Cytokines, immunology Flashcards
Type 1 Cytokines
IL-2, IFN-γ, IL-12, TNF-α
Type 2 Cytokines
IL-4, IL-5, IL-6, IL-13, IL-31
Type 17 Cytokines
IL-17, IL-21, IL-22, (IL-6, TNF-α)
Main pathogens fought by Th1
Viruses, intracellular pathogens (viruses, bacteria, protozoa, fungi)
Main pathogens fought by Th2
Multicellular Parasites, allergies, venoms
Main pathogens fought by Th17
Inflammation, extracellular pathogens (bacteria, fungi)
Activate neutrophils to throw NETosis
Cytokines to induce Th17
IL-23!!, TGF-β, IL-6
Cytokines to induce Th1
IL-12, IFN-γ
Cytokines to induce Th2
IL-4
Cytokines to induce TReg
TGF-β, IL-2
Cytokines to induce Th9
TGF-β, IL-4
IL-4 is produced by ____:
Th2 cells
Mast cells
Basophils
IL-4 induced conversion of Th0 to _____:
Th2 cells
IL-4’s role on Th1 cells
Suppression of Th1
(reduction of IL-2, IFN-γ)
IL-4’s role on Th17 cells
Suppression of Th17
IL-4’s role on B cells
Stimulates B cells to make IgG, IgE, MHC class II
IL-4’s role on macrophages
Activates macrophages
IL-4’s role on ILC2 cells
Activates ILC2 cells
Upregulates:
-IL-5
-IL-9
-IL-13
-CCL11 (eotaxin)
Main stimulator of eosinophils
IL-5
Cellular producers of IL-5
Th2 cells, mast cells, eosinophils
Cellular producers of IL-9
Th2 cells that are activated by IL-2, ILC2 cells, mucosal mast cells
Function of IL-9
-Promotes growth of helper T cells, mast cells
-Potentiates effect of IL-4 on IgE production
Cellular producers of IL-13
Th2, ILC2, Tfh13, NK, mast, DC2 cells
Functions of IL-13
Promotes Th2 response, suppresses Th1 and Th17 responses (similar to IL-4), activates eosinophils
Major cytokines produced by damaged epithelial cells or PAMPs on epithelial cells for Th2 response
-IL-25
-IL33
-TSLP
Cytokines that activate ILC2 cells
-IL-25
-IL33
-TSLP
Cytokines produced by ILC2 cells
IL-9 (mast cells, basophils)
IL-5 (eosinophil activation, recruitment)
IL-13 + IL-4 (B- cell production of Igs)
Which cytokine induces the IgM-IgG1-IgE pathway, where somatic mutation and selection occur to make high affinity IgE?
IL-13
(IL-4 alone induces IgM-IgE directly, which is lower affinity IgE)
What is present in Mast Cell granules?
- Histamine
- Serotonin
- Dopamine
- Kallikreins
- Proteases (tryptase, chymase)
- Proteoglycans (heparin, chondroitin sulfate)
- Neuropeptides
- Stored cytokines
What is synthesized by mast cells once activated?
- Leukotrienes
- Prostaglandins
- Platelet activating factor
- IL-1
- IL-3
- IL-4
- IL-5
- IL-6
- IL-9
- IL-13
- TNF-alpha
- TGF-beta
- SCF
- Chemokines
- Growth factors
- Neuropeptides
MHC for viral recognition
MHC class I
MHC expressed by infected cells
MHC class I
MHC for bacterial and allergen recognition
MHC class II
MHC expressed by dendritic cells
MHC class II
3 signals needed for naive T helper cells differentiation
1) MHC to TCR binding
2) Cell-Cell adhesion molecules (strong bond)
3) DC cytokines (ie IL-12 induces Th1)
Which cytokine is definitive for the Th1 response type?
IFN-gamma
Role of IFN gamma (type 2 interferon)
1) Activates M1, more MHC expressed on DC1s
2) Stimulates endothelial, keratinocytes, fibroblasts to secrete proinflammatory cytokines
3) Synergizes with TNF-alpha
JAK-1 dependent
Which cytokines are definitive of a Th2 response type?
IL-4, IL-13
Where is IL-4 produced? What’s its role?
Lymphoid organs, IgE production
Where is IL-13 produced? Whats its role?
Peripheral tissues, local allergic reactions
When are Th17 strongly produced?
Chronic inflammation
What is the function of Th17?
Trigger inflammation
B cell helpers
POTENT – need to balance Th17 with Treg
What makes ILC2 different from Th2?
Same cytokines, but ILC2 is present under body surfaces, not in lymphoid organs
Which cytokine does Th1 NEED for proliferation?
IL-2
Which cytokines do Th2 use for proliferation?
IL-2 OR IL-4 OR IL-1
(Does not depend on IL-2 like Th1 does)
Which hormones induce a Th2 response?
Low dose GCs
Beta agonists (catecholamines, bronchodilators)
**Also NaCl (activates NFAT5, higher Na in atopic skin than healthy skin, NaCl affects microbiome)
Which hormones induce a Th1 response?
