Vaccination and Intro to Mucosal Immunology Note PDF

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06.VACCINATION1. IMMUNISATIONA. Immunisation is the process whereby a person is made immune or resistant to an infectious disease B. Passive Immunisation: Immunity conferred by an antibody produced in another host. C. Active Immunisation: Resistance developed in response to stimulus by an antigen (i...

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06.02.2019

VACCINATION 1. IMMUNISATION A. Immunisation is the process whereby a person is made immune or resistant to an infectious disease B. Passive Immunisation: Immunity conferred by an antibody produced in another host. C. Active Immunisation: Resistance developed in response to stimulus by an antigen (infecting agent or vaccine) and is characterized by the production of antibodies by the host.

2. PASSIVE IMMUNISATION A. IgG can cross the placenta during pregnancy. Provides temporary protection, gone by 6 months. Some types of genetic immunodeficiencies may not be evident until this point. B. IgA is found in colostrum and breast milk and can line the GI tract in infants providing protection, but is not absorbed C. Presence of maternal antibodies may limit the infant’s response to live vaccines as they limit the vaccine strain’s ability to replicate. Wait until 12 months or provide booster. D. Pooled Ig: Total IgG immunoglobulin from plasma of >1,000 pooled donors e.g. IVIG E. Antitoxins such as those against the toxin of diphtheria, tetanus, botulism F.

Antibodies to virus such as rabies, hepatitis B virus (HBV), hepatitis C virus (HCV) may be used post-exposure to limit viral replication

G. Advantage: Immediate effect H. Disadvantages: short duration, may cause allergic reaction to Ig raised on other species, or due to difference between individuals (polymorphisms).

3. VACCINATION A. Vaccination is a method of giving antigen to stimulate the immune response through active immunisation. B. A vaccine is an immunobiological substance designed to produce specific protection against a given disease. Contains antigen. C. An adjuvant a substance which enhances the body's immune response to an antigen

4. IMMUNE BASIS OF VACCINATION I A. Secondary response: i.

Faster response

ii.

More antibody

iii.

Less IgM, more IgG (IgA or IgE)

iv.

Higher affinity antibody (affinity maturation)

5. KIMMUNE BASIS OF VACCINATION II To get started right away, just tap any placeholder text (such as this) and start typing. A. Human papillomavirus (HPV) is a very common sexually transmitted disease. Although commonly asymptomatic, almost all cases of genital warts and cervical cancer are due to HPV. B. The vaccine targets several “high risk” HPV types including HPV16, 18 (Cervix); HPV 6, 11, 16, 18 (Gardasil); HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 (Gardasil 9). C. Given to girls aged 12-13 years old.

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6. TYPES OF VACCINE Vaccines can be based on whole organisms, either live, attenuated or inactivated, or components of the infectious agent A. Live i.

Vaccination with live vaccinia virus elicits neutralizing antibodies that react with antigenic determinants shared with smallpox virus.

A. Attenuate live: ii.

Attenuated organisms replicate to a limited extent in the vaccinated individual but do not cause disease in healthy people.

B. Live attenuated: i.

Serial passage of virus in non-human cells may give rise to mutations that reduce virulence in humans.

ii.

Specific genes responsible for virulence of virus may be deleted or mutated in the vaccine strain, generating an immunogenic but avirulent virus.

B. Inactivated (killed vaccines):

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iii.

Can use heat or fixation, for example, with formalin. May not be as immunogenic, often include an adjuvant.

C. Toxoids: iv.

A chemically modified toxin, which is no longer toxic but is still antigenic.

D. Subunit: v.

Contains only the antigenic parts of the pathogen - those parts are necessary to elicit a protective immune response.

C. Polysaccharide (polypeptide) vaccine: i.

Purified or recombinant protein, or polysaccharide antigens can be given with an adjuvant. Polysaccharide vaccines are not immunogenic in children under 2 years of age, conjugate vaccines that use a polysaccharide linked to a protein.

