It’s simple! Immunity is “the ability of an organism (“self”) to resist a particular infection or toxin (“non-self” or antigen) by the action of specific antibodies or sensitized white blood cells.” Stated even more simply, “the immune response is our immune system’s reaction to an antigen. Simple? Yeah, right!
The title of the book (The Paradox of the Immune System) aims to identify and explain the contradictions that permeate the human immune system throughout. Its definition, self-versus-non-self, represents perhaps its most obvious paradox. It also sets the stage to explain how the system works to protect us 24/7. It functions as a natural, inherent process of our body and is called “innate (or natural) immunity.” But sometimes our innate immunity is insufficient to overcome an antigen, so it begins to “adapt” itself to function in specialized ways to increase its effectiveness (“gets tougher”).. This level is called “adaptive (or acquired) immunity.” Blog #9 addresses the molecular biology of the immune system, how innate (natural) immunity works to protect us, and what happens when it can’t complete the job.
The lymphoid organs of the body (Figure 1.1), particularly the thymus and bone marrow produce immune cells (Figure 1.2) including white blood cells (WBCs) like T and B lymphocytes, macrophages, neutrophils and other types, together providing the protective immune functions. And start thinking big here because we’re talking about trillions (with a T) of these immune cells. Additionally, the innate system includes gross anatomical structures, especially skin and mucous membranes as protection against antigens. As you are reading or listening to this blog, you are being
attacked constantly by countless antigens (dust, pollen, spores, virtually anything airborne or touching you) which your T helper cells (one of a class of T cells, T helper cells, henceforth TH) are recognizing as “foreign” and spontaneously activating an innate immune response. This includes the TH cells binding to a macrophage and the TH cell using its surface receptor proteins (things like CDs, HLAs, etc.) to bind the antigen and together forming an antigen-presenting complex or APC (Figure 1.3; also called dendritic cells because of their shape) and the process called the “immune synapse”, a very big deal.
Additional specialized TH cell receptors called toll-like receptors or TLRs are genetically programmed proteins to help the TH cell identify self from non-self and dangerous non-self-antigens from benign ones (ones that won’t cause trouble or are normal, like flora from the gut). This TLR or “antigen recognition system” as it’s referred to, serves as the “sentry” in the innate immune system. It programs the TH cells to “attack or stand down” thus, “usually” preventing the system from overworking or from attacking itself (and therein lies the “worst enemy” paradox we’ll be talking about later in the autoimmune discussions).
The activated APCs generate lymphokines, cytokines, interferons (that “interfere” with viral antigens), chemicals signals and proteins that start producing cytotoxic T cells (TC ) or a regulatory TREG cells and B cells, killer cells and plasma cells that produce antibodies that will recognize the attacking antigen (through their “antigen-encoding gene,” an amazing genetic feature), bind it, neutralize it and remove it through the lymphoid
system (lymphatics, nodes, etc.). This is called the “regulated” innate immune response and functions along with B memory cells (Bm) to protect (“anamnestic memory”) against reinfection. In some instances, albeit rare relative to the trillions of antigens being processed, the antigen load may prove to be too great, too virulent, not being removed quickly enough, or the immune system itself is suppressed for some reason (“immunosuppression”). The innate immune system keeps fighting harder while also creating an increasing accumulation of cells and chemicals
that can begin to produce physiological “stress” on the tissue and disrupts its homeostasis (notice how stress becomes an intrinsic antigen here in this otherwise evolving “normal” process). All this leads to a “dysregulated” immune system where confusion (or paradox) develops as to “who are the good guys and who are the bad guys?”
This dysregulated system now begins to interpret “too much self” as foreign and it starts to generate an increasing antigen-antibody response or a “hypersensitivity (overreaction) response” as part of its protective function. This is where the “adapting” innate immune system begins to transition into an “adaptive immune system” to deal with accumulated physiologic detritus, increasing physiologic stress, and “self” antigenicity. This adaptive immune system initiates a classic clinical process called “acute inflammation” which we will describe in detail in Blog #9, “The adaptive (aka “acquired”) immune system: from friend to foe.”
Discussion Questions:
As described in this discussion, the TH cells are innate immunity’s first line of defense against antigens. Loss or suppression of TH cells for any reason (e.g., a virus) can produce what clinical results?
We can understand hypersensitivity response and ultimate acute inflammation occurring from cellular response (T cell to B cell to antibodies), but what supplementary endogenous process is also beginning to contribute to the body’s response?
Comentários