Immunity and Vaccines LECTURE. pptx

Active immunity takes time to develop. It is superior to
passive immunity because (a) the duration of protection, like
that of the natural infection is frequently long-lasting
(b) with few exceptions, severe reactions are rare (c) the
protective efficacy of active immunization exceeds that of
passive immunization, and in some instances, approaches
100 per cent, and (d) active immunization is less expensive
than passive immunization. Vaccines are cheaper to produce
than are antisera. Elements which contribute to herd immunity are
(a) occurrence of clinical and subclinical infection in the
herd, (b) immunization of the herd, and (c) herd structure.
Herd structure is never constant. It is subject to constant
variation because of new births, deaths and population
mobility. An on-going immunization programme will keep up
the herd immunity at a very high level. Host defences against infection are at once local and
systemic, non-specific and specific, and humeral and
cellular. It is difficult to identify any infectious agent that fails
to stimulate multiple host defence mechanisms. The concept
of overlapping host defences is crucial to our understanding
of susceptibility to infection. This overlapping underlies the
reasonable measure of good health in the face of an
apparently significant host immune defect .Specific defences come into play, once microorganisms
have breached local defence mechanisms. By virtue of these
defences, the host is able to recognize, destroy and eliminate
antigenic material (e.g., bacteria, viruses, proteins, etc.)
foreign to his own. A person is said to be immune when he
possesses "specific protective antibodies or cellular immunity
as a result of previous infection or immunization, or is so
conditioned by such previous experience as to respond
adequately to prevent infection and/or clinical illness
following exposure to a specific infectious agent.active immunity depends upon the humoral and
cellular responses of the host. The immunity produced is
specific for a particular disease, i.e., the individual in most
cases is immune to further infection with the same organism
or antigenically related organism for varying periods
depending upon the particular disease.Humoral immunity comes from the B-cells (bone-marrow
derived lymphocytes) which proliferate and manufacture.
specific
antibodies
after
antigen
presentation
by
macrophages. The antibodies are localized in the
immunoglobulin fraction of the serum. lmmunoglobulins are
divided into 5 main classes - lgG, lgM, lgA, lgD and lgE .Moreover, many factors are involved in the maintenance
of immunity. Fatigue, strange surroundings, change of diet,
ingestion of drugs, and emotional shock are examples of
these factors that can produce a fall in immunity or a
lowering of the threshold at which resistance to infection
fails. Herd immunity (or community immunity) describes a type
of immunity that occurs when the vaccination of a portion.

1. Immun ity Dr . Hala Bashir Hashmi Community medicine

2. Learning o bjectives 2 To UNDERSTAND the immune system and how vaccines work in individuals and populations UNDERSTAND following terms: immunity, immunization, Vaccine, Vaccination Antibody , antigen Herd immunity

3. Learning Objectives 3 To understand the differences between Passive and Active immunity To understand how vaccines work To understand the differences between inactivated vaccines, toxoids and live vaccines Vaccination reactions, indications and contraindications

4. Definitions: Immune system = cells, tissues, and molecules that mediate resistance to infections Immunology = study of structure and function of the immune system “ it is a branch of biomedical science that covers the study of all aspects of the immune system in all organisms”

5. Immunity = resistance of a host to pathogens and their toxic effects “Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease or other unwanted biological invasion” Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system

6. Antigen 6 A live or inactivated substance (e.g. protein or polysaccharide) capable of producing an immune response “Anything that can be bound by an antibody”

7. Immunogen: It is a substance that is able to provoke an adaptive immune response if injected on its own. Immunogenicity: Ability to induce humoral or cell mediated immune response Antigenicity: Ability to combine specifically with the final products of the immune response.

