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Topic 2.

System Anatomy
Immune

Professor: Conchi Mora

Biotechnology Degree
University of Lleida
Courses 2023-2024
Histology Guide © Faculty of Biological Sciences, University of Leeds
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LYMPHOID ORGANS

Primaris Secondary
ENCAPSULATS:
- TIMUS
-MELSA
- MOLL DE L'OS -LIMFÀTICS GANGLIS
-NOT ENCAPSULATES:
-Mucosal immume system
-Do not organize into fol·licles (dispersed cells)
-Organitzat in fol·licles:

-MALT (Mucosal Associated Lymphoid Tissue):

- Digestive mucosa (GALT (Gut Associated Lymphoid
Tissue), Peyer's Plaques, Tonsil·les)
- Mucosa aparell respiratori (BALT (Bronchial Associated
Lymphoid Tissue)
- Mucosa aparell genito-urinary

- Immune system of cavitats and pell, etc.

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ORGANIZATION OF THE IMMUNE SYSTEM

- The immune system requires an anatomical and functional organization that

allows maximum efficiency in order to eliminate the pathogen.

• Anatomical organization:
Primary lymphoid organs (fetge fetal, moll de l'os and thymus): They are
generated (fetge fetal, moll de l'os) and educated (thymus, moll de l'os, fetge
fetal) the precursors of the cellular components (leukocytes) responsible for
adaptive and innate immunity, also responsible for the generation of
immunological tolerance versus self-antigens.
Moll de l'os: generation of hematopoetic precursors of lymphocytes T and
B, and of the rest of immune cells and of the blood. Maturation of lymphocytes
B. It also participates in the secondary humoral response as the main point of
production of immunoglobulins for plasma cells.

Timus: Differentiation and maturation of T lymphocytes

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ORGANIZATION OF THE IMMUNE SYSTEM

-Secondary lymphoid organs:

1. Encapsulates: A layer of teixit connectiu els defineix i aïlla.

a) Melsa: Filtering and elaboration of the adaptive response (humoral and

cellular) against antigens transported by the blood. Elimination
d´eritròcits i limfòcits decadents.

b) Lymphatic nodes/ganglis: Filtración of the lymph that drains the body

tissues and, therefore, detection of foreign antigens that exist in such tissues.
Muntatge of immune response (cellular and humoral) against the antigens. The
lymph nodes and lymphatic vessels form a network of surveillance and
supervision of the different organs and superficial structures
(visceres, skin, muscle, etc.).
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2. Non-encapsulated or diffuse: There is no physical delimitation per

a capsule of teixit connectiu:

This is how the protection of the mucous membranes

worked, since they are interchangable surfaces that are in contact
with the outside environment. This protection is based mainly on the
secretion of IgA type immunoglobulins. It is troba recobrint the tracts:

- Respiratory (pathogens acquired by inhalation)

- Gènitourinari (sexually transmitted pathogens)

- Gastrointestinal (pathogens resulting from ingestion)

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NON-ENCAPSULATED LYMPHOID ORGANS:

a) Not organized into follicles: groups of lymphocytes, plasma cells

and phagocytes. It enters the lung and the lamina propria of
the intestinal wall.

b) Organitzat in fol·licles:

Teixit limfàtic associat a mucoses (MALT)(Mucosa-Associated

Lymphoid Tissue) – (tonsils, palatines, linguals, Peyer's Patches,
appendix).
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HEMATOPOESI I MADURACIÓ DELS

LIMFOCITARIS PRECURSORS

Downloaded from: StudentConsult (on 22 January 2010 05:11 PM)

© 2005 Elsevier
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MOLL DE L'OS
-It is located on the entire internal part of the body.
- All the precursors of the blood cell types originated in the mole of
the blood in a process known as hematopoesi. In response to
puberty, hematopoesi is present in the ossos plans with the estern,
vertebrae, ossos iliacs and costelles. The mole consists of a green
part, formed by a reticular structure, containing adipocytes, stromal
fibroblasts, and hematological precursors.

