Program Name: Immunization Competencies Education Program Module 1 - The Immune System and Vaccines
Faculty:
Adapted by: Michael Boivin, B. Pharm. Susan Bowles, BSc Phm, PharmD, MSc Capital District Health Authority and Dalhousie University, Geriatric Ambulatory Care Danielle Grenier, MD Canadian Paediatric Society Alex Henteleff, BN, MEd Consultant Public Health Expert video commentary was kindly provided by: Upton Allen, MD, FRCPC, MBBS, FAAP Maryanne Crockett, MD, MPH Andrea Derban, BScN Simon Dobson, MD Joanne Embree, MD Ian Gemmill, MD, CCFP, FCFP, FRCP(C) Caroline Quach, MD, FRCPC, M. Sc.
CCCEP:
This continuing education lesson is designed primarily for community pharmacists and has been accredited by the Canadian Council on Continuing Education in Pharmacy (CCCEP) for 1 CEUs.
CCCEP File Number: 1066-2010-092-I-P
This online CME event is an Accredited Group Learning Activity (Section 1) as defined by the Maintenance of Certification program of the Royal College of Physicians and Surgeons of Canada. This program is recognized as 1 hour(s) of Continuing Professional Development. Family physicians may claim one (1) credit per hour of participation under Mainpro-M2.
Course Expiration Date: June 15, 2013
Sponsor: This module is developed in collaboration with the Canadian Paediatric Society, the Public Health Agency of Canada and Health Canada.
Competency: Explains how vaccines work using a basic knowledge of the immune system
Learning Objectives Upon successful completion of this section the health professional will be able to perform the following:
1. Compare and contrast innate and adaptive immunity. 2. Differentiate between the primary and memory immune response to a vaccine. 3. Differentiate between passive and active immunity. 4. Explain why some vaccines induce a memory response while others do not. 5. Name some host- and vaccine-related factors that affect the immune response to
vaccines. 6. Explain how the immunization schedule accommodates factors that affect the immune
response to vaccines. 7. Respond to the concern that giving too many vaccines will overload the immune system. 8. Discuss the pros and cons of immunity gained through immunization as opposed to
wild-type infection.
Test Your Current Knowledge Based on your current knowledge, please indicate if you feel the statement listed is true or false.
1. With a live attenuated vaccine the pathogen actually replicates in the patient’s body.
a. True
b. False 2. The innate immune system is crucial for inducing long-term immunity.
a. True
b. False
3. The adaptive immune response involves the activation of both the T cells and the B cells.
a. True
b. False
4. Subunit vaccines are safe to administer in patients who are immunocompromised.
5. Adjuvants are added to subunit vaccines to enhance and prolong immune response.
a. True
b. False
6. Closely spaced primary vaccine doses may be administered when a rapid induction of protection is desirable. This raises less persisting responses than when the same number of vaccine doses are given at longer intervals.
a. True
b. False
7. The response to subunit vaccines is comparable to “wild” type infection.
a. True
b. False
8. Multiple immunizations can be administered at a single time at different sites as the antigenic response will occur at different regional lymph nodes.
a. True
b. False 9. Memory B cells are crucial for long-term immunity as they consistently produce
antibodies to maintain this memory.
a. True
b. False 10. Adjuvants are not used in a large amount of vaccines as they dramatically increase the
risk of adverse effects.
a. True
b. False
Immunology Basics
Immunology is a complicated subject and a detailed review is beyond the scope of this lesson. For professionals administering immunizations, knowledge of the basic function of the immune system is useful in order to understand the physiological effect of vaccines once injected and the basis of recommendations for their use.1 Immunity is the ability of the human body to protect itself from infectious diseases. Some of the key concepts are innate immunity, passive immunity, and adaptive (active) immunity.
