Adaptive immunity/vaccine lecture A&P2 exam 2

partial ag/ab binding

Partial antigens are too small to trigger B cell activation because they cannot bind to the MHC. This form of recognition is involved with the allergic response to antibiotics. Haptens + carrier molecule

conjugate vaccines

Polysaccharide coatings disguise a bacterium's antigens so that the immature immune systems of infants and younger children can't recognize or respond to them. When making a conjugate vaccine, scientists link antigens or toxoids from a microbe that an infant's immune system can recognize to the polysaccharides. link up toxins with something that immune sx will actuallyr ecog. when sees polysac it will respond.

Neutralization

Prevents recognition of cell surface markers by blocking recognition sites comes in, bind up to microbes/virsues, not allow them to gain access to cells b/c machinery that recog self and nonself,part of nonself not able to gain access to cell

Stimulation of inflammation

Stimulate basophils and mast cells (WBCs that release heparin and histamine)

general rule of vaccines

The more similar a vaccine is to the disease causing form of the organism, the better the immune response to the vaccine

antibodies

Y shaped composed of: ag bind site variable segment constant segments of heavy and light chains B cells produce FIVE types of constant segment heavy chains btw heavy and light chains is the ag binding site

abx =/ ab

abx kill bacteria by destroying their cell membranes or inhibiting their growth

IgE

attaches as an individual molecule to exposed surfaces of BASOPHILS and MAST CELLS releases histamine and other chemicals that accelerate inflammation in immediate area upon binding of suitable ag allergic response

antibody binding

bind epitopes (specific sequences or molecules on invaders not entire invaders) on the antigen complete ab binding: involve binding to b cells. both arms of ab bind to 2 diff epitoopes on ag Triggers B Cell sensitization. Most microorganisms can have multiple to thousands of epitopes

seven mechanisms of ab action

neutralization opsonization precipitations/agglutination/aggregation attraction of phagocytes prevention of bacterial adhesion activation of the complement system part of innate immune sx relies on proteases and cytokines

DNA vaccines

new technological/experimental level. These vaccines dispense with both the whole organism and its parts and get right down to the essentials: the microbe's genetic material. use the genes that code for those all-important antigens. not yet realized in humans

primary and secondary response to agi

primary resp is igm then igg takes over after that; igm barely involved in secondary response

west nile virus vaccine proposed mechansm

1) RNA (single stranded genetic info) extracted from west nile virus, destroying the virus. RNA converted into DNA which represents WNV genome 2) genetic sequence for WNV generated from DNA 3) base don dna seq, prmers specific to the prM and E gene region are produced. these primers willin turn be used to generate a cdna fragment containg both the prM and E genes 4) cdna fragment is then inserted into a ciruclar piece of DNA called a plasmid 5) the plasmid carrying the prM and E genes are grown in large quantities in bacteria andpurified by column chromatography 6)purified dna plasmids carrying the prM and E genes make up investigational vaccine

flu vaccine mechanism- antigentic drift

1) flu vaccine has 3 flu strains, 2 A and 1 B strain that change from year to year 2) s/p vaccination, your body produced infection fighting ab agst the three flu strains in vaccine. 3)upon exposure to any of the 3 flu strain, ab latch onto virus HA ag, preventing flu virus from attaching to healthy cells and infecting 4) influenza virus genes made of RNA are more prone to mutation than genes made of DNA 5) if HA gene changes, so can the ag that it encodes, causing it to change shape 6) if the HA ag changes shape, ab that normally would match up to it no longer can, allowing newly mutated virus to infect body's cells

overview of adaptive immunity process

1) sensitization: ab on inactiv b ell binds ag, becomes sensitized b cell 2)activation: helper T cell attaches to sensiztized b cel via class II mhc complex and activate, cytokine costimulation btw t and b cell 3) division and differentiation: activated b cell divides anddiffs into memory b cells and plasma cells. plasma -->ab production. this part is stimulated by cytokines. 1) b cell finds an ag whic matches its R 2) waits until it is activated by a helper T 3) then b cell dvided to produce plasma and memory cells 4)plasma cells produce ab that attach to current type of invader 5) eater cells prefer inruders marked with ab and eat loads of them 6) if same intruder invades again, memory cells help the immunze sx to activate much faster vaccines utilie this process to "install a virus protection program"

The four most successful vaccinations in medical history

1)polio 2) measles 3) tetanus 4) small pox: used material from cowpox postures to "vaccinate" people to small pox. (still appears in biological warfare discussions) other successful vaccinations: rabies, rotavirus, pertussis, typhoid, influenza, chickenpox, meningococcal, HPV

Cytomegalovirus (CMV)

60-90% of population have had CMV infections At least 5,000 birth defects each year in the United States alone.