Testosterone
Which hormones induce low Th1 and Th2 responses?
High dose GCs, estrogen, progestin
Which type of T cell lives in the lymph nodes and helps regulate B cell antibody production (crucial for high affinity IgE production and acute anaphylaxis)?
Follicular helper T cells
Which cytokine stimulates Tfh cells to help make high affinity IgE?
IL-13
T or F: Are IgE easily destroyed by heat?
True
SCF is produced by _____:
-Fibroblasts
-Endothelial cells
Role of SCF
Activates Mast cells, Mast cell survival signal, regulates IgE production
What does SCF bind to on mast cells?
KIT surface receptor
What are the 3 types of granules in eosinophils?
1) Crystalloid granules, large/ specific
2) Primary granules, small
3) Dense vesicles, small
What is inside the crystalloid granule CORE of eosinophils?
-Major basic protein
-Eosinophil peroxidase
What is inside the crystalloid granule MATRIX of eosinophils?
-Eosinophil cationic protein
-Eosinophil-derived neurotoxin
(both are ribonucleases)
Which animals do NOT have crystalloid granule cores?
Cows, mink
What is the role of major basic protein (MBP)?
1) Disrupts plasma membranes of nearby cells
2) Stimulates histamine release from MCs, basophils
3) Activates neutrophils, platelets
4) Stimulates superoxide dismutase from macrophages
5) toxic to bacteria, helminths
What is the most common eosinophil granule protein?
Major basic protein (MBP)
Which protein is the reason for eosinophils staining pink?
Eosinophil cationic protein (ECP)
What is the role of eosinophil cationic protein?
1) Damage cell membrane
2) mast cell degranulation
3) Kills bacteria, viruses, parasites
What is the role of eosinophil-derived neurotoxin?
1) Damages myelinated nerves
2) Chemoattractant for immature DCs
What is the role of eosinophil peroxidase? (EPO)
Oxidizing agent; kills ingested bacteria (YES! Eosinophils are APCs, MHC cl II)
Differentials for chronic eosinophilia
-FAD
-CAFR
-Parasites
-Adverse drug reaction
-Bronchial asthma
-ECG
-Eosinophilic enteritis
-MCT
-Lymphomas
3 ways mast cells can be triggered to degranulate
1) IgE-mediated
2) Non-IgE mediated (LPS, PRRs, Drugs, complement peptides, IgG+antigen, neuropeptides)
3) Mas-related G-protein coupled receptor X2 (MRGPRX2) (Substance P, neurotensin, cathelicidins, beta-defensins, major basic protein, eosinophil peroxidase) –> some degranulation, limited cytokine synthesis. SLOWER AND FEWER GRANULES RELEASED
Which cell type is crucial in mast-cell late-phase responses?
Th17
True or False: basophils are phagocytic, like eosinophils
FALSE. Basophils are NOT phagocytic
(Eos are though!)
Which cell type is more common in reptiles/ turtles than mammals?
Neutrophils
What cytokine is the main basophil activator (promotes basophil fate, survival)?
IL-3
What are the 2 pathways to degranulation in basophils?
1) IgE-mediated
2) TSLP-mediated
What products are released by basophils in IgE-mediated degranulation?
-IL-4
-Histamine
-PAF
-Leukotrienes
-Prostaglandins
-Proteases
-Substance P
What products are released by basophils in TSLP-mediated degranulation?
-IL-4
-IL-6
-IL13
-Histamine
-Chemokines
-Proteases
-Substance P
What are effects of H1R binding?
1) Increased NO –> vasodilation
2) Increased prostaglandins, leaky vessels –> edema, hives, nasal discharge, ocular tears
3) Itch/pain
What are the effects of H2R binding?
1) Increased gastric acid
2) Increased vasodilation –> hypotension
3) Increased TLR expression on sentinel cells with H2Rs
What are the effects of H3R binding?
1) Appetite regulation
2) Cognition
3) Sleep
What are the effects of H4R binding?
1) Hypersensitivity
2) Chemotaxin, cytokine production by MC, Eos, DC, T cells
3) Modulates inflammation and pruritus in allergic disease
Role of Serotonin
1) Vasoconstriction –> hypertension
2) Important for acute inflammation in RODENTS
Little effect on vascular permeability
Role of Dopamine
1) Decreased lymphocyte proliferation
2) Decreased neutrophil, MC, NK function
3) MAJOR MEDIATOR OF ANAPHYLAXIS IN COWS
Role of GABA
Important for allergic asthma
Anaphylotoxins
C3a, C5a
Role of C3a, C5a
1) Proinflammatory
2) Chemoattractants
3) Vascular dilation, permeability
4) Kill bacteria
5) Smooth muscle contraction
6) Wheal and flare on intradermal rxns
7) Activate platelets, macs, neuts, eos
8) Bind receptors on MC –> degranulation
9) Release IL-6, TNF-alpha from B cells, monocytes
10) Regulate tissue fibrosis