Innate Immunity Innate immunity refers to nonspecific defence mechanism that comes into play immediately or within hours of an antigen appearing in the body. It is activated by chemical properties of the
antigen. The mechanisms of the innate immune system include anatomical barriers, secretory molecules and cellular components. These defence mechanisms are common amongst all normal individuals as they are born with them. Innate immunity comprises the inborn immune mechanisms that do not depend upon previous exposure to an antigen.2 Table 1 lists some of the key components of the innate immune system. One major component of the innate immune system is the antigen non-specific disease mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. Unlike adaptive immunity it does not recognize every possible antigen. It is designed to recognize molecules shared by groups of related microbes. These molecules include a wide number of highly conserved microbial structures and are called pathogen-associated molecular patterns (PAMP). Most of the body’s defence cells have pattern-recognition receptors (PRR) for these PAMP and so there is an immediate response against the invading microorganism. The steps involved in the innate system are listed below:
1. A foreign substance such as a toxin or microbe breaches the physical barriers of the innate immune system.
2. Pathogen-associated molecular patterns (PAMP) are recognized by pattern-recognition receptors (PRR).
3. PRR are on a large variety of defence cells including phagocytic cells (neutrophils, monocytes, macrophages), cells that release inflammatory mediators (basophils, mast cells and eosinphils), and natural killer cells (NK).
4. This binding promotes the release of inflammatory cytokines that are crucial to initiating the innate and adaptive immune system. Cytokines trigger innate immune defences such as inflammation, fever and phagocytosis in order to provide an immediate response against the invading organism They also stimulate the complementary immune response which promotes lysis of cells and phagocytosis of the infecting pathogen.
5. On the dendritic cells of the defence system there is a certain type of PRR called toll-like receptors that are responsible for the activation of the adaptive immune system.
Key points regarding the innate immune system:
• It is a fast-acting and immediate response to a foreign pathogen. • First line of defence. • It stimulates the adaptive immune response. • Innate immune response does not improve with repeated exposure to a given infection. • It has no memory of the invading pathogen.
Table 1- Components of the Innate Immune System3,4
• The integrity of the epidermis and mucosal membranes that are impermeable to most infectious agents
Physicochemical barriers
• The acidity of the stomach fluid
Antibacterial substances
• Fatty acids in sweat inhibit the growth of bacteria. • Lysozyme and phospholipase found in tears, saliva and nasal secretions can breakdown
the cell wall of bacteria and destabilize bacterial membranes. • The low pH of sweat and gastric secretions prevents growth of bacteria. • Defensins (low molecular weight proteins) found in the lung and gastrointestinal tract
have antimicrobial activity. • Surfactants in the lung act as opsonins (substances that promote phagocytosis of particles
by phagocytic cells).
Mechanical Factors • Normal intestinal transit and normal flow of bronchial secretions and urine eliminate infectious agents from the respective systems.
Biological Factors • The normal flora of the skin and in the gastrointestinal tract can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces.
Passive Immunity Passive immunity is immediate protection provided through the transfer of antibodies from immune individuals.1 This is most commonly passed through the placenta from mother to neonate and less commonly through the transfusion of blood or blood products including immunoglobulin.1 The cross-placental transfer of antibodies from mother to child is more effective against some infections (e.g. tetanus and measles) than for others (e.g. polio and whooping cough).1 With passive immunity the protection is temporary and commonly for only a few weeks or months.1
Adaptive (Acquired) Immunity Adaptive or acquired immunity is the specific protective mechanism as a consequence of infection with a disease causing agent or by deliberate immunization against that disease with vaccination.2 The adaptive immunity is quite different from the innate system as it:
• Is designed to remove a specific antigen. • Takes several days to become protective. • Immunity is long-term and can even persist for a lifetime.
