ABSTRACT: The immune system is split into innate and acquired immunity, with acquired immunity being further divided into humoral and cell-mediated immunity (CMII Humoral immunity involves antibodies, of which there are five types. Antibodies are important for helping destroy antigens in a range of ways and are produced by B-lymphocytes. Humoral immunity and CMI work together to protect the animal, with components of CMI being essential for mediation of the acquired immune system. Humoral immunity can be measured using serological tests, which have applications in disease diagnosis and assessment of the need for revaccination.

Immunology is the study of immune the system, which is one of the most important systems in the body. The immune system provides a complex defence mechanism against pathogenic organisms, involving humoral and cell- mediated responses. It protects against infection and is essential for survival.

Infection control is a primary responsibility for practising veterinary nurses, so it is important for them to appreciate the role of the immune system.

This article provides an introduction to immunology, focusing specifically on humoral immunity.

Acquired immunity

Overall, the immune system provudes either innate immunity and acquired immunity. Innate immunity refers to the anatomical barriers, such as cilia in the nostrils, hydrochloric acid in the stomach, and protective behaviours such as vomiting.1 Innate responses are generally more rapid than that of acquired immunity and are the first line of defence that an antigen must defeat.2

Acquired immunity is antigen-specific and is triggered by the recognition of antigens that have defeated innate barriers. Previous exposure can arise through natural exposure in the environment, such as disease transmission or vaccination. Acquired immunity is highly specific, meaning that this system can accurately identify foreign proteins and respond appropriately.3

This is in contrast to innate immunity which does not have specific responses. The acquired immune system has immunological memory, meaning that when a previously encountered antigen is presented again, the immune system is already prepared to deal with it rapidly. This is referred to as an anamnestic response.4

Within the acquired immune system,^ there are two ‘sub systems’ – the humoral immune system, which involves antibodies, and the cell-mediated immune system, which involves a range of different cells.

Two types of cells are particularly important in the CMI element of the acquired immune system. These are B and T lymphocytes which ultimately work to mediate acquired immunity.5 CMI will be covered in a later paper but, as the two systems work together, there will be reference to the cells involved.

Antibodies

There are five classes of antibodies, which are summarised in Table 1.

Antibodies are soluble and are found in plasma and extracellular fluids.6 Antibodies are globular proteins and are, therefore, referred to as immunoglobulins, and referred to by the abbreviation lg.7

All antibodies are produced by B-lymphocytes found in the bone marrow, in response to presented antigens making them highly specific.

There are types: IgG, IgA, IgM, IgE and IgD.8 B-lymphocytes are part of CM1 and are a clear example of how the two systems are linked.

Regardless of the antibody type, the general structure is the same, with four chains that are held together with disulphide bonds, resulting in a molecule that has a Y-shaped structure.7

Although all antibodies share the same structure, they can be distinguished by the number of binding sites present. Figure 1 shows the generic structure of an antibody, with the red square indicating the antigen at the binding site.

Figure 1: Generic antibody structure. (Adapted from the Animal Health Trust, 2009).’9

IgG has the most important role in the humoral immune system. It is the smallest antibody, and also the most numerous.8'4

Actions of antibodies

Anecdotally, one of the most common beliefs regarding antibodies is that they have the capability to destroy antigens. This is incorrect. Antibodies assist in the process involved to destroy antigens, but are not the immune component ultimately responsible for this. The first – and most significant – role of antibodies is the way in which they bind with antigens using the binding sites to form the immune complex, as shown in Figure 2.

Figure 2: Representation of the immune complex (Source: Purves et ai. 19951.10

Antibodies have three modes of action – neutralisation, osponisation and complement activation.

Neutralisation occurs when antibodies bind with antigens, preventing them from coming into contact with ‘self’ cells that would otherwise be infected or destroyed.6 The bound antigen and antibody is known as the immune complex. Neutralisation is a very direct method in which antibodies prevent antigens from causing damage.

When opsonisation occurs, antibodies bind with both the antigen and either a macrophage or neutrophil.16 Both cells are capable of phagocytosis and this binding process (opsonisation) essentially enhances the cells’ ability to phagocytose the antigen.

Finally, the complement system is a series of over 25 serum proteins and cell receptors which work to enhance acquired immunity.11 The complement system begins in the innate immune system with humoral immunity being involved in the later stages.6 However, this system is also triggered by antibody and antigen binding, and it is usually the antibodies IgG and IgM that are involved in this process.4

Once triggered, complement can coat the antigen and signal to other cells that the antigen requires elimination.12

Mass production of antibodies

After an antigen has been detec
ted, a sequence of steps involving the antigen, antibody and B-lymphocyte will occur as part of the humoral immune response with the ultimate goal of preparing the B-lymphocyte for the mass production of antibodies. These antibodies are described as being monoclonal as they are clones of each other and will be specific to the presented antigen.13

After this initial immune response, some of the B-lymphocytes will become memory B-lymphocytes, which are responsible for the provision of long-term immunity, as they multiply rapidly and produce antibodies in response to the presence of antigens.14

This process will be covered in more detail in a later paper.