-All blood cells come from a common precursor

(Hematopoetc Stem Cell or HSC). The levels are determined by
the presence of cytokines in the stromal cells and macrophages
present in the mole.
- In situations where the bloodstream is damaged or there is an
extraordinary requirement for blood production, blood and blood
can act exceptionally as hematopoetic organs.
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GS Travlos Toxicologic Pathology, (2006)

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HEMATOPOIESI I MATURATION OF THE DIFFERENTS

CÈL·LULES IMMUNITÀRIES PRECURSORS
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GS Travlos Toxicologic Pathology, (2006)

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TIMUS

- Bilobulat organ located at the top of the anterior mediasti. els

lobules to the seva vegada are divided into smaller lobulets
separats per fibrous septes. Each section of these lobulets in the forest is
divided into two functionally different zones:

a) The cortex, high cellularity: (positive and negative selection of DP thymocytes

(CD4+CD8+),
b) The medulla , low cel·lularitat: negative selection of autoreactive SP CD4+ or
CD8+ thymocytes)
c) Mort due to negligence of timòcits DP not reactius.

Thymic precursors enter the blood vessels

to the thymic cortex, both cells interact
cortical epithelial cells, which are selective
They positively migrate to the , on
medulla, the majority of which are T mature
lymphocytes, which supply the thymus
through the blood vessels.
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Downloaded from: StudentConsult (on 22 January 2010 05:23

PM) © 2005 Elsevier
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Types of cell phones:

- Non-hematopoetic origin: cortical and medullary epithelial cells cTECs = cortical

Thymic Epithelial Cells mTECs = medullary
Thymic Epithelial Cells

Foxn1nu (nude mice) Athymic animal model

-Hematopoetic origin: lymphocytic precursors (pre-thymocytes and thymocytes)

(cortex and medulla), mature lymphocytes (medulla), macrophages and
DCs (medulla)
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Types of cell phones:

ÿMedullary epithelial cells (mTECs) (negative selection).

AIRE (AutoImmune REGulator): causes ectopic expression of 200-1200 genes (salivary glands, pancreas, ovaries, etc.)

Autoimmune Polyendocrinopathy Syndrome type 1 (APS-1), also anomenat Autoimmune

Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED).

ÿCortical epithelial cells (cTECs): (positive and negative selection)

ÿDCs and macrophages (negative selection)

AY Chan and MS Anderson.

AnnAnnals of the New York Academy of Sciences (2015).
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THE MELSA
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LA
MELSA -This organ is encapsulated and divided internally by
trabecules or partial septes. It can become an organ with a
hematopoetic function in situations of special demand for blood
precursors.
-I counted the moll vermell and the blanc. The vermell moll (the
majority of the melsa) is the area of localization of the eritròcits
(criballatge and elimination of the vells or danyats). The white blood
cell (areas rich in lymphocytes) replenish circulating lymphocytes
from the blood (central arteriole) and its function is to trigger acquired
immune responses against pathogens present in the blood, especially
if they are particulates.
- The white moll is structured by volant branches of the splenic
arterioles called trabecular arterioles, and branches of the central
arterioles, and branches of the splenic arterioles, called follicular
arterioles. Thus, each functional unit of moll blanc contained a
central arteriole (part of a trabecular artery), and several follicular
arteries, which drain into the marginal sinus.
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PECULIARITATS OF MELSA IN HUMANS

-In humans, the marginal sinus is not histologically
different.
- The blood of the splenic artery, which is branched
In central arterioles and penicillary arteries (open
capillaries), they are frequently covered by PALS.
-Degut to the absence of marginal sinus, the
blood is directly from them. penicill·lars to the capillaries
of the vermella pulp and the perifol·licular zone.
-Ambdues, the perifol·licular zone and the vermella pulp have
open circulation (cordes spleniques) without delimitation
endothelial and both contact the venous sinusoids of the
vermella pulp.
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Gloria P Gómez-Pérez et al. 2014. Malaria Journal

Birte S. Steiniger, Immunology 2015

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- The Marginal Zone marks the limits of the white moll, and contains
lymphocytes B characteristics and macrophages specialties.