The adaptive immune response involves two systems including humoral immunity and cell-mediated immunity. It starts with antigen exposure An antigen is any substance (usually a protein or polysaccharide on the surfaces of viruses and cells) and is able to induce an immune response. These compounds are recognized by the immune system as foreign to the body. If the antigen is sufficient to elicit a response, they will activate the innate immune system (listed above) and immature dendritic cells that patrol throughout the body. When the toll-like receptors of the dendritic cells are exposed to an antigen they undergo brisk maturation, modulate specific surface receptors and migrate towards secondary lymph nodes, where the induction of T and B cell responses occur (cell mediated and humoral immunity).5 Cell-mediated immunity The mature dendritic cells (antigen presenting cells) provide antigen-specific and costimulation signals to T cells. These “danger signals” are required for the naïve T cells to mature into immune effector T4 or T8 cells.5 Effector lymphocytes are immune cells that encounter an antigen, proliferate and mature into a form capable of actively carrying out immune defences. The activated effector T4 cells have a variety of functions for the immune response. T-helper cells regulate the immune response with the cytokines they produce. The main functions of the effector T4 cells include:
• Stimulating the immune response of other cells such as the B-cells to produce antibodies (discussed later).
• Differentiating into T helper 1 (Th1), T helper 2 (Th2) and T helper 17 (Th17) cells. o Th1 cells produce cytokines that promote cell-mediated immunity especially
against intracellular microbes (such as viruses) by activating macrophages and cytotoxic T-lymphocytes. They also promote antibody production.
o Th2 cells produce cytokines that promote responses to helminths (parasitic worms) and allergens. They also promote the production of antibodies that neutralize microbes and toxins.
o Th17 cells promote inflammation and attracts neutrophils. It may help to remove extracellular organisms from the body.
The activated effector T8 cells are also known as the cytotoxic T lymphocytes. These cells are one of the body's major defences against viruses, intracellular bacteria, and cancers. They help to destroy infected cells and tumour cells. They recognize infected cells that have the specific antigen they were presented with by the mature dendritic cells and destroy these cells. Humoral immunity
Another key component of our immune system is humoral immunity. This process is initiated with B-lymphocytes. Naïve B lymophocytes are produced in the bone marrow and circulate until they encounter a protein antigen to which their specific surface IgM receptor binds.5 Antigen binding initiates the B cell activation and drives antigen-specific B cells towards the outer T cell zones of the secondary lymph node tissues.5 At this location, antigen-specific B cells are exposed to recently (<24 h) activated dendritic cells and T cells and they provide B cell activating signals. The interaction with the T cells helps rapidly drive B cell differentiation into antibody secreting plasma cells.5 Antibodies are proteins found in the blood that are produced in response to foreign substances (i.e. bacteria or viruses invading the body). Antibodies protect the body from disease by binding to these organisms and facilitate their destruction by a variety of mechanisms. Memory cells When the B-cells are differentiating into plasma cells that secrete antibodies a portion of these cells are converted to memory cells. These memory cells do NOT produce antibodies and do not protect the body like plasma cells. The pool of B-memory cells migrate to lymph nodes, to mucosal tissue, and circulate in the blood waiting to encounter the original antigen if it enters the body again (i.e secondary exposure). If they are re-exposed to the specific antigen, they rapidly convert to antibody secreting plasma cells. Some unique characteristics of the memory B cells are:5
• They are only generated in the initial cell mediated immune response described above. • They are resting cells that do not produce antibodies. • Memory cells undergo affinity maturation during several (4-6) months. • They rapidly (within days) differentiate into antibody secreting plasma cells upon re-
exposure to the antigen. This leads to a rapid response if the body is re-exposed to the pathogen, sometimes the infection is so mild the patient is unaware they are even infected.
• The antibodies they produce have a higher affinity than those produced by the primary plasma cells.
• Upon re-exposure to the antigen, they can convert to plasma cells with lower amounts of antigen and without the help of T-helper cells.
• They are believed to be responsible for long-term or even lifelong immunity.
The primary role of vaccines is to induce active (adaptive) immunity and provide
immunological memory.1 This is best achieved through immunization programs capable of activating the adaptive (active)
immune system as it induces long-term protection.5
Long-term immunity with vaccination is
only possible through the maintenance of antigen-specific immune memory cells that may be sufficiently efficient and can rapidly reactivate into immune effector cells when
exposed to the natural disease.5
Clinical Tip:
Multiple immunizations can be administered at a single time at
different sites as the antigenic response will occur at different regional lymph
nodes.
