Immune System

Auteur: Gepubliceerd op: 

The Innate Immune System

This is the first line of defense, let’s exemplify that. Imagine a battlefield: the enemies must first come in contact with for example a castle, they have to wreck the walls and all the barriers that protect the more intelligent species, which are the warriors, the army etc. Just like in the battlefield, in the microcosm, various microorganisms are exposed to mucosal membranes, the skin, hair etc. This is important because pathogens which are not capable of passing the basal membrane of tissues and cause a systemic infection (spread throughout the body), only cause local inflammation which is most of the time easy to manage. Otherwise, every infection could initially be systemic. Thus, this is the “passive” part of the Innate Immune System. Apart from that, several residing (host) cells facilitate the eradication of the pathogens and they are the “active” part of the Innate Immune System. As the archers on the top of the castle, these cells have immediate actions (against the invaders) which are not very specific and they have a terrible memory. These cells are namely: dendritic cells (DCs), macrophages, natural killer (NK) cells, granulocytes (basophils, eosinophils, neutrophils) and mast cells. The general function of the cells mentioned above is to present parts of the microorganisms invading the tissues to the cells of the adaptive immune system. In particular, eosinophils and mast cells are recruited against worms (helminths), whereas DCs and macrophages are phagocytic cells and thus they are the major antigen presenting cells (APCs) that initiate the adaptive immune response. The phagocytic cells are either infected by microbes (that evade phagocytosis) or “digest” microorganisms with the process of endocytosis. If it is for the APCs mentioned above, then they express two (both) cell surface proteins called “major histocompatibility complex” (MHC) - MHC class I & II. MHC class I is present on (nearly) all cells’ surfaces and it is vital for the recognition of the various cells as “normal - not affected”. Ogy0Gpecx9Riuv0TEy8TvjU_cdp-QnXsy-H8pB5_5Fwq-1f6_OS2iWZOYljAzCC69jletu52rgny4LErpiP5vsma7n53EgO1NykP3CDvJlIvM6g9NUyaeg0p4hvc9ZesDNB8kU0

As you can see in the picture, viruses or microbes that invade the cell are then “chopped” in proteasomes in order to make little antigens (antigenic peptides), which will then be transferred in the endoplasmic reticulum (ER) through the molecules TAP1/2. Then they will bind to MHC class I molecule (residing in the ER) and the complex MHC class I - antigen will be presented on the cell’s surface. The goal is that CD8+ Cytotoxic T Lymphocytes (CTL) (will be explained later) become activated and kill the infected cell, in order for the infectious agent not to be spread. On the other hand, what happens with APCs (only) when they digest a microbe is that an endosome is formed (e.g. containing the pathogen which will be broken down inside the endosome to form little antigens). Then the MHC class II residing in the ER gets activated and leaves the ER with the “CLIP”  sealing the molecule still bound to it (in a vesicle). Then the two vesicles fuse and the antigen takes the place of the CLIP. In the end, the complex MHC class II - Antigen will be exposed to the phagocytic cell’s surface, and this will lead to CD4+ Helper T Lymphocyte activation (explained later). This is also a point where the innate immune system activates the adaptive response. 


The Adaptive Immune System

This is a secondary response that can be perceived as the spies during the Cold War. The cells comprising this “surveillance” system are very slow-acting, have a substantial effect and an excellent memory. It can be generally categorized in two major categories determined by the cells involved in the responses, but both parts contain lymphocytes. The first category is called “humoral immunity”, and it involves only B lymphocytes. B lymphocytes, in particular plasma cells, secrete antibodies that are very precise and specific and recognize a great variety of antigens. This becomes possible through a very difficult to understand recombination procedure, the outcome of which is that the total repertoire of all possible antibodies produced is 10^11. What I would like to highlight is that the recombination process happens on the DNA level and due to that mature B lymphocytes have less DNA than normal. In addition , seeing as we get two genes for most traits, one from the mother and one from the father, this is also the case for the genes recombined for antibody production. However, we only want one active gene so that we have “monospecificity”. The process by which one allele becomes inactive so that specific antibodies are produced against one antigen is called “allelic exclusion”. The idea is that an antigen binds either on the antibody expressed on the cell’s surface or on free antibodies excreted by plasma cells. If the antigen binds on the antibody of the surface of a B cell, then B cells bind with specific receptors with CD4+ helper T cells that permit these B cells to replicate and produce “clones”  that produce antibodies against this antigen. On the other hand, the second category is called “cell-mediated immunity” and it involves T lymphocytes. CD4+ Helper T cells bind with MHC class II receptors (on APCs) and thus get activated to secrete cytokines and further promote the adaptive immune responses. CD8+ CTLs bind with MHC class I molecules and subsequently kill the infected cell. However, T cells also undergo recombination in order to express these two receptors. The differentiation process of the T cells happens in the thymus. At first, T cells are “double negative” and have no T cell receptors (TCRs). Next, they become “double positive” and express both CD4+ & CD8+ receptors. These two steps happen in the cortical area and residing APCs express MHC class II receptors there that are involved in the positive selection of the mature T cells. At last, the T lymphocytes become single positive expressing one of the two TCRs. This step happens in the medulla and residing DCs play a major role in negative selection of T cells. T cells that are “problematic” either die off (through apoptosis) or become Tregs (regulatory T cells) which are important in order to suppress the immune response and maintain homeostasis and self-tolerance (the ability of the immune system to recognize self-produced antigens).mrUTh4YtKeNZxlrzPH5609WsLLnCRn3NWyuW5d7_3qNdQgwwqPmPiKj-0CXbwh6dCuS7MOpEUUxnoXUgBySfg31Yx01H58Yr0nFjcJjPjhsz6YD-c-eVV6UOeu8HMb8o3lmZO6gYnSbPxfbUzodTdNmFgL2WthlsfbmsYYjXmt-rBSCwCBHObM1Lplbr9GWAIVm85yZkH711h-p_fIw1ILdCSrS3HPORkD4V-Z-kkY8OEcouEQVCAXRxq9BjYZfxrraLLdabNOHfsE



To sum up, the immune system is an intricate way of defending ourselves against the kingdom of microbes. There is a lot of interplay parts involved in the activation of the various responses and both the first and second line of responses are generally  correlated. Studying more from Abbas or Mims can really mess up everything in your mind but you have to endure!