The innate defences of the body

9 The innate defences of the body

The body has both ‘innate’ and ‘adaptive’ immune defences

When an organism infects the body, the defence systems already in place may well be adequate to prevent replication and spread of the infectious agent, thereby preventing development of disease. These established mechanisms are referred to as constituting the ‘innate’ immune system. However, should innate immunity be insufficient to parry the invasion by the infectious agent, the so-called ‘adaptive’ immune system then comes into action, although it takes time to reach its maximum efficiency (Fig. 9.1). When it does take effect, it generally eliminates the infective organism, allowing recovery from disease.

The main feature distinguishing the adaptive response from the innate mechanism is that specific memory of infection is imprinted on the adaptive immune system, so that should there be a subsequent infection by the same agent, a particularly effective response comes into play with remarkable speed. It is worth emphasizing, however, that there is close synergy between the two systems, with the adaptive mechanism greatly improving the efficiency of the innate response.

The contrasts between these two systems are set out in Table 9.1. On the one hand, the soluble factors such as lysozyme and complement, together with the phagocytic cells, contribute to the innate system, while on the other the lymphocyte-based mechanisms that produce antibody and T lymphocytes are the main elements of the adaptive immune system. Not only do these lymphocytes provide improved resistance by repeated contact with a given infectious agent, but the memory with which they become endowed shows very considerable specificity to that infection. For instance, infection with measles virus will induce a memory to that microorganism alone and not to another virus such as rubella.

Table 9.1 Comparison of innate and adaptive effector immune systems

  Innate immune system Adaptive immune system
Major elements
Soluble factors Lysozyme, complement, acute phase proteins, e.g. C-reactive protein, interferon Antibody
Cells Phagocytes
Natural killer cells
T lymphocytes
Response to microbial infection
First contact + + +
Second contact + + + + +
  Non-specific; no memory
Resistance not improved by repeated contact
Specific; memory
Resistance improved by repeated contact

Innate immunity is sometimes referred to as ‘natural’, and adaptive as ‘acquired’. There is considerable interaction between the two systems. ‘Humoral’ immunity due to soluble factors contrasts with immunity mediated by cells. Primary contact with antigen produces both adaptive and innate responses, but if the same antigen persists or is encountered a second time the specific adaptive response to that antigen is much enhanced.

Defences against entry into the body

A variety of biochemical and physical barriers operate at the body surfaces

Before an infectious agent can penetrate the body, it must overcome biochemical and physical barriers that operate at the body surfaces. One of the most important of these is the skin, which is normally impermeable to the majority of infectious agents. Many bacteria fail to survive for long on the skin because of the direct inhibitory effects of lactic acid and fatty acids present in sweat and sebaceous secretions and the lower pH to which they give rise (Fig. 9.2). However, should there be skin loss, as can occur in burns, for example, infection becomes a major problem.

The membranes lining the inner surfaces of the body secrete mucus, which acts as a protective barrier, inhibiting the adherence of bacteria to the epithelial cells, thereby preventing them from gaining access to the body. Microbial and other foreign particles trapped within this adhesive mucus may be removed by mechanical means such as ciliary action, coughing and sneezing. The flushing actions of tears, saliva and urine are other mechanical strategies that help to protect the epithelial surfaces. In addition, many of the secreted body fluids contain microbicidal factors, e.g. the acid in gastric juice, spermine and zinc in semen, lactoperoxidase in milk, and lysozyme in tears, nasal secretions and saliva.

The phenomenon of microbial antagonism is associated with the normal bacterial flora of the body. These commensal organisms suppress the growth of many potentially pathogenic bacteria and fungi at superficial sites, first by virtue of their physical advantage of previous occupancy, especially on epithelial surfaces, second by competing for essential nutrients, or third by producing inhibitory substances such as acid or colicins. The latter are a class of bactericidins that bind to the negatively charged surface of susceptible bacteria and form a voltage-dependent channel in the membrane, which kills by destroying the cell’s energy potential.

Defences once the microorganism penetrates the body

Despite the general effectiveness of the various barriers, microorganisms successfully penetrate the body on many occasions. When this occurs, two main defensive strategies come into play, based on:

Two types of professional phagocyte

Perhaps because of the belief that professionals do a better job than amateurs, the cells that shoulder the main burden of our phagocytic defences have been labelled ‘professional phagocytes’. These consist of two major cell families, as originally defined by Elie Metchnikoff, the Russian zoologist (Box 9.1; Fig. 9.3):

As a very crude generalization, it may be said that the polymorphs provide the major defence against pyogenic (pus-forming) bacteria, while the macrophages are thought to be at their best in combating organisms capable of living within the cells of the host.

Macrophages are widespread throughout the tissues

Macrophages originate as bone marrow promonocytes, which develop into circulating blood monocytes (Fig. 9.4) and finally become the mature macrophages, which are widespread throughout the tissues and collectively termed the ‘mononuclear phagocyte system’ (Fig. 9.5). These macrophages are present throughout the connective tissue and are associated with the basement membrane of small blood vessels. They are particularly concentrated in the lung (alveolar macrophages), liver (Kupffer cells) and the lining of lymph node medullary sinuses and splenic sinusoids (Fig. 9.6), where they are well placed to filter off foreign material (Fig. 9.7). Other examples are the brain microglia, kidney mesangial cells, synovial A cells and osteoclasts in bone. In general, these are long-lived cells that depend upon mitochondria for their metabolic energy and show elements of rough-surfaced endoplasmic reticulum (Fig. 9.8) related to the formidable array of different secretory proteins that these cells generate.

Phagocytosis and killing

Phagocytes recognize pathogen-associated molecular patterns (PAMPs)

The first event in the uptake and digestion of a microorganism by the professional phagocyte involves the attachment of the microbe to the surface of the cell through the recognition of repeating pathogen-associated molecular patterns (PAMPs) on the microbe by pattern recognition receptors (PRRs) on the phagocyte surface (Fig. 9.10). A major subset of these PRRs belongs to the class of so-called ‘Toll-like receptors’ (TLRs) because of their similarity to the Toll receptor in the fruit fly, Drosophila, which, in the adult, triggers an intracellular cascade generating the expression of antimicrobial peptides in response to microbial infection. A series of cell surface TLRs acting as sensors for extracellular infections have been identified (Fig. 9.11) which are activated by microbial elements such as peptidoglycan, lipoproteins, mycobacterial lipoarabinomannan, yeast zymosan and flagellin. Other PRRs displayed by phagocytes include the cell bound ‘C-type (calcium-dependent) lectins’, of which the macrophage mannose receptor is an example, and ‘scavenger receptors’, which recognize a variety of anionic polymers and acetylated low density proteins. Examples of intracellular PAMPs are the unmethylated guanosine-cytosine (CpG) sequences of bacterial DNA and double-stranded RNA from RNA viruses.

Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on The innate defences of the body

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