2. Lymphoid System Basics
• The immune system
• Cells, tissues and organs that function to
protect body from invasion and damage by
foreign cells, microbes, viruses and parasites
• The immune system is able to:
– differentiate between self (own) and non-self
(foreign & modified self) structures – specificity
– respond: immune response fights against
pathogens
– remeber antigens over long periods of time
3. Lymphoid System Basics
• Cells of the immune system:
– Lymphocytes
•T
•B
• NK
– Antigen presenting cells (APC):
dendritic cells, macrophages, B
lymphocytes
– Other: neutrophils
4. Lymphoid System Basics
• The lymphoid tissue consists of:
– numerous immune system cells
(lymphocytes, APC)
– stroma: reticular cells + reticulin fibres
– reticular cells: cell body with oval
euchromatic nucleus; long, thin processes
that contact eachother (desmosomes)
5. Lymphoid System Basics
• Two main tissue architecture types:
– Diffuse: uniform appearance
– Follicular: consists of lymphoid follicles
• Two types of lymphoid tissues:
– Encapsulated: connective tissue capsule
• spleen, thymus, lymph nodes
– Unencapsulated (or partly encapsulated)
• tonsils, Peyer’s patches, lymphoid
nodules in GI tract, respiratory tract,
urinary & reproductive tracts
6. 2 Types of Lymphoid Organs
• Central (primary) lymphoid organ: where
lymphoid precursor cells undergo antigen
independent proliferation and differentiation
– T cells in thymus
– B cells in bone marrow
• Peripheral (secondary) lymphoid organ:
where functional lymphocytes go including
lymph nodes, spleen, Peyer’s patches,
lymphoid nodules of GI and other tracts
7.
8. Peripheral Lymphoid Tissues
• Lymphocytes contact antigens and
divide and differentiate into effector B
cells and T cells
• Memory cells form that circulate for
years to provide extended immunity
9.
10. Lymphocytes
• Small cells
• About 20% of the leukocytes in circulation.
• These are the cells that recognize foreign
antigen - they can distinguish self from nonself. They have surface antigen receptors.
- Recognition of their specific antigen drives
differentiation and proliferation to produce a highly
specific and effective clone
- memory lymphocytes can persist for many years.
This is why vaccination works.
13. T Lymphocytes
T Lymphocytes (T cells)
• A thymus-derived (or processed) lymphocyte.
• ~75% of circulating lymphocytes
• 6-15 mm diameter (red blood cell 7.2 mm
diam.)
• Small T lymphocytes – scanty cytoplasm
• Large activated lymphocytes – more cytoplasm,
azurophilic granules
• 2 main subdivisions based on the expression of
specific surface markers.
• CD8 - cytotoxic T cells
• CD4 - helper T cells
14. T Lymphocytes
all express the T-cell antigen receptor (TCR)
(alpha/beta TCR)
Helper T cell express CD4; these cells typically induce
and coordinate the responses of the Cytotoxic T cell and
other cells of the adaptive immune response - cytokine
factories
Cytotoxic T cells express CD8; these cells kill their
targets – virus-infected, tumour and foreign cells.
Lymphocytes recognize their specific antigens in
association with major histocompatability antigens.
Helper T cells (CD4+) recognize antigen that is
presented in association with MHC class II
Cytotoxic T cells see antigen presented via MHC
class I
15. MHC Class I
&
Class II
Peptide Binding Groove
α2
α1
β2
α1
α3
b2-microglobulin
β2
α2
16. B Lymphocytes
B Lymphocytes
• defined by expression of surface
immunoglobulin - this acts as an antigenspecific receptor for the B lymphocyte (IgM and
IgD).
• ~5-15% of the circulating lymphoid pool.
• Express MHC class II molecules which are
important for presenting antigen to T cells.
• The main function of B cells is the production of
antigen-specific antibody (immunoglobulin).
• Once activated B cells terminally differentiate
into plasma cells.
20. Dendritic cells
• Interdigitating Dendritic Cells
• Follicular Dendritic Cells
• Germinal Center Dendritic Cell
• Langerhans’cell
•Located in peripheral tissues or
lymphoid tissues
•They can be activated in
inflammatory conditions
•Have the ability to uptake, process
and present antigens to T cells.
They are “professional” APC
21. Thymus 1
• Central lymphoid organ, with double
embryonuc origin: epithelial and
mesenchymal
• Thin capsule, lobular organization
• Each lobule has cortex (greater cell
density) with many T lymphocytes
surrounding lighter-stained medulla
• Epithelial reticular cells w/ large
euchromatic nucleus
• Hassal’s corpuscles (flattened epithelial
reticular cells)
24. Thymus
• Cortex: many lymphocytes,
macrophages, epithelial reticular cells
• Medulla: more epithelial reticular cells
and fewer lymphocytes
– mature T lymphocytes leave from here to
go to spleen and lymph nodes
– Hassal’s corpuscles: concentric layers of
epithelial reticular cells, core degenerated;
function/significance unknown
• After puberty thymus undergoes
involution and increases in connective
tissue and adipocytes
25. Thymus
• Thymocytes - precursor lymphocytes from the bone
marrow which enter the thymus via blood vessels.
