The immune system

Abstract

All organisms are connected in a complex web of relationships. Although many of these are benign, not all are, and everything alive devotes significant resources to identifying and neutralizing threats from other species. From bacteria through to primates, the presence of some kind of effective immune system has gone hand in hand with evolutionary success. This article focuses on mammalian immunity, the challenges that it faces, the mechanisms by which these are addressed, and the consequences that arise when it malfunctions.

Keywords: basic; immunology; review.

Figure 1. Antibody structure

Antibody cartoons are often drawn in a Y-shape, as on the left. This picture represents an IgG molecule, made from two identical heavy (red and blue) and two identical light (yellow and green) chains. The top of the Y (called the Fab region) contains two variable regions that each bind the same antigen. The bottom of the Y is the constant (Fc) region, which interacts with cell receptors, complement, etc. On the right is a crystal structure of an IgG2 antibody. The heavy chains (red and yellow) and light chains (blue and green) are identical. This antibody is ∼10 nm from bottom to top. (From TimVickers. https://commons.wikimedia.org/wiki/File:Antibody_IgG2.png)

Figure 2. The adaptive immune response to infection

Infection, detected by APCs, triggers specific T-cells that co-ordinate killing and antibody production which stop the infection.

Figure 3. Antigen processing I

A protein molecule (on the left) is digested by the cell and a fragment from it (shown in green) is loaded into an MHC molecule that is then displayed on the surface of the cell (on the right), oriented so that it can be scanned by T-cells. The MHC molecule is ∼7 nm tall above the cell membrane. Not to scale. Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute https://commons.wikimedia.org/w/index.php?curid=6292018

Figure 4. Antigen processing II

Internally produced and externally captured proteins are loaded on to MHC molecules inside APCs. Internally produced proteins are presented by MHC class I molecules, which are found on all the cells in the body. Externally acquired proteins are presented by MHC class II molecules on specialized APCs. Once loaded, molecules are exported to the cell surface.

Figure 5. MHC–TCR interaction

Crystal structure of the interaction between a TCR (the α and β chains) and human MHC (HLA DR α and β chains). The peptide antigen can just be seen at the interface between the two receptors. Influenza peptide, class II presentation https://commons.wikimedia.org/wiki/File:1FYT_T-cell_receptor_and_HLA_class_II_complex.png

Figure 6. TCR and T-cell selection

(A) The DNA encodes a large number of different possible sequences for the TCR. The code for the part of the TCR that recognizes antigen are selected at random from these sequences. Different structural elements are combined to make the final TCR. The resulting receptor is expressed at the cell surface and tested in the thymus. (B) Cells bearing each TCR are put through a number of screening tests. If the TCR cannot work with the individual's MHC molecules, or if it is useless or dangerous, it is destroyed. If it passes these tests, it is exported from the thymus.

Figure 7. Affinity maturation

Antibodies that fit quite well are selected early in the immune response. The antibody receptor (BCR) is mutated within daughter cells. Many of these mutations bind the antigen worse than the parent antibody, and cells producing these antibodies die. Some antibodies bind the antigen better than the parent, and these cells live.

Figure 8. Antibody responses to vaccination

Following the first immunization, increases in specific antibody can be detected. The levels of this fall but do not return to baseline. Following the boost, the secondary response is greater and the baseline is higher. Kinetics and levels vary between individuals and between different vaccines.

Figure 9. Overview of autoimmunity

An autoimmune episode starts (A) with the initiation or reactivation of an immune attack directed against self. The T-cells expand and traffic (B) to the site where the antigen is found, are activated and damage the tissue (C). With time, the response is regulated and subsides, although the immune memory remains (D). Future infection may then trigger a relapse of the remission (E).

Figure 10. Monoclonal antibody production and application

Immunization leads to B-cells producing antibodies that bind to an antigen of interest. Individual B-cells are fused with partners that immortalize them and the resulting B-cell hybridomas produce identical (monoclonal) antibodies indefinitely. Following screening, relevant hybridomas are selected and expanded to produce large quantities of uniform antibody-producing cells. Such antibodies have many applications, for example locating antigen in tissue samples, providing the basis of a specific test for pregnancy hormone or being genetically engineered to use in immunotherapy of disease. Pregnancy test: Nabokov, en.wikipedia.org/w/index.php?curid=36047325

Overview of the Immune Process

An immune response goes through a number of stages. It begins by recognising that there is a threat from an infection. The response is controlled and directed by a number of checking mechanisms that optimise the system in parallel with effector mechanisms that target, limit, damage or destroy the threat. To contain ongoing damage, regulatory mechanism can dampen responses, promote memory and establish a state of tolerance.