Thrush - Complement Cascade

Question 1

expression of Tdt indicates that

Answer 1

a B cell is rearranging its heavy chain genes

Question 2

which is associated with having a relatively short cytoplasmic tail (not likely a signaling molecule)

Answer 2

IgM

Question 3

when complement cascade occurs what happens?

Answer 3

1. causes cell lysis: MAC (C5b-9)
2. results in opsonization of Ag
3. mediates inflammation; mast cells, basophils and neutrophils result in release of histamine and other inflammatory mediators

Question 4

Major effector of the humoral immune response is ___ cascade. Most of proteins made by ____ cells and circulate in the inactive state

Answer 4

complement; liver

Question 5

describe the nomenclature of the C’ proteins

Answer 5

1. Proteins often designated by numbers
2. when activated, complement proteins are split into two components: smaller fragment is “a”
   larger fragment is “b”
   *except c2a is larger than c2b
3. bar over the top indicates that molecule is enzymatically active molecule

Question 6

What are the major pathways of the complement cascade

Answer 6

1. Classical
2. Alternative
3. mannan binding lectin pathway
   * initiation is diff…end result is the same

Question 7

Describe classical pathway

Answer 7

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

Question 8

____ binds to the Fc region of the antibody in the CH2 domain.

Answer 8

C1(q); upon binding, C1r activates C1s.

Question 9

After C1 binds it activates C4 and C2. ____ activates C3

Answer 9

C4b2a = C3 convertase

Question 10

___ is an important inflammatory mediator that floats away. _____causes degranulation of mast cell/ basophil

Answer 10

C3a; anaphylatoxin

Question 11

____ cleaves C5. C5a diffuses away and C5b binds to target cell. C5b binds C6-9 and forms ____ which causes lysis

Answer 11

C5 convertase; MAC

Question 12

In classical pathway ___ and ___ play a major role in inflammation

Answer 12

C3a, and C5a

Question 13

Describe alternative pathway

Answer 13

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

Question 14

what are some initiators of the alternative pathway

Answer 14

1. LPS
2. peptidoglycan
3. fungal/yeast cell wall (zymosan)
4. some viruses
5. Trypanosoma and other parasites
6. human IgG, IgA, and IgE in complexes
7. cobra venom factor.

Question 15

describe the MBP lectin pathway

Answer 15

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

Question 16

What are the complement receptors

Answer 16

1. CR1 (CD35): RBCs bind immune complexes. erythrocytes, neutrophils, monocytes, lymphocytes
2. CR2 (CD21): B cells; binds C3d, iC3b; uptake of immune complexes and B cell activation. impt in memory B cell activation
3. CR3 (CD11): monocytes, neutrophils, and NK cells. opsonization function

Question 17

How is the C’ activation regulated

Answer 17

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.

Question 18

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

Answer 18

negative; outermembrane; elastase; thick; capsuleC

Question 19

In order to lyse encapsultated bacteria usually need ___ and _____

Answer 19

C3b, antibodies

Question 20

Microbes that produce ___ of C’ proteins are usually inhibitory

Answer 20

mimics

Question 21

____ 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.

Answer 21

CH50; asseses classical pathway; genetic; infection; AH50; C3 and C4