8. Immunisation vs. Vaccination 8 Vaccination means administration of antigenic material ( vaccine ) to stimulate the immune system to develop adaptive immunity to disease. Immunization is the process whereby a person is made immune or resistant to an infectious disease, by administration of vaccine. means both receiving a vaccine and becoming immune to a disease, as a result of being vaccinated

9. Types of Immunity 9 Source: http://en.wikipedia.org/wiki/Immunological_memory

10. Immune system: Innate (natural) immunity 10 Physical barriers - skin and mucous membranes Chemical barriers – gastric and digestive enzymes Cellular and Protein secretions – lysozyme, complement, interferons, macrophages and white blood cells Defining characteristic: No memory persists afterwards

11. Adaptive (Acquired) immunity 11 The second level of defence Increases in strength and effectiveness with each encounter The foreign agent is recognised in a specific manner and the immune system acquires memory of it

12. Passive Immunity – adaptive mechanisms 12 Natural Maternal transfer of antibodies to infant via placenta Artificial Administration of pre- formed substance to provide immediate but short-term protection (immunoglobulin, anti- toxin) Give rapid protection within 48 hours Protection is temporary and wanes with time (usually few months)

13. Passive Immunity 13 Provided by administering Immunoglobulins for post-exposure prophylaxis e.g. Human Normal Immunoglobulin (HNIG) Collected from pooled human donations – contains antibodies to infectious agents common in the community, Hepatitis B immunoglobulin (HBIG), Varicella Zoster Immunoglobulin(VZIG), Rabies Immunoglobulin etc.  Involves using a blood derived product

14. Active Immunity – adaptive mechanisms 14 Natural Following contact with the organism Artificial Administration of agent to stimulate immune response ( vaccination ) Acquired through contact with a micro-organism / antigen e.g chickenpox, measles, rubella. following subclinical or in apparent infection e.g : polio, diphtheria. Protection often life-long but may need boosting

15. Active immunity 16 Humoral / Antibody mediated B cells Cell mediated T cells Killer / cytotoxic – destroy infected cells and micro- organisms Helper – stimulate and direct activity of B cells

16. Antibodies 17 Different types IgM, IgG , IgA, IgD, IgE Each antibody is specific for its antigen – no cross protection We have millions of different antibodies When B cells come into contact with their matching antigen, they are stimulated to divide into larger cells called plasma cells, which secrete huge amounts of antibodies

17. Antibodies - functions 18 These antibodies circulate and attack the micro-organisms that have not yet infected cells Antibodies gather on the micro-organism’s surface This blocks adhesion / cell entry of the antigen Neutralises and prevents organism’s replication Signals (cytokines) macrophages and other wbcs to come Kills organism via complement proteins – lysis Neutralises toxin Goal of vaccines is to stimulate this response

18. Ig G 80% of total immunoglobulin Secreted in high quantities in secondary exposures Cross the placenta Major functions neutralize microbes and toxins opsonize antigens for phagocytosis activate the complement protect the newborn 4-fold rise or fall indicates active infection A single positive sample indicates past exposure

19. Ig M Secreted initially during primary infection 6% of total immunoglobulins Cannot cross the placenta Major functions secreted first during primary exposure activates the complement Presence in newborn means infection Single positive sample in serum or CSF indicates recent or active infection Used to detect early phase of infection

20. Ig A 13% of immunoglobulins present in body secretions it provides primary defense mechanism at the mucous membrane

21. Immune response Primary immune response develops after exposure to antigen . latent period (3-10 days) IgM antibody ( next 2-3 DAYS reaches peak & then starts declining) IgG ANTIBODIES are formed( reaches peak in next 7-10 days and then declines over a period of weeks or month. Memory cells With kind permission from Nick Holmes Source: HPA 20

22. Secondary immune response is faster and more powerful Predominantly IgG antibody It has shorter latent period More rapid production of antibody Response is maintained for longer period of time Immune response and immunological memory cells are basis of vaccination and revaccination

23. Memory cells 24 After the body has eliminated the infection some of the B and T cells are converted into memory cells These can quickly divide into the specialised B and T cells if re-exposure to the infection occurs The immune system’s capacity to have a memory of previous encounters with an infection is the basis for vaccination.

