Drugs affecting the immune response

Chapter 20 Drugs affecting the immune response



CHAPTER CONTENTS


The immune system 400

Introduction 400

Specific immune response 401

Non-specific immunity 401

Allergy 402

Immunisation 402

Active immunisation 402

Tuberculosis: bacille Calmette–Guérin immunisation 407

Immunisation of children 408

Risk groups 408

Passive immunisation 409

Storage and disposal of vaccines 410

Conditions treated with drugs affecting the immune system 410

Organ transplantations 410

Autoimmune diseases 410

Cancer 410

Main drug groups 410

Immunosuppressants 410

Interferons 411

Nursing the immunosuppressed patient 412

Self-assessment questions 413


KEY OBJECTIVES


After reading this chapter, you should be able to:


• describe how vaccines elicit an immune response

• discuss the use of vaccines in the UK childhood immunisation programme

• list the use of both normal and specific immunoglobulins

• outline the rationale for the use of antiproliferative immunosuppressants in the treatment of autoimmune disorders

• discuss the nursing care of the immunosuppressed patient.


THE IMMUNE SYSTEM




INTRODUCTION


Every day of our lives, we come into contact with a large variety of micro-organisms such as viruses, bacteria and fungi. Many of these pathogens are capable of causing disease, yet most of the time we do not succumb to infection. Moreover, when we do, the course of disease is usually short-lived. The immune system is the body’s defence against potentially harmful substances and micro-organisms. Specific and non-specific mechanisms take part in the immunological response. The blood and lymphatic systems, bone marrow, thymus gland, liver and spleen interact to make this system effective. The bone marrow is responsible for the production of lymphocytes, which are primed in the thymus gland (T lymphocytes) and possibly the bone marrow itself (B lymphocytes). These immunologically competent cells, together with phagocytes (macrophages), circulate in the blood and lymphatic systems, liver and spleen, ready to react to an invasion by foreign substances (antigens).


In those patients in whom the immune system is defective and immunodeficiency has occurred, there can be a risk of overwhelming and sometimes life-threatening infections. Perhaps the best-known cause of such a condition is infection with the virus HIV, leading to AIDS (see Ch. 15). This virus infects and destroys particular cells of the immune system, without which the patient becomes very susceptible to a variety of bacterial, viral and fungal infections. Immunodeficiencies are also caused by certain rare genetic diseases. Another common immunodeficiency occurs following treatment with drugs that damage the immune system. For example, immunodeficiency is a common side-effect of chemotherapy for cancer, and patients undergoing such treatment become more susceptible to infections. The immune response can be used to positive effect with the use of vaccination and is one of the most effective methods of combating infectious disease.



SPECIFIC IMMUNE RESPONSE


When a foreign substance (antigen) enters the body, two different types of immunological response may occur (see Fig. 20.1).


image

Fig. 20.1 Humoral and cellular immunity.



HUMORAL IMMUNE RESPONSE (ANTIBODY-MEDIATED IMMUNITY)


On contact with the antigen, immunologically competent B lymphocytes change into plasma cells (effector cells). These plasma cells are capable of producing specific antibodies, the immunoglobulins. The antibody combines with the antigen (antigen–antibody reaction) and neutralises it, for example by coating bacteria to enhance their destruction by phagocytosis.


Another product of the primary contact of antigen with immunologically competent B lymphocytes is the memory cells. Memory cells are able to recognise the same antigen on a second contact, which results in a more rapid and sometimes more intense response. Plasma cells are formed much faster, which in turn results in a large amount of antibodies. The capability of the memory cells to recognise specific antigens sometimes years after the primary contact forms the basis of active immunisation against bacteria and their toxins.



CELLULAR IMMUNE RESPONSE (CELL-MEDIATED IMMUNITY)


Depending on the physicochemical properties of the antigen and its way of entry into the body, some antigens cause the production of sensitised lymphocytes, the T lymphocytes, which have antibody-like molecules on their surface (cell-bound antibody). The T lymphocytes are responsible for the specific cell-mediated immune response. On primary contact with the antigen, they proliferate like the B lymphocytes and produce memory cells and effector cells. Unlike B lymphocytes, T lymphocytes produce different types of effector cells that directly take part in the immune reaction:


• cytotoxic effector cells (killer T cells) that can destroy other cells; this reaction to foreign cells is especially important in the rejection of transplanted organs

• T helper cells, which cooperate with the cytotoxic effector cells and also take part in the humoral immune response

• suppressor T cells, which can suppress the function of B lymphocytes and other T lymphocytes.


NON-SPECIFIC IMMUNITY


Apart from the specific immune response, a number of non-specific antimicrobial mechanisms have been recognised. These non-specific factors often operate in conjunction with the specific immune response, which greatly increases the overall effectiveness. These non-specific mechanisms include:


• bactericidal lysozyme, which is present in tears and saliva

• phagocytosis – some leucocytes are able to ingest and kill bacteria

• acute inflammatory response to a foreign substance – release of histamine from sensitised mast cells

• the non-specific antiviral agent interferon, which is a lymphokine produced by T cells in response to viral infections; interferon inhibits the intracellular viral replication (it also acts on the immune system by increasing the cytotoxic activity of T lymphocytes and inhibits the mitosis of tumour cells).


