Vaccination
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lecture about vaccination and immunity
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Vaccination
- 1. Presented by : pediatric resident Dr. Shaikah A.O.B Copyright : Shaikah.A.O.B @ 2018
- 2. vaccines represent the most cost-effective life-saving device in history. majority of vaccines have been developed empirically little or no understanding of the immunological mechanisms by which they induce protective immunity.
- 3. BUT.. failure to develop vaccines against global pandemics as (HIV) despite decades of effort has underscored the need to understand the immunological mechanisms by which vaccines confer protective immunity………
- 4. Question raised up … What is Human immune system in simple worlds ? What is vaccine and vaccination ? How vaccine work ? why booster doses in vaccinations ? What we have to know more for our practice ?
- 5. Introduction to immune system
- 6. Introduction: Immune system a vast communication network of cells and chemical signals distributed in blood & tissue throughout the human body which regulates normal growth and development of the organism while protecting against diseases Immunity is the ability of the human body to tolerate the presence of material indigenous to the body (“self”), and to eliminate foreign (“nonself”) material. This discriminatory ability provides protection from infectious disease, since most microbes are identified as foreign by the immune system. Immunization is the process of inducing immunity against a specific disease.
- 7. Our immune system Where is immunity is ? cellular It is every where tissues Primary Secondary LN Spleen Thymus BM
- 8. Key aspect of immune system Key cells Sentinel cells in tissue : Macrophage , DCs, Mast cell Circulating cells : NPH , LYPH, Eosinophil Tissue cells : epithelial cell
- 10. The immune system can be divided into three line of defense 3rd 2nd 1st
- 11. How we have immunity ? Acquired /
- 12. Immunoglobulin 1- Homologous human hyperimmune globulins donated plasma of humans , antibodies in lesser quantities ( 15-18% protein) used for postexposure prophylaxis 2-Heterologous hyperimmune serum (antitoxin) produced in animals, usually horses (equine), antibodies against only one antigen S.F: serum sickness reaction to the horse protein 3-monoclonal antibody Manufactory(They are mass-produced from a hybridoma, created by fusing an antibody- producing B cell with a fast-growing immortal cell such as a cancer cell) Only for prevention of respiratory syncytial virus (RSV) infection It is called palivizumab (Synagis).
- 13. PRODUCT MAJOR INDICATIONS Immune globulin for intramuscular injection Replacement therapy in primary immunodeficiency disorders Hepatitis A prophylaxis Measles prophylaxis Intravenous immunoglobulin (IVIG) Replacement therapy in primary immune-deficiency disorders Kawasaki disease Immune-mediated thrombocytopenia Pediatric HIV infection Hypogammaglobulinemia in ch.B-cell lymphocytic leukemia Hepatitis B Ig (IM) Postexposure prophylaxis Prevention of perinatal infection in infants born to HBsAg+ mother Rabies Ig (IM) Postexposure prophylaxis Tetanus Ig (IM) Wound prophylaxis Treatment of tetanus Varicella-zoster Ig (VZIG) (IM) or IVIG Postexposure prophylaxis of susceptible people at high risk for complications from varicella Botulism IVIG human Treatment of infant botulism Diphtheria antitoxin, equine Treatment of diphtheria
- 15. You know this ! 1966
- 16. History and Introduction: Vaccination the process of introducing a substance to a host. Vaccination named from (vaccini) is a cowpox , Used in 1796 AD to induce immunity to variola (smallpox) in humans by sir Edward Jenner Immunization the process of both getting the vaccine and becoming immune to the disease as a result of the vaccine.
- 18. deconstruction of vaccine live attenuated vaccines BCG MMR OPV chickenpox yellow fever Smallpox (variola ) Inactivated Vaccines subunit vaccines HBV toxoid vaccines diphtheria and tetanus conjugate vaccine HIB MCV4 carbohydra te vaccines PCV Whole cell IPV HAV Pertussis viral: polio, hepatitis A, rabies, influenza* bacterial: pertussis*, typhoid*, cholera*, plague
- 19. Inactivated Vaccines Live Attenuated Vaccines Cannot replicate Need adjuvant Less affected by circulating antibody than live vaccines Always require multiple doses Immune response mostly humoral Antibody titer diminish with time May require periodic supplemental booster doses Attenuated form of the “wild” virus or bacterium Must replicate to produce an immune response Immune response virtually identical to natural infection Usually produce immunity with one dose* Severe reactions possible Interference from circulating antibody
- 20. HOW VACCINE WORK ?
- 21. specific antigen-presenting cells (APCs), essentially dendritic cells (DCs)
- 22. FROM INNATE TO ADAPTIVE IMMUNITY ACTIVATION: THE FIRST STEPS AFTER INFECTION
- 32. Booster doses; why? First dose does not produce protective immunity, but “primes” the immune system. A protective immune response develops after the second or third dose. In contrast to live vaccines, in which the immune response closely resembles natural infection. The immune response to an inactivated vaccine is mostly humoral (Ab).