24. Immunizing agents Vaccines Immunoglobulins antitoxins

25. Aim of an ideal vaccine 26 To produce the same immune protection which usually follows natural infection but without causing disease To generate long-lasting immunity To interrupt spread of infection

26. How vaccines work 27 Induce active immunity Immunity and immunologic memory similar to natural infection but without risk of disease Immunological memory allows Rapid recognition and response to infection Prevents or modifies effects of disease

27. Immune response to an ideal vaccine: 28 Vaccine is taken up by antigen-presenting cells activates both T and B cells to give memory cells antigen persists to continue to recruit B memory cells and produce high affinity antibody

28. Types of Vaccine 29 Live Attenuated Live organism with low virulence Inactivated Organism with no virulence Inactivated toxins “Toxoids” Subcellular fraction (incl conjugated vaccines) No virulence Genetically engineered Contains no original antigen product

29. Live attenuated vaccines 30 Weakened viruses / bacteria Achieved by growing numerous generations in lab Stimulates immune system to react as it does to natural infection Produces long lasting immune response after one or two doses Can cause mild form of the disease e.g. mini measles which is not transmissible CANNOT be given to immuno-compromised persons E.g. BCG / MMR / Varicella / Yellow Fever * when two live vaccines are required: -either they are given at different sites -or given with an interval of 3 weeks

30. Live attenuated vaccines Adverse effects Bacteria BCG Fatal dissemination of BCG infection, BCG osteitis Oral polio vaccine (OPV Vaccine- associated paralytic poliomyelitis (VAPP) in vaccines and their contacts (very rare at 0.0002–0.0004%) MEASLES Febrile illness, thrombocytopenic purpura, anaphylaxis Yellow fever Hypersensitivity reaction, vaccine associated neurotropic disease, Rota virus None reported virus

31. Inactivated vaccine 32 When adequate attenuation of live virus is not possible the vaccine is inactivated by chemical process or heat Less efficacious e.g cholera (50%) , pertussis (80% for 3 years Multiple doses Example: cholera, pertussis , IPV,covid-19

32. SUBUNIT VACCINES 33 Antigenic component of microorganism is used Toxoid Diphtheria, tetanus bacilli Protein vaccine Pertussis, influenza Recombinant vaccine Hepatitis B vaccine, covid-19 Polysaccharide base vaccine S. pneumoniae, salmonella Conjugated Pneumococcal, meningococcal

33. Conjugation Some bacteria (e.g. Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae ) have an outer coating of sugar molecules (called polysaccharides) Polysaccharide vaccines are poorly immunogenic in children under 2 years old and do not stimulate long term immunological memory Conjugate vaccines have enabled us to effectively protect children against Hib, Men C and pneumococcal diseases 30

34. C a rrier protein Polysaccharide linked to carrier protein Conjugate vaccine Ba c t er ia P o ly s a cc h a r i d e (sugar) coating Co n j ug a ti o n Conjugation is the process of attaching (linking) the polysaccharide antigen to a protein carrier that the infant’s immune system already recognises in order to provoke an immune response Source HPA 31

35. Components/excipients Adjuvant Antibiotics Preservatives stabilizers

36. What is the role of an adjuvant To enhance the immune response to the vaccine’s antigen Mode of actions are not precisely defined: To carry the vaccine antigen and to slow its release To provoke a local inflammatory response Activates innate cells E.g. Hep B, tetanus toxoid, diphtheria toxoid a d ju v an t e.g. Aluminium hydroxide 29

37. Examples of Vaccines 32

38. Live Attenuated Vaccines Disadvantage May reproduce features of the disease as sub- clinical or mild form of the infection May revert to virulent form (e.g. OPV) Cannot be given to immunosuppressed or pregnant patients 39 Advantage Potent, response close to the optimal naturally acquired immune response

39. Inactive Vaccines 40 Advantages Cannot cause infection Can be given to immunosuppressed and pregnant individuals Disadvantages Less immunogenic and require addition of adjuvants and booster doses

40. Do vaccines overload the immune system? 41 Within hours of birth, a baby’s gastrointestinal & respiratory tract are heavily colonised with bacteria Rather than overwhelming the immune system, vaccines help stimulate and strengthen it Immune systems need stimulation to develop well: allergies may result from too little immune stimulation in our cleaner environments There is no evidence that vaccines can overload the immune system. The immune system is designed to deal with a constant stream of foreign antigens on the surface and inside our bodies.

