Intro to Immunology Flashcards
Cathelicidins
Cathelicidins (CATionic HELIcal bacteriCIDal proteIN) are α-helical peptides
Human cathelicidin LL37 is highly expressed by PMNs and numerous mucosal and epithelial cell types.
Defensins
Defensins are β-strand peptides connected by disulfide bonds
cathelicidins and defensins - how they work
Most are short peptides (
HSC –> myeloid requires what signals
IL-3, GM-CSF
HSC –> lymphoid requires what signals
IL-7
what are cytokines
Cytokines are soluble secreted molecules involved in cell-to-cell signaling. All cytokines are proteins / glycoproteins.
what are chemokines
Chemokines are a large family of cytokines that can attract cells into inflamed tissues and play a role in leukocyte homing and recruit cells of the innate and adaptive immune response to fight off an infection
Major cytokine categories
Interferons Interleukins Colony stimulating factors chemokine tumor necrosis factors transforming growth factors
interferons
In general, these are cytokines that are important in limiting the spread of viral infections.
interleukins
Large group of cytokines produced mainly by T cells (also macrophages, dendritic cells, and epithelial cells, etc.). Variety of functions including causing neighboring cells to divide and differentiate.
CSFs
Primarily involved in directing the division and differentiation of bone marrow stem cells and precursors of blood leukocytes. Controls how many and what kind of leukocyte is to be produced
Chemokine
Chemotactic cytokine used to direct the movement of leukocytes around the body.
TNFs
Particularly important in mediating inflammation and cytotoxic reactions.
TGFs
Important in regulating cell division and tissue repair.
PLC pathway (example T cell)
TCR – PLC gamma 1 –> split PIP2 –> DAG and IP3– IP3 stimulates Ca release from ER – activate calmodulin – calcineurin –NFAT –>
IL-2 (T cell proliferation)
In B-cells, its a BCR and then PLC gamma 2
Ras/MAP Pathway
TCR mediated signals –> Ras/ Dag –> MAP kinase cascade –> gene activation (AP-1)
PKC pathway (example T cell activation)
TCR/CD3 –> DAG/PKCo –> signal… –> NF-kB pathway –> gene activation
PKC in general associated with
proinflammatory and activation events rather than regulatory processes
interleukin 1 family
IL-1alpha/beta/Ra/18/33
Proinflammatory mediators
Secreted early in immune response from presence of foreign antigen
Hematopoietin (Class I cytokine) family
IL-2, 3, 4, 5,6,7,12,13,15,21,23,
GM-CSF, G-CSF, GH, prolactin, erythropoeitin/hematopoietin
Sequence and functional diversity (similar 3D shape)
Interferon (class II cytokine) family
IFN- alpha/beta/gamma
IL-10, 19, 20, 22, 24
Antiviral (IFN) and modulators of immune responses
Tumor necrosis factor family
TNF-alpha, beta CD40L, Fas (CD95), BAFF, APRIL, LTB soluble or membrane bound immune system development, effector functions and homeostasis (signal development, cell survival, death) function as trimers
Interleukin 17 family
IL-17 a, B, C, D, F
Promote neutrophil accumulation and activation
Proinflammatory
Chemokines
IL-8, CCL19, CCL21, RANTES, CCL2 (MCP-1), CCL3 (MIP-1a)
Chemoattractant
Hematopoietin receptors
Receptors generally include two types of protein domains – an immunoglobulin domain and a fibronectin-like domain.
The fibronectin-like domain is referred to as the cytokine-binding homology region (CHR).
CHR is common to cytokine receptors from several families.
Three subfamilies of receptors.
gamma, beta, gp130
gp130 hematopoietin receptor
KO in mice is lethal
cytokine members include IL-6 and IL-12
Specificity comes from ligand-specific chains in dimers or trimers coupled with gp130