Cytokines

Question 1

Heavy Chain Class switching

Answer 1

• Class switching occurs in the germinal centers
• Occurs in response to cytokines secreted by Ti cells -CD40L mediated signaling plays a role in class switching
• Mutation in CD40L or CD40 leads to hyper IgM
• Mutation in AID (Activation Induced Deaminase) can lead to Hyper IgM

Question 2

IL-4 induces

Answer 2

Class switching to
IGg2, IgG4, IgE

also induces TH2

Question 3

IL-5 and TGF-B induces

Answer 3

Class switching to
IgA

IL-5: recruitment and activation of eosinophils

Question 4

INF-Y

Answer 4

Class switching to

IgG1 AND IgG3

Question 5

Affinity Maturation

Answer 5

Affinity of antibody produced in response to protein antigen, increases with persistent exposure to that antigen
• Occurs in germinal centers
• Increased affinity due to somatic mutation in the
hypervariable regions
• High affinity B-cells are selected by the antigen
• Non selected B-cells undergo apoptosis

Question 6

Production of Plasma Cells and Memory B-cells

Answer 6

• Activated B cells in the germinal center become either plasma cells or long lived memory B-cells

Plasma Cells
• Called plasmablasts when they enter blood
• Migrate to bone marrow or mucosal tissues
• Secrete antibody

 Memory B-cells
•  Do not secrete antibody
•  Circulate in blood
•  Survive for months or years
•  Respond rapidly to antigen reexposure

Question 7

Naïve T-cells

Answer 7

• Unstimulated T cells which first recognize antigens in peripheral
lymphoid tissue
• Respond by proliferating and differentiating into effectors cells
• Require 2 signals to be activated: antigen + MHC, co-stimulatory signal

Question 8

Effector T-cells

Answer 8

• Activated T-cells
• Recognize antigen at sites of infection or in the lymphoid organ and eliminate the microbe
• Do not require co-stimulation to perform their function

Question 9

Memory T-cells

Answer 9

• Long lived, T-cells that have already proliferated in response to antigen but now are functionally inactive but ready to respond to repeated exposure of antigen

Question 10

TH1 helpers

Answer 10

Induced by IL-12

secrete INF-Y, IL2, TNF-A

activate macrophages, nk, cd8 to become bactericidal
b cells to IGg3

Question 11

TH2 hellpers

Answer 11

induced by IL4

secrete IL4, IL5, IL-13 X

ACTIVATE b cells to secrete IgE AND IgG4 antibodies to control parasites
IL5- eosinophils

Question 12

TH17 helpers

Answer 12

Induced by TGF-B + IL-6 (together)

secrete IL-17

protect against extracellular bacteria and fungi by recruiting PMNs, proinflammatory

Question 13

TFH

Answer 13

Induced by IL-6

secrete cytokines from TH1 or TH2

provide help to B cells in lymphoid follicles for antibody production

Question 14

Tregs

Answer 14

Induced by TGF-B

secrete TGF-B + IL-10

surpress T cell responses and help prevent autoimmunity

Question 15

Cytotoxic CD8 T-cells

Answer 15

Kill virally infected or tumor cells

Question 16

Two different forms of Leprosy result from polarization of the CD4 T-helper response

Answer 16

TH1: low infectivity
granulomas and local inflammation, peripheral nerve damage,
not as intense, normal T cell responsiveness

TH2: high infectivity, disseminated infection, bone cartilage, and diffuse nerve damage, hypergammaglobinermia, low or absent T cell response

Question 17

How to CD4 and CD8 T cells work together

Answer 17

CD4 can secrete INFY
which helps activate macrophages and kill microbes in phagolysosomes

those can go and further activate CD8

Question 18

Interferon Alpha and Beta

INF-A and iNF-B

Answer 18

• Induced by viral infection
• Interferes with viral replication and triggers degradation of viral RNA
• Major source is plasmacytoid dendri5ti cells but antigen activated macrophages also produce it
• Activates NK and CD8+ T cells, classical dendritic cells
• Induces upregulation of MHC class I molecules on virally infected cells

Question 19

INF-Y

Answer 19

• Released by NK cells, TH1 cells and CD8+ T -Commits T cells to TH1 and inhibits TH2 and TH17
• Important in immunity against intracellular microbes
• Activates macrophages
• Acts on B cells to promote switching to IgG1 and IgG3 -Stimulates upregulation of MHC class I and enhances MHC antigen presentation

Question 20

Tumor necrosis factor TNF

Answer 20

• TNF-α (trimeric –membrane bound), TNF-β (lymphotoxin-α)
• Produced by macrophages, dendritic cells, endothelial cells
• Expressed as a membrane bound homotrimer but can be secreted
• Activates macrophages and induces NO production
• Activates endothelial cells to express proteins that TRIGGER BLOOD CLOTTING and stimulates expression of adhesion molecules (ICAM) to aid in CELL EXTRAVASION
• INCREASES VASCULAR PERMEABILITY to fluid and proteins
• Activates synthesis of ACUTE PHASE PROTEINS
• When released systemically in sepsis, can induce shock
• Receptors for TNF exist as trimers which signal via TRAF proteins which activate NF-κB &AP-1 transcription factors

Question 21

Pro-inflammatory Cytokines

Answer 21

IL-1β, IL-6, TNF-α (secreted by macrophages, DCs)
• Induce fever (pyrogens)
• Induce production of acute phase proteins
• Activate vascular endothelium (resulting in increased vessel permeability)
• Increase production of macrophages & neutrophils • Increase circulation of neutrophils
• Local and systemic effects if enter bloodstream

• IL-12 (secreted by DCs, macrophages, & TH1 cells) • Stimulates production of IFN-γ by NK and T cells which
stimulates more IL-12 production; positive feedback loop
• Enhances NK cell activity, promotes CTL cytotoxicity, promotes differentiation to TH1 cells

Question 22

TGF-β

Answer 22

• Activates naïve T cells to become Tregs and
produced by Tregs

• Also produced by non activated dendritic cells
• Anti-inflammatory
• Inhibits proliferation and differentiation of TH17, TH1, and TH2 cells
• Induces switching to IgA

Question 23

IL-13

Answer 23

stimulates epithelial cells to produce mucus

Question 24

IL-8

Answer 24

chemokine which attracts neutrophils

Question 25

TNF-α (mast cell derived)

Answer 25

• Increases level of adhesion molecules on endothelial cells which
promotes leukocyte traffic from blood to tissue
• Promote neutrophil and eosinophils in influx
• Activates macrophages