Cytokines Flashcards
Heavy Chain Class switching
- 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
IL-4 induces
Class switching to
IGg2, IgG4, IgE
also induces TH2
IL-5 and TGF-B induces
Class switching to
IgA
IL-5: recruitment and activation of eosinophils
INF-Y
Class switching to
IgG1 AND IgG3
Affinity Maturation
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
Production of Plasma Cells and Memory B-cells
• 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
Naïve T-cells
• 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
Effector T-cells
- 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
Memory T-cells
• 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
TH1 helpers
Induced by IL-12
secrete INF-Y, IL2, TNF-A
activate macrophages, nk, cd8 to become bactericidal
b cells to IGg3
TH2 hellpers
induced by IL4
secrete IL4, IL5, IL-13 X
ACTIVATE b cells to secrete IgE AND IgG4 antibodies to control parasites
IL5- eosinophils
TH17 helpers
Induced by TGF-B + IL-6 (together)
secrete IL-17
protect against extracellular bacteria and fungi by recruiting PMNs, proinflammatory
TFH
Induced by IL-6
secrete cytokines from TH1 or TH2
provide help to B cells in lymphoid follicles for antibody production
Tregs
Induced by TGF-B
secrete TGF-B + IL-10
surpress T cell responses and help prevent autoimmunity
Cytotoxic CD8 T-cells
Kill virally infected or tumor cells
Two different forms of Leprosy result from polarization of the CD4 T-helper response
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
How to CD4 and CD8 T cells work together
CD4 can secrete INFY
which helps activate macrophages and kill microbes in phagolysosomes
those can go and further activate CD8
Interferon Alpha and Beta
INF-A and iNF-B
- 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
INF-Y
- 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
Tumor necrosis factor TNF
- 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
Pro-inflammatory Cytokines
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
TGF-β
• 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
IL-13
stimulates epithelial cells to produce mucus
IL-8
chemokine which attracts neutrophils
TNF-α (mast cell derived)
• Increases level of adhesion molecules on endothelial cells which
promotes leukocyte traffic from blood to tissue
• Promote neutrophil and eosinophils in influx
• Activates macrophages
