Adaptive responses provide a ‘quantum leap’ in effective defence

10 Adaptive responses provide a ‘quantum leap’ in effective defence


Infectious agents frequently find ways around the innate defences

In Chapter 9, we discussed the many ways in which the primary or innate defences of the body may counteract microbial infection. However, infectious agents frequently find ways around these defences, as there is a huge number of different microorganisms surrounding us and they have a powerful ability to mutate, e.g.:

Adaptive responses act against microorganisms that overcome the innate defences

It is clear that the body needs to provide immune defences that can be ‘tailor-made’ to each individual variant of the different species of microorganisms. Ideally, these should link the organism directly into the various killing mechanisms of the innate system. In this chapter, we shall see how evolution has achieved this by inserting specific recognition sites on antibody molecules and on T cells. When an infectious agent enters the body, the lymphocytes respond to it and produce a reaction that is specific for that particular microorganism. Furthermore, the magnitude of this response increases with time, often to quite high levels, so that we speak of it as an ‘adaptive’ or ‘acquired’ response. We know that the body produces millions of different antibodies, which as a population are capable of recognizing virtually any pathogen that has arisen or might arise.

The role of antibodies

The acute inflammatory response

Antibodies act as adaptors to focus acute inflammatory reactions

Antibodies are immunoglobulin molecules (Fig. 10.1, Table 10.1) which are synthesized by host B lymphocytes (so-called because they mature in the bone marrow; see Fig. 11.2) when they make contact with an infectious microbe, which acts as a foreign antigen (i.e. it generates antibodies). Each antibody has two identical recognition sites that are complementary in shape to the surface of the foreign antigen and which enable it to bind with varying degrees of strength to that antigen. The recognition site is hypervariable in that antibodies of different antigen specificities each have a unique amino acid sequence in this region. This hypervariability is confined to three loops on the heavy and three on the light peptide chains, which make up the antibody molecule (Fig. 10.1) and are referred to as complementarity determining regions (CDRs) because they make complementary contact with the antigen. Thus, the amino acid sequences of these CDRs determine which antigen is recognized by a given antibody. Other sites on the antibody molecule are specialized for functions such as activating the complement system and inducing phagocytosis by macrophages and polymorphs (Fig. 10.2). Therefore, when a microbial antigen is coated with several of these adaptor antibody molecules, they induce complement fixation and phagocytosis, processes that the microbe may well have evolved to try and avoid. In this way, the reluctant microorganism becomes drawn into the innate defence mechanism of the acute inflammatory response. We will now examine the ways in which antibody can mediate these different phenomena.

Antibody complexed with antigen activates complement through the ‘classical’ pathway

When antibody molecules bind an antigen, the resulting complex activates the first component of complement, C1, converting it into an esterase (image). This initiates a second route of complement activation (Fig. 10.3) termed the ‘classical’ pathway, mainly because scientists discovered it before the ‘alternative’ pathway (see Ch. 9), although the evidence indicates that the alternative pathway is of greater antiquity in evolutionary terms. The activated first component splits off a small peptide from each of the succeeding components C4 and C2, the residual fragments forming a composite, the image, complex. The image complex has the enzymatic ability or property of a C3 convertase. Being an enzyme, the image protease creates large numbers of the image convertase which itself also having proteolytic activity, cleaves many C3 molecules, this so-called enzyme cascade providing a mechanism for the striking amplification of the relatively few initial complement activation events. image has a similar function to the alternative pathway C3 convertase, image, and the sequence of events following the splitting of C3 which generates an acute inflammatory response is indistinguishable from that occurring in the alternative pathway. C3a and C5a anaphylatoxins are formed, and C3b binds to the surface of the microbe–antibody complex (Fig. 10.4; compare Fig. 9.14). Subsequently, the later components are assembled into a membrane attack complex (MAC) (see Fig. 9.18), which may help to kill the microorganism if it has been focused onto a vulnerable site.

It is appropriate at this stage to recall the activation of complement by innate immune mechanisms involving the binding of mannose binding lectin (MBL) and C-reactive protein to carbohydrates on microbial surfaces (cf. Fig. 9.20), and it is noteworthy that both acute phase proteins activate the classical pathway albeit through different routes (Fig. 10.3).

The acute inflammatory reaction can also be initiated by antibody bound to mast cells

A specialized antibody, immunoglobulin E (IgE), has a backbone site with a high affinity for specific receptors on the surface of mast cells. When microbial antigen attaches to these cell-bound antibodies the surface receptors are cross-linked and transduce a signal to the interior of the cell. This signal leads to the release of mediators capable of increasing vascular permeability and inducing polymorph chemotaxis (Fig. 10.5).

Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on Adaptive responses provide a ‘quantum leap’ in effective defence

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