THYMUS AND SPLEENMohammad Mufarreh

Figure 20.10

Lymphoid Organs

Designed to gather, destroy infectious

microorganisms

Thymus Gland

The Thymus Gland:The Heart Of The Immune System

Anterior view of chest showing location and size of adult thymus

Anatomy

Thymus Structure

• The thymus is a primary lymphoid organ where T lymphocytes develop and undergo maturation.

• It consists of two lateral lobes, situated partly in the thorax above the heart, partly in the neck.

• Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of areolar connective tissue called trabeculae.

Thymus Structure

Haematoxylin and eosin 1 - lobules 2 - interlobular connective tissue 3- cortex 4 - medulla

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Thymus Structure

Each follicle is organized into two compartments:

• The cortex, is densely packed with immature T cells, called thymocytes .

• The medulla where there are fewer lymphoid cells (thymocytes).

• It also contains nest-like bodies, concentric corpuscles of Hassall.

Thymus structureCells

• Stromal-cell network composed of epithelial cells, dendritic cells, and macrophages.

• They make up the framework of the organ

and contribute to the growth and maturation of thymocytes.

• Many of these stromal cells (e.g. Nurse Cells, cTEC, mTEC) interact physically with the developing thymocytes.

Involution

• The thymus continues to grow between birth and puberty and then begins to atrophy; this thymic involution is directed by the high levels of circulating sex hormones.

Age Mass

birth about 15 grams;

puberty about 35 grams

twenty-five years 25 grams

sixty years less than 15 grams

seventy years as low as 5 grams

Function

• Development and maturation of T lymphocytes.

• Education of developing thymocytes by positive and negative selection.o Generation of MHC restriction (positive selection).o Induction of central tolerance (negative selection).

• Generation of diversity of TCR and immunological repertoire.

T Cell Development

T Cell Development

T Cell Development

Color Atlas of Immunology

Journey Through the ThymusNat. Imm. Rev.

Thymic Education

• The thymus induces the death of those T cells that cannot recognize antigen-MHC complexes and those that react with self-antigen– MHC and pose a danger of causing autoimmune disease.

• More than 95% of all thymocytes die by apoptosis in the thymus without ever reaching maturity.

Thymus and DiseaseThymectomy

• Thymectomized neonate mice show a dramatic decrease in circulating lymphocytes of the T-cell lineage and an absence of cell-mediated immunity.

• DiGeorge Syndrome characterized by congenital thymic aplasia, or congenital deficiency of a thymus.

• There is an absence of circulating T cells and of cell-mediated immunity and an increase in susceptibility to infectious diseases.

Thymus and Disease

• Severe combined immunodeficiency syndromes (SCID).

• Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) caused by mutations in the Autoimmune Regulator (AIRE) gene.

• Myasthenia gravis.• Thymomas and Lymphomas.• HIV/AIDS.

Thymus Paradox

• Surgical removal or involution of the thymus does not result in T cell immunodeficiency !!!!!!!!!!!!!!???

• Sufficient T cells are generated during fetal life that are long-lived and can perform homeostatic proliferation throughout the lifetime of the patient.

• Secondary thymi.

• Extra-thymic development of T-cells.

SPLEENThe Belly of The BeastA living Hell for intruders

Spleen•The spleen plays a major role in mounting immune responses to antigens in the blood stream.

•It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity.

•While lymph nodes are specialized for trapping antigen from local tissues, the spleen specializes in filtering blood and trapping blood-borne antigens; thus, it can respond to systemic infections.

Spleen

The red pulp (RP) is composed of open sinusoids containing blood. The white pulp (WP) contains lymphocytes. (White?)

Spleen

Spleen

Spleen

• red pulp: consists of a network of sinusoids populated by macrophages and numerous red blood cells (erythrocytes) and few lymphocytes;

• it is the site where old and defective red blood cells are destroyed and removed.

• white pulp: surrounds the branches of the splenic artery, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes.

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