Untitled Quiz

Cytokines and Their Functions

• Cytokines are low molecular weight proteins (<30 kDa) secreted by cells that mediate interactions and communications between cells.
• They are responsible for regulating intensity and duration of immune responses, development of cellular and humoral immune responses, stimulating or inhibiting cell activation, proliferation, and differentiation.
• Cytokines can induce the synthesis of other cytokines, resulting in cascades of cytokine activity.

Classification of Cytokines

• Cytokine families include:
  • Hematopoietic family
  • Interferon family
  • Tumor necrosis factor (TNF) family
  • Chemokine family
• Cytokine receptor families include:

  • Immunoglobulin (Ig) superfamily receptors, which are involved in cell-cell interactions and are characterized by their Ig-like domains.

  • Class I cytokine receptor family (hematopoietin receptor family), which includes receptors for cytokines that stimulate the growth and differentiation of hematopoietic cells.

  • Class II cytokine receptor family (interferon receptor family), which is responsible for responding to viral infections and triggering an antiviral response.

  • Tumor necrosis factor (TNF) receptor family, which plays a crucial role in regulating cell survival, differentiation, and apoptosis.

  • Chemokine receptor family, which is involved in the recruitment of immune cells to sites of inflammation.

  • Immunoglobulin (Ig) superfamily receptors, which are structurally related to antibodies and bind to cytokines, leading to activation of various signaling pathways.

  • Class I cytokine receptor family (hematopoietin receptor family), characterized by the presence of a conserved Trp-Ser-X-Trp-Ser (WSXWS) motif in their extracellular domains, and include receptors for cytokines such as erythropoietin, granulocyte-colony stimulating factor, and interleukin-2.

  • Class II cytokine receptor family (interferon receptor family), which includes receptors for interferons and interleukin-10, and is characterized by the presence of a conserved motif in their extracellular domains.

  • Tumor necrosis factor (TNF) receptor family, which includes receptors for TNF-α, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL), and plays a crucial role in regulating apoptosis and inflammation.

  • Immunoglobulin (Ig) superfamily receptors

  • Class I cytokine receptor family (hematopoietin receptor family)

  • Class II cytokine receptor family (interferon receptor family)

  • Tumour Necrosis factor (TNF) receptor family

  • Chemokine receptor family

Cytokine Secretion by TH1 and TH2 Subsets

• T helper 1 (TH1) subset (CD4+ T cells) produce IFN-γ, which:

  • Activates macrophages, stimulating microbicidal activity
  • Up-regulates major histocompatibility complex (MHC) class II expression
  • Induces the production of IgG2a antibodies
  • Enhances the activity of natural killer cells and cytotoxic T cells

• T helper 2 (TH2) subset (CD4+ T cells) produce IL-4, IL-5, and IL-13, which:

  • Promote the production of IgE antibodies
  • Stimulate the growth and differentiation of eosinophils
  • Induce the production of mucin by goblet cells in the respiratory tract

• T helper 1 (TH1) subset (CD4+ T cells) produce IFN-γ, which:

  • Activates macrophages, stimulating microbicidal activity
  • Up-regulates class II MHC expression
  • Induces antibody-class switching to IgG and supports phagocytosis and complement fixation
  • Promotes differentiation of Tc CD8+ cells
  • Inhibits TH2 population expansion

Adaptive Immunity

• Acts selectively and specifically through:
  • Antigen specificity
  • Diversity
  • Self/non-self recognition
  • Immunological memory
• Works through two mechanisms:
  • Humoral immune response (antibody production by B-lymphocytes)
  • Cell-mediated immune response (mediated by T-lymphocytes)

B Cells and Antibody Production

• B lymphocytes recognize antigens through membrane-bound immunoglobulins (B-cell receptors)

• Antigen presentation and activation of naive B cells stimulate clonal expansion and differentiation into:

  • Antibody-secreting plasma cells
  • Memory B cells, which can rapidly respond to future encounters with the same antigen

• Antibody production involves:

  • Class switching, allowing for the production of different antibody classes (IgM, IgG, IgA, etc.) with distinct functions
  • Somatic hypermutation and affinity maturation, leading to the generation of high-affinity antibodies

• B cells mature in the bone marrow and express antigen-binding receptors (membrane-bound antibodies)

• Activated B cells differentiate into plasma cells, secreting large amounts of antibodies

• Antibodies have a unique antigen-binding site and can have different tail regions

• Effector B cells can secrete antibody while still small lymphocytes, but the end stage is a large plasma cell secreting antibodies at a rate of about 2000 molecules per second