HistologyLymphoid System

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

Lymphoid System Basics

• Cells of the immune system:– Lymphocytes

• T• B• NK

– Antigen presenting cells (APC): dendritic cells, macrophages, B lymphocytes

– Other: neutrophils

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)

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

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

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

Lymphocytes

• Small cells• About 20% of the leukocytes in circulation.• These are the cells that recognize foreign

antigen - they can distinguish self from non-self. 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.

T Lymphocyte

B Lymphocyte

T LymphocytesT 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

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

MHC Class I & Class II

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b2-microglobulin 2

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Peptide Binding Groove

B Lymphocytes

B Lymphocytes

• defined by expression of surface immunoglobulin - this acts as an antigen-specific 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.

Cel. T

LGL

Small T lymph Large Granular Lymph - LGL

B lymphocyte Centrocyte

Plasma cell

Dendritic cell Macrophage

B lymphocyte

Antigen presenting cells

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

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)

Thymus: cortex and medulla

Thymus cortex Thymus medulla

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

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)

Thymic lobule

cortical thymocytes cortical thymocytes

subcapsular region

outer cortical

deep cortical

cortico-medular junction

medular region

cortical thymocytes

apoptotic thymocytes

macrophages

septum

reticuloepithelial cells

dendritic interdigitated cells

Hassall corpuscules

medular epithelilal cells

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.

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.

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)

Lymph follicle:

-Mantle = cap (dark)-Germinal center (light)

-centroblasts-centrocytes (cleaved nucleus)

Lymph follicle:

-Mantle (dark)-Germinal center (light)

-centroblasts-centrocytes (cleaved nucleus)

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

Lymph Nodes

• Capsule of dense irregular connective tissue, with incomplete septa

• Reticular fiber network

• Lymph sinuses: subcapsular -> interfollicular -> medular

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

Lymph node Lymphatic vessel, lymph node

Lymph node reticular stainCortex of lymph node withlymphoid nodule

Lymph node medulla Lymph node medulla withsinusoid and medullary cords

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.

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

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

Spleen sinus - ME

Spleen with red pulp andwhite pulp

Spleen red pulp

Spleen white pulp with surrounding red pulp

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

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.

Unencapsulated or Incompletely Encapsulated Lymphoid Tissue

• Lymphoid nodules

• Tonsils: palatine, pharyngeal, lingual

• Peyer’s patches

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

Palatine tonsilPharyngeal tonsil

Peyer’s Patches

• Lymphoid nodules in the lamina propria of the ileum (covered in detail in the digestive tract section)

Lymphocyte circulation