Zoonoses

Alternative forms of rapid antigenic shift any disease or infection that is naturally transmissible from vertebrate animals to humans. may be bacterial, viral, or parasitic, or may involve unconventional agents. As well as being a public health problem, many of the major zoonotic diseases prevent the efficient production of food of animal origin and create obstacles to international trade in animal products. animals are acting as a reservoir for these virsues as well virus harbored in duck and human, if these come together, can swap genetic material. now genomes are scrambeled with a lot of new variation added into the flu virus. now its like having hybridzation among animals. now it is really different than what immune sx saw last time- wont recog ex: influenza harbored in avian wildlife, lyme dz harbored from ticks, rats habor plagque and hemorrhagic fever, dogs rabies and leptosporosis, cats --toxoplasmosis (cat litter preg women), cattle salmonela and e coli,

religion and antivax mvmt

An analysis of religious objections concluded that most were based on fear and misinformation rather than founded in the religious doctrines. Virtually no major religion has stated opposition to vaccination, the major exception being Christian Scientists. vatican point of view: it is right to abstain from using these vaccines if it can be done without causing children, and indirectly the population as a whole, to undergo significant risks to their health proportional reason, in order to accept the use of these vaccines in the presence of the danger of favouring the spread of the pathological agent, due to the lack of vaccination of children

Attraction of phagocytes

Antibodies attached to antigens attract eosinophils, neutrophils, and macrophages once ab have actually attached to invader these wbc come in and destroy pathogen

agglutination

Antibodies link large numbers of antigens together ab bind up all bad stuff, can ppt out or phagocytose

Malaria

Around 19% of infant LBWs are due to malaria and 6% of infant deaths are due to LBW caused by malaria.

The foundation of modern immunology

Enders had heard the tales that dairymaids were protected from smallpox naturally after having suffered from cowpox. Pondering this, Jenner concluded that cowpox not only protected against smallpox but also could be transmitted from one person to another as a deliberate mechanism of protection. In May 1796, Edward Jenner found a young dairymaid, Sarah Nelms, who had fresh cowpox lesions on her hands and arms. On May 14, 1796, using matter from Nelms' lesions, he inoculated an 8-year-old boy, James Phipps. Subsequently, the boy developed mild fever and discomfort in the axillae. Nine days after the procedure he felt cold and had lost his appetite, but on the next day he was much better. In July 1796, Jenner inoculated the boy again, this time with matter from a fresh smallpox lesion. No disease developed, and Jenner concluded that protection was complete.

Opsonization

Enhances phagocytosis of smooth antigens/microbes by allowing for more efficient binding polysacc coat to certain microbes- makes difficulty for body to recog- smooth opsonizatinon can bind to smooth polysac ag and get them out of bloo dstream

H7N9

Human infections with a new avian influenza A virus have been reported in China. The virus has also been detected in poultry. zoonoses domestic ducks + wild birds + domestic poultry--->take the diff viruses present in each, get multiple reassortment events when come into contact in shared habitats-->jump to infect humans dif strains of virus mix and match--->super virus that can run rampant thruout human pop

breast feeding and immunity

Human milk composition provides the standard for human infant nutrition, including the bioactive components that safeguard infant growth and development composition of human milk is variable within feeds, diurnally, over lactation, and between mothers and populations. This variability has benefits for infant health and survival, but for high risk infants requiring close nutritional oversight, supplementation, and strategies for managing the variability of human milk feeds are needed.

B cells produce FIVE types of constant segment heavy chains

IgG IgE IgD IgM IgA

subunit vaccines

Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system. Subunit vaccines can contain anywhere from 1 to 20 or more antigens chop up dead microbe in pieces send a little bit in. essential ag trigger immune resp trick is uncovering which are essential ag that will actually trigger immune resp in body pro: Because subunit vaccines contain only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower. con: Downside is that you don't know which antigens will trigger the immune response ex hepatitis B

immune sx of newborn babies stronger than previously thought

It was generally believed that babies have an immature immune system that doesn't trigger the same inflammatory response normally seen in adults. Although babies need to protect themselves from the harmful pathogens they are exposed to from birth, it was thought that their T cells were suppressed to some extent to prevent inflammatory damage to the developing child. discovered that whilst T cells in newborn babies are largely different to those in adults, it is not because they are immunosuppressed; rather, they manufacture a potent antibacterial molecule known as IL8 that has not previously been considered a major product of T cells, and that activates neutrophils to attack the body's foreign invaders

