Vaccines

Question 1

Immunization

Answer 1

• The process of eliciting a long-lived state of protective immunity agaist a disease causing pathogen. Can be achieved via
  
  • Exposure to live pathogen followed by recovery
  • Vaccination/intentional exposure to forms of pathogen that don’t cause the disease
• Immune protection can also be achieved via the transfer of antibodies from mother to fetus or through injection of antiserum against a pathogen.

Question 2

Passive Immunization

Answer 2

• Preformed antibodies are transfered to a recipient Ex.
  
  • When IgG crosses the placenta to the developing fetus.
  • By injecting preformed antibodies (antiserum) from immune individuals
• Goal - transient protection or alleviation of an exisiting condition
• Passive immunization does not activate host’s immune system and thus generated no memory response and protection is temporary.
• Passive immunization is used in cases when children are born with congential immune deficiencies, when unvaccinated people are exposed to certain organisms (ex. tetanus, diphtheria, hepatitis, measles, rabies), used against poisonus snake and insect bites.

Question 3

Active Immunization

Answer 3

• Exposure to a pathogen either through natural infection by the organism or artificially via vaccine
• In active immunization, the immune system plays an active role - proliferation of T & B cells is induced resulting in formation of protective memory cells.
• With active immunization, a second exposure to a pathogen agent elicitis a secondary immune response that eliminates the pathogen or prevents disease mediated by its products
  
  • Goal is to trigger active immune response so that it will elicit protective immunity and immunologic memory.

Question 4

Types of vaccines

Answer 4

• Live, attenuated vaccines
• Inactivated/killed vaccines
• Subunit vaccines
• Toxoid vaccines

Question 5

Live/attenuated vaccines

Answer 5

• Microorganisms are disabled so that they lose their ability to cause significant disease, but retain their abililty for transient growth
• Some organisms are naturally attenuated - cannot give disease to human host but can immunize (ex. cowpox).
• Advantages - capacity for transient growth makes it so vaccines provide prolonged immune system exposure and more closely mimic growth patterns of “real” pathogen. Results in efficient production of memory cells and often only requries a single immunization
• Disadvantage - Live forms may mutate and revert to virulent forms in vivo (extremely rare). May produce enough virus to infect other people, this can be a problem for immunocompromised people.

Question 6

Inactivated/killed vaccines

Answer 6

• Treat pathogen with heat or chemicals. This kills the pathogen and makes it incapable of replication, but still allows it to induce an immune response to some of the antigens within the organism.
• Often require repeated boosters to acheive a protetive immune status (first dose just “primes the system).
• Because the microorganism don’t replicate, inactivated vaccines elicit predominantely a humoral antibody response and are less effective than attenuated vaccines at inducing cell-mediated immunity or an IgA response, which are key compoents of mucosally based reponse.
• However, inactivated are safer than attenuated.

Question 7

Subunit vaccines

Answer 7

• Using a speciifc, purified macromolecule derived from the pathogen to elicit an immune response. They do not contain live components of the pathogen, but differ from inactivared vaccines by only containing the antigenic parts of the pathogen
• Types:
  
  • Protein-based vaccines - specific, isolated, protein of pathogen presented
  • Polysaccharide (PS) vaccines - some bacteria are protected by a PS capsule that helps the organism evade the immune system. PS vaccines create a response against the pathogen capsule. Often not very immogenic (not effective in young children, no immune memory). Induces T-indenpent reponse (only activates B1 cells (no co-stimulation) and thus only produces plasma cells and no memory).
  • Conjugate subunit - Also creates a response against the molecules pathogen capsule. However, they bind the PS to a carrier protein that can induce a long-term protective response. Allows from stimulation of B2 cells and results in a T-dependent response and thus the formation of memory B cells.

Question 8

Toxoid vaccines

Answer 8

• Based on toxin produced by vertain bacteria. These toxins invade the bloodstream and are responsible for the symptoms of the disease. In toxois vaccines, the protein-based toxin is rendered harmless (toxoid) and used as the antigen to elicit immunity.
• These vaccines cannot cause the disease, rarely cause reactions and are stable and long lasting. However, they may requrie several doses and usually need an adjuvant.

Question 9

Vaccine Physiology

Answer 9

1. Prior to antigen exposure there are no memory B cells specific for that antigen and no spontaneous secretion of antigen specific antibody
2. Exposure to antigen via vaccination activates naive B cells (requires multiple cellular and molecular interactions, including APC processing, B cells, antigen presentation to T cells via MHC and signaling by costimulatory molecules and cytokines).
3. B cells are activated and they proliferate and differentiate into plasma cells that secrete antigen-specific antibodies and long-lived nonsecreting memory B cells with antigen-specific surface immunoglobulin B cells receptors
4. When memory B cells encounter the specific antigen that triggered their production, they proliferate and differentiate into plasma cells more readily than naive B cells. This response is more rapid and produces more antibodies than the primary response.
5. Plasma cells may be short lived so ongoing low-grade proliferation and differentiation of memory B cells into plasma cells are needed to sustain protective antibody levels. Proliferation and differentiation of memory B cells may be spontaneous or result from intermittent antigen expsoure (i.e., through microbrial carrier state or from expsoure to cytokines produced by nearby T cells in response to unrelated antigens).

