1
Q
antibodies (structure)
A
- Key to immunological specify
- Structure
○ 4 polypeptide chains
○ 2 large heavy chains
○ 2 smaller light chains
Bound by disulfide bonds
- Structure
2
Q
antibodies (constant and variable reasons, and which class)
A
- 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
3
Q
IgG antibody isotope
A
- 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
- Monomer with 4 classes
4
Q
IgA antibody isotope
A
- 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)
5
Q
IgM antibody isotope
A
- 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
6
Q
IgD antibody isotope
A
- Present in trace amounts in blood
- Exists in monomeric form on B-cell surfaces
- Plays role in B-cell activation
Function not well understood
7
Q
IgE antibody isotope
A
- In trace amounts in the blood
- Found on surfaces of mast cells and basophils
Amplify body’s response to invaders, orchestrate acute response
- Found on surfaces of mast cells and basophils
8
Q
allergy, how is it caused
A
- 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)
9
Q
how is Anaphylaxis caused
A
○ 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
10
Q
Complement as part of adaptive immunity
A
- Antibodies made as part of the adaptive response activate complement through the classical pathway
- Requires additional proteins, C3 main player
11
Q
Lectin-mediated pathway
A
- 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
- Produced by liver, binds sugars on bacterial cells
12
Q
Need 3 complement pathways because
A
- 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
13
Q
Gut mucosal immunity and microbiome
A
- 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
14
Q
slgA
A
- Secreted into lumen of the gut
- Coats microbiota components considered to be threats
Prevents bound microbes from penetrating barrier
- Coats microbiota components considered to be threats
15
Q
why are the positioning and response of TLRs is important
A
- 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
- Also on basal side of the layer (sees less antigens)
16
Q
Antibodies display antigenic specifity
A
- 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)
17
Q
what is Cross-protection
A
- 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
- Milkmaids contracted cowpox (similar to smallpox) but causes less prominent disease in humans, usually mild, and then wouldn’t contract smallpox (edward jenner)
18
Q
why is prevention better than a cure
A
- 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)
19
Q
types of vaccinations: killed whole organisms
A
- 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
20
Q
types of vaccinations: live attenuated organisms
A
- 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
21
Q
types of vaccinations: subunit vaccines
A
- 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
22
Q
types of vaccinations: nucleic acid vaccines
A
- 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
23
Q
why do we need repeated doses?
A
- 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
- Overcoming antigenic changes
24
Q
Getting the right exposure
A
- 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
- a live pathogen activates the immune system appropriately, part of that is where it starts its infection
25
herd immunity
* 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
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