Humoral Immunity Flashcards
Exam 2
What is considered humoral
macromolecules, found in ‘humors’, antibodies, complement, and can isolate effects from cells
What is humoral immunity (basic terms)
-If you filter cells out, what is left is humoral immunity
What is the first thing that needs to be done in humoral immunity
-first, B-cells must be activated, which can be
-dependent on T-cells (thymus-dependent or TD)
-Independent of T-cells (Thymas independent TI) therefore don’t need T cells
How can thymus independent antigens activate B-cells without T-cell help
-TI-1 antigens
-activate TLR and BCR
-LPS, polymeric carbohydrates
-called mitogens (growth-inducing)
-not species-specific
-high levels of antigen activate many B-cells
What is TI-2 antigens
-need to be polymers
-cross-link BCR’s
-must be mature B-cells
How does cytokines enhance activity even from TI antigens
-B/C bound to antigen AND DC binds same antigen through PRR (can even activate BC more)
What are the benefits of thymus-independent activation
-quick
-great for encapsulated bacteria (TI-2)
-generalist (many species can be targeted)
What is one con of thymus-independent activation
not very specific/ strong
What is linked recognition
when the activating T cells recognize the same antigen as the B-cell
-NOTE they do not recognize the exact same part of the antigen
What makes Thymus-dependent antigens specific/strong
uses linked recognition
What is an example of linked recognition
-hapten-small chemicals that are non-immunogenic alone but when attached to a carrier (usually a protein) become immunogenic
-this is called the hapten carrier effect
-many haptens on same carrier can cross-link BCR’s
What is another reason for the hapten carrier effect
B cells generate Ab against hapten while T cells recognize peptides from carrier protein phagocytosis
Explain how hapten carrier effect, linked recognition, and penicillin allergies all tie together
-many chemicals can spontaneously react with human proteins to form a hapten-carrier complex
-beta-lactams (penicillin), many carriers
-this leads to linked recognition and therefore a strong immune response
How does linked recognition prevent most autoimmunity/preserve self-tolerance
-robust immune response require both (BCR binds of antigen filled by presentation of right peptide and TCR binding the peptide:MHC complex)
-even before that, many other signals are needed to activate the B/T cells
How are antigens presented by macrophages
-opsonized antigens are recognized by complement receptors on subcapsular sinus macrophages
-present antigen to B-cells
-moves antigen to FDC
How are T cell and B cell interactions stabilized
-by SLAM (signaling lymphocyte activation molecules) proteins
-serve to maintain interactions
-also propagates signals
What is the primary focus of B cells after activation
-receive survival and proliferation signals
-divide (apparent after 5 days)
-differentiate
What are germinal centers
-goal: make Ab very fast
-found in follicles
-B cells AND Tfh
-form a dark and light zone
-form later than primary focus
What is the dark zone
-high proliferation and density
-mostly B cells called centroblasts
-low on BCR expression
What is the light zone
-can encounter FDC’s and Tfh
-B cells called centrocytes
-high on BCR expression
What is cyclic reentry
cells can move between the light and dark zone
What does cyclic reentry help with
somatic hypermutations
What is somatic hypermutation
-the fourth source of diversity in Ab
-increase in mutation rate of V-region of Ab
-NOT in C regions (don’t want to hypermutate so it can be recognized)
-accumulate step-wise (if favorable, passed on if not, B cells die)
How does somatic hypermutation happen
-mutations introduced through AID
-clones with higher Ab affinity are selected for
What is Activation-induces cytidine deaminase (AID)
-deaminates cytosine to uracil (must be ssDNA to allow for regulation)
-U is not normally found in DNA (in RNA tho)
-Also, U is a mismatch with G
-must be repaired
What will mutations generally do to the binding affinity
Generally decrease affinity
Where do B cells divide and mutate
in the dark zone
What leads to the different roles of Ab’s
The difference in constant regions
What is the first antibody that is usually made
IgM
How do you go from IgM to IgD
-both are made from the same mRNA transcript therefore you need alternative splicing
What else does alternative splicing result in
-how the secreted vs membrane-bound versions are made
How are the other Ig’s formed
-Class switching
-the same proteins of somatic hypermutation lead to ds breaks
How is AID guided to only the switch region
-switch regions are G-rich
-Form R-loops that stall RNAP
-Recruits AID
What does class-switching depend on
-depends on transcription, it can be regulated
What is the functional activity of IgM
Activates complement system
What is the functional activity of IgE
Sensitization of mast cells
What is the main purpose of IgM
to protect from blood infection
Describe IgM
-generally lowest affinity
-but highest avidity (10 diff binding sites)
What is the main purpose of IgA
-protection of epithelial tissues
-moved across epithelial membranes by pIgR
-NOTE: no phagocytes or immune cells in gut, so IgA’s main role is neutralization
What is the main purpose of IgE
-strongly bind to mast cells
-upon antigen binding, signals release of granule contents
-mostly beneath epithelial tissue
What is the main purpose of IgG
-main form in blood and extracellular fluid
-can be transported across the placenta (protect fetus with maternal Ab)
What is the hypothesis to why mRNA SARS-CoV2 leads to IgG4 class-switching
IgG4 is great for neutralization while not being proinflammatory
What are neutralizing antibodies
-bind and neutralize
-many pathogenic bacteria secrete toxins
-toxins create ideal environment (nutrient release from dead cells and kill/change immune cells)
Name the three components of proteins chains connected in toxins
-to get inside: binds receptors on target cell and drives endocytosis
-to kill: poison cells many ways
-antibodies block receptor binding
How do neutralizing antibodies target bacteria that grow extracellularly
antibodies can neutralize membrane proteins (adhesions/secretion)
What receptor recognizes the Ab constant region
-the Fc receptors
-each Ab type has different Fc regions
-Different cell types recognize this region
-recognition is through Fc receptors
How does Fc receptors play a key role in phagocytosis
-Ab variable region binds target
-Fc receptor bind Ab
-KEY: multiple Ab in region croll-link Fc receptors, leading to signal activation
What is antibody-dependent cell-mediated cytotoxicity
-Fc receptors playing a key role in NK killing of virus-infected cells
What if the target is too large and cannot phagocytize large, multicellular organisms
-Fc activation leads to degranulation of eosinophils
-Ab’s bind worm
-eosinophils Fc receptors bind these receptors
-release toxic granule contents
