Immunology 1 - lectures 1-5

Question 1

What are the three principal innate immune responses?

Answer 1

1) complement cascade
2) phagocytes (neutrophils, macrophages, dendritic cells)
3) Natural Killers

Question 2

What immune cells arise from the common lymphoid progenitor?

Answer 2

B cells, T cells, NK cells

Question 3

What immune cells arise from the common myeloid progenitor?

Answer 3

granulocytes (neutrophils, eosinophils, basophils)
monocyte derivatives (macrophages, mast cells, dendritic cells)

Question 4

What cell is the most abundant blood leukocyte and a major component of pus?

Answer 4

neutrophils

Question 5

When macrophages recognize a PAMP, what are the two major alarm signals it sends out and what do they do?

Answer 5

interleukin-1 and TNF-alpha.

1) activated nearby neutrophils
2) alters local endothelium
3) signals DCs to mature
4) signals hypothalamus to increase body temperature.

Question 6

MHC I -

1) what cells express
2) what’s the structure
3) where do the antigenic peptides come from?

Answer 6

1) all nucleated cells
2) structure: alpha-chain + beta2 micro globulin (peptide-binding cleft is in alpha chain).
3) antigenic peptides are derived from cell’s cytoplasm.

Question 7

MHC II

1) what cells express
2) what’s the structure
3) where do the antigenic peptides come from?

Answer 7

1) APCs (macrophages, B-cells, dendritic cells)
2) alpha + beta chains (both involved in cleft)
3) antigenic peptide derived from cell’s endocytic compartment.

Question 8

What is the classical pathway of the complement system?

Answer 8

C1q/r/s binds the constant region of IgG/IgM (attached to pathogen), activates intrinsic serine protease of C1r/s, cleaving C4, C4b attaches to pathogen surface, C4b2a acts as C3 convertase and begins complement cascade.

Question 9

What is the MB-lectin pathway of the complement system?

Answer 9

Mannose-binding lectin binds mannose on pathogen surface, activates intrinsic serine protease, cleaving C4, C4b attaches to pathogen surface, C4b2a acts as C3 convertase, begins complement cascade.

Question 10

What is the alternative pathway of the complement system?

Answer 10

C3bBb on pathogen surface acts as C3 convertase, begins complement cascade. Our cells have decay factors which prevent this process on our own cells.

Question 11

What effect do C3a, C4a and C5a have?

Answer 11

Increase vascular permeability, allowing for extravasation of complement, immunoglobulin, immune cells to site of attack.

Question 12

What are the four primary killing mechanisms of the lysosome in phagocytes?

Answer 12

1) acid hydrolases
2) proton pump
3) Lysozyme (disrupts peptidoglycan)
4) human beta-defensins (small cationic proteins that disrupt cell membranes)

Question 13

What are the important major pathogen-killing molecules in lysosomes?

Answer 13

superoxide, peroxynitrite, hypochlorous acid, hydrogen peroxide.

Question 14

What are the major Damage Associated Molecular Patterns (DAMPs) that trigger immune responses?

Answer 14

K+ efflux; chromatin-associated proteins outside the nucleus; cellular DNA outside the nucleus; extracellular ATP.

Question 15

What cytokines are produced in response to viral infections?

Answer 15

IFN-alpha; IFN-beta -> activates NK cells, increases MHCI presentation; recruitment of leukocytes.

Question 16

What do the Rig-like receptors recognize?

Answer 16

uncapped and dsRNA.

Question 17

TLRs:

1) What classes of pathogen do they recognize
2) Where do they recognize them
3) What pathways mediate their alarm system
4) What is the alarm?

Answer 17

1) bacteria, viruses, fungi, protozoa
2) cell surface / endosomes
3) NFkB, MAPK, IRF
4) IL-1beta, chemokines, interferons

Question 18

NLRs:

1) What classes of pathogen do they recognize
2) Where do they recognize them
3) What pathways mediate their alarm system
4) What is the alarm?

Answer 18

1) bacteria, viruses, cell distress
2) cytoplasm
3) NFkB, Caspase-1 (via inflammasome)
4) IL-1beta
(NLRP3 leads to cell necrosis)

Question 19

RLRs:

1) What classes of pathogen do they recognize
2) Where do they recognize them
3) What pathways mediate their alarm system
4) What is the alarm?

