week 11

Question 1

antibodies (structure)

Answer 1

• Key to immunological specify
  
  • Structure
    ○ 4 polypeptide chains
    ○ 2 large heavy chains
    ○ 2 smaller light chains
    Bound by disulfide bonds

Question 2

antibodies (constant and variable reasons, and which class)

Answer 2

• Constant and variable regions
  ○ Defined by constant regions of conserved aa sequences
  ○ Heavy chain defines antibody class (isotope)
  ○ Each class is common to a species
  § Isotope: defines various heavy chains of a species
  § Allotype: differences in the constant region shared by some but not all members of a species
  Idiotype: differences in the hypervariable region within an individual

Question 3

IgG antibody isotope

Answer 3

• Simplest, smallest, most abundant antibody in blood and tissue fluids
  
  • Monomer with 4 classes
    Binds and opsonizes microbes (allows phagocytes to grab easier), neutralizes viruses, activates classical complement pathway

Question 4

IgA antibody isotope

Answer 4

• Secreted antibody of mucosal surfaces
  
  • Found as a dimer linked by disulfide bonds to the j-chain protein
  • Secretory piece is wrapped around both molecules during secretion
    Secretory IgA (slgA) found in tears, breast milk, mucosal surfaces: can binds 4 antigens (same one)

Question 5

IgM antibody isotope

Answer 5

• Found as monomer on B-cells’ surfaces (part of receptor)
  
  • Commonly found as pentamer held together by J-protein
  • First antibody isotope detected during course of infection
    Can bind 10 antigens

Question 6

IgD antibody isotope

Answer 6

• Present in trace amounts in blood
  
  • Exists in monomeric form on B-cell surfaces
  • Plays role in B-cell activation
    Function not well understood

Question 7

IgE antibody isotope

Answer 7

• In trace amounts in the blood
  
  • Found on surfaces of mast cells and basophils
    Amplify body’s response to invaders, orchestrate acute response

Question 8

allergy, how is it caused

Answer 8

• Antigens (normally harmless to people) perceived as threats
  
  • Anti-allergen IgE triggers release of chemicals like histamine from mast cells
  • Causes itching, swelling, (if lungs)

Question 9

how is Anaphylaxis caused

Answer 9

○ Severe allergy
○ Excess histamine triggers smooth muscle contraction, interferes breathing when lung mucles contract, also weakens junctions between cells lining blood vessels
§ Causes them to leak
§ Fluid forced from circulation into tissues
§ Fluid has histamine, reaction spreads rapidly
○ EpiPens: Camp increases which increases circulation

Question 10

Complement as part of adaptive immunity

Answer 10

• Antibodies made as part of the adaptive response activate complement through the classical pathway
  
  • Requires additional proteins, C3 main player

Question 11

Lectin-mediated pathway

Answer 11

• Similar to classical
  
  • Produced by liver, binds sugars on bacterial cells
    Allow complement proteins to bind and trigger formation of C3 convertase, then the pathway is the same as the classical

Question 12

Need 3 complement pathways because

Answer 12

• Patients with deficiencies in complement are vulnerable to blood-borne pathogens that shapeshift
  ○ They change antigens to elude immune system
  ○ New antigens not recognized by antibodies, not caught

Question 13

Gut mucosal immunity and microbiome

Answer 13

• Gut immune system components
  ○ Epithelial barrier with T cells that have encountered antigens
  ○ Dendritic cells reach between epithelial cells to sample antigens from microbiota
  ○ Specialized cells called M cells sample antigens
  Sampled antigens constantly presented to macrophages B and T cells in layer under epithelial cells

Question 14

slgA

Answer 14

• Secreted into lumen of the gut
  
  • Coats microbiota components considered to be threats
    Prevents bound microbes from penetrating barrier

Question 15

why are the positioning and response of TLRs is important

Answer 15

• There are TLRs on epithelial cell side facing the gut lumen, sees antigens
  
  • Also on basal side of the layer (sees less antigens)
    TLRs on basal side more reactive than ones on the luminal side

Question 16

Antibodies display antigenic specifity

Answer 16

• Aka immunologic specificity
  
  • Degree to which an antibody recognizes an antigen, can distinguish between similar looking ones
  • Earlier clues came from smallpox, survivors did not get it again
    Variolation: pick off infected person’s scabs and rub it into a child’s skin so they would get a mild form of the disease to protect them later in life (2% they might die though)