Link between humoral and cell-mediated immunity

Although humoral immunity and CMI lie at either end of the spectrum, there is significant evidence for a connection between the two systems.8

Whilst the B-lymphocytes produce antibodies, the humoral immune system depends on these cells to produce its most important component in response to an antigen.8 Long-term antibody response to an antigen is made possible by memory B-lymphocytes, which are part of CMI.14

When opsonisation occurs in response to the formation of the immune complex, macrophages or neutrophils are involved and phagocytose the antigen.16 These cells are also part of CMI.

B and T-lymphocytes mediate the acquired immune system which is important because, if poorly controlled, immune-mediated disease can result.5 4 Day (2008) identifies the four classifications of immune-mediated disease as hypersensitivities, autoimmune disease such as immune-mediated polyarthritis (Figure 3), immune system neoplasia and immunodeficiencies.8

Figure 3: Photograph of a joint tap' in a dog with immune-mediated polyarthritis. Note the abnormal joint fluid.

It is clear that malfunctions in the immune system can have detrimental effects on animal health.

Assessing humoral immunity in practice

Serological tests can be used to assess humoral immunity, and these tests are based on the study of antigen-antibody binding.13 Serum samples are used and testing can be performed either by external laboratories or in-house following the introduction of the ImmunoComb VacciCheck test.15

Although these tests are commonly used for the diagnosis of disease, a study by Heayns and Baugh (2012) found that 69.5 per cent of veterinary surgeons would consider using serology to tailor vaccination protocols in dogs.13, 16

More information on serology can be found in an earlier paper entitled 'Serology – what is it and how can it be used in canine vaccination?’.15

Conclusion

Humoral immunity is part of the acquired immune system and involves antibody response to presented antigens. There are five classes of antibody that all share the same generic structure and have different characteristics and actions within the body.

Humoral immunity and cell-mediated immunity are both involved in the immune response to antigens and evidence strongly suggests that there are a number of links between both ‘sub systems’. 

Author

Bethaney Heayns BSc(Hons) RVN

Bethaney Heayns qualified as a RVN in 2008 and graduated with a First Class Honours Degree from Harper Adams in 2009. Beth's main interest is immunology, and she has a particular interest in serological testing. Beth is currently planning a research project involving serological testing in vaccination protocols.

To cite this article use either

DOI: 10.1111/j.2045-0648.2012.00244.x or Veterinary Nursing Journal Vol 27 pp 442-444

References

1. KINOT. T. J.. GOLDSBY. R. A. and OSBOURNE. B. A [2007] Immunology. 6th ed Basingstoke: W H. Freeman and Company

2.   COFFMAN. R. L„ SHER. A and SEDER. R. A (2010) Vaccine adjuvants; Putting innate immunity to work. Immunity. 33(4): 492-503

3.   AKIRA. S.. TAKEDA. K.. KAISHO. T. (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunology. 21(8) 675-680.

4.   TIZARD. I. R. (2009) Veterinary Immunology An introduction 8th ed Missouri Saunders Elsevier

5.  WERLING. D. and JUNGI, T W. (2003) TOLL-like receptors linking innate and adaptive immune response Veterinary Immunology and Immunopathology 91(1): 1-12.

6.   MURPHY. K.. TRAVERS. P. and WALPORT. M (2008) Immunobiology. 7th ed Abingdon: Garland Science

7.   PLAYFAIR. J. H L. and BANCROFT. G. J. (2005) Infection and Immunity 2nd ed. Oxford: Oxford University Press.

8.   DAY. M J. (2008) Clinical Immunology of the cat and dog London: Manson Publishing Ltd.

9.  ANIMAL HEALTH TRUST I2009I Diagram of an antibody. lOnlmel Available from: http://wwwaht.org.uk/images/immuno1 gif lAccessed: 14th August 2012)

10.  PURVES. W K.. 0RIANS, G. H . and HELLER. H C (1995) Life: The Science of Biology 4th ed Smauer Associates. Sunderland

11   CARROLL. M C. 120081 Complement and humoral immunity. Vaccine 26s: 128-133

12   CARROLL. M. V and SIM. R. B (2011) Complement in health and disease Advanced Drug Delivery Reviews 63: 965-975.

13.   DAY. M. J. and SCHULTZ. R. (2011) Veterinary Immunology – Principles and Practice London Manson Publishing Ltd

14.   NANAN. R.. HEINRICH, D.. FROSCH. M. and KRETH. H W. (2002) Acute and long-term effects of booster immunisation on frequencies of antigen-specific memory B-lymphocytes Vaccine. 20:498-504.

15.   HEAYNS. B J. (2011) Serology – what is it and how can it be used in canine vaccination? Veterinary Nursing Journal. 27(5): 190-193

16.  HEAYNS. B. J. and BAUGH. S. (2012) Survey of veterinary surgeons on the introduction of serological testing to assess revaccination requirements. Veterinary Record 170(3): 74-78

• VOL 27 • December 2012 • Veterinary Nursing Journal