ALLERGY


Allergies are very common and affect around one in four people in the UK at some time in their lives. Each year, the numbers increase by 5%, with many more children being affected. Allergies result when the immune system is hypersensitive and over-reactive. The system misidentifies harmless proteins as antigens and then reacts out of proportion to the threat. Any substance that triggers an allergic reaction is called an allergen (Box 20.1).The symptoms may be mildly annoying or a major illness (Box 20.2). Most allergens are not obviously harmful, and have no affect on those individuals who are not allergic. Allergens frequently contain protein, and it is the protein that causes the reaction. Drugs may also cause allergic reactions (e.g. penicillins; see Ch. 10).



Box 20.1 Common allergens



• House and dust mites

• Grass and tree pollens

• Pet skin flakes or hair

• Fungal or mould spores

• Food (milk, egg, wheat, soya, seafood, fruit and nuts)

• Wasp and bee stings

• Some medicines

• Plants

• Nickel, rubber, preservatives and synthetic resins


Box 20.2 Common symptoms of allergy



• Sneezing

• Wheezing

• Sinus pain

• Runny nose

• Cough

• Nettle rash or hives

• Swelling

• Itchy eyes, ears, lips, throat and palate

• Shortness of breath

• Sickness, vomiting and diarrhoea

Allergy tends to run in families. Someone with an allergic tendency produces far more than the normal amounts of an antibody immunoglobulin E. Allergic individuals also produce more than the normal numbers of mast cells. The mechanism in susceptible individuals involves the production of immunoglobulin E antibody directed against the antigens. Immunoglobulin E binds to the surface of the mast cells and basophils. Subsequent exposure to antigen triggers the release of various substances, predominant among which is histamine. In the worst case scenario, this can result in an anaphylactic reactions (see Ch. 10).


Whenever possible, the most effective way of treating allergies is to avoid all contact with the allergen causing the reaction. Antihistamines treat allergies by blocking the action of the histamine that is released from mast cells (see Ch. 13). Decongestants help to relieve symptoms such as a blocked nose, which is often caused by hay fever, and dust and pet allergies (see Ch. 24). Nasal sprays and eye drops are available; nasal sprays reduce swelling and irritation in the nose, while eye drops relieve sore, itchy eyes. Drugs such as sodium cromoglicate and corticosteroids can be used regularly to stop symptoms developing. These are commonly available as nasal sprays and eye drops.


Another form of treatment is hyposensitisation. This can help those who have a specific allergy (e.g. bee stings). The person is gradually introduced to more and more of the allergen to encourage the body to make antibodies that will stop future reactions. This type of treatment must only be carried out under close supervision from a doctor, because of the risk that it may cause an anaphylactic reaction.



IMMUNISATION


Immunity can be induced, either actively or passively, against a variety of bacterial and viral agents.



ACTIVE IMMUNISATION


The objective of vaccination is to provide protection against certain infections such as diphtheria and tetanus. Active immunity is induced by injection of antigen in the form of inactivated or attenuated live organisms or their products (toxins). This stimulates the production of antibodies and a population of primed cells, which can expand rapidly on renewed contact with the antigen and inactivate the invading organism or its toxins. This means prevention or at least minimisation of the disease. Established disease cannot be treated by this method.


Active immunisation is used for the routine vaccination of babies and children (UK immunisation schedule, Table 20.1), for opportunistic vaccination of previously non-immunised adults (Table 20.2), and for the vaccination of travellers going to specified areas and people at risk from infection through the nature of their work or their lifestyle (Table 20.3). Vaccines are very effective when administered correctly. However, basic personal hygiene remains vitally important, especially for travellers.


Table 20.1 UK childhood immunisation schedule







































Age at vaccination Vaccine(s) Notes
2 months DTaP/IPV/Hib plus PCV Pneumococcal vaccine introduced into UK immunisation schedule in 2006.
3 months DTaP/IPV/Hib plus MenC –
4 months DTaP/IPV/Hib plus MenC plus PCV –
In first year of life BCG vaccine (for neonates at risk only) For infants living in areas where the incidence of tuberculosis is greater than 40 per 100 000 or with a parent or grandparent born in a country with an incidence of tuberculosis greater than 40 per 100 000.
12 months Hib/MenC New combined vaccine introduced into UK schedule in 2006.
13 months MMR plus PCV Reviews undertaken on behalf of the Committee on Safety of Medicines and the Medical Research Council have not found any evidence of a link between MMR vaccination and bowel disease or autism.
Before school or nursery entry DTaP/IPV (low- or standard-dose diphtheria) plus MMR –
Before leaving school or before employment or further education Adsorbed diphtheria (low dose), tetanus (DTaP) and IPV An individual who has received five doses of tetanus vaccine is likely to have lifelong immunity. Individuals aged over 10 years should receive low-dose adsorbed diphtheria.