Answer 19

1) viruses
2) cytoplasm
3) IRF, NFkB, MAPK
4) interferons

Question 20

What do the following receptors bind and where?

1) TLR-4
2) TLR-5
3) TLR-3
4) TLR-7
5) TLR-9

Answer 20

1) LPS - plasma membrane
2) flagellin - plasma membrane
3) dsRNA - endosome
4) ssRNA - endosome
5) CpG DNA - endosome

Question 21

What do RIG-1 and MDA-5 recognize and how do they initiate signaling?

Answer 21

RIG-1: uncapped (viral) RNA
MDA-5: long dsRNA

Dock with IPS-1 on mitochondrial membrane, activate NF-kB and IRF-3 pathways.

Question 22

What antibody classes are expressed on the cell surface of naive B cells?

Answer 22

IgM and IgD

Question 23

Which antibody classes form multimers?

Answer 23

IgM - pentameric protein with 10 binding sites

IgA - dimeric protein with 4 binding sites.

Question 24

What are the four mechanisms by which antibodies fight infection?

Answer 24

1) neutralize toxin
2) opsonize, allowing phagocytes to eat bacteria.
3) obsonization, allowing for complement binding, allowing phagocytes to eat bacteria.
4) antibody-dependant cell-mediated cytotoxicity (NK cell killing via Fc region recognition).

Question 25

Which Ab classes are best for: 1) opsonization 2) complement activation 3) transport across epithelium 4) sensitization of mast cells

Answer 25

1) IgG1 2) IgM 3) IgA (gets antigen into gut) 4) IgE

Question 26

What regions give combinatorial diversity to antibodies?

Answer 26

Heavy chain: V, D, J | Light chain: V, J

Question 27

What enzymes allow for recombination of gene segments in Abx generation?

Answer 27

RAGs and TdT Recombination-Activated Genes recognize specific recombination signal sequences (RSSes) that allow for specific recombination of heavy and light chains. TdT inserts non-germline nucleotides at the junction after the RAGs have cut and lined up the VJ segments, allowing for even more diversity.

Question 28

What are two fundamental classes that immune system must respond to?

Answer 28

viruses: on a cell's MHC-1 tells CD8 T cell to kill. | extracellular bacteria: on an APC's MHC-2 tells CD4 T cell to help.

Question 29

What are the rules for binding MHC class I molecules?

Answer 29

Usually 9 AAs in length, with same NH2 orientation; most often peptides are anchored by side chains at 2nd and 9th AA to MHC pockets that confer specificity for a similar physical property (size, charge, hydrophobicity)

Question 30

What are the rules for binding MHC class II molecules?

Answer 30

variability in length due to open pocket, same NH2 orientation, peptides are anchored by side chains.

Question 31

What are the two major parts of the thymic architecture and how are they different?

Answer 31

peripheral cortex: dense with lymphoid cells, epithelial cells, important for positive selection. central medulla: fewer lymphocytes, contain dendritic cells and macrophages which are main mediators of negative selection.

Question 32

What determines whether a thymocyte will produce a alphabeta or a gammadelta TCR?

Answer 32

successful beta chain rearrangement: rearrangement competition occurs between beta, gamma and delta gene segments, a successful beta rearrangement signals alpha to begin rearranging, which shuts down gammadelta cell fate (successful beta rearrangement also uses double-negative thymocyte to become double-positive thymocyte.

Question 33

What event stops TCRalpha recombination?

Answer 33

Recognition of self-MHC complexes during positive selection (double-positive cells live for only 3-4 days unless rescued by TCR stim)

Question 34

How does the cell recognize a successful TCRbeta rearrangement?

Answer 34

TCRbeta expressed on cell surface, binds the pre-TCRalpha invariable chain, signals to block further rearrangement of beta chain and drives proliferation, differentiation to double positive cells and eventually alpha chain rearrangement.

Question 35

What cells mediate negative selection of T cells in the thymus?

Answer 35

bone-marrow-derived dendritic cells and macrophages in cortex and medulla.