Soluble Molecules
NK Cells
First line of defense against:
Tumor cells Virally-infected cells Other intracellular pathogens
NK Cell
Tumor Cell
Implicated in:
Transplant rejection Autoimmunity Spontaneous abortions
Christina Trambas, Cancer Council of Tasmania, http://www.ciml.univ-mrs.fr/fr/science/lab-eric-vivier/pour-specialistes
Functions of NK
1. Direct Cytotoxicity:
Target cell lysis
a. by perforines & granzymes b. By Ab dependent cellular cytotoxicity (ADCC)
Functions of NK (II)
2. NK secrete IFNs:
Enhance the activation of M Anti-viral activity
Discovery of Interferons
Isaacs and Lindenmann (1957) Found a substance that interfered with viral replication and was therefore named interferon Nagano and Kojima also independently discovered this soluble antiviral protein
tumors
Type I Interferons
Alpha: produced by leukocytes Beta: produced by fibroblasts
Largest group of interferons
Roles
Used to mobilize our 1st line of defense against invading organisms
immune
Inflammatory state*
Bind
to type 2 receptors
Second line
Componentes: I. Cells: NK, Phagocytes II. Soluble molecules III. Mechanisms
I.
Soluble molecules
recognition opsonization distruction cellular lysis
+phagocytosis
+ inflammation
Soluble molecules
recognition
1. Natural Ab (limitated
distruction
1. Interferons
(anti-viral proteins ) (Membranar Attack Complex)
2. Pentraxines
3. Collectins 4. Ficolines
specificity)
2. Complement
3. Beta lysine
4. Lactoperoxydase 5. Lysosim
(saliva & milk )
(antibacterial proteins)
(anti-bacterial enzyme))
Pentraxines:
CRP: plasma conc low (N) 1000 fold during infection (phase acute reactant)
collagen-like tail bound to lectinic calcium-dependent (C-type) sequence Role: recognize Man, Fru residuu
Soluble molecules
recognition
1. Natural Ab (limitated
distruction
1. Interferons
(anti-viral proteins ) (Membranar Attack Complex)
2. Pentraxines
3. Collectins 4. Ficolines
specificity)
2. Complement
3. Beta lysine
4. Lactoperoxydase 5. Lysosim
(saliva & milk )
(antibacterial proteins)
(anti-bacterial enzyme))
C Protein Sources
Nomenclature:
are designated by letter C followed by a number (C1-C9) fragments obtained by cleavege a/b** Factors: B, D, P, H, I
Source:
Factor B (zymogen)
Factor D (active protease FactorP /properdin
200
1-2
25
Decay Accelerating Factor, Membrane Cofactor 1, Complement Receptor 1, C1 Inhibitor etc. Inhibit formation of C3 convertase Breakdown and inactivate C3 and C5 convertase Inhibit formation of MAC
Regulatory Protein placed on the surface of host cell prevent/dissociate formation of Bb complex Decay Accelerating Factor/ Complement Receptor 1, Membrane Cofactor 1
Inhibition of activation of C
Plasma Factors:
H Factor: bound C3b & C3bBb complex Catalyze the activity of I factor I Factor (inhibitory): protease cleavage bound C3b inactiv C3b
The end
Interferon Family
Interferons are a family of related Lymphocytes secrete gamma () interferon, but most other WBCs secrete alpha () interferon Fibroblasts secrete beta () interferon Interferons also activate macrophages and mobilize NKs FDA-approved alpha IFN is used:
As an antiviral drug against hepatitis C virus To treat genital warts caused by the herpes virus
34
4 a. Interferon (IFN)
Interferon molecules leave the infected cell and enter neighboring cells
Interferon stimulates the neighboring cells to activate genes for PKR (an antiviral protein)
PKR nonspecifically blocks viral reproduction in the neighboring cell
35
The exact mechanism of type I interferons are not fully understood, but this is an idea of what happens:
Alpha and beta bind to heterodimeric receptor on cell surface. Alpha receptor is made up of at least 2 polypeptide chains: IFNa-R1 and IFNa-R2 IFNa-R1 is involved in signal transduction IFNa-R2 is the ligand-binding chain that also plays a role in signal transduction Ligation induces oligomerisation and initiation of the signal transduction pathway This results in phosphorylation of signal transductors and activators of transcription proteins, which translocate to the nucleous as a trimeric complex, ISGF-3. ISGF-3 activates transcription of interferon stimulated genes, with many biological effects.