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Histology

Lymphoid System

blokimmune system

fakultas kedokteran

universitas warmadewa


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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) structuresspecificity

respond: immune responsefights against

pathogens

remeberantigens over long periods of time


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Cells of the immune system:

Lymphocytes

T

B

NK

Antigen presenting cells (APC):

dendritic cells, macrophages, B

lymphocytes

Other: neutrophils


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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)


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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


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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


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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


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Lymphocytes

Small cells

About 20% of the leukocytes in circulation.

These are the cells that recognize foreignantigen - they can distinguish self from non-self. They have surface antigen receptors.- Recognition of their specific antigen drives

differentiation and proliferation to produce a highlyspecific and effective clone

- memory lymphocytes can persist for many years.This is why vaccination works.


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T Lymphocyte


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B Lymphocyte


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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 lymphocytesscanty cytoplasm

Large activated lymphocytesmore cytoplasm,

azurophilic granules 2 main subdivisions based on the expression of

specific surface markers.

CD8 - cytotoxic T cells

CD4 - helper T cells


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T Lymphocytes

all express the T-cell antigen receptor (TCR)

(alpha/beta TCR)

Helper Tcell 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 Tcells express CD8; these cells kill their

targetsvirus-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


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MHC Class I & Class II

33

12

b2-microglobulin 2

2

2

1

Peptide Binding Groove


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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.


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Cel. T

LGL

Small T lymph Large Granular Lymph - LGL


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B lymphocyte Centrocyte

Plasma cell


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Dendritic cell Macrophage B lymphocyte

Antigen presenting cells


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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


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Thymus 1

Central lymphoid organ, with doubleembryonuc origin: epithelial andmesenchymal

Thin capsule, lobular organization Each lobule has cortex (greater cell

density) with many T lymphocytessurrounding lighter-stained medulla

Epithelial reticular cells w/ largeeuchromatic nucleus

Hassals corpuscles (flattened epithelial

reticular cells)


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Thymus: cortex and medulla


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Thymus cortex Thymus medulla

Th


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Thymus

Cortex: many lymphocytes,

macrophages, epithelial reticular cells Medulla: more epithelial reticular cells

and fewer lymphocytes

mature T lymphocytes leave from here togo 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

Th


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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 allowsmature 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 preventautoimmunity (negativeselection).

Progenitor T cells (thymocytes) that recognize MHCclass I molecules but not self antigen are positively

selected for development This is where the entire repertoire of antigen-specificT cells is generated (the variety of TCRs is createdhere)


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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

Bl d th b i


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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 proliferatingthymocytes from the blood.

Th


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Thymus

Major functions

supports the proliferation and programming

of T lymphocytes.

It also secretes the hormone thymosin and

thymopoietinthat promotes the functionand maintainence of T lymphocytes in

particular.


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Lymphoid Follicles Nodules of densely packed lymphocytes

located in all peripheral lymphoidtissues. Most lymphocytes are B cells.

Two distinct areas

Mantledarker 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)


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Lymph follicle:

-Mantle = cap (dark)

-Germinal center (light)

-centroblasts

-centrocytes (cleaved

nucleus)


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Lymph follicle:

-Mantle (dark)

-Germinal center (light)

-centroblasts

-centrocytes (cleaved nucleus)


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Lymph Nodes


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Lymph Nodes

Throughout body, along lymph vessels

Numerous in axilla, groin, cervical areaand 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


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Lymph Nodes

Capsule of dense irregular connective

tissue, with incomplete septa

Reticular fiber network

Lymph sinuses: subcapsular ->

interfollicular -> medular


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Lymph Nodes

Cortex:

several primary and secondary (have

germinal centers) lymphoid follicles

HEPVhigh endothelium postcapillary

venules: specific adhesion molecules thatselect 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


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Lymph node Lymphatic vessel, lymph

node


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Lymph node reticular stain

Cortex of lymph node with

lymphoid nodule


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Lymph node medullaLymph node medulla with

sinusoid and medullary cords


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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 pulpfound between sinusoids has cell chords(Billroths chords) with mainly macrophages, reticularfibers and reticular epithelial cells

Marginal zone- forms border between the red and

white pulp. where lymphocytes leave blood to enterwhite pulp, and rbcs and plasma cells to enter redpulp.


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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


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Red Pulp

Reticular cells with cords of cellsbetween sinuses

Cords have macrophages, monocytes,

lymphocytes, plasma cells, rbc,granulocytes

Sinuses have irregular lumen,

incomplete endothelium and basallamina


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Spleen with red pulp and

white pulp

Spleen red pulp


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Spleen white pulp with

surrounding red pulp

S l i i l ti


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Splenic circulation

Arterial supply - from the splenic arteryit branchesinto several trabecular arteriesthat 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, thencontinues into the red pulp where it branches into

several penicillar arterioles

Open circulation modelpa open into medullary

sinuses

Closed circulation model - blood cells leave

sinuses then reenter but is described as a

continuous vascular channel


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Functions of Spleen

Functions

Filtration of blood- removal of antigenic materialand cellular debris by macrophages and dendriticcells, concentrated and presented to lymphocytes in

the white pulp.

Lymphocyte activation- both T and B lymphocytesare activated in the spleen. Plasma cells migrate fromthe white pulp into the red where they secrete Igs into

the venous blood.

Destruction of old/damaged RBCs- phagocytosedby macrophages and the hemglobin is broken down.


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Unencapsulated or Incompletely

Encapsulated Lymphoid Tissue

Lymphoid nodules

Tonsils: palatine, pharyngeal, lingual Peyers patches

Tonsils


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Tonsils

Incompletely encapsulated lymphoid nodules

Palatine: covered by stratified squamousnonkeratinized epithelium; crypts; underlying

connective tissue barrier

Pharyngeal: covered by ciliatedpseudostratified epithelium, no crypts

Lingual: smaller, at base of tongue; covered by

stratified squamous nonkeratinized epithelium;one crypt in each nodule


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Palatine tonsilPharyngeal tonsil


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Peyers Patches

Lymphoid nodules in the lamina propria

of the ileum (covered in detail in the

digestive tract section)


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L h t i l ti


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Lymphocyte circulation

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