7. B-CELL ACTIVAION To get started right away, just tap any placeholder text (such as this) and start typing. A. The BCR on the surface of a B cell can recognise antigen directly. However, they often require T cell help for activation. 3 signals

8. ANTIBODY ISOTYPE SWITCHING To get started right away, just tap any placeholder text (such as this) and start typing. A. Depending on signals, B cells can undergo isotype switching. Ex) change from making IgM (first one made) to either IgG, IgE or IgA

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9. SOMATIC HYPERMUTATION

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CONJUGATE VACCINES A. Bacterial polysaccharides are considered to be T cell – independent antigens. B. In order to generate maximal immune response, including isotype switching (IgG), somatic hypermutation and memory formation, these polysaccharides are linked to a carrier protein (“conjugate” vaccine). C. T cells specific for peptides derived from the carrier protein provide T cell help to the B cell response.

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TYPES OF VACCINE A. Live B. Live attenuated 5

C. Inactivated D. Subunit E. Toxoid F.

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Conjugate

12.

ADJUVANTS To get started right away, just tap any placeholder text (such as this) and start typing. A. In addition to the antigen, a vaccine will contain an adjuvant to enhance, modulate, and/or prolonging the immune response. B. Aluminium in the form of alum, or more recently aluminium hydroxide and aluminium phosphate, is commonly used. C. Monophosphoryl lipid A (a TLR agonist) has been used in Cervarix since 2009.

13.

ROUTES OF ADMINISTRATION A. Deep subcutaneous or intramuscular route (many vaccines) B. Oral route (Rotavirus, Sabin polio vaccine, oral BCG vaccine) C. Intranasal route (live attenuated influenza vaccine) D. Intradermal route (BCG vaccine) E. Scarification (small pox vaccine)

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SCHEME OF IMMUNISATION A. Primary vaccination i.

One dose vaccines (measles, mumps, rubella, yellow fever, BCG, smallpox, )

ii.

Multiple dose vaccines (DTaP/IPV/Hib, HBV)

B.

Booster vaccination i.

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To maintain immunity level after it declines after some time has elapsed (e.g. MMR).

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FEATURES OF EFFECTIVE VACCINES A. Safe: Must not cause illness or death B. Protective: Must protect from illness resulting from exposure to live pathogens C. Gives sustained protection: Protection must last several years D. Induces neutralising antibody: Prevent infection, esp. of cells that cannot be replaced e.g. neurons E. Induces protective T cells: Some pathogens, particularly intracellular, are more effectively dealt with by T cells F.

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Practical consideration: Low cost, biological stability, ease of administration, few side effects

VACCINE EFFICACY A. Absolutely protective (100%): yellow fever vaccine. B. Almost absolutely protective (99%): Smallpox, measles, mumps, rubella vaccines, and diphtheria and tetanus toxoids. C. Highly protective (80-95%): polio, BCG (disseminated childhood disease), Hepatitis B, and pertussis vaccines. D. Moderately protective (40-60%): Typhoid, cholera vaccine, and influenza killed vaccine.

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LIMITATIONS OF VACCINATION A. Generating effective vaccine for some infectious diseases has proved to be very difficult i.

HIV

ii.

Tuberculosis

iii.

Malaria

B. Antigenic drift (and antigenic shift) of influenza virus necessitates a new vaccine on an annual basis.

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ARE VACCINE SAFE? 8

In general, vaccines have one of the best safety profiles of any medicine A. Common complications include:

19.

i.

Reactions at the injection site

ii.

Mild fever, shivering, fatigue, headache, muscle and joint pain

iii.

Allergic reactions to vaccine components

IMMUNITY IN A POPULATION A. Vaccines provide protection to the individual but may also provide protection to a population (including unvaccinated individuals) if the levels of immunisation are high.

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VACCINE EFFICACY A. As fewer children were vaccinated against measles virus, the incidence of measles infections increased.

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MUCOSAL IMMUNOLOGY 21.

MUCOSAL TISSUE A. The mucosal surfaces are major sites of antigen exposure. B. Need to control pathogenic microbes, overgrowth of commensal organisms but also prevent inappropriate responses.

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LYMPHOID TISSUE A. Primary lymphoid organs (thymus and bone marrow) are the sites of origin or maturation of lymphocytes B. Secondary lymphoid organs are where lymphocytes become activated. i.

Encapsulated: Lymph nodes (antigen from the tissues) and spleen (antigen from blood).

ii.

Non-encapsulated: Mucosa-associated lymphoid tissues (MALT) – antigen from mucosa. MALT represents the largest immune surface area and largest number of immune cells.

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