Extra Stuff for Competition Flashcards
Describe the morphology + function of NK cells.
- large, granular lymphocytes without BCR/TCRs
- recognize virus-infected/tumor cells via MHC-I or Ab tagging
- action regulated by balance of activating (ex: NKG2D) or inhibiting (ex: NKG2A) receptors
- provide rapid response (~3 days) to viral infection
Decribe the features / function / abilities of gamma delta T cells
- have distinct TCR of gamma + delta chains
- can rearrage TCR for specificity or use more conserved TCR that recognizes PAMPs
- Functions:
- lyse stressed cells
- produce cytokines
- help B cells
- present antigens to alpha-beta T cells
- help dendritic cells mature
- regulate stromal cells using GFs
What are innate lymphoid cells?
- come from lymphoid precursor cells but lack rearranged TCR/BCR
- lack mature lymphoid markers but have lymphoid progenitor receptors
- have high capacity / diversity cytokine production
- regulate homeostasis in mucosa, skin, fat + lymphatics
- are self-renewing + don’t give rise to progenitors
What are 5 kinds of secreted PRRs?
- Soluble Lectins (includes MBL, surfactant + pentraxins such as CRP)
- Lipocalin / Mindin
- Cationic Peptides
- Antimicrobial Peptides
- Cathelicidins
what do NOD-like receptors do within cells?
are released into cytosol to recognize intracellular bacterial peptidoglycan
What do RIG-I-like receptors do within cells?
recognize viruses via dsRNA
What is somatic hypermutation?
- an increased rate of mutation seen in proliferating B cells
- occurs in “hotspots” in DNA hypervariable regions corresponding to CDRs on BCRs / antibodies
- occurs via cytidine deamination to uracil via AID and removal of uracil bases by UDG
Describe MHC-I structure.
- alpha 1 + 2 subunits make up peptide binding groove
- alpha 3 subunit has TM domain -> anchors to membrane
- (alpha3 is also binding site for CD8 on CTLs)
- beta-2 microglobulin associates with alpha sub-units (but does not bind membrane)
Describe MHC-II structure
- alpha1 and beta1 subunits make up peptide binding groove
- alpha 2 and beta2 both have TM domains -> anchor to membrane
- beta2 subunit is CD4 binding site
There was a horribly worded PP question that said
“List at least 4 features of cell ines”
based on the corrected answers I think they meant cancer cells…
- Transformation - different morphology
- Loss of “contact inhibition”
- Lack of need for GFs to proliferate
- Immortality
- Regaining of telomerase activity
What is important to note about the lineage of all the B cells in a single lymph node follicle?
- each follicle has one “founder” cell of which all other B cells in that follicle are descendents
What is unique about follicular dendritic cells?
What surface molecules do they express in order to carry out their functions?
- they do not leave follicles and can not engulf pathogens
- instead, they just hold onto antigens + express IL-6 for the activation of follicular Th cells
- express FcRs and CR3 (complement receptor) to bind antibodies and C3b, allowing them to tightly hold antigens
What are 4 functional results of Th cells stimulating B cells using their CD40L.
(CD40L on T cell stimulates CD40 on B cell)
- generation of germinal centers -> proliferation -> Ab production
- affinity maturation
- isotype switching
- memory cell generation
What two types of mutations can occur during somatic hypermutation?
- Transition Mutation - deaminated cytosine changes to uracil via AID enzyme and is then cut off and replaced with a different base
- Transversion - uracil is removed by UNG enzyme and an “apyrimidinic” residue results (means there is no base there… just blank space)
What are the Th-secreted cytokines which induce IgM to…
IgG class switch?
IgA class switch?
IgE class switch?
(other lectures had longer lists of cytokines for each class… B cell lecture had the simplest list)
- IgE - IFNy
- IgA - IL-5
- IgE - IL-4 and IL-13
What role does a somatic hypermutation enzyme have in class switching?
- AID (activation induced deaminase) - deaminates C to U
- DNA breaks are created at site of the Us which are in so-called “switch regions”
- repair of these breaks leads to recominbation + creation of a different switch region
What receptor on B cells produces a negative feedback inhibition?
- FcyRIIb - binds IgG that has already bound pathogens
- other epitopes on the antigen may simultaneously bind the same B cell’s BCR, but since the B cell can “detect” that IgG is already there -> inhibition + less production of IgG
Where do memory B cells reside?
- mantle zone of lymph follicle (outer ring surrounding germinal center)
What are some characteristics of memory B cells?
- have undergone class switch / affinity maturation
- can produce high affinity Abs IgG/A/E
- high affinity Th interactions + rapid plasma cell diff.
- higher capacity Ab production
What Fc receptor is responsible for the ADCC effects of antibodies?
- FcyRIIIA - on NK cells, binds IgG -> cellular cytotoxicity effects
What are MZ B cells?
- a B-2 cell type in the marginal zone of the spleen
- recognize T-independent sugar antigens, such as capsular polysaccharides
- secrete mainly IgM (with a somatically mutated sequence)
What are 5 general mechanisms of peripheral T cell tolerance?
Potentially auto-reactive T cells may tolerate self antigens due to…
- Ignorance - via physical barrier such as BBB
- Immune-privelege - cornea produces FasL, TGF-B + IL-10
- Apoptosis
- Anergy - absence of positive co-stim
- Becoming tolerogenic
- Suppression - by a Treg etc.
What region of the BCR genes is most likely to be autoreactive?
the V region of the VDJ genes
What do receptor revision and receptor editing happen in B cells to avoid auto-reactivity?
- Revision - in 2ndary lymph organ germinal centers
- Editing - in bone marrow in early development
- both via RAG recombinase reactivation
What kind of cell is common in “natural autoimmunity”?
- CD5+ B1 cell
- is polyreactive to essential/conserved molecules common to both humans and microbes
- secretes mostly low-affinity IgM
What kind of conserved molecules do we create “natural autoantibodies” against?
long list… just a review
- HSPs
- enzymes
- membrane proteins -beta 2 microglobulin
- cytoplasmic proteins - actin
- nuclear antigens - histones
- plasma proteins - albumin, IgG
- cytokines - IL-1
How can infections contribute to the development of autoimmunity?
- secretion of inflammatory mediators
- increased costimulation
- release of tissue antigens (via damage)
- molecular mimicry - host/pathogen cross-rxn
- superantigens
What cytokine can DCs secrete in autoimmunity that inhibits Treg’s suppressive functions?
IL-6
