clinical significance of spleen
except
a. After splenectomy to prevent from certain diseases
b. In case of splenic rupture
c. During bone development
d. None of the above

Which of the following is NOT a part of the

lymphatic system?
a. Thymus and spleen
b. Adenoids and tonsils
c. Bone marrow
d. Liver

Which of the following are you most likely to find in

the medulla of a lymph node?
a. T cells
b. B-cells
c. Stromal cells
d. Dendritic cells

Which of these is a lymphoid organ that is active in

young children, but decreases in size and
importance in adulthood?
a. Spleen
b. Adenoids
c. Lymph nodes
d. Thymus
e. Tonsils

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