Extra Stuff for Competition

Question 1

Describe the morphology + function of NK cells.

Answer 1

• 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

Question 2

Decribe the features / function / abilities of gamma delta T cells

Answer 2

• 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

Question 3

What are innate lymphoid cells?

Answer 3

• 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

Question 4

What are 5 kinds of secreted PRRs?

Answer 4

• Soluble Lectins (includes MBL, surfactant + pentraxins such as CRP)
• Lipocalin / Mindin
• Cationic Peptides
• Antimicrobial Peptides
• Cathelicidins

Question 5

what do NOD-like receptors do within cells?

Answer 5

are released into cytosol to recognize intracellular bacterial peptidoglycan

Question 6

What do RIG-I-like receptors do within cells?

Answer 6

recognize viruses via dsRNA

Question 7

What is somatic hypermutation?

Answer 7

• 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

Question 8

Describe MHC-I structure.

Answer 8

• 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)

Question 9

Describe MHC-II structure

Answer 9

• 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

Question 10

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…

Answer 10

1. Transformation - different morphology
2. Loss of “contact inhibition”
3. Lack of need for GFs to proliferate
4. Immortality
5. Regaining of telomerase activity

Question 11

What is important to note about the lineage of all the B cells in a single lymph node follicle?

Answer 11

• each follicle has one “founder” cell of which all other B cells in that follicle are descendents

Question 12

What is unique about follicular dendritic cells?

What surface molecules do they express in order to carry out their functions?

Answer 12

• 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

Question 13

What are 4 functional results of Th cells stimulating B cells using their CD40L.

(CD40L on T cell stimulates CD40 on B cell)

Answer 13

• generation of germinal centers -> proliferation -> Ab production
• affinity maturation
• isotype switching
• memory cell generation

Question 14

What two types of mutations can occur during somatic hypermutation?

Answer 14

• 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)

Question 15

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)

Answer 15

• IgE - IFNy
• IgA - IL-5
• IgE - IL-4 and IL-13

Question 16

What role does a somatic hypermutation enzyme have in class switching?

Answer 16

• 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

Question 17

What receptor on B cells produces a negative feedback inhibition?

Answer 17

• 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

Question 18

Where do memory B cells reside?

Answer 18

• mantle zone of lymph follicle (outer ring surrounding germinal center)

Question 19

What are some characteristics of memory B cells?

Answer 19

• 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

Question 20

What Fc receptor is responsible for the ADCC effects of antibodies?

Answer 20

• FcyRIIIA - on NK cells, binds IgG -> cellular cytotoxicity effects

Question 21

What are MZ B cells?

Answer 21

• 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)

Question 22

What are 5 general mechanisms of peripheral T cell tolerance?

Answer 22

Potentially auto-reactive T cells may tolerate self antigens due to…

1. Ignorance - via physical barrier such as BBB
2. Immune-privelege - cornea produces FasL, TGF-B + IL-10
3. Apoptosis
4. Anergy - absence of positive co-stim
5. Becoming tolerogenic
6. Suppression - by a Treg etc.

Question 23

What region of the BCR genes is most likely to be autoreactive?

Answer 23

the V region of the VDJ genes

Question 24

What do receptor revision and receptor editing happen in B cells to avoid auto-reactivity?

Answer 24

• Revision - in 2ndary lymph organ germinal centers
• Editing - in bone marrow in early development
• both via RAG recombinase reactivation

Question 25

What kind of cell is common in “natural autoimmunity”?

Answer 25

• CD5+ B1 cell
• is polyreactive to essential/conserved molecules common to both humans and microbes
• secretes mostly low-affinity IgM

Question 26

What kind of conserved molecules do we create “natural autoantibodies” against?

long list… just a review

Answer 26

• HSPs
• enzymes
• membrane proteins -beta 2 microglobulin
• cytoplasmic proteins - actin
• nuclear antigens - histones
• plasma proteins - albumin, IgG
• cytokines - IL-1

Question 27

How can infections contribute to the development of autoimmunity?

Answer 27

• secretion of inflammatory mediators
• increased costimulation
• release of tissue antigens (via damage)
• molecular mimicry - host/pathogen cross-rxn
• superantigens

Question 28

What cytokine can DCs secrete in autoimmunity that inhibits Treg’s suppressive functions?

Answer 28

IL-6