• Thymocytes proliferate and mature in the thymus but
only 1-3% survive the selection process that allows
mature T cells to enter the peripheral circulation.
• In this tissue, specialized APCs scan for T cells that
may self-react; these cells are killed so as to prevent
autoimmunity (negative selection).
• Progenitor T cells (thymocytes) that recognize MHC
class I molecules but not self antigen are positively
selected for development
• This is where the entire repertoire of antigen-specific
T cells is generated (the variety of TCRs is created
here)
27. Blood-thymus barrier
•Blood supply and blood-thymic barrier - nonfenestrated
endothelium, thick basal lamina and reticular cell sheath form
the barrier found in the cortex separating proliferating
thymocytes from the blood.
28. Thymus
• Major functions
– supports the proliferation and programming
of T lymphocytes.
– It also secretes the hormone thymosin and
thymopoietin that promotes the function
and maintainence of T lymphocytes in
particular.
29. Lymphoid Follicles
• Nodules of densely packed
lymphocytes located in all peripheral
lymphoid tissues. Most lymphocytes are
B cells.
• Two distinct areas
– Mantle – darker stained, mainly small,
resting lymphocytes
– Germinal center (defines “secondary” or
“reactive” lymphoid follicles): lighter
stained, larger, activated B cells –
centroblasts and centrocytes (latter with
cleaved nuclei)
30. Lymph follicle:
-Mantle = cap (dark)
-Germinal center (light)
-centroblasts
-centrocytes (cleaved
nucleus)
33. Lymph Nodes
• Throughout body, along lymph vessels
• Numerous in axilla, groin, cervical area
and thoracic/abdominal mesenteries
• Filter lymph before it returns to
vasculature
• Hilum, concave side, arteries, nerves
enter; veins and efferent lymph vessels
leave the organ
• Afferent lymph vessels enter convex
surface
37. Lymph Nodes
• Cortex:
– several primary and secondary (have
germinal centers) lymphoid follicles
– HEPV – high endothelium postcapillary
venules: specific adhesion molecules that
select lymphocytes that will enter the organ
• Paracortical (deep cortical)
– diffuse lymphoid tissue with many T cells;
• Medula
– cell chords (lymphocytes, plasma cells)
– sinuses which join to form efferent vessels
42. Spleen
• Largest lymphatic organ
• Many macrophages; rbc phagocytosis
• Thick capsule of dense irregular connective tissue w/
trabeculae dividing pulp incompletely
• White pulp with lymphoid tissue
• Red pulp found between sinusoids has cell chords
(Billroth’s chords) with mainly macrophages, reticular
fibers and reticular epithelial cells
• Marginal zone - forms border between the red and
white pulp. where lymphocytes leave blood to enter
white pulp, and rbc’s and plasma cells to enter red
pulp.
43.
44. White Pulp
• Central arteries with encircling lymphoid
tissue
• Periarterial lymphatic sheaths (PALS)
around small arteries, mainly T cells
• Lymphoid follicles comprise mostly B
cells
• Reticular epithelial cells & macrophages
45. Red Pulp
• Reticular cells with cords of cells
between sinuses
• Cords have macrophages, monocytes,
lymphocytes, plasma cells, rbc,
granulocytes
• Sinuses have irregular lumen,
incomplete endothelium and basal
lamina
49. Splenic circulation
• Arterial supply - from the splenic artery it branches
into several trabecular arteries that enter the hilum
of the spleen. These branch to enter the
parenchyma of the spleen as central arteries. The
central arteries branch into marginal sinuses, then
continues into the red pulp where it branches into
several penicillar arterioles
– Open circulation model – pa open into medullary
sinuses
– Closed circulation model - blood cells leave
sinuses then reenter but is described as a
continuous vascular channel
50. Functions of Spleen
Functions
• Filtration of blood - removal of antigenic material
and cellular debris by macrophages and dendritic
cells, concentrated and presented to lymphocytes in
the white pulp.
• Lymphocyte activation - both T and B lymphocytes
are activated in the spleen. Plasma cells migrate from
the white pulp into the red where they secrete Igs into
the venous blood.
• Destruction of old/damaged RBCs - phagocytosed
by macrophages and the hemglobin is broken down.
52. Tonsils
• Incompletely encapsulated lymphoid nodules
• Palatine: covered by stratified squamous
nonkeratinized epithelium; crypts; underlying
connective tissue barrier
• Pharyngeal: covered by ciliated
pseudostratified epithelium, no crypts
• Lingual: smaller, at base of tongue; covered by
stratified squamous nonkeratinized epithelium;
one crypt in each nodule
