Thursday, October 13, 2016

Cells and Organs of the Immune System

Back to blogging about Immunology!

Describe the cells of the immune system and their function

I've already mentioned some of the immune system cells in an earlier post, but I'm going to give a refresher on those cells as well as introduce some others.
  • Granulocytes: so-called because they have granules that can be seen under the microscope. All of these are found in the circulation. There are three main types:
    • Neutrophils: First to arrive on the scene. Phagocytose microbes.
    • Eosinophils: Phagocytose antibody-coated parasites. Also play roles in allergic responses.
    • Basophils: Also play roles in parasite immune responses, allergies and inflammation.
  • Mast cells: Granular cells found in the tissues. There is some debate over whether these are considered to be granulocytes or not. These also have roles in allergies and parasite expulsion.
  • Monocytes and Macrophages: Monocytes exist in the circulation, but once they enter the tissue they can differentiate into macrophages. Both monocytes and macrophages play roles in phagocytosis. They also play roles in antigen presentation (well macrophages do at least, not so sure about monocytes).
  • Dendritic cells: One of the main antigen-presenting cells (i.e. cells that process and present antigen to T-cells, which you'll meet later). In this way, they form a "bridge" between innate and adaptive immunity. They have different subtypes, classified mainly according to where they're found.
    • Langerhans cells: found in epidermis and mucosal membranes
    • Interstitial dendritic cells: found in most organs
    • Interdigitating dendritic cells: found in T-cell areas of secondary lymphoid tissues and in the thymus
    • Circulating dendritic cells: found in the blood and lymph
    • Follicular dendritic cells: found in the B-cell rich follicles. These are a bit different because they do NOT function as an antigen-presenting cell. Instead, they express high levels of complement and Fc receptors, allowing them to bind immune complexes (a fancy name for optimised antigens- I've mentioned optimisation here) and store them, which in turn might help facilitate B-cell activation.
  • Lymphocytes: These come in two main types- B cells and T cells.
    • B-cells: Make antibodies (humoral immunity).
      • Plasma cells: Specialised B-cells that secrete antibodies.
      • Memory cells: Help the body "remember" an antigen.
    • T-cells: Have different subtypes with different functions:
      • Cytotoxic T-cells (CD8): Kill infected cells (cell-mediated immunity).
      • Helper T-cells (CD4): Mediate the immune response.
  • NK cells: Cells of the innate immune system that help to kill stuff.
    • NK T-cells: A subset of NK cells that also have T-cell properties.
  • Platelets: These aren't really whole cells, but rather small fragments of megakaryocytes. They can release inflammatory mediators and are involved in clogging up wounds and releasing stuff that aids in wound repair.
  • Red blood cells: Not sure if these are really part of the immune system, but they're on the slides so I'll include them anyway. These transport oxygen around the body.
All of the cells in the blood are formed during a process called haematopoiesis. The main pluripotent stem cells involved here are called haematopoietic stem cells. They can further differentiate into two main types of progenitors: myeloid and lymphoid. These progenitors can then further differentiate into other types of cells. Lymphoid progenitors tend to differentiate into NK cells, T-cells and B-cells, whereas myeloid progenitors tend to develop into the other types of blood cells. Dendritic cells are a bit of a wildcard because they're thought to be able to develop from either progenitor, and also from monocytes.

Describe the organisation of the lymphoid system

The lymphoid system, just like so many other systems of the body, are made up of organs which are joined by connecting vessels called lymphatics. The lymphatics transport lymph, which is basically derived from the interstitial fluid of tissues. Lymphatics join up until they form the thoracic duct, which dumps its contents into the right brachiocephalic vein, effectively returning everything to the circulation. (More info on lymph vessels here.)

Explain the different roles of the primary and secondary lymphoid tissues

The primary lymphoid organs (bone marrow and thymus) are the main organs involved in the haematopoiesis of immune cells. All blood cells originate in the bone marrow, and the thymus (located in the anterior mediastinum) is where T-cells complete their development. The secondary lymphoid organs, which include lymph nodes, the spleen and mucosa-associated lymphoid tissue (MALT), are mainly involved in trapping antigens that enter the body through various routes. Let's look at some of these organs in more detail!

Lymph nodes

Lymph nodes are mainly involved in trapping local tissue antigen. Their structure looks somewhat like a kidney turned on its side. Incoming (afferent) lymphatics enter the lymph node on one side and outgoing (efferent) lymphatics leave on the other, after being filtered. Blood vessels also run through the lymph node, including high endothelial venules (HEV) which allow naïve lymphocytes to leak out and enter the lymph node.

The inside of the lymph node can be broken down into several compartments. The outer cortex contains follicles, which is pretty much the B-cell zone of the lymph node, but macrophages and follicular dendritic cells hang out there too. Germinal centres, which are regions of intense B-cell activation, also develop within the outer cortex.

Further inside the lymph node is the paracortex. This is the "T-cell zone" of the lymph node, but interdigitating dendritic cells hang out here too.

Even deeper inside is the medulla. This is where plasma cells hang out. (And yes, I recognise that plasma cells are B-cells, and these ones aren't in the B-cell zone. So maybe I lied about the outer cortex being a B-cell zone.)

Spleen

While the lymph nodes filter lymph, the spleen filters blood. Fun fact: in one day more lymphocytes pass through the spleen than all lymph nodes combined.

The spleen has lots of bits and pieces that you need to know about. Trabeculae provide the main structural support of the spleen. Blood is supplied to the spleen via the splenic artery, which splits into arterioles which end in vascular sinusoids. Blood then exits via the splenic vein.

The two main compartments of the spleen are the red pulp and white pulp. They're kinda easy to remember because the red pulp deals with red cells (it removes the old and defective ones) and the white pulp deals with white cells (specifically lymphocytes, which are activated here). The two compartments are separated by the marginal zone, which is where blood-borne microbes and antigen are trapped.

Dendritic cells transport antigen from the marginal zone to another area called the PALS. PALS stands for periarteriolar lymphoid sheath. The PALS surrounds the arteriole and mainly contains T-cells, which become activated when antigen is presented to them.

Just like lymph nodes, the spleen also contains follicles which contain mainly B-cells, as well as macrophages and follicular dendritic cells. The B-cells here are mainly activated in response to signals from T-cells.

Mucosa-Associated Lymphoid Tissue (MALT)

MALT protects the mucosa, as the name suggests. It can be further categorised into BALT (bronchial-associated lymphoid tissue), GALT (gut-associated lymphoid tissue) and so on. MALT actually makes up the bulk of lymphoid tissue.

MALT isn't just one big messy thing covering our epithelial surfaces. It actually does have some degree of organisation, as seen in the Peyer's patches in the ileum. MALT has special cells called M-cells, which deliver antigen to underlying immune cells. One last thing to know about MALT is that it is biased towards IgA production (as opposed to other kinds of antibodies) and has some specialised lymphocytes called mucosal homing receptors.

And that's it for that lecture! Lots of facts to remember...

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