Rubella

Largely removed from the population due to vaccinations In an epidemic in Philadelphia in 1965, 1 percent of all babies were born with congenital rubella syndrome, which can also cause deafness, developmental disability, low birth weight and seizures

types of vaccines

Live, attenuated vaccines Inactivated vaccines Subunit vaccines Toxoid vaccines Conjugate vaccines DNA vaccines Recombinant vector vaccines once vaccines get in all kick up adaptive sx in similar ways but some diff using a little ag piece of dz causing organism may not be as efficient as entire organism that causes dz but still effective

Reasonable side effects to a vaccination (anthrax)

Mild Problems: Reactions on the arm where the shot was given: Tenderness (about 1 person out of 2) Redness (about 1 out of 7 men and 1 out of 3 women) Itching (about 1 out of 50 men and 1 out of 20 women) Lump (about 1 out of 60 men and 1 out of 16 women) Bruise (about 1 out of 25 men and 1 out of 22 women) Muscle aches or limitation of arm movement (about 1 out of 14 men and 1 out of 10 women) Headaches (about 1 out of 25 men and 1 out of 12 women) Fatigue (about 1 out of 15 men, about 1 out of 8 women) Severe Problems: Serious allergic reaction (very rare - less than once in 100,000 doses).

paper that fueled anti vax mvmt

Most misinformation stems from a 1998 article suggesting suggested that the measles, mumps, and rubella (MMR) vaccine may predispose to behavioral regression and pervasive developmental disorder in children (n = 12). This paper was partially retracted by the authors and fully retracted by the journal 1000's of papers have been published refuting those claims ($$$) In 2010, a five-member statutory tribunal found that Wakefield acted both against the interests of his patients, and "dishonestly and irresponsibly" in his published research

Prevention of bacterial adhesion

Most notably in the saliva, mucus, and perspiration

obstacles to vaccine availability

Toxicity/safety Poor efficiency Time (Phase 1, 2, 3 trials) Demand Profit

immunologic properties of human breast milk

cellularelements: macrophages (predominant cell), T and B cell lymphocytes non-cellular elements: immunoglobulins (secretory IgA, predominant also IgG, IgM, and IgE mucins- block infection by viruses and bactera cytokines: range of il stimulate a newborns immune sx; IL-6, 7, 8 ,10, FNgama, TGFbeta. cellular and noncellular cmpnts of breast milk contribute to immunity t and b cells transfered from mother to child from milk. giving immunity, now baby does not have to generate these things or be exposed to all these diff pathogens, picking it up from mom

Live, attenuated vaccines

contain a weakened version of the living microbe. closest thing to a natural infection, these vaccines are good "teachers" of the immune system: elicit strong cellular and antibody responses and often confer lifelong immunity with only one or two doses. easy to produce con: The remote possibility exists that an attenuated microbe in the vaccine could revert to a virulent form and cause disease. Usually need to be refrigerated to stay potent. can weaken with heat, radiation, diff chemicals. hurdle for worldwide/dvlping nation pop- ex ebola. practicality problem ex:Most successful again viral pathogens: measles, mumps, and chickenpox (but also cholera)

What other part of the flu virus could be targeted to avoid an evolutionary response?

could target other parts of the flu virus that are not variable to stop it from evolving but we have limited technqiues on targeting these. flu researchers are working on dveloping vaccines that target the nonvaraible parts of the virus b/c then could use same flu vaccine year by year until pop mutations are acquired. eliminate virus mutations, only pop mutations

IgM

first class of ab secreted after an ag is encountered igM concentration declines as IgG production accelerates IgM circulates as a five ab starburst anti A and anti B ab responsibile for the agglutination of incompatible blood types are IgM ab IgM ab may also attack bacteria that are insensitive to IgG first responder. then iggs kick in to do heavy lifting

IgA

glandular secretions like mucus, tears, saliva, semen attack pathogens before they gain access to internal tissues circ in blood as ind movleulces or in pairs epithelial cells absorb them from blood and attach a secretory piece, which confers solubility before secreiting the IgA molecules onto the epithelial surface restrictive group of ab. target ag before they get into body.

