MICR 505 EXAM 4

Which cells produce IFN-gamma? What cell does IFN-gamma target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th1, NK, ILC1s

Macs, DCs, T cells, B cells

Mac Activation, IgG class switch, Promote Th1, Inhibit Th2

Cytokine group: Type 1 and 3

Which cells produce IL-17? What cell does IL-17 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th17, ILC3s, (gamma-delta T but in that case mostly works on non-immune/structural cells in barrier tissues)

Epithelial, Endothelial, Neutrophils, Fibroblasts, Phagocytes

Recruit Neutrophils, Promotes Inflammation

Cytokine group: Type 1 and 3

Which cells produce TNF-Beta (lymphotoxin)? What cell does TNF-Beta target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th1

PMNs, Tumor cells

Kill Tumors, Activate PMNs, Activate Endothelium (allows trafficking)

Cytokine group: Type 1 and 3

Which cells produce IL-2? What cell does IL-2 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th0 and Th1

Lymphocytes

Lymphocyte proliferation

Cytokine group: Type 1 and 3; Growth/Differentiation/Proliferation/Hematopoiesis

Which cells produce IL-12,13? What cell does IL12,13 target? What is the result of this signaling pathway? What cytokine group is this a part of?

DCs, Macs

NK cells, CD4 Th1 and Th17

Activate T cell IFN-gamma or IL-17 production

Cytokine group: Type 1 and 3

What is the Type 2 immune response important to?

allergy, helminth infections and wound healing 

What is the Type 1 and 3 immune response important to?

inflammatory innate to adaptive response

What is the immunosuppressive immune response important to?

immunosuppression and anti-inflammatory response

Which cells produce IL-4? Which cells does IL-4 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th0 and Th2, Tfh, ILCs

B and T cells

T and B growth/differentiation; IgG, IgA, IgE production; Th2 response; allergy response

Cytokine group: Type 2

Which cells produce IL-5,13? Which cells does IL-5,13 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th2

B cells, Eosinophils (helminth infections)

T and B growth/differentiation; IgG, IgA, IgE production; Th2 response; allergy response

Cytokine group: Type 2

Which cells produce IL-10? Which cells does IL-10 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Th2 and Treg

B cells, CD4 Th1 and Th17 (Th17 in low amounts)

B cell growth, Inhibit Th1 and Th17 responses

Cytokine group: Type 2; Immunosuppressive/Anti-inflammatory

Which cells produce TGF-Beta? Which cells does TGF-Beta target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 Treg

B cells, T cells, Macs, DCs

Immunosuppression of all immune responses, promote oral tolerance, wound healing

Balance between Th1/17 and Treg is ________ or ________ by cytokines. One prominent example is ______. When this balance is dysregulated in the intestinal microbiota it can lead to _______ _______ (_____’_ ______)

maintained; disrupted

TGF-Beta

chronic inflammation (Crohn’s Disease)

Which cells produce GM-CSF/M-CSF? Which cells does GM-CSF/M-CSF target? What is the result of this signaling pathway? What cytokine group is this a part of?

Stromal cells, T cells 

BM progenitor cells, Stem cells, Precursor cells

Hematopoiesis; growth and differentiation of monocytes and granulocytes

Which cells produce IL-3? Which cells does IL-3 target? What is the result of this signaling pathway? What cytokine group is this a part of?

CD4 T, keratinocytes

BM progenitor cells, Stem cells, Precursor cells 

Hematopoiesis; growth and differentiation of monocytes and granulocytes

Cytokine group: growth/differentiation (also prolif, hematopoiesis)

Which cells produce IL-7? Which cells does IL-7 target? What is the result of this signaling pathway? What cytokine group is this a part of?

BM, Stroma

BM progenitor cells, Stem cells, Precursor cells

Growth of Pre-B cells, T cells, and NK cells

Cytokine group: growth/differentiation (also prolif, hematopoiesis)

Which cells produce IL-8/CXCL8? Which cells does IL-8/CXCL8 target? What is the result of this signaling pathway? What cytokine group is this a part of?

Fibroblasts, Neutrophils, Macs

Phagocytes

Recruit cells to the infection site

Cytokine group: Chemotactic agents

What is the source of C5a? Which cells does C5a target? What is the result of this signaling pathway? What cytokine group is this a part of?

Complement cascade

Phagocytes

Recruit these cells to the infection site 

Cytokine group: Chemotactic agents 

How many other chemotactic agents are there? What do they target?

over 30 more

Neutrophils, B cells, T cells, Macs, DCs, NK cells, Mast cells etc.

What do chemokines do?

coordinate interactions of innate and adaptive responses 

What are the 4 families of chemokines? What is it based on?

CXCL, CCL, XCL, CX3CL

Structural differences

What 3 functional categories can chemokines be broken into?

pro-inflammatory, mixed function, homeostatic

What are the 4 families of receptors?

CXCR, CCR, XCR, CX3CR

Release of _____ attracts cells to the injury/infection site. Binding of _-_______ allows lymphocyte to roll along endothelial cell receptors. Then ______ on lymphocytes bind ______ ______ and ________ to the site of injury/infection.

Chemoattracts; L-selectin; chemokines; chemokine receptors; transmigration

What is the consequence of the wound healing process being overactive? What cytokines cause this?

Too much collagen deposition is damaged tissue → stiff organ → organ failure

IL-4, IL-13, TGF-Beta

What cytokine is involved in the transition from the lymphoid progenitor to B lymphocyte?

IL-7

What cytokine is involved in the transition from the lymphoid progenitor to T lymphocytes?

(Thymus) IL-7, others.

What are the key cytokines known to support transition from the myeloid progenitor to innate immune cells (megakaryo; baso CFU; eos CFU; granulocyte-monocyte CFU)?

IL-3, GM-CSF, IL-1, IL-6

Which cytokines are known to support the transition from granulocyte-monocyte CFU to neutrophils?

IL-3, GM-CSF, G-CSF

Which cytokines are known to support the transition from granulocyte-monocyte CFU to monocytes?

IL-3, GM-CSF, M-CSF

What makes NSG mice particularly useful for humanized immune system models?

NSG mice lack mature T, B and NK cells which allows successful engraftment of human hematopoietic stem cells and development of a functional human immune system for research

Why are human cytokines often supplemented in NSG humanized mouse models?

Mouse cytokines do not efficiently support development of human immune cells - especially myeloid/innate lineages so human cytokines must be added for robust multilineage reconstitution in NSG mice

____ affinity receptors can be effective in very low numbers per cell

High

Complete receptor usually consists of _____ ____ ___ polypeptide chain

more than one

Are cytokine receptor chains shared?

yes 

A STAT dimer acts as _______ _______

transcription factors

What are the major types of cytokine receptors?

CT1GTT

Cytokine/hematopoeitin receptor

TNF receptor

IL-1 receptor

GPCR (7-membrane spanning)

TGF-Beta receptor

Tyrosine kinase growth factor receptor

What is the adaptor protein for cytokine signaling class I (cytokine/hematopoietin receptor)? What’s the pathway?

JAK

• cytokine binding leads to dimerized receptor and bringing together JAKs

• JAKs activate each other and phosphorylate of tyrosine residues on the receptor

• STAT (transcription factor) is then recruited and bound to the receptor, where JAK can also phosphorylate STAT

• phosphorylated STATs dimerize and translocate to the nucleus to initiate gene transcription

What are the “4” types of cytokines?

Type 1

Type 2

Type 3

Immunosuppressive

What are the 3 modes of action for cytokine signaling?

Autocrine (self)

Paracrine (nearby)

Endocrine (remote) - distant sites cia circulation