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*Immunology > Cytokines > Flashcards

Cytokines Flashcards

1
Q

IL-1

A

From monocytes, macrophages, etc

Fever,acute phase response, induces IL-2R expression and I’ll-2 synthesis in T cells

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2
Q

IL-1

A

Monocytes, macrophages, many others

Pyrogen (fever), acute phase response; induces IL-2R expression and IL-2 synthesis in T cells; enhances adhesion molecule expression on leukocytes and endothelial cells

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3
Q

IL-2

A

TH1, others

T cell growth factor; activates T cells and NK cells

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4
Q

IL-3

A

T cells, others

Stimulates hematopoiesis

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5
Q

IL-4

A

TH2, mast cells, others

Promotes TH2 development; inhibits TH1 development; promotes IgE or IgG4 synthesis by B cells

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6
Q

IL-5

A

TH2, mast cells

Eosinophil development; class switching to IgA in B cells

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7
Q

IL-6

A

macrophages, others

Stimulates acute phase protein synthesis; low-level pyrogen, stimulates differentiation of B cells to plasma cells

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8
Q

IL-7

A

Bone marrow and thymic stromal cells, some T cells

Growth factor for pre-T and pre-B cells

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9
Q

IL-8

A

Macrophages, fibroblasts, endothelials, others

Chemokine that attracts neutrophils and naive T cells

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10
Q

IL-10

A

Treg

Inhibits T cells, macrophages, others; protects against autoimmunity

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11
Q

IL-12

A

Activated macrophages, dendritic cells, B cells

Activates TH1 and NK cells

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12
Q

IL-13

A

TH2 cells

B cell growth factor; class switch to IgE or IgG4

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13
Q

IL-17

A

TH17 cells

Pro-inflammatory, promotes neutrophil migration and differentiation, defensin production

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14
Q

IL-22

A

TH17 cells, others

Promotes defensin production by stromal and epithelial cells

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15
Q

IFN-a AND IFN-b (Type 1)

A

Most cell types

Induced by intracellular pathogens; anti-viral; induces class I MHC expression

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16
Q

IFN-g

A

TH1 cells, NK cells

Selects TH1 subset; inhibits TH2 subset; activates macrophages, NK and Tc cells; enhances respiratory burst in macrophages; causes class switch to IgG3; promotes class I and II MHC expression

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17
Q

TNF-a

A

Macrophages, others

Inflammation; induces shock and cachexia; enhances adhesion molecule expression; enhances phagocytosis and respiratory burst in macrophages; induces fever, acute phase protein release

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18
Q

TNF-b

A

TH1, Tc cells

Kills infected cells, tumors by inducing apoptosis

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19
Q

GM-CSF
M-CSF
G-CSF

A

T cells, macrophages, mast cells, natural killer cells, endothelial cells and fibroblasts

Promotes growth of granulocytes and/or monocytes, as indicated by name

20
Q

Some potent superantigens include:

A
  • TSST-1: toxic shock syndrome toxin 1 made by Staphylococcus aureus
  • Enterotoxins from S. aureus that cause food poisoning
  • Pyrogenic toxins produced by Streptococcus pyogenes
21
Q

TNFA and IL-1 are particularly damaging,

A

SHOCK
•Low blood pressure

  • Fever
  • DIC (disseminated intravascular coagulation, i.e. platelet deposition)
  • Cardiovascular shock
  • Cachexia (wasting of muscle and fat)
22
Q

Superantigens

A

microbial toxins that stimulate as many as one in five T cells. They do not need to be processed by an APC in order to stimulate T cells. They bind simultaneously to Class II MHC molecules on the APC and the β chain of the TCR. They induce release of all the T cell and macrophage cytokines discussed so far.

23
Q

CD8+Tc Cell Functions

A

The major functions of CD8+Tc cells are the killing of infected host cells, tumor cells, and foreign tissue grafts.

•They kill their target cells by secreting:

  • Perforin, which punches holes in the target cell membrane
  • Granzymes that enter through the holes to induce caspase-mediated apoptosis
  • Granulysin, which mediates killing of Listeria, Mycobacterium spp., and other intracellular bacteria

•Tc cells express the surface proteinFas ligand(FasL)

  • FasL binds to “death receptor” Fas (CD95) on the infected cell
  • Engagement of Fas by FasL activates caspases that induce apoptosis in the target cell

•Apoptotic cells are rapidly phagocytosed, preventing spread of virions without inflammation

24
Q

CD8+Tc Cell Functions

A

The major functions of CD8+Tc cells are the killing of infected host cells, tumor cells, and foreign tissue grafts.

