Helper T cells: co-ordinating the immune response
While cytotoxic T cells are assassins, taking out infected or cancerous cells, T helper cells mainly tell other immune cells what to do. If T helper cells had egos they’d probably be offended by the ‘helper’ tag: they’ve also been called Conductors or Generals of the immune system, ensuring that we respond appropriately to each danger and don’t waste energy or risk self-harm by excess inflammation.
The critical role of T helper cells is shown by HIV/AIDS: HIV infects T helper cells and as the illness progresses the level of T helper cells falls, leading to AIDS, Acquired Immune Deficiency Syndrome, where patients sucumb to all kinds of opportunistic infecitons - which is primarily caused by a lack of T helper cells.
The two major types of T helper cell are Th1 and Th2, which I’ll feature in this post, more characters to come in a second post.
Th1 helper cells: driving response to acute infections
A Th1 helper cell response targets acute infections, whether viral or intracellular bacteria. Mainly it tackles microbes that have got inside cells, and one of its roles is to activate cytotoxic T cells so they start killing off infected cells. Th1 helper cells also fire up macrophages, making them better at engulfing bacteria, and macrophages are also needed to clear up the debris after cytotoxic T cells have done their job. T helper cells also stimulate B cells, making them produce forms of antibody that mark out viruses and bacteria for further attack.
The primary Th1 cytokine is interferon gamma. The aim of a Th1 response is an aggressive response to wipe out the invader. Inappropriate Th1 activation can lead to autoimmunity.
Th2 helper cells: response to chronic infections, especially worms
A different approach is called for with chronic infections that live outside cells, particularly parasites such as worms that dwarf individual immune cells. I know, most people don’t suffer from worms now but throughout our human history they have been a big threat (just as they are to cats and dogs now, hence the need for 'worming') and our immune system has evolved to defend us from them.
Th2 triggers B cells to produce lots of neutralising antibodies – attempting to ‘gum up’ the offending parasite rather than killd them. These antibodies also attract immune cells called eosinophils and mast cells which attack parasites with toxins and other weapons, swarming over parasites a bit like ants:
Th2 type response: Human Eosinophils Coat a Worm - YouTube
Parasites can be hard to shift, especially worms as they are eucaryotic multicellular organisms like us so much more difficult for the immune system to target these without harming our own cells. So Th2 responses often settle for containing an infection, rather than eradicating it. This can be a better option than expending too many resources on a war it can't win, or causing too much inflammation and self-harm.
The Th2 system also deals with toxins.
When there Th2 response gets out of hand the result can be allergy, such as asthma.
Th1/Th2 balance
What matters here is that the immune system produces an
appropriate response to the particular threat, eg Th1 for acute viral infections and Th2 for parasitic worms. Sometimes the immune system gets it wrong (see below) and produces too much of one type of response, and some studies suggest that ME/CFS patients T helper cell response leans too far to Th2. That remains to be confirmed.
Th1 or th2?
The type of t helper response is set when a T helper cells is first activated. A brand new T helper cell that emerges from the Thymus is sometimes called 'naive' or Th0 as it hasn't yet been exposed to an antigen. It's activated when a specialist antigen presenting cell such as a macrophage presents antigen to it's T cell receptor (note that as before, T cell receptors each recognise a specific antigen and only respond to that, much like antibodies). This activation happens in lymph organs such as lymph nodes under the arms, when macrophages and other cells seek out T helper cells in response to an infection (though naive T helper cells also head out into the blood looking for action).
Whether that naive Th0 T helper cell develop down the Th1 route or Th2 route depends on cytokines. T helper cells exposed to the cyotkine IL-12 develop into Th1 cells that will target cellular invaders, while those exposed to IL-4 become Th2 cells targeting extracellular invaders.
Although this diagram shows things as a nice clear choice, leading to either Th1 or Th2 cells, the reality - as is often the case with the immune system - is more complex. Th1 and Th2 cells represent extremes, but some cells will be a bit of both.
Leprosy: the wrong Th1/Th2 balance
Leprosy is a good example of the need for the right T helper response. It’s a bacterial infection caused by
Mycobacterium leprae and most people can fight it off fairly easily: their macrophages (scavenging immune cells) hoover up the bacteria and destroy them. In a minority of cases the some bacteria survive inside the macrophages, and this is where the Th1/Th2 balance comes in. With a more aggressive Th1 response the bacteria are largely contained, though they can spread slowly, resulting in some skin and nerve damage over a long period of time.
But for some reason, some patients mount more of a Th2 response, which isn’t appropriate for an intracellular parasite and allows the bacteria to spread more readily, destroying skin, bone, cartilage and nerves: this is leprosy.
To come: other types of T helper cells with critical roles – aggressive Th17 cells and chillin’ T regs