Histology Lymphoid System

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immune system fakultas kedokteran universitas warmadewa

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, Peyers 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, Peyers 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 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.

T Lymphocyte

B Lymphocyte

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

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

Peptide Binding Groove

2 3

2 2

1 2

b2-microglobulin

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.

Cel. T

LGL

Small T lymph

Large Granular Lymph - LGL

B lymphocyte

Centrocyte

Plasma cell

Antigen presenting cells

Dendritic cell

Macrophage

B lymphocyte

Dendritic cells
Interdigitating Dendritic Cells
Follicular Dendritic Cells Germinal Center Dendritic Cell

Langerhanscell
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 Hassals 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 Hassals 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 cortical thymocytes apoptotic thymocytes outer cortical

macrophages
septum reticuloepithelial cells dendritic interdigitated cells Hassall corpuscules medular epithelilal cells

deep cortical cortico-medular junction

medular region

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 stain

Cortex of lymph node with lymphoid nodule

Lymph node medulla

Lymph node medulla with sinusoid 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 (Billroths 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 rbcs 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 and white 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 Peyers 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 tonsil

Pharyngeal tonsil

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

Lymphocyte circulation