•They kill their target cells by secreting:

  • Perforin, which punches holes in the target cell membrane
  • Granzymes that enter through the holes to induce caspase-mediated apoptosis
  • Granulysin, which mediates killing of Listeria, Mycobacterium spp., and other intracellular bacteria

•Tc cells express the surface proteinFas ligand(FasL)

  • FasL binds to “death receptor” Fas (CD95) on the infected cell
  • Engagement of Fas by FasL activates caspases that induce apoptosis in the target cell

•Apoptotic cells are rapidly phagocytosed, preventing spread of virions without inflammation

25
Q

T Cell Activation Requires 2 Signals

A

Signal 1: interaction between the TCR and the peptide/MHC complex on the APC. CD4 or CD8 acts as a co-receptor molecule

Signal 2 is provided by multiple co-stimulatory interactions between cell surface molecules on the T cell and the APC. (CD40L, CD28, CTLA-4)

26
Q

T cell molecule:

CD40L

CD28

CTLA-4

A

APC and function:

CD 40- enhance CD28-B7 interaction, class switching in B cells

B7- secretion of IL2 and expression of IL2 receptor; required for T cell act and prol

B7- inactivates Tcell, wanes immune response

27
Q

Major function of CD4 T cell

A

cytokine production

28
Q

TH1 Cells

A

promote cell mediated immunity, and delayed type hypersensitivity

good against intracellular pathogens: activate Tc, NK cells, and macrophages

IFN-g above plus class switch to IgG3 (opsonize antigens and activates compliment) up regulates MHC 
prevents TH2 maturation

produce IL2

promoted by IL12/IFNg

29
Q

TH2 Cells

A

promote anti-worm immunity and immediate hypersensitivity reactions (allergies)

-They secrete:

▪IL-4 and IL-13: induce class-switch to IgE and IgG4 synthesis by B cells

▪IL-5: induces class-switch to IgA, activates eosinophils

  • IL-4 produced by mast cells and mature TH2 cells promotes maturation of developing TH2 cells and prevents maturation of TH1 cells
  • IL-4 induces the transcription factor GATA-3, which directs TH2 development
30
Q

TH17 cells

A

cells promote immunity to extracellular bacteria and fungi

  • May contribute to autoimmune diseases, e.g., multiple sclerosis, psoriasis, and rheumatoid arthritis
  • They secrete:

▪IL-17: promotes neutrophil migration and differentiation

▪IL-22: induces cells in the skin and digestive system to synthesize defensins (antibacterial peptides)

-The cytokines involved in TH17 development are controversial but may include transforming growth factor beta (TGFb), IL-6, IL-21, and IL-23.oTH17 development is regulated by the RORgt transcription factor

31
Q

Treg Cells

A

cells suppress the differentiation and functions of TH1, TH2, TH17, monocytes, macrophages, and other cell types

Protect the body from autoimmune reactions

They secrete:

▪IL-10: generally immunosuppressive for T cells and macrophages

▪TGFβ (transforming growth factor beta): inhibits T cell and macrophage function, promotes wound healing

Treg development is promoted by TGFb

Treg development is regulated by the Foxp3 transcription factor

Mutations in Foxp3 lead to IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome). IPEX manifests with autoimmune enteropathy, psoriasiform or eczematous dermatitis, nail dystrophy, and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid. Boys are affected, while girls are carriers and might suffer mild disease.

32
Q

Cytokine Receptor-Mediated Signal Transduction

The binding of a colony stimulating factor, interferon, or interleukin to its receptor results in signal transduction in a step-wise fashion: (6)

A

The binding of a colony stimulating factor, interferon, or interleukin to its receptor results in signal transduction in a step-wise fashion:

  • Receptor-ligand binding causes receptor polypeptides to dimerize or polymerize at the target cell surface
  • The juxtaposed cytoplasmic tails of the receptor polypeptides activate JAK tyrosine kinases
  • The JAK kinases phosphorylate the cytoplasmic domains of the receptorand the STATtranscription factors (signal transducers and activators of transcription) in the cytoplasm
  • Once phosphorylated, STATs dimerize and then translocate to the cell nucleus, where they bind to enhancer regions of certain genes
  • The genes are transcribed into RNA and translated into proteins
  • Inhibitors of the JAK-STAT pathways comprise therapies for several organ cancers (breast, prostate, pancreas), blood system cancers (polycythemia vera, multiple myeloma, essential thrombocythemia), and autoimmune diseases (psoriasis, rheumatoid arthritis, ulcerative colitis, dry eye syndromes)
33
Q

Proteins on the T cell surface

A

TCR

CD3

CD4

CD8

34
Q

Proteins on the APC

A

The degree of similarity between the MHC molecules of donors and recipients will determine whether a graft is accepted or rejected. The function of MHC molecules is to present processed antigens to T cells. In humans, the MHC is called the HLA (human leukocyte antigens).