Vaccines can be made from inactivated (killed) or attenuated live organisms, secreted products (e.g. tetanus toxoids), recombinant components or the constituents of cell walls. Some vaccines contain inactivated bacteria or viruses. Other vaccines contain only the antigens that are important for protection. The ability of a vaccine to exhibit its response in the body is determined by the type of vaccine administered. These include live attenuated vaccines, inactivated vaccines and subunit vaccines Live Attenuated Vaccines This type of vaccines contains whole, living bacteria or viruses that induce their immunity by actively replicating within the host.6 Live vaccines are attenuated which means the vaccine strains are weakened so that the infection is usually not apparent or very mild in contrast to the natural or “wild” infection. The organism in the vaccine replicate within the person and it mimics a natural infection. Following injection microorganism particles rapidly disseminate throughout the vascular network and reach their target tissues.5 This replication and dissemination throughout the body stimulates dendritic cells at multiple sites in the body and causes their migration to multiple lymph nodes.5 This leads to a multiple foci T and B cell activation.5 With this large immunogenic response most recipients produce immunity with one dose.7 Live attenuated vaccines are contraindicated in patients with immunodeficiencies as these vaccines can lead to uncontrolled replication of the vaccine virus. This includes patients such as those with long-term immunosuppressive therapy for organ transplantation [high dose steroid therapy (≥ 2mg/kg/day, or ≥ 20 mg per day for ≥ 14 days], chemotherapy, or immunosuppressive agents such as cyclosporine) and in inflammatory conditions (i.e. inflixmab for inflammatory bowel disease or arthritis).6 Patients who are immunocompromised have no absolute contraindication for live attenuated vaccines early in the course of their illness, but as their condition progresses the risk of using live vaccines also increases.6
Inactivated Vaccines The vaccine contains killed bacteria or virus therefore there is no risk of uncontrolled replication of the virus in immunocompromised persons.6 While these vaccines can induce broad immunity when multiple antigens are present, the immune response might be blunted in persons who are not fully immunocompetent.6 With the absence of microbial replication seen with live attenuated vaccines, vaccine induced activation remains more limited both in time and space.5 Non-live vaccines activate innate response at their sites of injection and the site and route of administration is more important than with live vaccines.5 Most of these vaccines should be injected in a well vascularised muscle as they contain a large number of patrolling dendritic cells capable of interacting with the vaccine.5 Subcutaneous injections are generally less effective due to the limited number of dendritic cells in the adipose tissue.5 Adjuvants (discussed later) are commonly added to these formulations to increase immune response. Inactivated vaccines almost always require multiple doses. The first dose does not produce protective immunity, but “primes” the immune system.7 A protective immune response develops after the second or third dose.7 Unlike live vaccines, the level of response is not comparable to a “wild” infection and the protection provided by the vaccine will diminish over time.7 For this reason some inactivated vaccines may require periodic supplemental doses to increase or “boost” antibody levels.7 Subunit Vaccines Subunit vaccines contain purified products that usually come from the bacteria or virus that causes the natural infection but may also be synthesized using recombinant technology.6 The end products include proteins, polysaccharides and protein-polysaccharide conjugates.6 These vaccines have excellent safety profiles and facilitate the preparation of a variety of combination products with multiple antigens to different infections.7 The disadvantage of these products is they do not elicit a high immune response compared to live vaccines.6 The adaptive immune response to a subunit vaccine varies according to whether the vaccine antigen is a protein or a polysaccharide. Subunit vaccines based on protein antigens or conjugated polysaccharide-protein antigens are T-dependent vaccines whereas polysaccharides generate a T-independent response.8 Of special note in this group are the polysaccharide-only antigens. The polysaccharides to do not elicit a large local immune response and they reach the lymph nodes not through activated dendritic cell transport but through the blood. They reach the marginal zones of the lymph nodes and bind to B-cells that undergo maturation to plasma cells independent of the T helper cells. This leads to a significantly poorer response and does not stimulate the production of memory cells. This leads to a rapid decrease in antibody protection over a short period of time. Revaccination with certain polysaccharide immunizations may even induce a lower antibody response than the first immunization, a phenomenon known as vaccine hyporesponsiveness.5
