Lymphatic Organs: Immune System Overview

• Here are the study notes about the lymphatic organs

General Information About the Immune System

• The immune system consists of organs and cells.
• Organs and cells work to protect the body against aggressors of all kinds.
• There are two types of cells, cells of innate immunity and cells of adaptive immunity.
• Cells must recognize and tolerate self and recognize and reject non-self.
• Adaptive immunity cells are produced by lymphoid organs (OL).

Types of Lymphoid Organs

• Primary (central) lymphoid organs or OL I

• Secondary (peripheral) lymphoid organs or OL II

• OL I: Bone Marrow (MO) and Thymus

• OL II: Spleen, Lymph nodes and MALT

Central (Primary) Lymphoid Organs

• Appear early in embryonic life before secondary lymphoid organs
• Located outside antigen penetration routes
• Site of maturation and differentiation of immunocompetent cells (LT & LB)
• In OL I, LT and LB differentiate and become functional.
• In mammals, LT develops in the thymus, and LB develops in the bone marrow
• LT & LB acquire the antigen recognition repertoire in OL I

Bone Marrow

• Spongy bone is the site of hematopoiesis
• Bone marrow occupies the free space in flat bones, ribs and sternum, vertebrae, pelvis, skull and in the epiphyses of long bones
• There are two types of bone marrow: yellow and red
• Yellow bone marrow contains fat cells and is inactive
• Red marrow is active and is the site of hematopoiesis and B lymphopoiesis.
• Lymphopoiesis B happens in bone trabeculae which happens from the endosteum to central vein sinus

Thymus

• Bilobed organ located in the thorax above the aortic bifurcation
• Each lobe is subdivided into lobules
• Each lobule consists of an outer cortex and an inner medulla
• It is a lymphoepithelial organ
• Epithelial cells = Thymic epithelial cells (TEC)
• Thymus lymphocytes are called thymocytes
• Thymic epithelial cells (TEC) nourish cells are under the capsule.
• TECs engulf or internalize thymocytes
• TECs secrete thymic hormones
• Cortical TECs express MHC I & MHC II molecules and involved in the education of Thymocytes
• Medullary TECs are involved in the education of Thymocytes.
• Dendritic cells of the cortico-medullary junction are involved in the generation of the T repertoire
• Macrophages of the cortico-medullary junction are involved in the elimination of deleted T clones
• Corpuscles of Hassall in the thymic medulla have an unknown function
• In the thymus, LT differentiation occurs from the direction of cortex → medulla
• Thymus develops from the 3rd and 4th pharyngeal pouches which also give rise to the parathyroids.
• The absence of development of these pouches is the cause of Digeorge syndrome.
• The cortex contains numerous immature thymocytes (95%) on a framework of specialized epithelial cells called nourishing cells << nurse cells ->> secreting thymic hormones and cytokines.
• The medulla is sparsely populated, containing thymocytes (5%) more mature, which are in contact with Hassal's corpuscles, dendritic cells and macrophages.
• Thymocytes go through different stages of maturation, double negatives, double positives, and positive selections
• Double positive cells go to positive selections
• Each single positive thmocyte goes through negative selection
• Thymocytes becomes a mature T lymphocyte that leaves the thymus via blood
• Finally migrates to the OL II
• The thymus undergoes involution from puberty onwards without disappearing completely.

Peripheral (Secondary) Lymphoid Organs

• Develop later than OL I
• Filled with LT, LB, and APCs.
• Located on the routes of antigen penetration
• Site of the immune response
• Examples include the spleen, lymph nodes and mucosa-associated lymphoid tissue (MALT).
• Lymph nodes ensure the surveillance of many territories.
• They are small kidney-shaped organs, measuring 1 to 15 mm in diameter and arranged along the lymphatic pathways
• They drain the lymphatic circulation, which is oriented in one direction, from tissues → lymph nodes → blood.

Lymph Node Structures

• Afferent Lymphatic Vessel and Efferent Lymphatic Vessel

• HEV: High Endothelial Venule

• Paracortex Zone T

• Cortex Zone B: Secondary follicle and Primary Follicle

• Medulla

• The different histological zones at the lymph node level can be involved during a RI according to the attacking Ag.

• In the case of an Ag inducing a cellular RI, the paracortex is the site of LT activation, it hypertrophies.

• In the case of an Ag T-independent ➔ the cortex is the site of LB activation, it hypertrophies.

• In the case of a T-dependent Ag -> the paracortex and cortex are involved, they hypertrophy, and there will be formation of a follicle.

Spleen

• Located in the left hypochondrium
• Largest encapsulated lymphoid organ
• Does have lymphatic circulation
• Directly connected to the bloodstream
• Functions as a filter for blood circulation, allowing purification of blood at 100 to 200 ml/min.
• Captures Ag injected into the circulation

Spleen Structures

• Red pulp destroys senescent erythrocytes (+ + +) → Graveyard of GR
• White pulp is lymphoid tissue in the form of a periarteriolar sheath or PALS (around a central artery)
• The PALS includes an zone around the artery that's T-dependent
• B-dependent zone which organized into follicles I and II
• Marginal zone located at the border between red and white pulp

Mucosa-Associated Lymphoid Tissue (MALT)

• Includes aggregates of lymphoid cells located under the epithelia of the skin and gastrointestinal and respiratory tracts
• Pharyngeal tonsils and Peyer's patches of the intestine are two lymphoid formations annexed to the mucous membranes
• Examples include GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus-Associated Lymphoid Tissue) and NALT (Nasopharynx Associated Lymphoid Tissue).
• MALT covers an area of 400 m² of mucous membranes.
• This implies a high number of lymphocytes
• MALT faces diverse antigenic stimulations characterized by the production of secretory IgA +++ (capable of crossing the mucous membranes and thus ensuring their protection).
• System is linked to the environment and capable of adapting permanently
• GALT shares plaques, nodules, and ganglions called the inductive compartment.
• The lamina propriety shares epithilium and is the inductive compartment as well.

Circulation of Lymphocytes

• Mature LT (naïve) leave the thymus through the blood

• They penetrate the ganglion through the blood

• They cross the high endothelium of the blood vessels (HEV)

• The interaction involves leukocyte adhesion molecules

• LT localizes on the T-dependent areas which guided by leukocyte adhesion molecules.

• Naive LT circulate from one organ to another through the lymphatic route

• TE effectors leave the OL II through the blood and return to the peripheral tissues through the blood

• Lymphocyte localization in privileged territories is dependent on the type of adhesion molecules used is called homing.