Class I HLA

Class II HLA

35
Q

T cell receptor for antigen (TCR)

A
  • The two polypeptide chains of the TCR have variable (V) and constant(C) region exons whose rearrangement is mediated by the RAG-1 and RAG-2 enzymes of the VDJ recombinase. However, unlike antibodies, TCRs are not secreted and do not undergo affinity maturation
  • 95% of all T cells express a and b chains. ab-TCR molecules recognize protein antigens presented by MHC molecules
  • 5% of T cells express the gd-TCR and recognize lipids, glycolipids, and phospholipids presented by the CD1 molecule. gd-T cells protect mucosal epithelial cells in skin, gut, lung, etc. from bacteria. Most are cytotoxic cells
36
Q

CD3

A

always found associated with the TCR. Its 6 protein chains (g-d, dd, ??) transmit a signal to the T cell nucleus when TCR binds to antigen

37
Q

CD4

A

a co-receptor found on all TH cells and Treg cells. It is a single-chain transmembrane glycoprotein that binds to class II MHC molecules on antigen-presenting cells

38
Q

CD8

A

a co-receptor found on all Tc cells. It is a transmembrane glycoprotein comprising an a chain and a b chain. It binds to class I MHC molecules on antigen-presenting cells, including infected, nucleated cells.

39
Q

Class I HLA molecules

A

re found on all nucleated cells and platelets, but not on red blood cells. They present antigen to Tc cells expressing the CD8 molecule. Class I HLA molecules are composed of an a chain encoded by the HLA-A, HLA-B, and HLA-C genes on chromosome 6;and the b2-microglobulin chain encoded on chromosome 15.

40
Q

Class II HLA molecules

A

are constituitively expressed by the professional APCs, which include dendritic cells, macrophages, monocytes, and B lymphocytes. Expression of class II HLA can be induced on other cell types by interferon gamma (IFNg). Class II molecules present antigen to TH and Treg cells that express CD4. They are composed of an a chain and a b chain encoded by the HLA-D region genes (HLA-DP, HLA-DQ, HLA-DR) on chromosome 6.

41
Q

Describe the inheritance of HLA genes.

A

HLA genes are inherited as a single unit on each copy of chromosome 6 inherited from a child’s parents. Therefore, 50% of a child’s HLA genes will be identical to his mother’s HLA genes, and 50% will be identical to his father’s HLA genes.

42
Q

Genes that are inherited together as a unit from each parent are called…

A

haplotypes.

Humans have two HLA haplotypes, one from the mother and one from the father. There is a 25% likelihood that a child will be a perfect HLA match to one of his siblings from shared parents.

43
Q

Class I HLA molecules present ____ antigens,

A

endogenous

  • Viral antigens are processed by proteasomes(enzyme complexes)
  • Peptide fragments are transported by TAP molecules (transporter of antigenic peptides) to the ER (endoplasmic reticulum)
  • Peptide fragment is loaded into the Class I molecule, and then transported within a Golgi body to the surface of the host cell
  • Tc cells with TCRs specific for the viral peptides are induced to kill the host cell
44
Q

Class II HLA molecules present ____ antigens

A

exogenous

Phagosome or endosome fuses to an acidic vesicle→change in pH activates proteolytic enzymes(cathepsins)that degrade the engulfed microbe

  • Meanwhile, Class II molecules are being synthesized in the ER of the phagocytic cell, along with an invariant chain (Iior CD74)
  • The invariant chain blocks the Class II peptide binding groove from becoming loaded with endogenous peptides
  • When a Golgi body containing the Class II molecule fuses to the vesicle containing the degraded microbe, the invariant chain is destroyed, and the microbial peptides are loaded into the groove of the Class II molecules
  • The Class II/microbial peptide complex is then transported to the surface of the host cell for presentation to TH cells with TCRs specific for the microbial antigens
  • TH cells are induced to secrete cytokines
45
Q

Antigen cross-presentation

A

Dendritic cells have a unique method of presenting exogenous antigens to CD8+Tc cells in conjunction with Class I MHC molecules

  • The dendritic cell takes up the exogenous antigen by phagocytosis or pinocytosis
  • The antigen is transferred from the acidic vesicle to the cell cytoplasm
  • The antigen is degraded by the proteasome, and the resultant peptides are trafficked to the endoplasmic reticulum by TAP molecules
  • Antigenic peptides occupy the grooves of MHC Class I molecules and are transported to the cell surface for presentation

*Immunology (6 decks)

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