Immune system

All organisms have what can be considered an immune system, which is basically a biological system designed to prevent predation by microbes. When the organism you are studying is itself a microbe, this definition becomes somewhat confusing. Bacteria, for instance, have an 'immune system' designed to combat bacteriophages (viruses that infect bacteria). They do this by simultaneously expressing enzymes that cut DNA at certain sequences, and enzymes that protect DNA from this enzyme by methylating the same sequence. Therefore, the bacterium's DNA will not be damaged by the first enzyme because of the presence of the second enzyme. However, when a bacteriophage attempts to infect this bacterium, the viral DNA has not been protected, and gets degraded by the first enzyme.

However, we usually refer the the immune system of multicellular animals, usually vertebrates, when we talk about immune systems.

Table of contents

1 Recognizing self and non-self: the problem of immunity 2 Structure of the immune system 2.1 Innate immune system 2.1.1 Physical barrier 2.1.2 Phagocytic cells 2.1.3 Anti-microbial proteins 2.2 Adaptive immune system 2.3 The intersection between innate and adaptive immune systems 3 Disorders of the human immune system 4 See also

Recognizing self and non-self: the problem of immunity

We may conceive of an arrangement where the cells of self are marked, so that they are not attacked by its own defense mechanism. But not all foreign cells may be destroyed since some must be assimilated for nourishment. Therefore, the immune system must have the capacity to detect self and some nonself. But since self needs to assimilate some nonself for its survival, it cannot mark itself. It is easier to mark potentially dangerous selves. But if only certain nonselves are marked, how does the body prepare to defend itself from selves not seen? The defense system must have the capacity to transform itself to deal with future dangers. It must also have the capacity to change, since the self itself evolves with time. An additional challenge to understanding is the mechanism by which sexually reproducing organisms prevent the growing embryo from being destroyed by the immune system of the 'mother'. It is believed that this is achieved by the specialized tissue such as the placentum in placental mammals. New theories attempt to solve some of these paradoxes. One such is the 'danger theory' proposed by Polly Matzinger which suggests that cellular apoptosis signals and directs the immune mechanism. Another is the 'Pathogen-Associated Molecular Pattern' theory proposed by Charles Janeway which suggested that conserved molecular patterns found on pathogens provide a context in which a particular antigen is recognized.

Structure of the immune system

Innate immune system

The study of the innate immune system has recently flourished. Ealier studies of innate immunity utilized model organisms that lack adaptive immunity such as the plant Arabidopsis thaliana, the fly Drosophila melanogaster, and the worm Caenorhabditis elegans. Recent advances have been made in the field of innate immunology with the discovery of the toll-like receptors, which are the receptors in mammals that are responsible for a large proportion of the innate immune recognition of pathogens. There is strong evidence that these toll-like receptors are responsible for sensing the "pathogen-associated molecular patterns" and/or providing the "danger signal" as speculated by Janeway and Matzinger, respectively.

Physical barrier

Phagocytic cells

Phagocytosis involves chemotaxis, where phagocytic cells are attracted to microorganisms by means of chemotactic chemicals like microbial products, complements, damaged cells and white blood cell fragments; chemotaxis is followed by adhesion, where phagocytes are sticked to microorganisms. Adhesion is enhanced by opsonization, where proteins like opsonins are coated on the surface of the bacterium. This is followed by ingestion, where phagocytes extends their projections, forming pseudopods that engulf the organism. Finally the bacterium would be digested by the enzymes in the lysosome.

Anti-microbial proteins

The complement system is a very complex group of serum proteins which is activated in a cascade fashion, and there are three pathways of activation - classical, alternative and lectin. Only alternative pathway is of significance here though - because classical pathway is activated by the adaptive immune system, the antigen-antibody complex - alternative pathway activates C1,C4,C2,C3,C5 and finally C6 to C9, which forms the membrane attack complex. Lectin pathway activates C2, C3, C4, and some C1 homologue calcium-dependent lectin family proteins.

Complement binding will result in cytolysis, chemotaxis, opsonization and inflammation. Last but not least, interferon α and β are important for resistance to viral infection.

Adaptive immune system

• The humoral immune system, which acts against bacteria and viruses in the body liquids (such as blood). Its primary means of action are immunoglobulins, also called antibodies, which are produced by B cells (B means they develop in the bone marrow).
• The cellular immune system, which takes care of other cells that are infected by viruses. This is done by T cells, also called T lymphocytes (T means they develop in the thymus). There are two major types of T cells:
  • Cytotoxic T cells (T_C cells) recognize infected cells by using T-cell receptors to probe the surface of other cells. If they recognize an infected cell, they signal the cell to become apoptotic ("commit suicide"), thus killing that cell and any viruses it is in the process of creating.
  • Helper T cells (T_H cells) interact with macrophages (which ingest dangerous material), and also produce cytokines (interleukins) that induce the proliferation of B and T cells.
  • In addition, there are Regulatory T cells (T_reg cells) which are important in regulating cell-mediated immunity.

• adjuvants - Although the text book explanation of the adaptive immune system would suggest that the adaptive immune system could raise antibodies and T-cells specific to any antigen, including artificial peptides, introduced to a mammal, the fact was that, in order to induce a robust immune response, the antigen had to be delivered with an adjuvant. The most commonly used adjuvant was Freund's Complete Adjuvant, an emulsion of oil and mycobacterium. It was later discovered that toll-like receptors, expressed on innate immune cells, are critical in the activation of adaptive immunity.
• antigen presentation - It was known that T-cell activation required other cells to process and present antigens. These cells were called antigen presenting cells (APC), and this function was thought to be performed by macrophages and/or B-cells in vivo. However, isolated macrophages and B-cells were not potent antigen presenting cells. The later discovery of dendritic cells (DC) (by Ralph Steinman) demonstrated that there existed a specialized cell type for this function. Dendritic cells are a type of myeloid cell derived (probably) from monocytes whose main function appears to be the activation of T-cells. Here you have an innate immune cell that is critical in the function of adaptive immunity.

On the other hand, an "overactive" immune system is a feature of a large number of different autoimmune disorders, such as lupus erythematosus, type I diabetes (sometimes called "juvenile onset diabetes"), multiple sclerosis, psoriasis, and rheumatoid arthritis. In these the self-recognition ability of the immune system fails and it attacks a part of the patient's own body.

See also

• antigen/antigenic determinant/epitope/hapten/memory cell
• autoimmune disorders:
  • aplastic anemia
  • Type I diabetes mellitus
  • Graves disease
  • Guillain-Barré syndrome
  • lupus erythematosus
  • multiple sclerosis
  • myasthenia gravis
  • optic neuritis
  • psoriasis
  • rheumatoid arthritis
• CD4 receptor/CD8 receptor/perforin/apoptosis/clonal selection
• immunotherapy
• lymphatic system/lymphocyte
• macrophage
• major histocompatibility complex/class I MHC/class II MHC
• monoclonal antibody/polyclonal antibody

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