-The T lymphocytes are located in the PALS (periarteriolar

lymphoid sheath), or periarteriolar lymphatic area, enveloping the
central arteriole, i,

- The B lymphocytes are troben forming the follicles that are between the
marginal sinus and the PALS. There are primary follicles (non-stimulated
B cells) and/or secondary follicles (germinal center (B actius lymphocytes))
recovered from the Mant of non-stimulated B lymphocytes.
- In general, the functional organization of the white mole of the melsa is
analogous to that of the lymphatic ganglia. Non-hematopoietic stromal cells
produce the chemokines CXCL13 (attraction of B lymphocytes to the follicles
(CXCR5)), and CCL19, CCL21 (attraction of T lymphocytes to the PALS
zone, (CCR7)).
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-The blood antigens arrive at the marginal sinus transported by

circulating DCs or the macrophages existing in the marginal sinus.

- The green moll is formed by vascular sinusoids, different from

the marginal ones, which contain erythrocytes, macrophages, DCs,
some lymphocytes and plasma cells. These sinusoids empty into
venules, and finally into the splenic vein, which returns blood from
the membrane to the circulation through the portal circulation. The
macrophages of the vermell moll phagocytize erythrocytes and
microbial particles that have been opsonized (recoberted by anti-
cossos).
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LIMFÒCITS ACTIVATION PHASES

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THE MELSA
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LIMFÀTICS GANGLIS (LN or Lymph Nodes)

-Lymphoid organs encapsulated highly organitzats.

-They contain a framework of reticular cells, organized in spaces
called sinus. The lymphatic ganglia capture the lymphatic fluid (the
lymph) which is the plasma filtrate of the interstitial fluid existing
between the cells of the associated veins, through the afferent
lymphatic vessels, which empty into the subcapsular sinus. The
lymph passes through the B and T zones respectively to reach the
medullary sinus, where it has macrophages and returns to the
lymphatic circulation through the efferent lymphatic vessels. The
efferent lymphatic vessels converge into larger caliber vessels,
eventually all emptying into the thoracic duct, a large lymphatic vessel,
which flows into the superior vena cava (2 liters of lymph are recovered
from the blood flux per day; The cor pumps in promig 8000 liters of
blood per day).
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Blanchard L and Girard JP, Angiogenesis 2021

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Blanchard L and Girard JP, Angiogenesis 2021

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-The lymph transports existing antigens to the tissues where they come
from, along with soluble factors (pro-inflammatory cytokines, PAMPs,
chemokines, etc.), to the lymphatic ganglia, which act as a filter and
“monitor” of potential proteins that activate the tissues. . The lymph also
transports dendritic cells (DCs) from the veít tissue, which activate T verges
lymphocytes, as well as lymphocytes from the inflamed tissues.

- The lymph nodes enter the lymph nodes through the artery, and stop the
circulation through the HEVs (High Endothelial Venules), entering the
lymph nodes. The activated lymphocytes coming from the affected
tissue enter the ganglia with the afferent lymphatic vessels and leave
the ganglia with the efferent lymphatic vessels.

-The lymph can also carry tumor cells from the organ in the primary tumor,
and the presence of these cells in the ganglia that drain the organ affected
by the tumor (gangli sentinella), can be an indicator of metastasis.
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- Zones B (outer cortex) and T (paracortex, or zone that surrounds the

follicles) are clearly differentiated and separated, thanks to the differential
chemotactic action of the chemokines secreted in zone B and in zone T.
The cells Residents of the T zone (LN stromal cells and interdigitating
dendritic cells (iDCs) secrete the chemokines CCL19 and CCL21,
which are ligands of the CCR7 receptor, expressed by T lymphocytes.

-The resident cells of zone B secrete CXCL13 , which is linked to the

CXCR5 receptor, expressed by B lymphocytes.