The Differences Between Natural Infection and Vaccine Immunity There are two methods for achieving immunity to a microbe: natural infection and by
vaccination.9 Natural infection occurs when a patient is exposed to someone in the community with the disease, contracts the disease, and develops symptoms.9 The patient will contract the disease and develop symptoms. This infection can also lead to complications associated with the disease. Usually natural infection leads to the induction of memory and the patient is protected long-term.9 Vaccines can be used to stimulate the immune system to develop antibodies to the bacteria or virus. Unlike natural immunity it will normally require multiple injections to provide the same level of protection (exception is live attenuated vaccines). The response to some vaccines is not as long as natural infection and will require booster shots to provide long-term immunization. Both the natural infection and vaccine immunity will protect against infection from the bacteria or virus. The difference with vaccinations is that the person does not have to endure the illness and its potentially life-threatening complications to induce immunity.9
Adjuvants Adjuvants are commonly added to subunit vaccines and many inactivated vaccines to enhance the immune response. The incorporation of adjuvants into vaccine formulations is aimed at enhancing, accelerating and prolonging the specific immune response towards the desired response to vaccine antigens.10 Advantages of adjuvants include enhancement of the immunogenicity of antigens, modification of the nature of the immune response, reduction of the antigen amount needed for a successful immunisation, the reduction of the frequency of booster immunisations needed and an improved immune response in elderly and immunocompromised patients.10
• The only adjuvants currently used in routine immunization are the aluminum salts (aluminum hydroxide, aluminum phosphate or potassium aluminum sulphate).6 None of the currently available adjuvants trigger the degree of innate immune response that is elicited by live vaccines whose immune potency far exceed that of non-live vaccines.5
• The pH1N1 vaccine used an adjuvant containg DL-a-tocopherol, squalene and polysorbate 80. More information of this adjuvant is available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/legislation/interimorders-arretesurgence/prodinfo-vaccin-eng.php
Adjuvants are believed to increase the danger signals and trigger a sufficient activation of the innate immune system.5 These adjuvants:
• Are delivery systems that prolong the antigen deposit at the site of injection, recruiting more dendritic cells into the reaction.
• Are immune modulators that provide additional differentiation and activation signals to monocytes and dendritic cells.5
• Have been shown to be safe over decades of use.6 Rarely adjuvants cause injection site reactions including subcutaneous nodules, granulomatous inflammation (growth or lump) or contact hypersensitivity.6
Determinants of Vaccine Response There are a number of determinants that modulate the intensity of vaccine antibody response. These factors are listed in table 2.
Table 2 – Determinants of Vaccine Antibody Response5
Vaccine Type • The nature of the vaccine directly influences the activation of the innate immune system and vaccine response.
• Live attenuated vaccines have a significantly higher antibody response and persistence in the patient.
• Polysaccharide only antigens have limited immune response and no memory.
Vaccine Adjuvants and
Carrier Proteins
• The addition of adjuvants enhances immune response and extends the duration of B and T cell activation.
• Conjugating a polysaccharide with a carrier protein leads to a significantly higher immune response.
Optimal Antigen Dose
• Higher doses of non-live antigens (up to a certain threshold) elicit higher primary antibody responses.
Interval between priming doses
• Closely spaced (1–2 weeks) primary vaccine doses may be administered when a rapid induction of protection is desirable, e.g., prior to travel. However, this raises less persistent responses than when the same number of vaccine doses are given at longer (1–2 months) intervals.
• A minimal interval of 4 weeks between primary doses allows development of successive waves of antigen specific primary responses without interference.
Interval before boosting
• The maturing process of the memory cells takes several months. • A classical prime then boost immunization schedule allows 4-6 months to elapse
between priming and boosting doses. • This has lead to the development of the generic 0,1,6 month schedule for many
vaccines.