haptens and early pregnancy tests

hcg hapten carrier conugate and anti-hcg ab test procedure: urine + anti cg ===>incubate-->+hcg carrier conjugate--->observe for visible clumping possible reactions: negative rxn not pregnant: visible clumping b/c hcg remains on hapten carrier conjugate which binds anti hcg ab and clumps positive reaction, pregnant hcg in urine+ anti hcg ab + hapten carrier conjugate--->no visible clumping +hcg, prevents clumping by binding up with carrier conjugates

IgD

individual molecule on surfaces of B cells can bind ag in extracell fluid can play a role in sensitization of the B cell involved

IgG

largest and most diverse class of ab 80% of all ab resistance agst many viruses, bacteria, and bacterial toxins can cross the placenta, maternal IgG provides passive immunity to the fetus during embryo dvlpmt antiRh AB produced by Rh negative moters arealso IgG ab and produce HDN

anti vax mvmt

loosely organized subculture which blames modern vaccination for a wide range of health problems. Arguments range from vaccines are "unnatural," to vaccines cause disease, to vaccines contain mercury, to aborted baby parts are used as ingredients in vaccines, to vaccines are a form of government oppression, to implementation of socialized medicine, to vaccines promote social evils (big pharma), to vaccines contain government tracking chips. Vaccines cause autism, multiple sclerosis, SIDS 2/2 misunderstanding correlation vs causation crosses sociopolitical boundaries: *Each person that backs anti vax mvmt has a slightly different stance on the subject rarely based in medical or scientific consensus*

Inactivated vaccines

produced by killing the disease-causing microbe with chemicals, heat, or radiation. pro: more stable and safer than live vaccines: The dead microbes can't mutate back to their disease-causing state. Inactivated vaccines. don't require refrigeration, and they can be easily stored and transported in a freeze-dried form, con: Stimulate a weaker immune system response than do live vaccines. So it would likely take several additional doses, or booster shots, to maintain a person's immunity. ex: polio, annual flu shot

hemagglutinen

protein on outer coating of flu virus Current vaccines produce antibodies that recognize this protein; focus on "head" region which is good at stimulating the production of protective antibodies, but also most rapidly evolving and variable portions and most susceptible to antigenic drift. hemagglutinen- targetng what is going on in head region but ton of variation in that head region. ton of ability for natural selection to act on this variation

adaptive immunity

receptors: highly specific (T and B cell receptors) kinetics: slows days - weeks; regulated +; amplification +; self discrimination +; duration long (months/yrs); memory + immunity acquired from breast feeding and vaccines

vaccinations strategies

successful timing/scheds of vaccinations eliminate dz

the flu

three types of influenza virus-A, B and C -the A and B types can cause flu epidemics. - Influenza A virus is found in human and many other animals. -There are over 100 subtypes of Influenza A virus. -All subtypes have been found in wild birds, which are thought to be a natural reservoir of Influenza A virus and the source of influenza A viruses in all other animals. Flu viruses undergo mutations when they spread from place to place. Each year, it is essential to identify new flu virus variants and produce vaccines against them to avoid flu epidemics. affects small children, immunocompromised, and elderly poorly based on population and how evolving- mutations- dvlp new flu vaccines each year

recombinant vaccines

use an attenuated virus or bacterium to introduce microbial DNA to cells of the body. "Vector" refers to the virus or bacterium used as the carrier. pcr clone, stick in plasmid to generate a lot of it. bacteria do all heavy lifting, collect dna which becomes vaccine vector- picking up virus you know you can control, using that to deliver dna into carrier body. not yet realized in humans

toxoid vaccines

used when a bacterial toxin is the main cause of illness. Scientists have found that they can inactivate toxins by treating them with formalin, a solution of formaldehyde and sterilized water. Such "detoxified" toxins, called toxoids, are safe for use in vaccines. ex: prevention of diphtheria, tetanus and botulism

antigeneic drift

flu evolves in response to our antibodies. During the course of a flu epidemic, many people gain immunity to the strain of the virus that is currently circulating. Through the process of natural selection, any flu virus particles that happen to carry mutations that allow them to slip by the defenses of common antibodies will be favored, produce more copies of themselves, and eventually, spread to more new victims. *NATURAL SELECTION* exposed to flu strains, ab do job but some of the mutated viruses get thru that ab do not recognize, these move on to the next generation