immune system + vaccine principles

1a) role of key cells in immune system

< blood stem cells in bone marrow —> branch into:
1) myeloid stem cells producing:

red blood cells (carry oxygen)

platelets (clot blood)

myeloblasts - develop into granulocytes ( engulf bacteria), eosinophils (defend against parasites + contribute to allergic reactions) + basophils (release histamine during inflammation)

2) lymphoid stem cells forming lymphoblasts

—> mature into B lymphocytes (make antibodies for specific pathogens), T lymphocytes (kill infected or abnormal cells) and NK cells (destroy virus infected + cancer cells without prior activation

1b) role of organs in the immune system

< bone marrow makes blood stem cells which develop into all white blood cells

< thymus is where T lymphocytes mature and recognise harmful invading pathogens

< lymph nodes are small filtering centres which trap germs + allow immune cells to communicate and activate

< spleen filters blood, removes old cells + helps mount immune responses to blood borne pathogens

< tonsils + adenoids guard the entrance to throat + nose + help detect germs that enter through mouth or airways

< mucosa e.g. in nose, digestive tract + respiratory tract - contains immune cells that provide a first line of defence at body surfaces

< skin acts as a physical barrier, stopping pathogens from entering body

1c) how do molecules contribute to immune response elicited by vaccines

< when vaccine given - it stimulates immune response to produce coordinated response involving several important molecules

< antibodies are proteins produced by B cells that specifically bind to antigens in the vaccine - they neutralise pathogens + mark them for destruction by other immune cells

< vaccination triggers release of cytokines are signalling molecules that mediate + regulate immunity, inflammation + haematopoiesis - they include interleukins, interferons + tumour necrosis factors

< complement system: group of proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens from an organism - play a role in inflammation and pathogen lysis

2) innate immunity

< first line of defense

< responds quickly to pathogens in a nonspecific manner

< rapid response

< involves: macropahges (primary white blood cells), natural killer cells, dendiritc cells, neutrophils, eosinophils, basophils

< T cells and NK cells

adaptive immunity

< slower response

< highly specific to particular pathogen with an ability to remember past infections

< leading to a more rapid and efficient response upon subsequent exposures to the same pathogen

< involves T cells + NK cells

< involves B cells which produces antibodies

< involves T cells (CD4+ CD8 cells)

what is a vaccine?

< a biological substance which safely stimulates the immune system to recognise and defend against specific pathogens, preventing further infection + illness

< work by introducing either weakened organisms, killed organisms, or purified components of a pathogen to train the immune system to respond more effectively when exposed later

live attenuated vaccines

< contained pathogens that have weakened so they can replicate only poorly within the body and cause only a mild controlled infection

< more effective - real infection at appropriate body site, induces appropriate immune response to the pathogen

< examples include measles, mumps, rubella, yellow fever and BCG

< these vaccines provide long-lasting immunity and produce immune responses similar to natural infection including induction of IgA and cytotoxic T cells

< attenuation can be achieved by: serial passage through culture in vitro, e.g. polio (sabin oral vaccine), growth at a low temperature or genetic modification, although a theoretical risk exists that the organisms could revert to virulence so live vaccines are unsuitable for people who are immunocompromised

< inexpensive, sometimes given orally, often provide long-term protection without adjuvants

< however, they require careful handling and cold storage and are not appropriate for immunocompromised individuals

< immune response: igG, IgA, cell mediated (cytotoxic T cells for viral infections)

inactivated killed vaccines

< contain organisms that have been rendered non-replicating e.g by heat or chemical treatment

< safer as can’t cause infection but side effects may still occur

< organism can’t multiply, multiple doses are often required and immunity may be still shorter-lived

< vaccines usually induce mainly IgG responses and may not trigger strong cytotoxic T-cell activity

< e.g. inactivated polio, hepatitis A and influenza vaccines

subunit vaccines

< contain only selected components of a pathogen rather than the whole organism

< may consist of purified proteins, recombinant proteins, peptides or polysaccharides

< generally very safe but often require adjuvants, such as aluminium salts or lipid-based formulations to enhance immune responses

< several modern vaccines use this approach including pertussis, hepatitis B and the novavax covid 19

< safer, fewer side effects but require adjuvants, multiple injections,

< subunit vaccines include several sub-types:

< toxoid vaccines contain chemically inactivated toxins such as diptheria and tetanus,

< polysaccharide or capsule vaccines use bacterial surface carbohydrates

< conjugate vaccines link polysaccharides to carrier proteins in order to stimulate T and B cell immunity as seen in Haemophilus influenzae type b vaccine

< recombinant protein vaccines are produced in expression systems such as yeast or baculovirus

more recent technologies include

< virus-like particle vaccines, such as those against human papillomavirus, outer membrane vesicle vaccines against group B meningococcus and protein-polysaccharide conjugates

< in addition, recombinant viral vector vaccines use viruses (for example adenoviruses) engineered to express pathogen antigens inside host cells

< this strategy has been used for ebola and several SARS-CoV-2 vaccines

< nucleic acid vaccines, including DNA and RNA vaccines, deliver genetic instructions that allow host cells to produce the relevant antigen temporarily

< mRNA vaccines for covid-19 showed this technology, and similar approaches are being applied to RSV

non living vaccines

< such as killed and subunit forms

< safer and more stable

< but more costly to produce

< require injections and boosters

< need adjuvants to produce a sufficient immune response

< most vaccines currently in use are though to protect primarily by inducing antibody formation, although some modern designs aim to stimulate strong T-cell responses as well

herd immunity

< population immunity

< occurs when a large portion of a community (|herd) becomes immune to a disease, making the spread of disease from person to person unlikely

< the whole community becomes protected - not just those who are immune

< herd immunity can be achieved through vaccination or through previous infections

< important as it helps protect those who can’t be vaccinated, such as new-borns or individuals with certain medical conditions

importance of herd immunity

< for infections spread by person to person contact, risk of disease to a unvaccination person dramtically reduced if 80-95% population vaccinated

< NB not spread by person to person contact e.g. tetanus

why does herd immunity choice matter?

< it matters because of the concept of herd immunity

< when no, one is immunised, disease spreads through the population

< when some of the population is immunised, disease spreads through some of the population

< when most of the population is immunised, spread of the disease is constrained

variolation

< pus taken from a smallpox blister + introduced via a scratch to an uninfected person to confer protection

< practiced in africa and asia for centuries before first reports in europe