Age • Extremes of age of life have shorter antibody persistence. • Younger infants have immune system immaturity. • Older patients have a gradual deterioration of their immune system
• Patients who are immunocompromised are less likely to mount as good an antibody response as immunocompetent patients
Responding to the Concerns of Parents – Patient Counselling Tip
Immunization Myth – “Administering vaccines weakens and overloads the child’s immune system” 1
From birth and in early infancy and childhood, humans are exposed to countless numbers of foreign antigens and infectious agents in the everyday environment. Responding to these stimuli helps the
immune system to develop and mature. Compared with exposure in the natural environment, vaccines provide specific stimulation to a very small number of antigens. Responding to these
specific antigens uses only a tiny proportion of the capacity of an infant’s immune system. If an infant’s immune system could be exhausted by multiple vaccines, one would expect vaccinated
children to be at a higher risk of serious infections. Studies to investigate whether vaccines increase susceptibility to serious infections have shown no evidence of such an effect, with infection rates
generally being lower in vaccinated children.
Vaccine Immunology Summary Vaccine immunology is a complex subject. The information in this section only provides a quick and simplified overview of the factors responsible for appropriate vaccine response. A basic understanding of vaccine immunology is crucial to appreciate the interaction of these products with the immune system of patients. Visit www.AdvancingPractice.com to watch Dr. Simon Dobson summarize the primary and secondary immune response to a vaccine. Visit www.AdvancingPractice.com to watch Dr. Simon Dobson as he discusses the induction of memory cells and the role of booster immunizations using human papillomavirus as an example. Key Learning Points
1. The innate immune system is a non-antigen specific defence mechanism. It is comprised of physical barriers as well as a system to identify common pathogen-associated molecular patterns (PAMP) by pattern recognition receptors (PRR)
2. The innate immune system is fast-acting, stimulates the adaptive immune response, does not improve with repeated exposure and has no memory
3. Passive immunity is immediate protection provided through the transfer of antibodies from immune individuals. This is most common in pregnancy but can also occur through the transfusion of blood or blood products containing immunoglobulins. This protection is temporary
4. The adaptive immune system is an antigen specific defence mechanism. It normally takes several days to become protective but the immunity is long-term and can even persist a lifetime
5. Steps to a cell-mediated immune response include: o Dendritic cells exposed to the antigen at the site of infection mature and
modulate surface receptors and migrate towards the secondary lymph nodes o These mature dendritic cells present the antigen and help to activate naïve T-
cells o Effector T4 cells are helper cells that facilitate the humoral immune response o Effector T8 cells are cytotoxic cells that help to destroy infected cells
6. The humoral system is responsible for antibody production. Steps of humoral response
include: o An antigen binds to a naïve B-lymphocyte, activates the B-cell and drives the
specific B-cell towards the outer T-cell zones of the lymph nodes o Activated effector T4 cells cause the conversion of activated B-cells into
antibody secreting plasma cells o These antibodies protect the body from disease by binding to organisms and
facilitating their destruction by a variety of mechanisms
7. Most of the cells involved in the primary immune response die within a matter of weeks. If the immune response was sufficient a small number of B-cells are converted to memory cells. These cells:
o Do not produce antibodies o Rapidly mature to antibody secreting cells with re-exposure to the antigen
(secondary exposure) o Are believed to be responsible for long-term immunity
8. The goal of vaccines is to induce adaptive immunity and provide immunological
memory. This will help to protect the patient in the future if they are exposed to the wild disease
9. The key vaccine types are: o Live attenuated vaccines – Containing weakened virus or bacteria that replicate
in the body o Inactivated vaccines – Containing killed a bacteria or virus o Subunit vaccine – Containing purified products that usually come from the
bacteria or virus that causes the natural infection but may also be synthesized using recombinant technology. The end products include proteins, polysaccharides and protein-polysaccharide conjugates
10. Several factors can influence antibody response. These include:
o Vaccine type o Adjuvants o Antigen dose o Interval between priming dose o Interval before boosting o Age of the patient o Certain medical conditions
Discussion Forum 1. Vaccine immunology is a complex topic and can be difficult to explain to patients. Are there any strategies or education sources that you have found helpful when discussing this topic with your patients? 2. The antivaccine movement suggests that immunizations will overload or “use up” a child’s immune system. Do you have any counselling tips that you can share that helped when educating your patient on these myths? 3. Please describe two examples of information/key learning you acquired through this program that are immediately applicable to your practice and patient counselling
