Lymphatic system · Developmental categories •Primary = central lymphatic organs –those in...
Transcript of Lymphatic system · Developmental categories •Primary = central lymphatic organs –those in...
Lymphatic system
Lymphoid organs and main paths of lymphatic vessels. Junqueira's Basic Histology, 14e, 2016
The lymphoid system
consists of: capsulated
lymphoid organs (thymus,
spleen, tonsils, and lymph
nodes); diffuse lymphoid
tissue; and lymphoid cells,
primarily T lymphocytes (T
cells), B lymphocytes (B
cells), NK and dendritic cells
and
macrophages.
Types of immunity
The innate immune system (IIS)
• The IIS (nonspecific) consists of:
• complement,
• mononuclear phagocytes (neutrophils
monocytes and tissue macrophages)
• NK cells
• mastocytes
Antigen-presenting cells (APCs): macrophages,
lymphoid dendritic cells, Langerhans cells (epidermis),
follicular dendritic cells and B cells
Different cell types are active in the innate immunity
Junqueira, Basic Histol, 11 ed
The adaptive immune system (AIS)
The adaptive immune system (specific) has four
characteristics:
- ability to recognize self molecules from nonself
ones,
- memory,
- specificity,
- diversity.
The cells of the adaptive immune system, T and B
cells, and Antigen Presenting Cells (APCs),
communicate with one another by the use of
signaling molecules (cytokines).
Adaptive immune system functions to defend
the organism by mounting:
humoral immune responses against soluble
antigens (foreign substances )
AND
cell-mediated immune responses against
antigens present on the cell surface of
- microorganisms,
- tumor and transplanted cells, and
- virus-infected cells.
Main cell types of adaptive immune
response
Developmental categories
• Primary = central lymphatic organs– those in which lymphocytes are produced or mature
– red bone marrow, thymus gland
• Secondary = peripheral lymphatic organs– those in which mature lymphocytes play active roles
in immune defense reactions, proliferate, complete differentiation
– red bone marrow, lymph nodes, spleen, tonsils, and various isolated microscopic lymphatic nodules, especially those found in lamina propria of the mucosa of the GI, respiratory, urinary, and reproductive tracts, i.e., MALT = mucosa-associated lymphatic tissue.
Bone marrow is a central lymphoid
organ: it contains precursors of T,
B, and NK lymphocytes.
B cell precursors differentiate in
bone marrow microenvironment
into mature B lymphocytes.
T cell precursors travel in blood
into thymus which is a central
lymphoid organ for T cell
development.
Differentiation of B and T cells into
mature cells occurs mainly during
foetal life!
‘Immunocompetent’ B and T cells
leave central lymphoid organs and
settle in SECONDARY ORGANS.
They encounter specific antigens
there and react specificaly.
Th =
helper
Tc = cyto-toxic
Junqueira, Basic Histol, 11 ed
Date of download: 2/27/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved.
(a) All T lymphocytes have cell surface protein receptors (TCRs) with variable regions that
recognize specific antigens. Cell activation requires costimulation by the TCR and either CD4 or
CD8, which characterize helper and cytotoxic T cells, respectively.
(b) B-cell receptors (BCRs) are IgG-like immunoglobulin molecules projecting from the
plasmalemma.
From: The Immune System & Lymphoid Organs: Specific receptors on T and B lymphocytes.Junqueira's Basic Histology, 14e, 2016
CD4 and CD8 are co-receptors, their presence defines
type of the cell-mediated response
= cytotoxic T cell
Differentiation of T cells in the thymus
Date of download: 2/27/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved.
(a) The TCR and CD4 proteins of a helper T cell (Th cell) bind antigens presented on MHC class II molecules and with
interleukin-2 (IL-2) stimulation, the lymphocyte is activated and proliferates.
(b) Cytotoxic T lymphocytes, or CTLs, recognize and bind abnormal (e.g. viral) peptides on MHC class I molecules, and triggered
by IL-2 from helper T cells the CTLs proliferate.
