Lymphoreticular system

Introduction

Also known as the reticuloendothelial system or mononuclear phagocytic system. 

• It is second line defense system of the body
• Phylogenetically this system is very primitive, no animal can live with out this system
• This system is very effective in host protection even in the absence of B / T lymphocytes
• Embryological hematopoietic stem cells derive from ventral mesoderm of the yolk sac
• First mononuclear phagocyte appear on 12day of gestation in the liver

It is comprised of primary lymphoid organs (bone marrow, Bursa of Fabricius, the foetal liver and the thymus) which are responsible for the production of lymphocytes, and the secondary lymphoid organs (lymph nodes, spleen and mucosal-associated lymphoid tissue) which function to provide an environment where lymphocytes can react to antigen from the tissue fluid, blood, and mucosal surfaces.

lymphoreticular system if of 2 types

• Lymphoid systemàlymphoid cells lymphoid organs
• Reticular systemà Phagocytic cells with scavenger function

 Lymphoid organs are of 2 types

1. Central(Primary) lymphoid organ (Where lymphocyte proliferate, develops & matures) eg- Thymus
2. Peripheral (secondary) lymphoid organaLymph nodes, spleen, mucosa-associated lymphoid tissue(MALT).

Cells of a Lymphoreticular system (four types)

1. Lymphocyte-  T- lymphocyte and B-lymphocyte.
2. Null cell/ LGL
3. Phagocytic cells Macrophages 
4. Dendritic cells.

• The main functions of the lymphoreticular system are the removal of senescent cells and production of immune cells. The human body contains 10¹² lymphocyte out of which  10⁹ are renewed daily. Mature  B and  T cells before they encounter antigen are called Naive cells.
• Most potent stimulator of Naive T-cells is Mature Dendritic cells→ mature langerhans dendritic cells reach to naive T cells in the lymph nodes and present antigen to these cells and activate them

1) T-lymphocytes

Once formed in the bone marrow, T progenitor cells migrate to the thymus (hence the name “T cell”) to mature and become T cells.

• Thymus-derived lymphocyte, constitutes 60-70%  of peripheral lymphocytes.
• Found in the parcortical area of lymph nodes and  periarteriolar sheaths of the spleen.
• Antigen binds to the TCR T cell receptor which is responsible for signal 1.
• Demonstration of TCR gene  bysouthernblot  analysis  is  a molecular marker of T lineage cell.
• All lymphocyte contain CD-3 molecule  which  are  involved  in  transduction  of signal  1.
• Other  surface  molecules  or co-receptors  include  CD 2, CD 4 or  CD  8,  CD  11a,  CD 28.  Antigen interaction with T lymphocytes precipitates the release of lymphokines, substances that modulate other aspects of the immune response.,  CD 40.
• CD 4 is  expressed  on  50%  of  T cells which help to produce immunoglobulins,  while 30% expressed  CD 8, they are strict aginst virus infected cells
• All T cells express T cell receptors, and either CD4 o  CD8.NOT BOTH.
• Antigen interaction with T lymphocytes precipitates the release of lymphokines, substances that modulate other aspects of the immune response.

Mature T cells should recognize only foreign antigens combined with self-MHC molecules in order to mount an appropriate immune response.

Undergo two selection processes:

1. Positive selection–  ensures MHC restriction by testing the ability to distinguish between self and non-self proteins.
2. Negative selection- tests for self-tolerance. Negative selection tests the binding capabilities of CD4 and CD8 specifically.

2) B-Lymphocytes 

• 10-20% of peripheral lymphocytes
• responsible for humoral immunity
• present in bone marrow, peripheral lymphoid tissue,  e.g. lymph node (superficial cortex), spleen(white pulp), tonsils and extra lymphatic organs e.g- GIT.
• In spleen and Lymph node it forms lymphoid follicles, Unlike T cell, it responds to free Antigen.
• B cell act as Antigen presenting cells. 
• other molecules  are complement  receptor,  Fc receptors,  CD  21 (receptor  of  EBV), 
• CD 40  (essential for interaction of T and  B cell which cause  B cell maturation so a mutation in CD 40 ligand cause immunodeficiency called X-linked hyper-IgM syndrome).
• first Ig class to appear on the B cell surfaces is IgM.

3) Null cell/Large Granular Lymphocyte (LGL) 

• Do not bear TCR or surface Ig and are non-adherent, non-phagocytic,against virus infected cells.
• They together with macrophage form innate immunity in comparison of adaptive immunity by lymphocytes.
• Constitute 5-10% of peripheral lymphocytes
• LGL express: Receptor for Fc portion of IgG (CD-16) which is used for ADCC (antibody dependent cell-mediated cytotoxicity).

They are classified as:

1. ADCC lymphocyte
2. NK cell- two types 1) LAK- lymphokine-activated killer cell  2) NK/T cells-

Antibodies do not induce proliferation of NK cells. NK cells express CD3, CDI6 & CD56 and also but less commonly CD2 & CD8.

4) phagocytic cells

it is of two types

1) mononuclear macrophages of blood and tissue

1. blood macrophages(monocytes) are largest of lymphoid cells
2. tissue macrophages(histiocytes) are microglia in CNS, Kupffer in the liver, Alveolar macrophage in lung, Oestoclast in bone, Sinus histiocyte-spleen, lymph node.
3. the half -life of blood monocyte is about 1day while of tissue.

2) Microphages

• These are polymorphonuclear leucocytes of blood-neutrophil, eosinophils and basophil, they do not have any role in specific immune processes.

Dendritic cells

• These are antigen-presenting cells to T cell during a primary immune response.
• Bone marrow-derived cells of the lineage
• They have little or no phagocytic activity.

these are of three types.

• Interdigitating dendritic- Found in lymph nodes and non lymphoid organs, eg- heart and lung, most potent antigen present is CD4.
• Langerhans cells-process and present antigens which reach the dermis.
• Follicular dendritic cells-Bear Fc receptors for IgG, hence can trap antigen bound.

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