4. Are there any additional topics on vaccine immunology that you feel would be helpful?
Post Test
1. Which of the following is NOT a component of the innate immune response a. It is a non-specific immune response b. It is an inborn immune mechanisms that do not depend upon previous exposure
to an antigen c. It recognizes every possible antigen d. It is the first line of defence
2. Which of the following are the initial steps of cell-mediated immunity a. Antigen entry, exposed to toll-like receptors on dendritic cells, dendritic cell
mature and migrate to regional lymph nodes b. Antigen entry, activation of B-cells, this matures dendritic cells and stimulates T-
cells to produce antibodies c. Antigen entry, activation of T-helper cells and this stimulates antibody secretion
by the dendritic cells d. Antigen entry, T4 and T8 cells mature and start to release antibodies
3. Which of the following is true regarding memory B-cells? a. They are part of the innate immune response b. They secrete large amounts of antibodies to keep the levels high to prevent
reinfection c. Upon re-exposure to the antigen, they can convert to plasma cells with lower
amounts of antigen d. They can produce a large amount of antibodies if activated but the antibodies
have a lower affinity for the antigen 4. Which of the following statements regarding adjuvants is TRUE?
a. Most of the adverse effects with adjuvants can be minimized if they are injected subcutaneously
b. Adjuvants increase the danger signals and trigger a sufficient activation of the innate immune system
c. Adjuvants are normally added to all vaccine types to increase immune response d. Adding an adjuvant to a subunit vaccine triggers the innate immune response to
the same degree as a live vacccine 5. Which of the following factors determines the vaccine response?
a. Conjugation of with a carrier protein b. Interval between priming doses c. Age d. All of the above
Your colleague has called you to ask your opinion regarding one of his patients. He explains the patient is immunocompromised but through discussions is in need of some immunizations. He knows that you have a keen interest in immunization and he wanted your opinion.
6. Which type of vaccine should be avoided in immunocompromised patients? a. Live attenuated vaccine b. Subunit vaccine c. Inactivated vaccine d. Any vaccine with an adjuvant
7. If you were to give an inactivated vaccine to an immunocompromised patient which of the following is a concern?
a. Potential for growth of the virus or bacteria in the immunocompromised patient b. Site and route of administration is important to ensure full response from the
dendritic cells c. Blunted immune response due to being immunecompromised d. Both (b) and (c)
References
1. Salisbury D, Ramsay M, Noakes K. Immunisation against infectious disease. London: TSO; 2006.
2. Cruse J, Lewis R, Wang H. Immunology Guidebook. London: Elsevier; 2004. 3. Virella G. Medical Immunology. New York: Marcel Dekker; 2005. 4. Innate or non-specific immunity. Available at:
http://pathmicro.med.sc.edu/ghaffar/innate.htm [Accessed February 28, 2010]. 5. Plotkin S, Orenstein W, Offit P. Vaccines. London: Elsevier; 2008. 6. National Advisory Committee on Immunization. Canadian Immunization Guide. Seventh.
Ottawa, Ontario: Public Health Agency of Canada; 2006.
7. NCIRD. Pubs/PinkBook/Chapters. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/pink-chapters.htm [Accessed February 28, 2010].
8. Baxter D. Active and passive immunity, vaccine types, excipients and licensing. Occup Med (Lond). 2007;57(8):552-556.
9. Gold R. Your Child's Best Shot. 3rd ed. Ottawa, Ontario: Canadian Paediatric Society; 2006.
10. Committee for Medicinal Products for Human Use (CHMP). GUIDELINE ON ADJUVANTS IN VACCINES FOR HUMAN USE. London: The European Medicines Agency Evaluation of Medicines for Human Use; 2005.
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