Immunology 1.4 C* Flashcards
MIC
MHC class I-related chain
for infected cells that have had their receptors down regulated by viruses, NK cells recognize these and kill the cell.
LAD
leukocyte adhesion deficiency
inability of leukocytes to migrate into sites of infection: history of overwhelming infections. often lethal.
early symptom** delayed loss of umbilical cord***
no PMNs and macros in sites of infection.
higher levels in blood.
type 1 interferons
antiviral response that results in cells having a higher level of resistance to infection than unactivated cells.
response driven by JAC STAT pathway.
Main effect: resistance of viral replication, and infection.
recognized by NK cells.
immunomodulatory.
type 2 interferons
produced by Nk cells. AKA gamma interferon.
Activates Macrophages.
what induces liver to produce acute phase proteins?
IL-6
acute phase proteins
manose binging lectin,
c- reactive protein
c-reactive protein
opsonin, induces phagocytocis
C’ functions
opsonization and phagocytocis- binds C3b, recognized by phagocyte, then its eaten.
stimulation of inflammatory reactions- recruits and activates leukocytes by C5a and C3a
complement mediated cytolysis- recruits components, forms pore, osmotic lysis of microbe.
C’ tags are permanent
true
C3 convertase
cleaves C3 so that it can tag bacteria for destruction.
C3a, part of C3 will then recruit phags
AKA C3bBb
covalent likage to substrate
form a covalent bond, permanently marking it.
3 ways that complement is activated
Classical - least important.
Lectin - activated by acute phase proteins. has to go to liver first.
Alternative - doesn’t need antibody, most important. first to act.
they all lead to cleavage of C3 to C3a and b. C3b can also cleave C3 to make more C3a
C1-9 with 4 out of line.
the classical pathway
lectin pathway doesn’t use C1
alternative activates C3 directly.
amplification
C3 cleavage
Alternative pathway
main way to activate complement.
C3 cleavage driven by:
Factor B- forms C3bBb complex aka C3 convertase
Factor D- cleaves B when bound to C3b to Ba and Bb
Properdin- stabilizes complexes formed by other factors. positive regulator. accelerator.
regulation of C3 activation
Factor H+
Factor I- inhibitor, slows down consumption of C3
^^^ if missing this then you are more susceptible to encapsulated bacteria.
C5
initiates assembly of membrane attack complex in solution
activated by C5 convertase, activates terminal part of complement
MAC
membrane attack complex.
formed by complement, poly 9 forms the pores.
C8 deficiency
recurrent Neisseria infections to to lack of MAC
C3 mutations
no complement response!!!!!
severe, recurrent infections
C5 mutations
increased complement activation, deplete C3, recurrent infections.
C1inh mutation
angioedema
MBL
member of the collectin family of proteins
uses specific set of MASP proteases
cleaves C4, then C2.
Classical C3 convertase
C4bC2b
calssical pathway
utilizes bound antibody
need to bind multiple arms of C1.
best antibody for activation of c’
IgM
CR1
major activation receptor for macros and PMNs
immune complex disease
lack CR1 or liver receptors
inability to clear bloodstream of immune complexes
kidney is site of deposition. Nephritis.
regulation of complement
- specific activation
- short half life
- regulation
C1 inhibitor
serine protease inhibitor. SERPIN family.
also helps regulate clotting
Hereditary HAE
C1 deficiency
DAF
decay acclerating factor
cell surface membrane of host, dissociates C2b
CD59
inhibits formation of MAC
Paroxysmal nocturnal hemoglobinuria
missing CD59
complement induced RBC lysis. via random activation of MACs on RBCs
acquired. CD59 just goes missing.
PIGA - x linked
Familial Atypical Hemolytic Uremic Syndrome
associated with lack of control of converts activation.
means complement cascade is always activated.
missing Factor H, factor I, mutation in C3, increased C3 consumption.
what is controlled most carefully?
C3 convertase. its generation and stability.
which is a most common infection with complement deficiencies?
Neisseria species
