Cytokines Flashcards

1
Q

Cytokines: Definition

A

Soluble proteins that regulate immune system’s innate and adaptive responses
- Communication molecules
- Can be induced in response to stimuli or through T and B receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cytokine: Extra

Production and collaboration

A

Production: through ligation of cell adhesion molecules or through recognition of antigens/molecular patterns by host lymph
- Cytokines often act in concert with each other
- Network of cytokine expression = regulates leukocyte activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cytokine: Effects

A

In vivo: regulation of growth, differentiation, gene expression by many cell types

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How Do Cytokines Exert Effects?

3 ways

A

Autocrine: affecting the same cell that secreted it
Paracrine: affecting target cell close by
Endocrine: systemically and far travel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cytokines: Differentiation

A

Major families: tumor necrosis factor (TNF), interferons (IFN), chemokines, etc.

Colony stimulating factors (CSFs): IL3, EPO, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do Colony Stimulating Factors CSF do?

A

Act on bone marrow
- specific cell lineages to develop

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cytokines: Interleukins

3 criteria

A

IL-1 through IL-36
Three criteria
1. Have had genes cloned
2. Must be inducible in leukocytes
3. Biological activities in inflammatory processes must be catalogued

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cytokine: Properties

4 different ways they work

A

Pleiotropism: one cytokine multiple functions
Redundancy: multiple cytokines, same function
Synergy: amplified or different effects when working together
Antagonism: counteraction, activation vs. inhibitory cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cytokines of the Innate Immune System

6 of them

A
  • Type I Interferons (IFN a, IFN b)
  • Tumor Necrosis Factor (TNF)
  • Interleukin 1beta (IL-1b)
  • Interleukin 10 (IL-10)
  • Transforming growth factor beta (TGF b)
  • Chemokines (several)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Type I Interferons: Purpose

3 things

A

Interfere with viral replication and cell division
- Activates NK cells (because viruses can downrate MHC class I expression)
- Enhances MHC class I proteins
- Active against other inflammatory processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cytokines: Inflammation

A

Recruits effector cells to area: causes fever or swelling, inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cytokines: Tumor Necrosis Factors

Innate immunity

A

TNF-a: most prominent one
- Secreted by active monos and macros, activates T cells through induction of MHC class II expression and other things
- Causes vasodilation and increased vasopermeability
- Main trigger is lipopolysaccharide: G- bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cytokines: Interleukins

3 ILs, what do they do?

A

IL-1 family: IL-1a, IL-1b, IL-1RA (receptor antagonist)
- IL-1a and IL-1b: proinflammatory cytokines, made by macros and monos
- IL-1b: most systemic activity, fever, phagocyte activation, acute phase protein production
- IL-1: endogenous pyrogen, induce fever in acute phase response
- IL-1: makes vascular cell-adhesion molecules
- Recognition of lipopolysaccharides by TLR 4 on monos and macros, makes IL-1b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cytokines: Chronic Inflammation

A

Many disease states have chronically increased inflammatory cytokines, they predict mortality
- Seen in rheumatoid arthritis, Chrohn’s disease, sepsis, HIV, binge drinking, etc.
- TNF-a and IL-1 common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Chemokines: Definition

A

Family of cytokines that enhance motility and promote migration toward the source of chemokine

Chemoattractant cytokines

  • Can activate some cells
  • Immune cells move toward they
  • Some induced, some constitutive
    - IL-8, CCL2, fractalkine, SDF1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Chemoattraction: Cytokines and Chemokines

Process?

A

Recognizing and activation by pathogens or PAMPs, macros in tissue release cytokines and chemokines
- IL-1 and TNFa make endothelial cells express cellular adhesion molecules (CAMs)
- Chemokines recruit leukocytes to the site

17
Q

Cytokines: Innate and Adaptive Bridge - IL6

IL-6

A

IL-6 produced by both lymphoid and nonlymphoid cells
- IL-1 triggers secretion of IL-6
- IL-6 affects inflammation, acute phase reactions, activation states of B and T cells
- Stimulates B cells to proliferate and differentiate into plasma cells
- Induce CD4+ T cells to make more pro and anti-inflammatory cytokines

18
Q

Cytokines: In the Adaptive Immune System

A

Mostly made by T cells, directly affects function of T and B cells (more than in innate)

19
Q

Cytokine: IL-2 in Adaptive Immunity

A

T-cell growth factor
- Both T and B cells, lytic activity in NK cells
- Can also activate proliferation of Th2 cells

IL-7 is another cytokine that can induce proliferation, helps with survival of memory

20
Q

Cytokines: Adaptive Immunity - Helper T Cells

A

Four main subclasses: TH1, TH2, TH17, T-regulatory
- TCR recognizes antigen, clonal expansion occurs
- Differentiation into subclasses is influenced by cytokines

21
Q

CD4+ TH1 vs. TH2

And Functions

A
  • TH1: protects against intracellular pathogens
  • TH2: interleukins, help B cells produe antibodies against extracellular pathogens
22
Q

TH1 Cells: IFN-y

A

TH1 cytokines make IFN-y: affects RNA expression levels of many genes
- Regulation/activation of many cells
- Stimulates antigen presentation by MHC I and II molecules
- Is a type II IFN: invovlved in regulation of cell function

23
Q

TH2 Cells: IL-4

A

TH2 cells: antibody-mediated immunity, B cell activation and class switching

IL-4 regulates TH2 immune activities
- Expressed on lymphocytes and nonhematopoietic cell types,
- Neutralizes IgG
- Production of IgE
- Suppression of macrophage
- Eosinophil activation

24
Q

Importance of TH1 vs. TH2

Leprosy- bacteria that live in macrophages, two forms

A

Tuberculoid: induces cell mediated response (TH1), form granulomas and clear bacteria from macrophage
Lepromatous: produces humoral response (TH2), bacteria cannot be controlled, systemic disease

25
Q

Immune Suppression Regulatory Cells (Tregs)

What are they and what do they produc

A

T cells, key role in establshing peripheral tolerance to self-antigens, allergens, tumor/transplant antigens, and infectious agents
- Inhibits immune response by direct contact or by cytokines
Produces: IL-10 and TGF-beta

26
Q

Tregs: Transforming Growth Factor Beta (TGF-b)

What it does

A

Induces antiproliferatve activity
- Regulator of cell growth, apoptosis, migration, inflammatory response
- Down regulates inflammatory response when no longer needed
- Foxp3 produced by TGF-b, causes Tregs to suppress other T cells

Anti-inflammatory cytokine

27
Q

Tregs: IL-10

A

Anti-inflammatory, suppressive on TH1 cells
- Inhibits antigen presentation and stimulates CD8+ T cells
- Antagonist to IFN-y, down regulator of immune response

28
Q

TH1 Cytokines

A
  • IFN-y
  • IL-2
  • TNF-b
  • Chemokines
  • TNF-a
  • IL-3
29
Q

TH2 Cytokines

A
  • TNF-a
  • IL-3
  • IL-4
  • IL-5
  • IL-6
  • IL-10
30
Q

TH1 Function Overview

A
  • Macrophage activation
  • Neutrophil activation
  • Complement-binding and opsonizing antibodies

more innate immunity

31
Q

TH2 Functions Overview

A
  • Total antibody production
  • IgE production
  • Eosinophil/mast cell production/activation
  • Neutralizing IgG
  • Suppress macrophages

more adaptive immunity/regulation