Question 10

Why vaccines are given at certain times

Answer 10

• Starts at 2 months of age - this is when inherited protection begins to wear off. Vaccines given before this time will likely just be cleared from the system.
• Recommendation for age tha vaccines are given based on age-specific risks for the disease, for complications, and for best response. Vaccines are generally recommended for members of the youngest age group at risk for experiencing the disease when efficacy and dafety have been shown.
• Although most live vaccines provide immunity after one dose some people don’t response - give a second dose as most people who don’t respond the first time respond the second time.
• Important to follow the immunization schedule - spacing that has been shown to develop the strongest immune response

Question 11

Adverse reaction to vaccination

Answer 11

• Minor reactions
  
  • Usually occur within a few hours of injection
  • Resolve after short time and pose litte danger
  • Local - pain, sweeling, or redness at injection site
  • Systemic - fever, malaise, muscle pain, headache, or loss of appetite
• Severe reactions
  
  • Usually do not result in long-term problems
  • Can be disabiling, but rarely life threatening (with treatment)
  • Includes seizures and allergic reactions

Question 12

Herd Immunity

Answer 12

• Prevention of spread of contagious disease within a population that occurs if a high enough proportion are immune to the disease.
• This is an important concept in vaccination as they are not 100% effective. With herd immunity, if most people are vaccinated it will protect people where the vaccine worked poorly.

Question 13

Function of Antibodies

Answer 13

• Activates B lymphoctyes
• Bind to pathogen and activate complement (forms membrane attack complexes causing cell lysis).
• Neutralize/immobilize antigen (completly coasts surface of antigen so that it is unable to do its normal function).
• Opsonization - bind to surface and promotes/enhnaces phagocytosis
• Antibody-dependent cellular cytotoxicity - antibody binds pathogen for targeted killing by NK cells.
• Triggers mast cell degranulation

Question 14

B cell activation

Answer 14

• There are 2 ways that naive B cells can be activated. One is completely dependent on assistance from helper T cells (T-cell dependent activation) and the second is independent of T cell help (T-cell indepdent actication).
• Regardless of the type of activation, B cell activation requries two signals.

Question 15

T cell dependent activation

Answer 15

1. Clustering of B cell’s receptors and their associated signaling molecule (receptor crosslinking). (This alone is not enough to fully activate a B cell - need a second signal).
2. In T-cell dependent actication, the second signal is supplied by helper T cells. The surface of an activated helper T cell has a protein called CD40L. When CD40L “plugs” into a protein called CD40 on the surface of B cells, the co-stimulatory signal is sent. If the B cells receptors has been crosslinked, the B cell is activated by this signal.

Question 16

T cell independent activation

Answer 16

1. B cells can also be activated without T cell help. This occurs when the antigen has may repeated epitopes on its surface, which can crosslink many B cells (polysacchaide antigens have this effect). The crosslinking of so many BCRs can partially substitute for co-stimulation by CD40L and result in B cell proliferation.
2. In this case, the second signal is a “danger signal” that indicated an attack is on. An example of is, is that B cells can recognize PAMPs that are characteristic of certain pathogens.

• This is an important response because helper T cells only recognize protein antigens (only peptides are presented on MHC II). So without T cell independent activation, many pathogens would be missed.

Question 17

T cell activation

Answer 17

• T cells must recieve co-stimulation to be activated.
• First, the T cell much bind to MHC, the next the T cell must recieve a co-stimulatory signal to be activated. The co-stimulation is an amplifer that strengthens the “I’m engaged” signal sent by T cell receptors. This lowers the threshold number of TCRs which much be crosslinked by MHC peptide complexes.
• A number of different molecules have been identified that can co-stimulate T cells. One of these are B7 proteins, expressed on the surface of APCs. B7 molecules provide co-stimulation to T cells by “plugging into receptor molecule CD28 on T cell surface.

Question 18

B cell memory

Answer 18

• When B cells are activated during initial response to an invader, three kinds of B cells are generated.
  1. Short-lived plasma B cell - produced in lymphoid follicles of secondary lymphoid organs. Cells than travel to the bone marrow or spleen and produce laarge quantities or antibodies.
• Two types of memory B cells are also produced. Generation of both types require T cell help.
  2. Long-lived plasma cells - takes up residence in bone marrow and continuously produce modest amounts of antibodies. It is these cells that make the IgG antibodies that can provide life-long immunity to subsequent infection. \
  3. Central memory B cells - reside in secondary lymphoid organ where they slowly proliferate to maintain a pool of central memory B cells to replace long-lived plasma cells. Futhermore, if another attack occurs, central memory B cells can quickly produce more short lived plasma B cells.

Question 19

T cell memory

Answer 19

• After naive T cells are activated they proliferate and go out into the tissue (effector T cells). After the attack has been replused, most of the T cells die by apoptosis, but some of them, the memory effector T cells, remain in the tissue. If another attack occurs, they rapidly reactivate, proliferate, and destroy the invader.
• Other activated T cells do not go out into the tissue, but remain in the secondary lymphoid organs and the bone marrow (central memory T cells). During a subsequent attack, central memory T cell activate quickly and after a brief period proliferate. Most mature into effector T cells while others remain in the secondary lymphoid organs.