- 33. DISEASE HEALTHY PEOPLE 2010 COVERAGE GOAL FOR 19-35 MO Smallpox — Diphtheria 4 doses, ≥90% Measles 1 dose ≥90% Mumps 1 dose, ≥90% Pertussis 4 doses, ≥90% Polio (paralytic) 3 doses, ≥90% Rubella 1 dose, ≥90% Congenital rubella syndrome 1 dose, ≥90% Tetanus 4 doses, ≥90% H. influenzae type b and unknown (<5 yr) ≥3 doses, ≥90%
- 34. What we have to know for our practice ?
- 36. Time intervals between vaccine doses
- 37. CONDITIONS CAN AFFECT RESPONSE TO VACCINES Simultaneous administration of immunoglobulin Immunosuppression Sickle cell disease and other causes of hypersplenism Malnutrition and chronic disease Nephrotic syndrome Prematurity (some evidence premature babies may have sub-optimal response to Hib and Hep B vaccines but should be scheduled on basis of their actual date of birth)
- 38. highlighted side effect Generally common injection site reactions mild fever shivering Fatigue irritability •loss of appetite headache muscle and joint pain rare anaphyl actic reaction Specific PCV F .C. MMR Measles 11 wk Mumps 2-4 wk ITP 15-35d Encephalopat hy 6-12 days F.convu. OPV PPM DTP Encephalopat hy 0-22 d Seizures 0-2d HHE 0-24h BCG Suppurative LA 2-6 month BCG ostilitis 1-12month Disseminated BCG infection HBV GBS
- 39. Special situation : Primary immunodeficiency : T lymphocyte (cell-mediated and humoral) • All live vaccine B lymphocyte (humoral) • BCG,OPV,Typhoid Phagocytic function (Chronic granulomatous disease, leukocyte adhesion defect) • Only live bacterial vaccine Complement deficiency • No contraindication Need frequent PCV and MCV
- 40. SECONDARY immunodeficiency disease SPECIFIC IMMUNODEFICIENCY CONTRAINDICATED VACCINES* RISK-SPECIFIC RECOMMENDED VACCINES* HIV/AIDS OPV[†] Smallpox BCG LAIV Withhold MMR and varicella in severely immunocompromised persons Pneumococcal Consider Hib (if not administered in infancy) and meningococcal vaccination Malignant neoplasm, transplantation, immunosuppressive or radiation therapy Live viral and bacterial,depending on immune status[‡ Pneumococcal Asplenia None Pneumococcal Meningococcal Hib (if not administered in infancy) Chronic renal disease LAIV Pneumococcal Hepatitis B**
- 41. Thanks for your attendance
- 42. Reference Immunology and Vaccine-Preventable Diseases – Pink Book – Principles of Vaccination How Vaccines Work, NIH – National Institute of Allergy and Infectious Disease US How Vaccines Work, HPA, UK https://www.cdc.gov/vaccines/index.html
Editor's Notes
- Immunization is one of the most beneficial and cost-effective disease-prevention measures
- Adenoids begin forming in 3rd month of fetal development Palatine tonsils begin development in 3rd month of fetal development Fully formed by 7 month Tonsillitis most commonly affects children between the ages of 3 and 7, ***The thymus gland has dual embryonic origin. Thymic epithelium develops during the 6 week of gestation, from the ventral diverticular epithelium of the third pharyngeal pouch along with the thyroid and parathyroid gland Settled in يعسكر في معسكر camp
- First Line of Defense The primary defence against infectious disease are the surface barriers that prevent pathogens from entering the body These surface barriers include intact skin (protect external boundaries) and mucous membranes (protect internal boundaries) Both the skin and mucous membranes release chemical secretions which restrict the growth of microbes on their surfaces If pathogens cannot enter the host body, they cannot disrupt normal physiological functions and cause disease Second Line of Defense The second line of defence against infection are the non-specific cellular and molecular responses of the innate immune system These defences do not differentiate between different types of pathogen and respond the same way upon every infection Phagocytic leukocytes migrate to infection sites and engulf foreign bodies (dendritic cells then present antigens to lymphocytes) Inflammatory responses increase capillary permeability at infected sites, recruiting leukocytes but leading to localised swelling Antimicrobial proteins (such as cytokines and complement proteins) regulate immune activity within the body Fever increases body temperatures to activate heat-shock proteins and suppress microbial growth and propagation Third Line of Defense The final line of defence against infection are the lymphocytes that produce antibodies to specific antigenic fragments Each B cell produces a specific antibody, and the body has millions of different B cells capable of detecting distinct antigens Helper T cells regulate B cell activation, ensuring that antibodies are only mass-produced at the appropriate times Both B and T cells will differentiate to form memory cells after activation, conferring long-term immunity to a particular pathogen
