Important Cytokines

A 35-year-old man who recently immigrated to the USA from Mexico comes to the physician because of a 6-month history of lesions on his face and chest. He has a history of asthma and atopic dermatitis. Physical examination shows the findings in the photograph. Which of the following cytokines is most likely to be increased in these lesions? (A) Interferon gamma (B) Interleukin-4 (IL-4) (C) IL-12 (D) Transforming growth factor (TGF)-α (E) TGF-β

(B) Interleukin-4 (IL-4) Required for class switching to IgE excess IL-4 plays a part in allergic disease, causing production of IgE

INF-y

* * * * * * * *

TNF-a

* * * * * * * *

IL-6

**Responsible for acute inflammation *Induces COX synthesis and prostaglandin PGE2 release in anterior hypothalamus -> Fever *Activates osteoclasts *Monocytes, macrophages and bone marrow cells secrete this cytokine but the major producer is the TH2 type of T helper cells. *Stimulates differentiation of B cells into plasma cells ***Induces Th0 differentiation into Th17 along with TGF-B*

IL-10

*Attenuates inflammatory response (along with TGF-B) *Decreases expression of MHC class II and Th1 cytokines. *Inhibits activated macrophages and dendritic cells **Also secreted by regulatory T cells*

IL-5

*Enhances class switching to IgA **Stimulates the growth and differentiation of eosinophils* *Promotes growth and differentiation of B Cells (similar to IL-4)

IL-4

*Induces Th0 differentiation into Th2 *Enhances class switching to IgE and IgG1 *On resting B cells, and on macrophages, IL-4 increases MHC II expression *On activated B cells, proliferation and differentiation is stimulated

Match the feature with the cytokine/s *Induces Th0 differentiation into Th2 *Increased production in Familial Mediterranean Fever *Induces Th0 differentiation into Th17 *Increase osteoclastic effect *Primary cytokine responsible for increased liver synthesis of acute phase reactants *Activate eosinophils *Responsible for acute inflammatory response *Major chemotactic factor for neutrophils *Class switching to IgE *Class switching to IgA *Most similar to the effects of GM-CSF *Secreted by T-Regs *Promotes differentiation into Tregs *Attenuate inflammatory response *Induces Th0 differentiation into Th1 *Mast cell activation

*Induces Th0 differentiation into Th2: IL-4 *Increased production in Familial Mediterranean Fever: IL-1 *Induces Th0 differentiation into Th17: IL-6, TGF-B, IL-23 *Increase osteoclastic effect: IL-1, IL-6, TNF-a *Primary cytokine responsible for increased liver synthesis of acute phase reactants: IL-6 *Activate eosinophils: IL-5 *Responsible for acute inflammatory response: IL-1, IL-6, TNF-a *Major chemotactic factor for neutrophils: IL-8 *Class switching to IgE: IL-4, IL-13 *Class switching to IgA: IL-5, TGF-B *Most similar to the effects of GM-CSF: IL-3 *Secreted by T-Regs: IL-10 *Promotes differentiation into Tregs: TGF-b *Attenuate inflammatory response: IL-10, TGF-B *Induces Th0 differentiation into Th1: IFN-y and IL-12 *Mast cell activation: IL-9

IL-1

*Most notably secreted by macrophages *Responsible for acute inflammation *Induces COX synthesis and prostaglandin PGE2 release in anterior hypothalamus -> Fever *Acts as a costimulator for CD4 activation *Induces chemokine secretion to recruit WBCs *Induces B cells to multiply *Activates endothelium to express adhesion molecules **Activates osteoblasts (increased bone resorption)* *Activates chondrocytes for cartilage breakdown

IL-3

*Secreted by activated T-Cells *Supports growth and differentiation of bone marrow stem cells into myeloid progenitor cells (granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte, dendritic cells) *Function is quite similar to GM-CSF.

IL-2

*Secreted by both CD8 and CD4 cells *Causes proliferation of T Cells (CD4, CD8, and regulatory) *Can cause B Cell proliferation as well *Required by growing T Cells as a growth factor *Enhances activity of NK Cells **IL-2 from CD4 TH1 cell provides 2nd signal for CD8 activation* *IL-2 from CD4 TH1 cell can cause proliferation of itself

Which one of the listed substances is secreted by malignant plasma cells in individuals with multiple myeloma and is the osteoclast-activating factor (OAF) that produces the characteristic lytic bone lesions? A. Interleukin 1 B. Interleukin 6 C. Tumor necrosis factor β D. Transforming growth factor β E. Platelet-derived growth factor

A or B? Some say that IL-1 is OAF and both TNF-a and IL-6 also increase osteoclastic activity by increasing OAF

A patient with advanced metastatic melanoma decides to join an experimental treatment protocol in the hope that it will cause regression of his tumor masses. Malignant cells are aspirated from several of his lesions and transfected in vitro with the gene encoding IL-3 production. The transfected tumor cells are then reinfused into the patient. Mobilization of which of the following cells from the bone marrow would be likely to result from this treatment? A) Antigen presenting cells B) B lymphocytes C) NK Cells D) Plasma cells E) T lymphocytes

A) Antigen presenting cells Tumor cells transfected with the gene encoding IL-3 would produce IL-3. This is a cytokine that acts on the bone marrow to cause production and mobilization of myeloid cells. The oal of such therapy would be to induce the production of antigen-presenting cells, which might increase the presentation of of tumor-cell antigens to cells important in cell-mediated cytotoxicity

Which type of immune cell is the principal source of interleukin-3 (IL-3)?