41. Vaccine failures 42 Primary failure an individual fails to make an adequate immune response to the initial vaccination (e.g. in about 10% of measles and mumps vaccine recipients) Infection possible any time post vaccination Secondary failure an individual makes an adequate immune response initially but then immunity wanes over time a feature of most inactivated vaccines, hence the need for boosters

42. Immunoglobulins Maternal IgG is transferred across the placenta Passively acquired IgG from mother can suppress response to DTP, Polio, and Hib vaccine for about 2 months Maternal antibody to measles may interfere for up to a year 37

43. .Normal human immunoglobulins e.g measles, hepatitis A .specific human immunoglobulins post exposure prophylaxis of hepatitis B, rabies and tetanus 44

44. 45 Avoids immune interference If another live vaccine is given while the immune system is making a primary immune response, the activation of the innate immune system may neutralise the second live vaccine so that it does not work. Hence we wait 4 weeks to allow the immune system to recover Human normal immunoglobulin contains antibodies to many infections including measles. These antibodies will neutralise any live vaccine. Hence we wait 3 months for the antibody level to fall

45. Time intervals between vaccine doses 46 Antigen combinations Recommended minimal interval between doses 2 or more killed vaccines No minimum interval Doses of same killed vaccine 4 weeks apart, 8 weeks for PCV Killed and live vaccines No minimum interval 2 or more live vaccines 4 week minimum interval if not administered simultaneously Immunoglobulin and live vaccines 3 months (12 weeks)

46. Adverse event following immunization (AEFI) 47 Vaccine reaction Immunization error Co-incident

47. Brain stroming Some vaccines against bacterial infections contain inactivated substances or chemicals (toxins and other compounds) that those bacteria make. A. True B. False Fever and soreness at the site of the injection are two mild reactions that may occur after getting a vaccine. A. True B. False

48. Dynamics of transmission 49 If an infection is to persist, each infected individual must, on average, transmit that infection to at least one other individual. If this does not occur, the infection will disappear progressively from the population

49. What is herd immunity? 50 The indirect protection from infection of susceptible members of the population, and the protection of the population as a whole, which is brought about by the presence of immune individuals

50. Herd immunity 51 To achieve herd immunity the percentage of individuals who need to be vaccinated depends on the disease and the vaccines used. Only for transmissible infectious diseases

51. Why herd immunity is important No vaccine is 100% effective e.g. measles vaccine is 90- 95% effective so out of every 100 children given the vaccine 5-10 will not be protected Some people unable to receive live vaccines e.g the immunocompromised Herd immunity is the most effective way of protecting people who do not respond to vaccines or can’t be given them for medical reasons 48

52. example Polio Diphtheria Small pox eradication Measles

53. Cold chain

54. S u mm a r y 55 It is possible to provide passive immunity by using immunoglobulins or active immunity by using vaccines. There are different types of vaccine manufactured by different methods Vaccines contain antigens resembling those of natural infections and stimulate the immune system to make a primary response and a memory response . Booster doses of vaccine reinforce the memory response Knowledge of how vaccines stimulate the immune system can be applied to answering questions such as scheduling intervals, age-dependent responses, the basis for non-response in some individuals, herd immunity and elimination of infection.

55. 56 k Park Textbook of preventive and social medicine 25th.pdf Immunity and How Vaccines Work, NIO http://www.immunisation.ie/en/Downloads/TrainingManual/PDFFile_16731_en.pdf How Vaccines Work, HPA, UK www.hpa.org.uk/webc/hpawebfile/hpaweb_c/1279888300493 Core Topic 2 Training Slides, HPA, UK 2012 http://www.hpa.org.uk/EventsProfessionalTraining/HealthProtectionAcademy/AdditionalOpportunitiesAndInformation/ImmunisationTrainingResources/hp acadvacc05SlideSetsforCoreCurriculumTeaching/ Concepts of Immunity, HPA www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1279889319696 How Vaccines Work, NIH – National Institute of Allergy and Infectious Disease US www.niaid.nih.gov/topics/vaccines/understanding/pages/howwork.aspx The Science of Immunisation; Q&A. Australian Academy of Science 2012 www.science.org.au/immunisation.html Power Point Lecture Presentations for Biology; 8 th Edition, Neil Campbell & Jane Reece. 2008 https:// www.google.ie/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&cad=rja&ved=0CEcQFjAE&url=http%3A%2F%2Fwww.unc.edu%2Fcourses%2F20 06spring%2Fenvr%2F133%2F001%2FENVR133_Lecture9.ppt&ei=wphzUp3CJeqw7Abf5ICIBA&usg=AFQjCNG5vLdm66i_7FmexsigYiui7OG2pA