L43, L45- Humoral Mediated Immunity Flashcards
describe the subunits and makeup of MHC-I and MHC-II
MHC-I: α1, α2, α3, β2 microglobulin; Ag binds α1/α2, one transmembrane domain, one cytoplasmic tail
MHC-II: α1, β1, α2, β2; Ag binds α1/β1, two transmembrane domains and cytoplasmic tails
the humoral adaptive immune response is responsible for neutralizing/eliminating (1), mediated by (2) produced by (3); this is the principal defense mechanism against (4) microbes
1- extracellular microbes (+ microbial toxins)
2- Abs
3- B cells
4- encapsulated microbes rich in polysaccharides and lipids
Thymus dependent Ags are (1) type Ags processed by (2) and recognized by (3). They assist in (4), (5), and (6).
1- protein
2- APCs
3- Th cells
4- B cell activation
5- heavy chain isotype switching (class switching)
6- affinity maturation
NOTE- protein Ags w/ no Th cell => weak or no Ab response
Thymus independent Ags are (1) type Ags and are limited in (2) and (3), therefore only (4) can be generated in response
1- non-protein
2- class switching
3- affinity maturation
4- IgM
protein Ags recognized by B cells and Th cells have the following elements in response…
-Ig isotype switched: IgG, IgA, IgE
-high affinity Ig
-long lived plasma cells
Note- occurs in spleen + other lymphoid organs
non-protein Ags (lipids, polysaccharides, etc) recognized by just B cells have the following elements in response…
-mainly IgM
-short-lived plasma cells
(-lower affinity Ig)
Note- occurs in spleen, lymphoid organs + mucosal tissues, peritoneal cavity
thymus dependent Ags usually have (1) B cells as responders
thymus independent Ags usually have (2) and (3) B cells as responders
1- follicular B cells (B2 cells)
2- marginal-zone B cells (spleen)
3- B1 cells (mucosal tissue, peritoneum)
thymus independent (TI) Ags activate B cells via….
PRRs (pattern recognition receptors): TI-1 lipopolysaccharides, TI-2 highly repetitious molecules (ex. flagella)
B cells migrate to germinal centers with the help of (1), then migrate to paracortex of lymph node with the help of (2)
1- CXCR5 (cortex, light zone of germinal center- CXCR4 for dark zone)
2- CCR7
within secondary lymphoid organs follicular dendritic cells and Tfh cells produce (1) in to promote the expression of (2) and to assist in (3) and (4) within B cells; note (2) also downregulates (5), a repressor gene associated with B cell proliferation
1- TGF-β 2- AID (activation induced cytidine deaminase) 3- somatic hypermutation 4- class switching 5- blimp-1
in the spleen (1) is responsible for carrying B cells to the (2) region rich in T cells- once activated, (3) helps carry B cells to (4)
1- CCR7
2- PALS (periarteriole lymphoid sheaths)
3- CXCR5
4- primary follicles in marginal zone (surrounding germinal center in B cell zone)
germinal centers arise (1) days after initial exposure to thymus dependent Ag in lymph node, and the following three events occur in the germinal center: (2), (3), (4)
1- 7-10 days
2- affinity maturation via somatic hypermutation
3- class switching
4- formation of plasma and memory B cells
Signal 1 of B cell activation includes (1) and (2) forming a complex with (3) as the signaling sequence
1- Ig (usually IgM)
2- Igα, Igβ
3- ITAM
Signal 1 of B cell activation includes the following three proteins as co-receptors and one protein as an inhibitory co-receptor (include functions)
- CD19- cytoplasmic tail for signal transduction
- CR2- C3d from complement receptor
- TAPA-1- transmembrane molecule
-CD22- cytoplasmic tail for signal transduction via ITIM (immunoreceptor tyrosine-based inhibitory motif)
describe function of ITIM
- immunoreceptor tyrosine-based inhibitory motif is associated with CD22 (cytoplasmic tail for signal transduction)
- functions to deactivate B cells (negative regulation)
- important in preventing autoimmunity
list the two important Signal 2 interactions for B cell activation
- CD40L (T cell) - CD40 (B cell)
- CD28 (T cell) - B7 (B cell)
(assuming CKs and their receptors are Signal 3)
generation of Tfh cells depends on co-stimulatory….