T cell activation requires costimulation of at least two receptors and causes cell proliferation
that produces many effector cells and a smaller population of memory cells.
Activation of CD4+ Th cells by their contact with APCs leads to the
secretion of many cytokines which promote proliferation of B cells and
their final differentiation to plasma cells
Junqueira 2011
IgG structure: 2 heavy and 2 light chains
After papain digestion one gets: Fab – Antigen-binding fragment, and Fc fragment that binds the antibody molecule to the cell membrane
Types of light chains: κ, l
Types of heavy chains:
a,d,e,g,m:
Hence, Ig types: A,D,E,G,M
Site of Ig binding to
plasma membrane
receptorof several cel
types
Pawlina, Histology. Text&Atlas, 2020
2 light chains and 2 heavy chains form an
antibody molecule (“monomer”). The
chains are linked by disulfide (S-S) bonds.
The variable regions (Fab) near the
amino end of the light and heavy chains
bind the antigen.
The constant region (or Fc) of the
molecule may bind to surface receptors
CL, constant part
of light chain
Date of download: 2/27/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved.
From: The Immune System & Lymphoid Organs: Basic structure of an immunoglobulin (antibody)Junqueira's Basic Histology, 14e, 2016
2 light chains and 2 heavy
chains form an antibody
molecule (“monomer”). The
chains are linked by
disulfide bonds.
The variable portions
(Fab) near the amino end
of the light and heavy
chains bind the antigen.
The constant region (or
Fc) of the molecule may
bind to surface receptors of
several cell types.
Various specific and nonspecific functions of antibodies. Junqueira's Basic Histology, 14e, 2016
The important mechanisms
by which the most common
antibodies act in immunity.
(a) Specific binding of antigens
can neutralize or precipitate
antigens, or cause
microorganisms bearing the
antigens to clump (agglutinate)
for easier removal.
(b) Complement proteins and
surface receptors on many
leukocytes bind the Fc portions
of antibodies attached to cell-
surface antigens, producing
active complement, more
efficient phagocytosis
(opsonization), and NK-cell
activation.
◼ accumulation of ‘unencapsulated’, spherical masses of dense aggregates of:
◼ small B lymphocytes in an outer core
◼ the germinal center, a central mass of:
- antigen-presenting macrophages and
- larger, more metabolically active, proliferating B lymphocytes and plasma cells
Lymphoid nodule is a site of proliferation and
differentiation of lymphocytes in active
immune responses
primary secondary2 types
Uncapsulated lymph nodule: in the middle germinal center –
rich in dividing B cells (lymphoblasts). Its dark, peripheral
region, marginal zone, (corona, mantle), contains mainly
small, newly formed adult B cells.
Other cell
types: FDCs
(follicular
dendritic
cells),
macrophages,
Th cells, and
reticular cells.
Wheather’s Funct Histol, 4 ed
Thymus
A lobed primary lymphatic and
an endocrine organ located in
the mediastinum, which is
responsible for T cell
development.
Thymus is largest at birth and
shrinks over time, being
replaced by CT and adipose
tissues. Thymus atrophy is
caused by the increased
blood level of sex hormones..
Junqueira, Basic Histol, 11 ed
Date of download: 2/27/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved.
(a) The thymus is a bilobed organ in the mediastinum that is most active and prominent before puberty and
undergoes involution with less activity in the adult.
(b) A child’s thymus, showing connective tissue of the capsule (C) and septa (S) between thymic lobules, each
having an outer cortex (Co) and incompletely separated medulla (M) of lymphoid tissue. (H&E; X40)
(c) After-involution the thymus shows only small regions of lymphoid tissue, here still with cortex (Co) and
medulla (M), and these are embedded in adipose tissue (A). Age-related thymic involution reduces production of
naïve T cells and may be involved with the decline of immune function in the elderly. (H&E; X24)
From: The Immune System & Lymphoid Organs: Thymus.Junqueira's Basic Histology, 14e, 2016
A connective tissue
capsule surrounds the
thymus. The septa of
the capsule divide
parenchyma into
incomplete lobules,
each of which contains
a cortical and
medullary region.