BCG, bacille Calmette–Guérin; DTaP, diphtheria, tetanus, pertussis (acellular, component); Hib, Haemophilus type b conjugate vaccine (adsorbed); IPV, inactivated poliomyelitis vaccine; MenC, meningococcal group C conjugate vaccine; MMR, measles, mumps and rubella vaccine, live; PCV, pneumococcal conjugate vaccine.


Table 20.2 Adult immunisations in those previously unimmunised























Individuals Vaccine Notes
Unimmunised women of childbearing age MMR Should be tested for rubella antibodies and seronegative women offered rubella immunisation – exclude pregnancy before immunisation.
Any unimmunised adults DTaP Three doses at intervals of 4 weeks. Booster dose at least 1 year after primary course and again 5–10 years later. (Booster doses may be required in travellers going to high-risk areas at 10-year intervals.)
At risk individuals BCG Contacts of those with active respiratory tuberculosis.
    Previously unvaccinated new immigrants from countries with a high incidence of tuberculosis, occupational health risk.

BCG, bacille Calmette–Guérin; DTaP, diphtheria, tetanus, pertussis (acellular, component); MMR, measles, mumps and rubella vaccine, live.


Table 20.3 Other vaccines used for specific circumstances
















































Vaccine Indications for use
Anthrax vaccine Individuals who handle infected animals or are exposed to infected animal products. Laboratory staff working with Bacillus anthracis.
Botulism antitoxin Postexposure prophylaxis of botulism.
Cholera vaccine Travellers to endemic or epidemic cholera areas.
Hepatitis A vaccine Laboratory staff working with the virus; patients with haemophilia treated with factor VIII or factor IX; travellers to high-risk areas; individuals at risk due to their sexual behaviour; patients with chronic liver disease; staff and residents of homes for those with learning difficulties; sewage workers; parenteral drug abusers; close contacts of confirmed cases of hepatitis A.
Hepatitis B vaccine Parenteral drug abusers; close contacts of case/carrier; infants born to mothers with hepatitis B; haemophiliacs receiving blood products; chronic renal failure; carers of dialysis patients; healthcare personnel who have direct contact with blood/body fluids; morticians and embalmers; staff and patients of daycare or residential accommodation for learning difficulties; inmates of custodial institutions; travellers to areas of high prevalence at increased risk or staying for long periods; families adopting children from countries with a high prevalence of hepatitis B.
Influenza vaccine Patients with respiratory disease, chronic heart disease, chronic liver disease, chronic renal disease, diabetes mellitus, immunosuppression (disease or treatment), HIV infection; persons aged over 65 years of age; healthcare workers directly involved in patient care.
Meningococcal A, C, W135, Y vaccine Travellers going to risk areas (particularly those going to the Haj in Saudia Arabia).
Pneumococcal vaccine Those aged over 65 years; patients with asplenia or splenic dysfunction, chronic respiratory disease, chronic heart disease, chronic renal disease, chronic liver disease, diabetes mellitus, immune deficiency because of disease; presence of cochlear implant; presence of cerebrospinal fluid shunt.
Rabies vaccine Laboratory staff who handle rabies vaccines; staff working in quarantine stations; animal handlers and vets likely to be bitten by infected wild animals; bat handlers; travellers going to endemic areas for > 1 month or at increased risk.
Smallpox vaccine Laboratory workers handling pox viruses (contingency plans for the wider use of vaccine in event of post-eradication era outbreak are being considered).
Tick-borne encephalitis vaccine Travellers going to those areas of high risk (e.g. forested areas of central and eastern Europe and Scandinavia).
Typhoid Travellers to countries where sanitation standards may be poor.
Varicella zoster vaccine Not recommended for routine use. May be used for seronegative individuals who come into close contact with varicella infection or have a high risk of severe varicella infection.
Yellow fever vaccine Travellers going to endemic areas. Laboratory staff handling the virus or clinical material from patients.


TYPES OF VACCINES USED FOR ACTIVE IMMUNISATION




Live attenuated vaccines.

Live attenuated vaccines such as those against measles, mumps and rubella (MMR), tuberculosis (bacille Calmette–Guérin, BCG), varicella zoster, smallpox and yellow fever contain strains of attenuated live organisms that, although non-pathogenic, are still capable of producing specific antibodies. Some live vaccines may contain small amounts of agents, such as an antibiotic arising.


There is now overwhelming evidence that MMR does not cause autism. Over the past 7 years, a large number of studies have been published looking at this issue. For the latest evidence, see the Department of Health’s website.

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  3. Pharmacokinetics and pharmacodynamics
  4. Drug treatment of infections

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May 13, 2017 | Posted by in NURSING | Comments Off on Drugs affecting the immune response

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