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IHL Exam 1 > Cytokines of innate immunity (Heck) > Flashcards

Cytokines of innate immunity (Heck) Flashcards

1
Q

Examples of Type I Cytokine Receptors

A

Hematopoietin R

Jak-STAT

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2
Q

Type II Cytokine R

A

Jak-STAT

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3
Q

IL-1 Family R types

A

TLR, receptor for IL-1 and IL-18

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4
Q

What are the cytokine R

A

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

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5
Q

Categories of cytokines

A

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

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6
Q

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

A

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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7
Q

What are the systemic effects caused by moderate quantities of TNF

A

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

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8
Q

What are the systemic effects caused by too much TNFa

A

Septic Shock, thrombus formation, hypoglycemia

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9
Q

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

A

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

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10
Q

which proteins act as an opsonin and activate complement

A

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

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11
Q

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

A

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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12
Q

How is C reactive protein used clinically

A

measured to monitor inflammatory response

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13
Q

How does TNFa cause septic shock

A

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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14
Q

What produces TNFalpha

A

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

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15
Q

What activates release of TNFalpha

A

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

PAMP recognition

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16
Q

Two pathways of TNF type R

A

Gene Expression of inflammatory mediators using MAPK or NFkB

Apoptotic- extrinsic pathway

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17
Q

role of IL-1

A

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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18
Q

What produces IL-1

A

Mononuclear phagocytes
Neutrophils
Epithelial cells
Endothelial cells

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19
Q

What activates the release of IL-1

A

TLR activation by PAMPs or LPS

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20
Q

What are the systemic activities of IL-1

A

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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21
Q

Systemic activities of IL-6

A

Fever and production of acute phase proteins

22
Q

What are chemokines and what are their general role

A

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

23
Q

What cells produce chemokines

A

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

24
Q

What activates the production of chemokines

A

TLR signaling

TNF or IL-1 signaling

25
Q

What does R activation from chemokines do?

A

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

26
Q

What 2 cells do chemokines act on systemically

A

Endothelial Cells and Leukocytes

27
Q

How do chemokines work on endothelial cells

A

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

28
Q

How do chemokines work on leukocytes

A

Alternating polymerization and depolymerization of actin

29
Q

What is the role of IL-12

A

Mediator of early innate immune response

30
Q

What produces IL-12

A

Activated dendritic cells
Activated macrophages
(In response to microbe)

31
Q

What activates the production of IL-12

A

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

32
Q

What are the 4 general systemic activities of IL-12

A

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+)

33
Q

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

A

IFN stimulates macrophages to kill engulfed bacteria.

34
Q

How does IL-12 contribute to grame - sepsis

A

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

35
Q

What is the role of Type I interferons

A

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

36
Q

What produces Type I interferons a and b

A

IFN-a in Immune cells(dendritic and mononuclear phagocytes)

IFN-b in systemic cells like Fibroblasts

37
Q

What activates Type I IFNs

A

Viral nucleic acids and mononuclear phagocytesCD40

38
Q

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

A

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)

39
Q

What are the systemic activities of IFNs

A

sequester lymphocytes in lymph nodes to enhance antigen dependent activation

40
Q

What is the role of IL-10

A

Inhibit innate immune response in macrophages and dendritic cells

41
Q

How does IL-10 inhibit innate response

A

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

42
Q

What produces IL-10

A

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

43
Q

What are the innate responders to Extracellular bacteria

A

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

44
Q

What are the innate responders to intracellular bacteria

A

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

45
Q

What are the innate responders to Viruses

A

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

46
Q

What do IL-15 and IL-18 do

A

15 causes NK and T proliferation

18 causes NK and T cells to produce IFN-gamma

47
Q

Septic shock symptoms

A

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

48
Q

What is measured to Dx septic shock

A

TNF and IL6 circulating

49
Q

What test do we measure IFN gamma in blood

A

latent TB

50
Q

When a patient rejects a transplant what cytokine is detected

A

IL-2R

51
Q

Give exmaples of cytokines used for Tx

A

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

52
Q

What cytokines do we block clinically

A

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

IHL Exam 1 (11 decks)

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