Effector B Cells Flashcards
1
Q
5 Features of Antibodies
A
- Plasma cells secrete them in secondary tissues or bone marrow then they enter blood —> peripheral sites of inflammation AND mucosa
- Production starts w/in week of infection
- Continuously secreted by plasma cells (long-lived) in bone marrow so that there is an immediate attack on secondary infection
- Memory cells do NOT secrete antibodies (if they bind antigen they differentiate into antibody-producing cells
- Fab and Fc regions are segregated and have diff functions
2
Q
Which antibody isotype has longest half-life and why?
A
IgG (3 weeks)
IgG binds FcRn in endosomes of epithelial cells and phagocytes —> IgG recycled back to circulation or tissue fluids instead of lysosomal degradation
3
Q
Neutralization
A
Antibodies bind and block
- Block microbial surface molecules that are used to bind host cells and enter for initial infection - Neutralize microbes moving from cell-to-cell - Prevent binding of toxins to host cell receptors - Block penetration of microbe through epithelial layer
4
Q
5 Steps of Opsonization/Phagocytosis
A
- 1- several IgG molecules bind microbe
- 2- binding of opsonized microbe to Fc receptors on phagocyte (gamma heavy chains of IgG binds FCgammaRI on phagocyte)
- 3- binding leads to phagocyte’s plasma membrane wrapping microbe and creating endosome
- 4- binding also leads to intracellular signaling —> inc NO/ROS/proteolytic enzymes
- 5- phagosome fuses w/ lysosome —> microbe killed
**especially encapsulated bacteria (pneumococci)
5
Q
Which Fc receptor provides gamma feedback?
A
Fc gamme RIIB
Prevents activation of DCs and macrophages
6
Q
ADCC
A
- NK cells have Fc gamma RIIIA (CD16) which bind IgG antibodies attached to infected/opsonized cell —> signals —> NK cells release granule proteins —> kill opsonized cell
- Cells infected w/ enveloped viruses express surface viral glycoproteins that can be recognized by specific antibodies and may enhance this process
7
Q
How does IgE work?
A
- Process
- 1- IgE binds worm
- 2- Binding of worm promotes eosinophils Fc-epsilon-RI receptor binding Fc of IgE
- 3- Receptor binding + IL-5 from Th2 helper T cells —> activation of eosinophils —> release granules including proteins that kill worm
- IgE also binds/activates mast cells —> secrete cytokines including chemokines that attract more leukocytes to kill worm
- Plasma levels of IgE are low b/c such high affinity for Fc receptor on mast cells that most is bound to them
8
Q
5 Major Results of Complement System
A
- Opsonization - C3b coats microbes then binds CR1 or CD35 receptor on phagocytes
- Cell lysis - MAC complex induces osmotic lysis (only for microbes w/ thin walls and little/no glycocalyx)
- Inflammation - C3a and C5a are chemotactic for neutrophils, stimulate release of inflammatory mediators from various leukocytes, act on endothelial cells to inc movement of leukocytes into tissues, mast cell degranulation, activate monocytes to produce IL-1 and IL-6
- C3d binds CR2 on B cells to enhance their activation
- Complement-dependent antigen display - complement proteins bound to antigen-antibody complex recognized by follicular dendritic cells; they then present to more B cells to activate more B cells and select B cells w/ highest affinity
9
Q
Complement Activation in General
A
3 Paths
All result in…
- cleaving of C5 —> C5b –> C6, C7, C8, C9 all bind complex nucleated by C5b; then C9 polymerizes to form pore in membrane that water and ions can travel through to cause microbe death (Called “Membrane Attack Complex” or MAC)
10
Q
Alternative Path of Complement Activation (6 Steps)
A
ANTIBODY-INDEPENDENT
- 1- C3b deposited on microbe surface; stable covalent bond w/ microbial proteins and polysaccharides
- 2- C3b binds Factor B protein