ICOS (T cell) binding ICOS-L (APC)
Tfh cells secrete IL-_ to stimulate Ab production proliferation
IL-21
class switching requires (1) enzyme
besides unique CK combinations for specific Ig switching, (2) is absolutely necessary
1- AID
2- CD40 (B cell) interaction with CD40L (T cell) + thymus dependent Ag
explains X-linked hyper-M syndrome
- Th don’t express CD40L
- => Pts can only express IgM
- no memory cell populations, no germinal centers
(1) region of Ig changes in isotype switching
(2) region of Ig changes in affinity maturation via (3) process
1- constant region
2- variable region
3- somatic hypermutation / point mutations (AID is required)
describe how AID works
(adenosine induced cytidine deaminase)
creates point mutation in DNA by deamination of Cytosine base
in thymus independent B cell activation microbes become covered in (1) which is recognized by (2) on B cells; in addition B cells have (3) that can recognize microbial products directly
1- C3d
2- C3d receptor / CR2 / CD21
3- Toll-Like Receptors (recognizing PAMPs, DAMPs)
list the outcomes of B cell activation
- increased survival, proliferation
- interaction with Th cells
- responsiveness to CKs
- migration from follicle to T cell zone
- Ab secretion (IgM secretion)
describe Ab feedback
- Ab-Ag complex binds to B cell Ig and Fc receptors
- Fc tail binds FcγRIIB receptors on B cells
- => inhibition of receptor mediated B cell activation
how do neonates have longer IgG half-lives (IgGs from mother)
Neonatal FcRn: IgG ingested by endothelial w/in endosome (pH < 7) and binds FcRN –> complex is recycles and IgG is released (pH > 7)
what are the two general critical B cell pathologies
- Autoimmune diseases
- Malignant transformation of B cells and their precursors
list the non-complement effects of Abs
- neutralize microbes/toxins
- opsonization and phagocytosis of microbes
- Ab dependent cellular cytotoxicity (NK cells)
list the results after Ab activation of complement through the classical pathway
- lysis of microbes
- phagocytosis of microbes via opsonization from C3b
- inflammation (C3a, C5a)
describe the process of neutralization of microbes using Abs
Ab uses Fab segment to bind to microbe (typically virus) and prevents it from binding to cell surface receptor and blocking fusion of microbe and target cell
(ex. IgA outside of body in gut does this constantly)
(1) and (2) receptors bind IgG and are found on (3) cells for phagocytitic function
1- FcγRI (high affinity)
2- FcγRIIA (low affinity)
3- macrophages, neutrophils, eosinophils
Note- Fc binds Ig, Fab binds complement
(1) receptor binds IgG to function in feedback inhibition
(2) receptor binds IgG to stimulate ADCC and is found on (3) cells
(4) receptor binds IgE and is found on (5) cells
1- FcγRIIB
(Ab-dep cellular cytotoxicity)
2- FcγRIIIA
3- NK cells
4- FcεRI
5- mast cells, basophils, eosinophils
Note- Fc binds Ig, Fab binds complement
explain ADCC
Ab-dep. cellular cytotoxicity: FcγRIIIA on NK cells recognize IgG which stimulates the destruction/killing of Ab coated cells
describe eosinophil-mediated killing of helminths
- IL-4 (via Th2) stimulates IgE class switching
- IL-5 (via Th2) activates eosinophils (enhancer)
- IgE binds helminths –> activates eosinophils via FcεRI
- eosinophil degranulation / release of toxic mediators –> destroys parasite
in complement pathway, (1) receptor on phagocytes recognizes (2) as the opsonin
1- CR1
2- C3b
(Note- C3b can also assist in stimulating MAC formation => lysis of microbes)
- Ig(1) is the best opsonizer
- Ig(2) is the most potent neutralizer (its only function)
- Ig(3) is is involved in the sensitization of mast cells
- Ig(4) activates complement
1- IgG1
2- IgA
3- IgE
4- IgM
Ig(1) transports across epithelium
Ig(2) transports across placenta
1- IgA
2- IgG1
Abs serve as protective factors in the following 2 sites….
- mucosal organs
- fetus/neonate gut
- IgA works in both places
describe how fetus/neonate receive maternal Igs
- placenta: IgG1
- colostrum: IgG, IgA
list three microbial methods to evade humoral immune system
- Ag variation: rapid switching of Ags to become unrecognizable by Abs (or complement)
- inhibition of complement
- blocking via hyaluronic acid capsule
what are natural passive acquired immunities
Igs received from mother (placenta and colostrum)
list the 3 types of Vaccines
1) whole: killed/live-attenuated cells/viruses
2) acellular/subunit: Ags from bacteria/viruses, usually from surface or neutralized toxins
3) recombinant vaccine: microbial Ags are cloned into another organism
describe the response and requirements of whole vaccines, killed/inactivated
-weaker immune response
-humoral response only
-multiple doses and boosters required
(note- no refrigeration, easy to store/transport)
describe the response and requirements of whole vaccines, live-attenuated
-strong immune response
-humoral + cell mediated response
-fewer doses and boosters required
(note- needs refrigeration, difficult to store/transport + danger of reversion mutation to wild-type)
describe the response and requirements of acellular and subunit vaccines
- 1-20 Ags w/in vaccine
- usually less side-effects compared to whole vaccines
i) Toxoid (acellular)- bacterial toxins
ii) conjugate (acellular)- encapsulated bacteria, no cell mediated immunity
iii) subunit- viral components
describe the response and requirements of recombinant vaccines
i) recombinant vectors: selected genes for microbial Ags cloned w/in vector, cloning host produces Ag for vaccine
ii) DNA: plasmid encoding Ag injected, expressed in host cells –> strong humoral and cell mediated response (in development)
live attenuated vaccines are given to infants after (1) age because of (2)
1- 12 mos of age
2- maternal Abs may destroy organisms before infant can develop their own immunity
Ig_ is the only useful isotype useful in diagnosis neonatal infections
IgM
(1) is the most vulnerable time for infants in reference to immunity because of (2)
1- 3-12 mos.
2- maternal IgG has disappeared (maternal IgA still present, only IgM being produced by baby)