Thymus does not
contain lymphoid
nodules.
Reticular Epithelial Cells (REC) originate from endoderm and form a
meshwork in which T cells are tightly packed.
REC are pale cells with large, ovoid nucleus. They have long
processes that surround the thymic cortex, isolating it from both
connective tissue septa and medulla.
The processes, which are filled with bundles of tonofilaments, form
desmosomal contacts with each other.
Each REC surrounds
ca. 50-200 immature T
cells (thymocytes) in
the thymus cortex,
they are called
‘nourishing’ or ‘nurse’
cells
Junqueira, Basic Histol, 11 ed
REC produce thymosin, serum thymic factor, and thymopoietin which
help in the transformation of immature T cells into immuno-competent T
cells.
REC are of six types. Some REC present MHC I and MHC II molecules to
developing T cells.
Besides REC thymus stroma contains macrophages and dendritic cells.
REC Junq
ueira,
Basic
Histol
11 ed
Thymocytes
• Thymocytes are immature T cells present within thymic cortex in
different stages of differentiation.
• They are surrounded by processes of REC, which segregate
thymocytes from antigens during their maturation.
• They migrate toward the medulla as they mature.
• However, most T cells (95%) die in the cortex and are phagocytosed
by macrophages. These are T cells whose receptors recognize self
proteins (self-antigens), undergo apoptosis and never reach the
medulla.
• Surviving T cells are naïve, ie. not specifically immuno-competent.
• They leave the thymus and are distributed to secondary lymphoid
organs by vascular and lymphatic systems.
Thymic
selection of
functional but
not self-
reactive T cells.
Positive selection occurs in the cortex
and allows survival only of T cells with
functional TCRs that recognize MHC
class I and class II molecules.
Junqueira's Basic
Histology, 14e, 2016
Negative selection occurs in the medulla and allows
survival only of T cells that do not tightly bind self-
antigens presented on dendritic cells there.
Junqueira,
Basic
Histol14 ed
Blood-thymus barrier
• It exists in the cortex only, making it an immunologically protected region.
• It ensures that antigens escaping from the bloodstream do notreach T cells that develop in thymic cortex.
• It consists of the following layers:
- endothelium of the thymic capillaries and associated basal lamina,
- perivascular connective tissueand
- cells: pericytes and their basallaminae, macrophages, and RECs
Pawlina, Histology. Text&Atlas, 2020
Thymus - medulla
• The inner lighter area, medulla, contains larger
more mature T-lymphocytes going through the
final developemental stage.
• Hassall corpuscles are accumulations of altered
RECs in thymic medulla. They display various
stages of keratinization and increase in number
with age. Unknown function.
Lymph nodes are small encapsulated
structures positioned along lymphatic
vessels to filter lymph and facilitate
antibody production. Valves in the
lymphatic vessels ensure the one-way
flow of lymph, indicated by arrows.
The three major regions of a lymph node
include the outer cortex receiving lymph
from the afferent lymphatics, an inner
paracortex where most lymphocytes
enter via high endothelial venules
(HEVs), and a central medulla with
sinuses converging at the efferent
lymphatic.
The cortex of lymph nodes contains
lymphoid nodules, sinuses, and the
paracortex. The medulla is composed
of medullary sinuses and medullary
cords.
Lymph node. Junqueira's Basic Histology, 14e, 2016
Schematic diagram of lymphocyte
circulation within a lymph node
Afferent lymph vessel
→Subcapsular sinus →
Intermediate (radial)
sinuses →
Medullary sinuses →
Efferent lymph vessel
emerges out of hilum
Pawlina, Histology. Text&Atlas, 2020
Paracortex or inner cortex is located between cortex and
medulla. It is composed of a non-nodular arrangement of
mostly T cells (T-dependent area of the lymph node).