Activated T-Cells

The image depicts steps in an immunologic activation pathway This pathway is most important for which activity of the immune system? A) Antibody production B) Antigen presentation and defense against intracellular pathogens C) Defense against parasites by eosinophils D) Immediate Allergic Hypersensitivity Reaction E) Neutrophil Chemotaxis

B) Antigen presentation and defense against intracellular pathogens

A couple brings their newborn son to the emergency department. He has been running high fevers and has not been eating. The pediatric resident draws blood cultures and performs a lumbar puncture. The results of the blood work are shown in the figure. Which of the following cytokines is a major chemotactic factor for the cell type shown? A) IL-2 B) IL-4 C) IL-8 D) IL-1 E) IL-6

C) IL-8

58-year-old man comes to the physician because of blood in his urine. He had a nephrectomy 10 years ago because of injuries sustained in a motor vehicle collision. Evaluation shows renal cell carcinoma in his remaining kidney and pulmonary metastases. Interleukin-2 (IL-2) therapy is started. Three weeks later, CT scan confirms regression of the tumor. Which of the following most likely caused the regression? A) An effect of IL-2 on tumor vascularization B) Cytotoxic effects of IL-2 on tumor cells C) Increased natural killer cell activity D) Induction of antitumor antibodies by IL-2 E) Induction of B-lymphocyte proliferation F) Spontaneous remission

C) Increased natural killer cell activity

Which of the following is the most likely consequence of impaired synthesis of IL-1? A. Enhanced phagocytic activity of circulating macrophages B. Enhanced production of antibody by B lymphocytes C. Impaired antigen processing by circulation macrophages D. Impaired function of T lymphocytes E. Impaired production of leukotrienes by neutrophils

D. Impaired function of T lymphocytes

A 36-year-old farmer has been exposed to poison ivy on several different occasions and usually develops very severe skin lesions. He enrolls in an immunological study at an urban medical center. A flow cytometric measurement of T cells reveals values within the normal range. An increased serum concentration of which of the following cytokines would decrease the likelihood of a delayed-type hypersensitivity reaction in this individual? A. Gamma interferon B. IL-2 C. IL-4 D. IL-8 E. IL-10

E. IL-10 IL-10 is produced by Th2 cells and inhibits Th1 cells. Because the response to poison ivy is a delayed-type hypersensitivity response and therefore is mediated by Th1 cells and macrophages, inhibiting their activity would minimize the severity of the reaction

What inhibits interleukin-4 dependent immunoglobulin E synthesis?

IFN-y

___________________ (IL-3/IL-7) favors development of lymphoid precursors in the bone marrow ___________________ (IL-3/IL-7) favors development of myeloid precursors in the bone marrow

IL-3: myeloid IL-7: lymphoid

Along with IL-4, what other cytokine can induce class switching to IgE? Along with IL-5, what other cytokine can induce class switching to IgA?

IL-4 and IL-13: IgE IL-5 and TGF-B: IgA

Which cytokines promote differentiation into TH1? Which cytokines promote differentiation into TH2? Which cytokines do TH1 cells release? Which cytokines do TH2 cells release? Which cytokines do TH1 cells release that inhibit TH2 differentiation? Which cytokines do TH2 cells release that inhibit TH1 differentiation? Which cytokines promote differentiation into TH17? Which cytokines do TH17 cells release? Which cytokines promote differentiation into TReg? Which cytokines do TRegs release?

Into TH1: IFN-y and IL-12 Into TH2: IL-4 TH1 release: IFN-y and IL-2 TH2 release: IL-4, IL-5, IL-6, IL-10, IL-13 TH1 release to inhibit TH2: IFN-y TH2 release to inhibit TH1: IL-4, IL-10 Into TH17: IL-6, TGF-B, IL-23 TH17 release: IL-17 Into TReg: TGF-B TReg release: IL-10 (predominant) and TGF-B

Name five types of cells that may secrete IL-1

Macrophages (most notably) B cells Monocytes Osteoblasts (to activate osteoclasts)

In the Macrophage-lymphocyte interaction, macrophages and other APCs release _________ which stimulates T cell to differentiate into Th1 Th1 cells release __________ to stimulate macrophages

Macrophages release IL-12 TH1 cells release IFN-y

Which of the following cytokines are helpful in formation and maintenance of granuloma respectively? a) TNF -alpha ; IFN-gamma b) IFN gamma; TNF -alpha c) IFN-gamma; IFN-gamma d) TNF-alpha; TNF- alpha e) none

b) IFN gamma; TNF -alpha IFN gamma forms granuloma TNF-alpha maintains

A 50 year old woman with severe rheumatoid arthritis is started on infliximab (anti-tumor necrosis factor-alpha). This therapy has been shown to increase the production of CD25 positive T cells. Which of the following is likely, therefore to become elevated in this patient? a)IFN-gamma b)IL-1 c)IL-2 d)IL-10 e)TGF-beta

d)IL-10 CD25 positive TReg cells have been shown to have a role in maintenance of self-tolerance, and therefore, defects in these cells are being blamed in many cases of autoimmune disease. TReg cells secrete IL-10 which is an anti-inflammatory cytokine