- *Active immunity is stimulation of the immune system to produce antigen-specific humoral (antibody) and cellular immunity. Unlike passive immunity, which is temporary, active immunity usually lasts for many years, often for a lifetime. *Passive immunity often provides effective protection, but this protection wanes (disappears) with time, usually within a few weeks or months. infant receives from its mother. Antibodies are transported across the placenta during the last 1–2 months of pregnancy. As a result, a full-term infant will have the same antibodies as its mother. These antibodies will protect the infant from certain diseases for up to a year Primary immune response develops in the weeks following first exposure to an antigen Mainly IgM antibody Secondary immune response is faster and more powerful Predominantly IgG antibody
- Ig: 1- Homologous human hyperimmune globulins are antibody products that contain high titers of specific antibody. These products are made from the donated plasma of humans , However, since hyperimmune globulins are from humans, they also contain other antibodies in lesser quantities. Hyperimmune globulins are used for postexposure prophylaxis for several diseases, including hepatitis B, rabies, tetanus, and varicella. 2-Heterologous hyperimmune serum is also known as antitoxin. This product is produced in animals, usually horses (equine), and contains antibodies against only one antigen, antitoxin is available for treatment of botulism and diphtheria. A problem with this product is serum sickness, an immune reaction to the horse protein. 3- monoclonal antibody product is available for the prevention of respiratory syncytial virus (RSV) infection. It is called palivizumab (Synagis).
- usual dose of IG is 100 mg/kg or 0.66 mL/kg monthly. The usual interval between doses is 2-4 wk depending on trough IgG concentrations ( I.M) ((subcutaneous (SC) human IG, which has been licensed to treat patients with primary immunodeficiencies.)) The major indications for passive immunity are to provide protection to immunodeficient children with B-lymphocyte defects who have difficulties making antibodies, persons exposed to infectious diseases or who are at imminent risk of exposure where there is not adequate time for them to develop an active immune response to a vaccine, and persons with an infectious disease as part of specific therapy for that disease IG contains 15-18% protein, is predominantly IgG S.F of IG is pain and discomfort at the injection site and, less commonly, flushing, headache, chills, and nausea. More-serious (rare) included chest pain, dyspnea, anaphylaxis, and systemic collapse. Patients with selective IgA deficiency can produce antibodies against the trace amounts of IgA in IG preparations and develop reactions after repeat doses. These reactions can include fever, chills, and a shocklike syndrome IG contains 15-18% protein, is predominantly IgG ( I.M) IVIG Reactions to IVIG range from 1 to 15%. Some of these reactions appear to be related to the rate of infusion and can be mitigated by decreasing the rate. Such reactions include fever, headache, myalgia, chills, nausea, and vomiting. More serious reactions rarely have been reported, including anaphylactoid events, thromboembolic disorders, aseptic meningitis, and renal insufficiency
- https://www.youtube.com/watch?v=I_xh-bkiv_c
- A young Brazilian child, photographed in 1966, whose skin has lesions caused by the milder form of the smallpox virus, variola minor
- inoculation or variolation” (for smallpox).Variolation (inoculation)- introduced to Europe from Turkey by , who witnessed variolation in Istanbul, came back UK and had her daughter inoculated. She then advised the royal family to have their children inoculated .As a safeguard, the procedure was first tested on six prisoners (death penalty). All survived and pardoned. Royal children inoculated and survived and variolation became fashionable in Europe in In August 1721, In 1796, Jenner vaccinated James Phipps, did more vaccinations in 1798, and was the first to publish evidence that cowpox protected against smallpox, was safer than variolation, and that his vaccine could be maintained by arm-to-arm transfer.
- Currently available whole-cell inactivated vaccines are limited to inactivated whole viral vaccines (polio, hepatitis A, and rabies). Inactivated whole virus influenza vaccine and whole inactivated bacterial vaccines (pertussis, typhoid, cholera, and plague) are no longer available in the United States. Fractional vaccines include subunits (hepatitis B, influenza, acellular pertussis, human papillomavirus, anthrax) and toxoids (diphtheria, tetanus). A subunit vaccine for Lyme disease is no longer available in the United States. ***toxoid
- 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 releas e To provoke a local inflammatory response Activates innate cells E.g. Hep B, tetanus toxoid, diphtheria
- Time intervals between vaccine doses Allows each immune response to develop – e.g. primary immunisation (1 month) This allows the next response to be a true secondary response – i.e. faster and bigger and with higher affinity Ig G Time intervals between vaccine doses 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
- injection site reactions (pain, swelling and redness)