L24 - Properties And Functions Of Ab Flashcards
What is a common misconception about antibodies
Antibodies can’t actually kill anything on its own.
What’s the purpose of Antibodies
- partner w innate cells
- give specificity of adaptive immunity to innate
Describe the structure of an antibody
- Y shaped
- constant region defines function
- variable region defines Ag specificity
Fill in the gaps:
- Ab change constand regions allow _____ called ____ or ____
- 2 Ag binding sites permits _____ which improves ____
- the variable Ag binding sites can undergo ___ to increase affinity for Ag called _____ ____
- different effector functions
- isotype switching or class switching
- cross-linking
- neutralisation
- mutations
- affinity maturation
What are the 2 types of antibodies
Membrane and secrete form
What are the diff antibody classes or isotopes and what is it defined by and how does it allow diff effector functions?
IgM, IgD, G, E and A
- B cell subsets are defined by which antibodies they produce
- type of antibody is defined by which constant region is used
- by switching between different chains, antibodies gain diff effector functions
What were the first isotopes produced that are the only ones able to be produced simultaneously by a B cell
IgM and IgD
Regarding IgM and IgD, what are its functions and how is it produced simultaneously? What determines which subset is created first?
IgD function unknown, IgM first response Ab, they are produced by differential RNA splicing (DNA is not changed)
What are some characteristics of class/isotype switching? Which classes? Is it reversible or non-reversible? What enzymes aids this?
- mechanism that B cells use to produce IgG. IgA or IgE
- irreversible change in DNA (can’t go back)
- can only produce one isotype at a time
- AID is the enzyme that cuts and gamma region will get added
What controls class switching and tells B cells which isotype to produce?
Th cells and cytokines
Describe IgM as the first line of defence
- produced before affinity maturation so has lower affinity
- it forms pentamers via J chain (5 so very efficient)
- good ad binding repeating epitopes and efficient at activating complement -> compensates for lower affinity
What pathway does antibodies activate?
Complement via classical pathway
- activated by Fc region of certain antibody classes
What is the rank of efficiency of the innate complement response in terms of antibodies?
IgM>IgA>IgA
Why is IgM best complement ‘fixer’
It has a pentameric structure
- C1 binds antibodies which starts cascade
- to activate C1 it has to bind to at least 2 antibodies
- bc we have so much in our bloodstream so it would always be activated
- causes conformational change and alllows complement cascade to activate (only against microbes and not for antibodies just floating around)
- IgM already has 5 antibodies so as soon as it binds it can activate C1 → so IgM is better at activating
- IgM in blood takes planar form so it doesn’t get activated in blood
How is IgA adapted to protect mucosal surfaces like the gut?
IgA exists as a monomer in serum but forms a dimer with a J chain for mucosal immunity. The J chain enables transport across the intestinal epithelium into the lumen. Secretory IgA is resistant to low pH and digestive enzymes, making it ideal for the gut. It neutralizes pathogens by cross-linking them into immune complexes, preventing their attachment to the epithelium and aiding their removal with feces. IgA has weak ADCC and complement activity, reducing the risk of tissue damage in sensitive mucosal areas.
How is Ab functions linked to innate immune cells
Through Fc Receptor binding to Fc region of an Ab which gives specificity of adaptive immunity to innate immune cells
What Ab isotype binds what FcR. How does this define effector function
Different Ab isotypes bind different FcR:
FcyR - binds IgG
FcaR - binds IgA
FceR - binds IgE
• Different innate cells express different types of FcR
• Innate cell expression of FcR defines which Ab isotypes they work in partnership with and so defines effector function
How does opsonisation occur via FcR
IgG and IgA can act as opsonisation to prepare to eat so phagocytosis is improved
How does FcR stimulate ADCC
Ab direct innate cells to kill via FcR (e.g. IgG coats surface antigen and brings it to NK cell)
Activates eosinophil to kill extracellular pathogens
Why do antibodies have 2 binding sites
To favour cross linking. There is hinge region so it can bind to w diff antigens and build up of antigen allows cross linking
Why is antigen cross-linking necessary for antibody activation of immune cells?
Cross-linking of antibodies bound to antigens is required to activate Fc receptors (e.g., FcγR, FcαR) on innate immune cells. This clustering signals infection and triggers immune responses like phagocytosis or cytotoxicity.
Why don’t free (unbound) antibodies activate immune cells? What happens when Ag links multiple Ab
Free antibodies do not cross-link Fc receptors, so they fail to activate innate immune responses. This prevents inappropriate immune activation in the absence of infection, acting as a safeguard against unnecessary inflammation.
When Ag links multiple Ab it indicates infection so want innate cells to kill. Multiple IgG have higher avidity for FcR allowing them to bind
How does antibodies mediate neutralisation?
- clumps toxins and pathogens tgt
- clearance of toxins by immune complexes
- hinders pathogen mobility so they can be mopped out
- useful for diagnostic assays
How does IgE “arm” mast cells and create antigen-specific memory in innate immunity?
After first exposure to an antigen, IgE binds with high affinity to FcεR on mast cells—even without antigen. This doesn’t activate the mast cell but “arms” it by giving it antigen-specific receptors. Upon re-exposure, antigen cross-linking of IgE on the mast cell surface triggers activation and degranulation. This gives innate cells like mast cells a memory-like, rapid response to specific antigens.
What is IgE’s role in immunity and how is it involved in allergies?
A: IgE evolved to defend against parasitic helminths by arming mast cells. Upon antigen cross-linking, mast cells rapidly degranulate, releasing inflammatory mediators. This fast response also causes allergic reactions and is responsible for the speed of anaphylaxis. IgE class-switching takes time, but once bound to mast cells, it transfers adaptive memory to innate cells. Repeated allergen exposure can worsen or improve allergies depending on the immune pathways activated.
What is somatic hypermutation
Mutation rate of gene segments of activated B cells is 100 000 fold greater than normal mutation rate of humans
High mutation rate in the VDJ areas and it changes affinity of antibody to its antigen pr even which antigen it recognises
After somatic hypermutation, how is B cell selected?
After somatic hypermutation B cell tested to see if can still bind it’s Ag:
1) Looses ability to bind Ag - B cell dies
2) Binds Ag with worse affinity - B cell survives but outcompeted
3) Binds Ag with higher affinity - B cell outcompetes those with lower affinity
Selects for B cells producing Ab with highest affinity for Ag
What is affinity maturation and what are some characteristic
Affinity maturation = the overall process by
which activated B cells increase their Ab’s affinity for Ag
• Mechanism = somatic hypermutation.
• Tends to occur after or at same time as class switch from IgM, so IgM Ab often lower affinity.
• IgG, IgA, and IgE tend to be higher affinity than IgM and IgD
• Could theoretically result in B cells specific for self-Ag.
Why does affinity maturation have to be tightly controlled? How is it controlled?
- to prevent the accidental creation of self-reactive Ab
- only takes place in specific location (LN & spleen)
- T cells decides if B cell is specific or needs to die (if it doesn’t receive survival signal it will die)
- so it needs T cell permission to undergo affinity maturation
• After affinity maturation a B cell must present the Ag it recognises to a T cell
• If a T cell still recognises the Ag it means the B cell is still microbe specific and is allowed to survive.
• If a T cell no longer recognises the Ag then affinity maturation has likely changed the B cells specificity for Ag. This means the B cells is either no longer useful, or potentially self-reactive and so is deleted.
• T cells do not undergo affinity maturation
How do colonial expansion, isotype switching and affinity maturation fit together?
No particular order but has specialised areas in the lymph node
Dark zone = proliferation
Light zone = class switching and maturity
