Chapter 5 b- recognition responses

Question 1

what are cytokines?

Answer 1

low molcular weight proetins that work as messengers of the immune system

Question 2

what is included in a cytokine?

Answer 2

interleukins - secreted by leukocytes and act on other leukocytes

Monokines

Lymphokines

chemokines - related but manage cell migration

Question 3

what happens when a stimulus is induced?

Answer 3

indcuing stimulus - cytokine relase - chemokine receptor - Target cella ctiavtion

Question 4

What are the three ways cytokines act?

Answer 4

autocrine - act on self

paracrine - release cytokines that go and bind a receptor directly (most common)

endocrine - release cytokines that go through circulation and then travel to a receptor

Question 5

there are 5 properties of chemokine what are they?

Answer 5

Pleiotrophy

redundancy

synergy

Antagonism - some receptors have different affinity then others

Cascade indcution

Question 6

what is the IL-2R definceny?

Answer 6

a x-li nked severe combined immunodefinceny

IL-2R is essential for activation of T cells

no T cells and no NKC

this is an example of redundancy

Question 7

cytokine receptors communicate with the nucleus via a signal transduction pathway to change gene expression and influence cell fate and activity. Describ the key proteins in this pathway

Answer 7

activation of JAK (Janus Kinase) family tyrosine kinases, phosphoryaltion of recpetor

Tyrosine phosphorylation of STAT (signal transduction activator of transcription) by JAK kinase

leades to specific gene transcription

Question 8

Pyrogen (fever causing) cytokines

Answer 8

IL-1, IL-6, TNF - alpha

Question 9

pro-inflammatory cytokines

Answer 9

IL-1, IFN - gamma, TNF - alpha

Question 10

anti-inflammatory cytokine

Answer 10

TGF- beta

Question 11

anti-viral cytokines

Answer 11

IFK-gamma, IFN-alpha/beta

Question 12

Chemokines

Answer 12

IL-8 attarct neutrophils
MIP-1alpha and MIP-1bata attarct monocytes and NK cells

Question 13

explain the process of extrvasation

Answer 13

chemokines contorll the process

rolling - naive T cell rolls over surface

Activation - through rolling it binds to the chemokine and actiavtion occurs meaning integrings are relases

arrest/ ahesion - integrings are key for adhesion

laslty transendothial migration occurs

Question 14

chemokine vs cytokine

Answer 14

chemokine - cell migrate and a subset with in cytokine

cytokine

Question 15

cytokine are abel to upregulated chemokine receptos what does this cause ?

Answer 15

regulates cells ability to enter tissues

Question 16

what is the objective of anti-inflammatory drugs?

Answer 16

block extravasation

Question 17

what are some anti-inflammatory drugs?

Answer 17

antibody-based therapies

corticosteroids

Question 18

how does antibody - based therpay work? and examples.

Answer 18

they bind integrin or other ahdesion molecules

used for kideny trasnplants
autoimmune dissease: crohns, MS, rheumatoid arteritus

Question 19

how do corticosteroids work?

Answer 19

a more borad approch

interacte with steroid hormone

decrease lymphocyte circulating
lymphotcte lysis

inhibtis almost all cytokine production/secretion (NF-kappa beta)

inhibits T cell, macrophages, and neutrophil activation

Question 20

cytokine also regulate hematopoeis, what is used to trest chemotherpy and bone marrow recipient patients

Answer 20

G-CSF, GM-CSF used to promote neutrophil actovtion in the myeloid pathway from granolycytes progenitor

Question 21

What is Septic shock/ sepsis

Answer 21

endotoxins produced by gram-negative bacteria stimulate DC and macrophages via TLRs to overproduce IL-2 and TNF-alpha

superantigens

leading to ischmia(lack of blood flow) and sterile inflammation

too much inflammation as too many cytokines are releses

Question 22

how do we neurtalize TNF-alpha and IL-2

Answer 22

TNF-alpha neutralized via antibody

IL-a is neutraluzed with soluble IL-1(IL-1Ra)

Question 23

what is a cytokine storm

Answer 23

occurs in healthy individuals when immune systems are activated with not enough breaks

over activation of the immune system

for diseases like influenza, SARS, COVID-19

Question 24

what are some cytokine related diseases?

Answer 24

spesis/ septic shock
cytokine strom
cancers
autoimmunity and other immune based disease

Question 25

talk about cancers

Answer 25

HTLV (human T cell leukemia virus): IL-2

myelomas, cardiac myxoma cells, cervical cancers, bladder cancer: IL-6
-autocrine
-enhance proliferation

hodkin’s lymphoma: IL-5

Question 26

talks about autoimmunity and other immune-based diseases

Answer 26

SLE(lupus): IL-10

over actiavtion of the immune system

Question 27

what are some cytokine based therapies?

Answer 27

cytokine inhibitors/antagonist
- TNF inhibtors, IL-1Ra for RA/chronic inlfmamamtion
-IL-2R as clinical marker for chronic T cell activation

reversing cellular deficiencies
-G-CSF and GM-CSF to escalate the rate of reconstitution following chemotherapy or bone marrow transplant

treatment of immunodeficiencies
-G-CSf for x-linked agammalobulinemia
-IL-2 for SCI, IFN-gamma for leukocyte adhesion deficiencies
-IL-2 antibody stabilizes recombinant (injected) IL-2 in the circulation (paradox)

Question 28

treatment of T-cell leukemia and transplant patients

Answer 28

blocking antibodies tp prevent T-cell activation by IL-2

Conjugate toxins to cytokine analog to target TH cells that express abnormally high amount of CD25(IL-2gamma chain)