Cytokines of innate immunity (Heck) Flashcards by Andrea Parsons

Examples of Type I Cytokine Receptors

Hematopoietin R

Jak-STAT

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Type II Cytokine R

Jak-STAT

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IL-1 Family R types

TLR, receptor for IL-1 and IL-18

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What are the cytokine R

Type I, Type II, IL-1 Family, TNF, and GPCRs

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Categories of cytokines

Mediators and regulators of innate immunity, mediators and regulators of adaptive immunity, mediators of hematopoiesis

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The role of TNFa in the acute inflammatory response to gram negative bacteria

Stimulates recruitment of neutrophils and monocytes to infection site and activates them by:
Induces vascular cells to express selectin,
induces vascular cells and macrophages to secrete chemokines,
stimulates mononuclear phagocytes to produce IL-1
stimulates microbicidal action of neutrophils and macrophages

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What are the systemic effects caused by moderate quantities of TNF

fever, secretion of acute phase proteins and the production of leukocytes

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What are the systemic effects caused by too much TNFa

Septic Shock, thrombus formation, hypoglycemia

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What does IL-6 initiate the production of, and from where

hepatocytes start to sythesize serum amyloid protein, C reactive protein, fibrinogen, mannose binding lectin and SP-A and SP-D

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which proteins act as an opsonin and activate complement

C reactive protein when binds to phophorylcholine and Mannan-binding lectin when it binds to mannose residues on bacterial surfaces

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what 2 processes work in adjunct to cause decreased viral and bacterial replication, and increased antigen presenting

Increased body temp from hypothalamus

Protein and energy mobilization to allow increased body temp in response from TNFalpha (and IL-6 and IL-1)

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How is C reactive protein used clinically

measured to monitor inflammatory response

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How does TNFa cause septic shock

endotoxin shock. In high quantities, it inhibits myocardial contractility and sm mm tone. Stimulates tissue factor for coagulation and inhibits the inhibitor thrombomodulin.
low blood glucose due to overuse of muscles and underproduction by liver

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What produces TNFalpha

Activated mononuclear phagocytes, antigen-stimulated T cells, NK cells and Mast cells.

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What activates release of TNFalpha

TLR activation by LPS (gram-)
INFgamma by T cells and NK cells

PAMP recognition

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Two pathways of TNF type R

Gene Expression of inflammatory mediators using MAPK or NFkB

Apoptotic- extrinsic pathway

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role of IL-1

similar to TNF. mediates local inflammation and induces expression of Integrin Ligands on endothelial cells so extravasation of leukocytes can happen

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What produces IL-1

Mononuclear phagocytes
Neutrophils
Epithelial cells
Endothelial cells

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What activates the release of IL-1

TLR activation by PAMPs or LPS

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What are the systemic activities of IL-1

Induces fever, acute phase proteins and neutrophil/platelet production
Does not induce apoptosis
Can’t cause apoptosis by itself
Induces production of IL6

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Systemic activities of IL-6

Fever and production of acute phase proteins

What are chemokines and what are their general role

Chemotactic cytokines that have a roll in the cell trafficking during inflammation

What cells produce chemokines

Leukocytes, Endothelial Cells, Epitehlial cells, Fibroblasts, lympoid organs

What activates the production of chemokines

TLR signaling

TNF or IL-1 signaling

What does R activation from chemokines do?

modulates the cytoskelteon and integrin affinity. chemokines stimulate T cell integrins to transform from low affinity to high affinity state for ligand binding and cause clustering so tight adhesion for Tcell to APC cell

What 2 cells do chemokines act on systemically

Endothelial Cells and Leukocytes

How do chemokines work on endothelial cells

Chemokines can diffuse through endothelium and bind heparin sulfate on proteoglycans in lumen to be displayed to leukocytes. This increases extravasation and promotes angiogensis after tissue injury

How do chemokines work on leukocytes

Alternating polymerization and depolymerization of actin

What is the role of IL-12

Mediator of early innate immune response

What produces IL-12

Activated dendritic cells Activated macrophages (In response to microbe)

What activates the production of IL-12

TLR activation LPS Intracellular bacteria (Liseria) and viruses APCs stimulating T cells(CD40)

What are the 4 general systemic activities of IL-12

stimulates NK and both types of T cells to make IFN gamma causes gram - sepsis T helper differentiation(CD4+) Induces Cytotoxic functions of NK and Cytotoxic T cells (CD8+)

What is the result of IL-12 stimulating IFN gamma production

IFN stimulates macrophages to kill engulfed bacteria.

How does IL-12 contribute to grame - sepsis

LArge amounts of IL-12 induce IFN gamma which with LPS induces TNF--> septic shock

What is the role of Type I interferons

Interfere with viral inception, involved in early innate immune response and intracell microbes

What produces Type I interferons a and b

IFN-a in Immune cells(dendritic and mononuclear phagocytes) | IFN-b in systemic cells like Fibroblasts

What activates Type I IFNs

Viral nucleic acids and mononuclear phagocytesCD40

What is the local result of R activation with Type I IFNs

Induces proteins which inhibit viral replication machinery- paracrine activity to protect neighbors Increases MHC I expression to increase the CTL (CD8+) mediated killing (prevent spreading of virus)

What are the systemic activities of IFNs

sequester lymphocytes in lymph nodes to enhance antigen dependent activation

What is the role of IL-10

Inhibit innate immune response in macrophages and dendritic cells

How does IL-10 inhibit innate response

Limit production of IL-12 thereby IFN gamma and also inhibits the expression of MHC II

What produces IL-10

Activated macrophages, Regulatory T cells (CD25+) and non-lymphoid cells like keratinocytes

What are the innate responders to Extracellular bacteria

TNF, IL-1 and chemokines to promote extravasation and the main responder are neutrophils

What are the innate responders to intracellular bacteria

IL-12 and INF gamma to promote phagocytosis and stimulate adaptive responses Main responder is macrophages

What are the innate responders to Viruses

Type I INFs and IL-12 to inhibit replication Activate NK and enhance cytotoxic activity Main responder are NK cells

What do IL-15 and IL-18 do

15 causes NK and T proliferation | 18 causes NK and T cells to produce IFN-gamma

Septic shock symptoms

Hyper or hypothermia, Tachycardia, hypotension, tachypnea, acute hyperventilation with respiratory alkalosis, mental status changes (obtundation) and a patient hx suggestive of new infection

What is measured to Dx septic shock

TNF and IL6 circulating

What test do we measure IFN gamma in blood

latent TB

When a patient rejects a transplant what cytokine is detected

IL-2R

Give exmaples of cytokines used for Tx

IFN-a for chronic hepatitis and hematologic cancers IFN-b for multiple sclerosis IL-12 in clinical trials to boost immunes response GM-CSF to recover from chemotherapy and BM transplant EPO to treat anemia and chronic renal failure

What cytokines do we block clinically

Basiliximab to prevent IL-2 from binding R to inhibit transplant rejection anti TNF and IL1 ab to treat rheumatoid arthritis and inflammatory bowel disease