-The interaction between lymphocytes B and T is necessary in those T-

dependent humoral responses (antigens proteins), and is produced,
thanks to the increase in the expression of CCR7 to lymphocytes B after
the seva stimulation by the antigen, ia the increase of CXCR5 to the
surface of the T activats.
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-Zone T allows the T lymphocytes to interact with the iDCs; the B , zone
allows the B lymphocytes to interact with the antigen (soluble or on the
surface of FDCs). Subsequently, when both T and B lymphocytes have seen
antigen stimulation in the respective six areas, they will interact with each
other, and the T lymphocytes will migrate cap to the follicles ( Th follicular
lymphocytes) and will help the B lymphocytes. generate a powerful humoral
response (germinal center reaction), also releasing the lymph node through
the efferent lymphatic vasculature. The activated B lymphocytes first migrate
to the follicle together with the Th follicular lymphocytes and form the germinal
centers, and a differentiated layer of plasma cells migrates to the mole.
-The primary follicles consist of B lymphocytes that stimulate. -
Secondary follicles are formatted by B lymphocytes after exposure
to the antigen, they are formatted by an external or Mant zone (B
lymphocytes not stimulated by the antigen in which they were
exposed, IgM+ and IgD+) and the Germinal Center. The Mant
surrounds the germinal center, organized into three main zones:
on the centroblasts (proliferatius, sIgD- sIgMlow), centròcits (non-
proliferative, more sIg), secondaris B blasts (donant alloc to
plasma cells (no sIg) i cells B memory next to the corresponding isotip)
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PHASES OF ACTIVATION OF LIMFÒCITS ALS GANGLIS

LIMFÀTICS
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GERMINAL CENTER REACTION

1. Maturation per afinitat: Somatic hypermutation (SHM) and clonal selection
2. Canvi d'isotip (IG Class Switch)

Klein and Dalla-Favera Nat. Rev. Immunol. 2008

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Klein and Dalla-Favera Nat. Rev. Immunol. 2008

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1. https://www.youtube.com/watch?v=XpFPMskIFM8

2. https://www.jove.com/video/3720/intravital-imaging-of-
the-mouse-popliteal-lymph-node
Min 7:30

Bid.udl.cat
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DISTRIBUTED BY THE GANGLIS LIMFÀTICS

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LYMPHOID ORGANS

Secondary
•ENCAPSULATS:
-MELSA
Primaris -LIMFÀTICS GANGLIS

- TIMUS
•NO ENCAPSULATS:
- MOLL DE L'OS -Mucosal immume system:
Do not organize into fol·licles (dispersed cells)
Organitzat in fol·licles:
MALT (Mucosal Associated Lymphoid Tissue), p.ex.:
- Digestive mucosa (GALT (Gut Associated Lymphoid Tissue), Plaques of
Peyer, Tonsil·les),
- Mucosa aparell respiratori (BALT (Bronchial Associated Lymphoid
tissue),
- Mucosa aparell genito-urinary.

- Immune system of cavitats and pell, etc.

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MUCOLS IMMUNE SYSTEM

-Responsible for the response against pathogens such as ingestion, inhalation,

and sexual transmission. Most of the knowledge comes from studying the
gastrointestinal tract.
- The immune system does not encapsulate the lamina propria, between the
epithelial cells that recover the tract and the lymphoid follicles associated with
the mucosa (MALT).
Mucosal immune system not organized in follicles:
In the lamina propria: activated T lymphocytes (CD4+ majoritàriament), activated
B lymphocytes, plasma cells, DCs, macrophages, eosinophils and mastocytes.
-Mucosal immune system organized in fol·licles:
-- Peyer's Plaques (PP) (primary intestine): similar structure to the zones B of
the melsa and the lymphatic ganglis, consists of lymphoid fol·licles, which, if
secundaris contain germinal centers. Among the follicles of a mated Peyer's patch
is troben lymphocytes T (Thf). But the majority of the lymphocytes of a Peyer's
patch are B. Among the epithelial cells of the intestine and above the PP are the
M cells (of “membranous” or “microfold”), specializing in capture antigens from
the intestinal lumen by pinocytosis, transport them through the cell by
transcytosis, to release them to the PP. Structures analogous to the PP are
linked to the genitourinary and respiratory tracts. The humoral response is d'IgAs.
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https://www.youtube.com/watch?v=gnZEge78_78