Thursday, 24 April 2008

S320: Book 3 - Immunology

OK - now this book is a bit of a struggle. There are an awful lot of molecules and proteins introduced here, and any number of interactions between them. There is also the two disk interactive CD to take in, and all in all there is a lot going on here.

Let me see what I can remember. Well first there are the leukocytes, which come in all sorts of flavours. There are
  • Macrophages - which attempt to gobble up bacteria and similar agents and kill them with bursts of free radicals.
  • B cells - which were first discovered in the Bursa of chickens, hence B, but happily are manufactured in the bone in humans - so can still be called B cells without anyone getting confused. B cells produce antibodies, when requested to. They start as naive cells, and then go through a selection process where their antibodies are refined and the best survive to become plasma B cells which produce antibodies. Some also go on to become memory B-cells.
  • NK cells - these are natural killer cells, licensed to kill. They inspect cells of the body, and any that are not presenting the right documentation are terminated. This often happens under viral infection when MHC presenting is turned off by the virus in an attempt to avoid Tc cells. They usual kill by triggering the self destruct sequence built into all cells, but they also carry a gun, a protein called perforin which can punch holes in the cells surface and so start it leaking its contents.
  • Basophils - help in the control of inflammation.
  • Neutrophils - mainly used for anti-bacterial defence.
  • Eosinphils - used for defence against parasitic worms.
  • Mast cells - produce histamines and cause inflammation responses.
  • Dendritic cells - look a bit like nerve cells. They consume stuff and present it for inspection using MHC2. They tend to hang around in lymph glands.
  • T cells, of which there are many, and are produced in the Thymus - hence the T.
    • T helper cells, which come in at least two varieties. TH1, TH2. They use MHC1 and CD4 receptors for detection.
    • TH1 cells work in conjunction with macrophages, recognising antigens presented by macrophages, and releasing TNF and IFN╬│ cytokines that activate macrophages (but damp down TH2 activity).
    • TH2 work with B cells, recognising antigens presented on them, and activating them with various interluekin cytokines, and so help to make antibodies. They also prompt B-cells into class switching behaviour.
    • T-memory cells, which help in the memory of infection and so help ward off subsequent attacks.
    • Tc cells, also know as cytotoxic T cells, which are killers. They sample the MHC presented fragments of proteins presented on the cells surface. If they recognise one of these fragments as foreign, they press the cells self destruct button. They also carry the perforin guns as backup. They use the CD8 and MHC1 together for detection.
So TH1 work with macrophages (cell mediated response), and TH2 with B cells (antigen response). The body will usually use one pathway or the other, and if it chooses TH1, then the interaction between TH1 and macrophages acts to shut down the TH2 and B cell pathway, and vice versa.

There is also a number of antibodies, which can appear in several different forms, such as
  • IgA - produced by B-cells and makes its way across mucosal surfaces to help block infection.
  • IgD, helps activate B cells, but not used much elsewhere.
  • IgE - produced by B cells, they attach to mast cells and basophils. When these then pick up antigen using these antibodies, they release inflammatory cytokines which attract macrophages.
  • IgG - produced by B cells, and found in plasma, and attaches to bacteria to labelled them to be attacked.
  • IgM - expressed by naive B-cells as receptors.
(no - I'm not sure what happened to B,C,F,H etc.)

The main signalling is done via the Major Histocompatible Complex, in two versions, called MHC1, and MHC2. All cells express MHC1, and the MHC1 contains within a groove bits of proteins found in the cell during cleanup. So all cells display what they are currently using, which allows Tc cells to check they are valid. MHC2 is expressed by macrophages, B-cells and dendritic cells, and is used to show bits of proteins that they have ingested recently. So in the case of macrophages, this might be bits of bacteria or viral particles. Its important they don't use MHC1 for this, or else the Tc cells would come round and have (fatal) words with them.

Then there is a profusion of chemicals that are produced by these cells and work with one another. Signalling molecules which include
  • interleukins (ILs) - produced by TH2 cells to kick B cells into action. This also slows down macrophages, so they don't fight too much.
  • interferons (IFNs) - produced as a result of viral infection to signal to other cells they are under attack. Also produced by TH1 cells to kick macrophages into action. This also slows down B cells.
  • colony stimulating factors - that bits a blur
  • chemokines - lots of these
  • tumour necrosis factors - another signalling molecule
Then there is the complement system. This is yet another arm of the immune system, which encourages macrophages to come towards the site of infection, and can also promote its own attack using a membrane attack complex that punches holes in the cell walls.

All in all there is a lot to keep straight, and to keep track of what influences what.

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