Explainer: how does the immune system work?

Explainer: how does the immune system work?

Our immune system - we take it for granted until it begins to fail us. Unfortunately, with a diagnosis of CLL, we immediately become lifetime members of a vulnerable group of immune compromised patients, forgotten/ignored or at the very least, poorly understood by society. We learn that we can't have live vaccines and that other vaccines don't work that well for us (but we should have the vaccinations anyway, because surviving the actual disease may no longer be a minor matter).

In this article, Steven Maltby, Post-doctoral Fellow in Immunology & Genetics and Vicki Maltby, Post-doctoral fellow, both at University of Newcastle, Australia, give a basic overview of how our immune system works to keep us safe from bacteria, fungi and viruses.


The article differentiates between our Innate immune response, which is mainly provided by our neutrophil white blood cells (which is most of them) and our “adaptive” immune response, provided by our B and T lymphocytes or as the article calls them, T and B cells (which make up most of the balance of our white blood cells). It's the B cells that escape the two quality control checks mentioned in the article and cause our CLL symptoms, which can include autoimmune complications sometimes observed in CLL.


Photo: Flame Heath (ASTROLOMA_CONOSTEPHIOIDES), with thanks again to Jay for the identification

8 Replies

  • Thank you so much for this, Neil. I have been thinking of asking a question about immune deficiency for a few days - if my neutrophils are still within normal limits, although at the lower end of the range, am I still at risk - and your post has answered this for me.

    What amazing flora you have in Australia! Love the pictures, and Cilcanda's


  • What a good article! Thanks Neil

    A step further forward in my education...only into another road-block! So the AIHA is explained by the CLL cells disrupting the 'education' of my white cells (not sure if T or B), which causes them to attack red blood cells....leading to the autoimmune anaemia. Solution, take the spleen out (where the attacking was done). However, the disrupted education must still be on-going, so those rogue cells still around! So why do these badly educated cells stop (at least for now) their attacks just because their first battle-ground has gone (and given liver takes over spleen blood-cleaning functions - so it is not as if functions have stopped)?! No one can offer explanation yet!

    I am also still curious on the statistic that c10% of CLLers get AIHA....after 18 months of realising that is my main immediate problem, I have only come across 3 others with same issue on this/Aus/US sites! Where are the others?! or are the stats wildly wrong?!

  • Andy, to answer your question, in the conclusion of the first paper I've referenced below, it states: "The predilection in CLL for autoimmune disease attacking the formed elements of the blood is only partially understood and may be related to the ability of CLL cells to process and present antigens derived from blood cells, in contrast to their poor general performance as antigen presenting cells. The mechanisms leading to autoimmune cytopenia in CLL are complex and involve interactions between the malignant B-CLL cells, abnormally functioning T cells, the microenvironment, and the immune system."

    My rough translation - it seems that CLL B cells in concert with T cells (which they influence to protect themselves by the way), are more effective at incorrectly attacking blood cells than they are at attacking foreign bodies.

    More on AIHA and other autoimmune complications accompanying CLL:

    CLL and autoimmunity: a systematic review - Haematologica May 2011


    "CLL is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells in orchestrating the production of polyclonal autoantibodies, are increasingly well understood. Recent studies show that autoimmune cytopenia is not necessarily associated with poor prognosis. On the contrary, patients with anemia or thrombocytopenia due to immune mechanisms have a better outcome than those in whom these features are due to bone marrow infiltration by the disease (my emphasis - Neil).



    The occurrence of immune cytopenia has been reported to range from less than 5% to 38%. In the most recent studies, the proportion of patients presenting with autoimmune cytopenia at some point during the course of their disease ranges from 4.3% to 9.7%. The most common complication is AIHA (about 7%) whereas the incidence of ITP, and particularly autoimmune neutropenia and PRCA, is lower in most studies (<1–2%)."

    and from:

    Autoimmune Complications in CLL March, 2011 by Clive Zent and Neil Kay of Mayo Clinic


    "Although the common etiology of cytopenia was BM failure (54%), an appreciable number of patients had other causes of their cytopenia including autoimmune disease (18%), non-CLL related disorders (11%), long term complications of treatment of CLL (4%), and splenomegaly (3%). In this recent series of patients autoimmune cytopenia was thus responsible for 25% of cytopenias that could be attributed to CLL"


  • Neil

    Thanks for these - only just got round to them. I have not seen the second article before and it certainly adds to my knowledge....but it does appear exact mechanisms not understood (and so treatments given 'because they work' rather than knowing 'why/how' they work: nor does it explain why so few AIHAers appear to be around (it might be AHIA often linked to more advanced CLLers, so all mention hidden within CLL treatments, so patients don't realise they also have AIHA: however, as the articles make clear (and I in my case) the AIHA can be first symptom and needs treatment way before CLL becomes a problem/needs treatment)


  • Andy, it's frustrating when there are such large variations reported in the levels of auto-immune complications in different studies. It would be nice if someone could actually do some research into why there is such variation and also perhaps explain the disparities. I suspect that some of it is because of classification differences. I also presume that in many individuals with leukaemia, that part of the reason for lowered blood cell counts is that if the individual has an enlarged spleen, then blood cells are more likely to be withdrawn from circulation earlier, as there's a greater filtering effect from the additional spleen volume. This is all surmise on my part; I haven't read that much on the subject, but that's how it appeared to me when I tried to understand why my blood counts were trending down. How much was due to bone marrow involvement and how much was due to a swollen spleen? I suspect both are happening.

    As you note, there are many medical treatments that are performed because they've been done historically and are deemed to work - and in fact may do so for some patients. Despite the recent drive to "Evidence based medicine", there are a lot of medical procedures 'grandfathered' into medical best practice. Given the time and funding, I'm sure that individualised medicine would bring great benefits. We'd know for example who would respond well to steroid treatment for AIHA and who would benefit more from a splenectomy - and save putting patients like yourself through a treatment regime that was destined to fail. It's definitely a case of the more you know, the more you realise that you don't know...


  • Thanks Neil another great article. Being a gardener I love the pictures,keep them coming. I have 2 questions 1what is aiha? And 2 newdawn said that we could make posts private, have looked and still unsure how to do it.

    Thanks in advance.


  • Sue, AIHA is Auto-Immune Haemolytic Anaemia, in other words, anaemia caused by the body's B cells mistakenly creating antibodies (immunoglobulins) to attack and destroy red blood cells.

    Step 6 in the Help section on how to create a post describes how you set a post private:


    The post creator can always make their post private at any time and that makes all the replies private. If you want to reply with some sensitive information and you aren't the author, just reply saying you want to reply in more detail when the post/question has been set private. Either the author or one of the administrators should then change the topic so you can reply and have your answer only visible to CLL Support members within Health Unlocked.


  • Clear article - thanks for posting.

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