Thrush - Complement Cascade Flashcards
expression of Tdt indicates that
a B cell is rearranging its heavy chain genes
which is associated with having a relatively short cytoplasmic tail (not likely a signaling molecule)
IgM
when complement cascade occurs what happens?
- causes cell lysis: MAC (C5b-9)
- results in opsonization of Ag
- mediates inflammation; mast cells, basophils and neutrophils result in release of histamine and other inflammatory mediators
Major effector of the humoral immune response is ___ cascade. Most of proteins made by ____ cells and circulate in the inactive state
complement; liver
describe the nomenclature of the C’ proteins
- Proteins often designated by numbers
- when activated, complement proteins are split into two components: smaller fragment is “a”
larger fragment is “b”
*except c2a is larger than c2b - bar over the top indicates that molecule is enzymatically active molecule
What are the major pathways of the complement cascade
- Classical
- Alternative
- mannan binding lectin pathway
* initiation is diff…end result is the same
Describe classical pathway
activated by interaction of C1 with the Fc region of antibodies; IgM and IgM. Interaction only occurs if multiple Fc region in close proximity to C1. A single IgM can initiate classical pathway, need at least two IgM’s
____ binds to the Fc region of the antibody in the CH2 domain.
C1(q); upon binding, C1r activates C1s.
After C1 binds it activates C4 and C2. ____ activates C3
C4b2a = C3 convertase
___ is an important inflammatory mediator that floats away. _____causes degranulation of mast cell/ basophil
C3a; anaphylatoxin
____ cleaves C5. C5a diffuses away and C5b binds to target cell. C5b binds C6-9 and forms ____ which causes lysis
C5 convertase; MAC
In classical pathway ___ and ___ play a major role in inflammation
C3a, and C5a
Describe alternative pathway
Critical for the opsonization function of C’. Activated by cell surface components forgein to host: LPS. C3 in low levels splitting by itself. C3b component interacts with other microbe. Eventually end up with C5b binding to antigenic surface and then MAC
what are some initiators of the alternative pathway
- LPS
- peptidoglycan
- fungal/yeast cell wall (zymosan)
- some viruses
- Trypanosoma and other parasites
- human IgG, IgA, and IgE in complexes
- cobra venom factor.
describe the MBP lectin pathway
proteins that bind carbohydrates. Have lectin binding domain (to bind microbe) and a collagen domain (interact with cells= opsonin). After activation, MBP acts like C1 and activates C2 and C4. Rest of pathway similar to classical pathway
What are the complement receptors
- CR1 (CD35): RBCs bind immune complexes. erythrocytes, neutrophils, monocytes, lymphocytes
- CR2 (CD21): B cells; binds C3d, iC3b; uptake of immune complexes and B cell activation. impt in memory B cell activation
- CR3 (CD11): monocytes, neutrophils, and NK cells. opsonization function
How is the C’ activation regulated
C3 spontaneously gets activated. Complement proteins can kill our own cells. Molecules in our cells can control complement activation. If a lot of complement is being activated, our cells will die.
Microbes have evaded C’ proteins. Some of these include gram ____ bacteria that have long chain polysaccharides to LPS which prevent insertion to MAC. Also gram negative bacteria with certain ______ proteins. MAC will then interact with outermembrane protein and not cell membrane. Also bacteria that produce ______ bc they inactivate anaphylatoxins. Also gram positive bacteria with ____ peptidoglycan layer causes MAC to not efficiently get to cell membrane. Gram positive bacteria with ____ decreases opsinization
negative; outermembrane; elastase; thick; capsuleC
In order to lyse encapsultated bacteria usually need ___ and _____
C3b, antibodies
Microbes that produce ___ of C’ proteins are usually inhibitory
mimics
____ asseses ability of serum to lyse sheep RBCs sensitized with rabbit IgM. CH50 is reduced in patients who have a ____ defect in one of the complement components, or during an inflammatory process. CH50 increases during an _____. _____ measures the alternative pathway. Serum ___ and ___ levels is used for following treatment of lupus patients.
CH50; asseses classical pathway; genetic; infection; AH50; C3 and C4