Question 17

what is Cross-protection

Answer 17

• Inoculation of cowpox worked to protect against smallpox
  
  • Milkmaids contracted cowpox (similar to smallpox) but causes less prominent disease in humans, usually mild, and then wouldn’t contract smallpox (edward jenner)
    Cold virus= several types of viruses that give same cold-like symptoms, which is why we get so many colds in our lives and need a flu shot every year

Question 18

why is prevention better than a cure

Answer 18

• Suffering an infection with a pathogen results in immune response to the pathogen, acquired immunity driven protection against infection and comes with risk of infecting others nearby, leads to epidemics or pandemics
  
  • Instead we trick body into seeing pathogen and raising immune response without risk of the disease itself
  • Vaccination works because of our adaptive immune response, must be primed against particular antigen, then can be protected, can be protected without getting it
    Term vaccination: from protection of cows (cowpox origin)

Question 19

types of vaccinations: killed whole organisms

Answer 19

• Take pathogen, kill it, administer that into a patient and it provides antigens the immune system needs to mount the immune response without getting the disease since the pathogen is dead
  
  • Benefits: easy to produce, many antigens presented to immune system for robust response
  • Drawbacks: complete inactivation of organism can be difficult to achieve
    Examples: vaccines against Hepatitis A

Question 20

types of vaccinations: live attenuated organisms

Answer 20

• Organisms that have been weakened before administration, give immune system advantage
  
  • Benefits: pathogen infection process is appropriate, many antigens are presented to immune system for a robust response, body sees whole organism which allows it to see entire host of antigens and you get a better response
  • Drawbacks: can be difficult to produce, contraindicated for those immunocompromised, cold chain distribution required
    Examples: BCG, sabin polio vaccine

Question 21

types of vaccinations: subunit vaccines

Answer 21

• Selected, purified antigenic components of pathogens
  
  • Benefits: easy to produce, no chance of infection (no pathogen, just the antigen)
  • Drawbacks: can be hard to find a protective antigen
  • Example: toxoid vaccines
    Toxoids: recognizing that many pathogens produce toxins, behave as toxins without being toxic

Question 22

types of vaccinations: nucleic acid vaccines

Answer 22

• mRNA vaccines contain mRNA that codes for specific antigen, wrapped in lipid layer and injected
  ○ Taken up into the cell and the cell briefly (mRNA half-life quick) makes target antigen long enough for the antigen to stimulate an immune response
  
  • Benefits: once set up, super-easy to manufacture, and relatively quick to get to market no chance of infection
  • Drawbacks: cold chain distribution required, very poor public understanding/excessive fearmongering
    Examples: spikevax and comirnaty against SARS-CoV-2

Question 23

why do we need repeated doses?

Answer 23

• Boosting response
  ○ First dose=early synthesis of IgM, then IgG is produced
  ○ Second=booster, rapid response since B cells were formed during first response, IgM is effective but has low ability to protect, IgG better protective
  § Ensures sufficient antibodies with sufficient reactivity towards antigen that will protect against reinfection
  
  • Overcoming antigenic changes
    ○ Some pathogens change their antigens, or mutates
    § A vaccine may be only for an antigen that ends up changing over time or lost
  • Waning memory
    ○ Memory T and memory B cells can lose specify for their antigen as they replicate
    ○ Eventually become unprotective
    Ex: need tetanus shot every 10 years

Question 24

Getting the right exposure

Answer 24

• Live attenuated vaccines superior to inactivated, subunit, or mRNA vaccines
  
  • a live pathogen activates the immune system appropriately, part of that is where it starts its infection
    Ex: person can still get mild form of disease through natural infection despite getting vaccine, antibody response I protective against severe disease, but does not elicit the typical lung mucosal response, vaccine still works but was not expose in the body correctly

Question 25

herd immunity

Answer 25

* Not all people within a community must be vaccinated to protect the community, but the number of those required to protect the community depends on transmission rate, population density, etc. (transmissible diseases) Important: protects the immunocompromised, they cannot be vaccinated due to medical reasons therefore rely vaccination of others