Inflammation: Immune Cells

Question 1

Where do myeloid cells originate from? i.e. what progenitor gives rise to what

Answer 1

1. CMP –> neutrophils, basophils, eosinophils, mast cells, macrophages, monocytes, DCs
2. YSP –> mast cells and macrophages –> persist into adulthood (self-maintained by M-CSF, but slowly replaced by monocyte derived MFs over the years)

Question 2

What are 6 functions of neutrophils?

Answer 2

1. phagocytosis
2. degranulation (antimicrobial factors = hydrolytic enzymes, MMPs, myeloperoxidases, defensins)
3. ROS and cytokine production
4. antibody dependent cellular phagocytosis
5. antibody dependednt respiratory burst
6. NETosis (release chromatin to capture pathogens)

Question 3

What is the role of PAD4 in NETosis?

Answer 3

citrulliates histones –> decondenses DNA

Question 4

What cells produce ROS and RNS? Give a couple examples of ROS

Answer 4

cells = endothelial cells and leukocytes

1. superoxide (O2-)
2. hydrogen peroxide (H2O2)

Question 5

What is the antimicrobial role/tissue damage of ROS and RNS? (4)

Answer 5

1. lipid peroxidation
2. cellular damage
3. nucleic acid damage
4. deterioration of metabolic processes

Question 6

What triggers eosinophil degranulation and what two major proteins are in the granules?

Answer 6

degranulation triggered by FcER and complement R

proteins = MBP and ESP

Question 7

What are three subsets of DCs and their key markers (TFs)?

Answer 7

1. pDC –> Irf8
2. cDC1 –> Zbtb46
3. cDC2 –> Irf4

Question 8

What are the differences between immature and mature DCs?

Answer 8

immature –> mature:
* low co-stim molecules –> high
* low MHC-II expression –> high
* low secretion of pro-inflammatory cytokines –> high
* high phagocytic capacity –> low
* low CCR7 expresion –> high (migrate to LN)
* low glycosis –> high
* tolergenic or inhibiotry signals (IL-10, TGFb; mediate tolerance to an apparent non-pathogenic molecule)

Question 9

Describe how DCs activate CD4 T cells, what phenotypes can these T cells take on, whats the function of each phenotype?

Answer 9

Activation:
1. peptide-MHC-II/TCR interaction (signal 1)
2. PRR signaling –> CD80/86 to CD28 (signal 2)
3. PRR signaling –> polarzing cytokines (signal 3)

Phenotypes + functions:
1. Th1 –> fight intracellular pathogen
2. Th2 –> fight parasites
3. Th17 –> fight extracellular pathogen

Question 10

Where do lymphocytes originate from? i.e. what cell gives rise to what

Answer 10

CLP –> ILCs, B cells, T cells, NK cells, pDCs

Question 11

What are some characterisitcs of ILCs?

Answer 11

1. unconventional or germ-line Ag Rs
2. fast responders
3. VDJ recombination

Question 12

Name 3 innate B cells, their primary localization, and principle function

Answer 12

• FO B cell: 2o lymphoid organs, mainly in B cell follicles; participate in T-dependent immune responses
• MZ B cell: 2o lymphoid organs, mainly in the splenic marginal zone; housekeeping function (natural IgM), first responders to blood-borne pathogens
• B1 B cell: peritoneal and pleural cavities; house keeping function (natural IgM), first responders to mucosal pathogens

Question 13

What adaptive and innate cells are involved in the following immune responses + what triggers these responses:
* intracellular defense module
* extracellular defense module
* barrier immunity module
* cytotoxic module

Answer 13

• intracellular defense module: intracellular bacteria and viruses; cDC-1, Th1, ILC1
• extracellular defense module: extracellular bacteria; cDC2, ILC3, Th17
• barrier immunity module: parasites; cDC2, ILC2, Th2
• cytotoxic module: viruses; cDC-1, CTL, NK

Question 14

What are 7 functions of Abs, name the main isotypes that perform these functions

Answer 14

1. neutralization (all)
2. complement activation - IgG1/3, IgM
3. opsonization - IgG1/3, IgA1/2
4. degranulation - IgE
5. mucosal protection - IgA1/2
6. placental transfer - IgG1/3
7. ADCC - IgG1