In paracortex circulating lymphocytes gain access to lymph
nodes via postcapillary (high endothelial) venules, HEVs.
Junqueira,
Basic
Histol, 11
ed
High endothelial venules (HEVs) - places of lymphocyte migration (ARROWS)
from blood into lymphatic nodule: information about antigens ENCOUNTERED IN
BLOOD is carried through HEV’s walls to the site of antibodies’ production
Junqueira, Basic Histol, 11 ed
Sinuses are endothelium-lined
spaces that extend along the
capsule and trabeculae and
therefore are called subcapsular
and cortical (radial) sinuses
Medullary sinuses are endothelium-lined spaces
that receive lymph from the cortical sinuses.
Medullary cords are the accumulations of mainly
macrophages and plasma cells in the medulla.
Junqueira,
Basic
Histol, 11
ed
Lymph node functions
• Production and maintenance of T and B cells, and
storage of memory cells (especially Th cells).
• Accumulation of antigens delivered to lymph nodes
to be recognized by T cells, inside and at the surface
of APCs; thus initiation of an immune response.
• Lymph filtration, phagocytosis of lymph components:
microorganisms, neoplastic cells, cell rests.
• Site of lymphocytes recirculation: blood → lymph
node → lymph → blood due to the presence of HEVs.
Main components of the spleen: capsule with its trabeculae,
accumulation of lymphocytes (‘white pulp’), and ‘red pulp’:
reticular tissue filled up with blood corpuscules.
Junqueira, Basic Histol, 11 ed
Spleen
White pulp of the spleen = many
lymphocytes around central
artery in lymphoid nodule +
PALS = periarterial lymphatic
sheath (layer rich in T cells, T-
dependent zone)
Red pulp of the spleen - contains many
reticular cells, red blood cells, macrophages,
lymphocytes and platelets.
Old erythrocytes express a carbohydrate
marker, which macrophages recognize, bind
and then phagocytose old RBCs.
Spleen is the major site of the destruction of
old platelets.
Blood flow in the spleen
Spleen a. → trabecular a. → central
artery (white pulp a.) encircled by
PALS = periarterial lymphatic sheath
made of T cells
→ penicillar arterioles
pulp arterioles,
→ macrophage sheathed arterioles,
→ terminal arterial capillaries
→ SINUSOIDS →
→ pulp veins
→ trabecular veins
→ spleen vein
Pawlina, Histology. Text&Atlas, 2020
SEM: spleen sinusoid, M, macrophages in the red pulp.
Spleen’s red pulp sinusoidshave various diameter and
‘leaky’ walls
Junqueira, Basic Histol, 11 ed
Blood flow in the spleen. Junqueira's Basic Histology, 14e, 2016
Marginal zone of spleen’s lymphoid nodule
• It is a sinusoidal region between the and white pulp,
located at periphery of lymph nodules and PALS
• Receives blood from capillary loops derived from the
central artery and thus is the first site where blood
contacts the splenic parenchyma
• Is richly supplied by avidly phagocytic macrophages
and other APCs (dendritic cells, B lymphocytes)
• It is the region where circulating T and B lymphocytes
enter the spleen before becoming segregated to their
specific locations within organ.
Functions of the spleen
Immunological defense:
- Phagocytosis of antigens and their presentation by
APCs
- Production of antibodies by B-cells (plasma cells)
- Destruction of old erythrocytes
- Destruction of old platelets
- Storage of ferritin (protein that binds iron)
People can live after splenectomy performed after
capsule’s rupture (car crash) or in some hematologic
diseases
Comparisons of the Major Lymphatic Organs
Pawlina, Histology. Text&Atlas, 2020
Kierszenbaum, 3rd ed.