- 3- Factor B broken down by Factor D (plasma protease) —> Bb fragment
- 4- Bb attached to C3b is referred to as alternative pathway C3 convertase (acts as enzyme and breaks down more C3)
- C3 convertase is stabilized by properdin (positive regulator of complement system )
- 5- Continue to build up more and more C3b and C3bBb that bind microbe; eventually they bind another C3b —> C3bBb3b which functions as a C5 convertase
- 6- C5 convertase cleaves C5 —> initiates later steps in complement activation
11
Q
Mannose-Lectin Path of Complement Activation
A
ANTIBODY-INDEPENDENT
1- Attachment of plasma mannose-binding lectin (MBL) to microbes
2- serine proteases structurally related to C1 proteases of classical path are associated w/ MBL (MASP1 and MASP2) —> cleave C4 —> SAME AS CLASSICAL
12
Q
Classical Path of Activation (7 Steps)
A
ANTIBODY-DEPENDENT
- 1- IgM or IgG1/2/3 binds antigen
- 2- Now Fc region of antibody can bind C1 (made of binding component C1q and 2 proteases C1r and C1s)
- 3- attached C1 becomes enzymatically active and cleaves C4 —> C4b
- 4- C4b attaches to antibody or microbial surface near antibody and binds C2
- 5- C2 also cleaved by C1 —> C4b2a complex (AKA classical pathway C3 convertase)
- 6- Cleaves C3 —> C3b which binds C42ba complex —> C4b2a3b complex (function as C5 convertase)
- 7- C5 convertase cleaves C5 —> initiates later steps in complement activation
13
Q
3 Regulators of Complement and Diseases Associated w/ Deficiencies
A
- C1 inhibitor - (C1 INH) - stops complement activation at C1 activation
* *Deficiency = hereditary angioedema (excessive C1 activation leads to production of vasoactive proteins —> edema in larynx) - Decay Accelerating Factor (DAF) - suface protein that disrupts Bb to C3b binding AND C4b to C2a binding —> blocks C3 convertase; terminates both classical and alternative activation
* *Paroxysmal Nocturnal Hemoglobinuria = acquired deficiency in heme stem cells of enzyme that makes anchor for surface proteins including DAF; unregulated complement activation —> RBC death - Factor I cleaves C3b into inactive fragments; Factor H is its cofactor
* *Atypical Hemolytic Uremic Syndrome - factor H mutation that compromises its ability to bind to cells; clotting, vascular and renal abnormalities
* *Predisposition to macular degeneration
14
Q
Mucosal Immunity
A
- IgA prod in mucosal tissues
- TGF-beta induces the isotype switching to IgA and is prod at high levels in mucosal lymphoid tissues
- IgA producing B cells activated in secondary lymph tissues are attracted to mucosal lymph tissue by chemokines prod in mucosal tissue
- Some IgA prod by subset of B cells called B-1 cells (secrete IgA in response to non-protein antigen w/o T cells help)
- Process
- 1- B cells in lamina propria beneath epithelial barrier and prod IgA here
- 2- poly-Ig receptor on basal surface binds IgA, endocytoses it into vesicles and transports it to luminal surface
- 3- Receptor is cleaved by protease —> IgA released into lumen w/ portion of poly-Ig receptor (called the secretory component) still bound which protects antibody from degradation in lumen of gut (gut has proteases in lumen)
- 4- Antibody can now bind microbes in lumen and block them from binding and crossing epithelial barrier
**IgA-mediated humoral immunity is used to protect against poliovirus (use oral immunization)
15
Q
Neonatal Immunity
A
- Neonates acquire maternal IgG in 2 ways…
- In pregnancy - Maternal IgG binds neonates Fc receptor (FcRN or FcRB for Brambell) in placenta then actively transported to baby’s circulation
- After birth - infant ingests maternal antibodies via colostrum and milk —> ingested so mucosal immunity for baby
- Protected from whatever mother has been exposed to or vaccinated for
