Antibody Effector Function (Exam IV) Flashcards
FcGammaRIIB1is expressed by
Naive B Cells, and prevents B cells for being involved in secondary responeses when there is a preexisting antibody response against the pathogen
Naive B cell binds pathogen
IgM + FcyRIIB1
Naive B cell is activated and becomes an antibody producting plasma cell
Production of low affinity IgM antibodies
Primary response
Naive B cell binds pathogen coated with specific anibody
A negative signal is giveb to the Naive B cell to prevent the activation
No production of low affinity IgM antibodies
Secondary reponse
Memory B cell binds pathogen
Memory B cell is activated and becomes an antibody-producing plasma cell
Production of high affinity IgG
Secondary response
First pregnancy of RhD- mother carrying a RhD+ fetus
- primary immune response, IgM plus low amounts of low affinity IgG
- Minor destruction of fetal erythrocytes by anti-RhD IgG
healthy newborn baby
Second and subsequent pregnancies of RhD- mother carrying a RhD+ fetus
- secondary immune response, abundant, high affinity IgG transcytosed to fetal circulation
- massive destruction of fetal erythrocytes triggered by anti RhD IgG
Anemic newborn babies
First and subsequent pregnancies of RhD- mother carrying a RhD+ fetus and infused with anti-Rh IgG
- Primary immune response to RhD is inhibited by the prescence of RhD specific IgG
healthy newborn babies
RhoGam
Anti RhD+ response to people that are RhD-
IgM
- first antibody to be produced in an immune response
- Produced in pentameric form, binds pathogens strongly and activates complement through the classical pathway
- Due to its large size, it is limited in its ability to leave the bloodstream and penetrate infected tissues
High aviditiy (10 binding sites)
Somatic hypermutation, affinity maturation and isotype switching lead to
the production of high affinity IgG and monomeric IgA
Smaller size of high affinity IgG and IgA allows
these antibodies to be able to exit the bloodstream and enter the sites of infection
IgG is actively transported across
vessel endothelium by specific receptors
FcRN
transport IgG from the bloodstream to the extracellular spaces
FcRn process
- Fluid phase endocytosis of IgG from the blood by endothelial cells of the blood vessels
- the acidic pH of the endocytic vesicle causes association of IgG with FcRn, protecting it from proteolysis
- When reaching the basolateral face of the endothelial cell, the basic pH of the extracellular fluid dissociates IgG from FcRn
Transcytosis.
Specific function of IgM, IgG and monomeric IgA
- provide antigen-binding functions within the fluids and tissues of the body
- Protect from blood-borne infection or septicemia
Dimeric IgA
- protects the mucosal epithelial surfaces
- Made by plasma cells in the lamina propria, but needs to be transported acorss the epithelium
- Dimeric IgA (not monomeric) binds to a receptor on the basolateral surface of the epithelial cells called the Poly Ig Receptor
- Facilitates trancytosis of IgA.
Poly Ig Receptor
Specific for IgA dimers and IgM pentamers
Found on the basolateral surface of the epithelial cells.
IgA + Poly Ig receptor
- binding of IgA to a receptor on basolateral face of epithelial cell
- receptor mediated endocytosis of IgA
- Transport of IgA to apical face of epithelial cell
- Receptor is cleaved, IgA is bound to mucus through the secretory piece (lumen)
Multiple functions of dimeric IgA
- IgA can export toxins and pathogens from the lamina propria while being secreted
- IgA is able to bind and neutralize antigens internalized in endosomes
- Secreted IgA on the gut surface can bind and neutralize pathogens and toxins
- Secrted IgA binds pathogen on M-cell surface and takes it to lymphoid tissue
- secreted IgA picks up antigen in the endosomes of the M cell and takes it to lymphoid tissue
antibodies in our blood
IgG, IgM, monomeric IgA
antibodies in our respiratory system, digestive system, urogential tract
dimeric IgA
All these places are lined with mucosal epithelia.
only isotype that can cross the placenta
IgG
primary form of antibody found in breastmilk
Dimeric IgA
an infants first year of life:
declines in maternally transferred antibodies coupled with development of their own IgM, IgG, IgA.
- while they are in utero, the fetus recived passivly transferred maternal IgG. declines within about 9 months
- 3 months - 1 year = transient low IgG levels (developoing its own IgG)
- first antibody to appear in a babys life: Newly synthesized IgM
Neutralization
Antibody interfering the interaction between the virus and its preferred receptor on the cell surface
- may be receptor or ligand
- virus prefers to a specific host cell protein.
Ex: IgA binds to virus which prevents it to bind to a receptor/ligand on cell surface leading to virus not infecting the individual.
Toxin Neutralization
- toxin binds to cell surface receptor
- Endocytosis of toxin:receptor complex
- Dissociation of toxin to release active chain which poisons cell
The toxin wants to bind the receptor in order to go through endocytosis of the cell and release toxins.
- Neutralizing antibody blocks binding of toxin to cell surface receptor
^^ this happens if an antibody is able to prevent the toxin from binding to receptors on the surface
antibodies against S. pyogenes F protein inhibit its ability to function as an adhesion to cause disease; neutralization
Neutralization:
- Child with anitbodies against S. pyogenes
- Antibodies prevent the attachment of bacteria to the tissues; most bacteria are swept to the gut
- Bacterial population is limited and kept as a steady state; child remains healthy
Disease:
- sister without anitbodies against S. pyeogenes
- bacteria stay in the pharynx and multiply
- bacterial population expands out of control and damages its environment; sister suffers from sore throat
Complement fixation
Pentameric IgM is a perfect ligand for C1q
- initiates the classical pathway
- IgM and C1 are closely related, and if one is missing, ones complement system would be impaired.
(10 antigen binding sites)
Binding of at least two molecules of IgG to pathogen or particle is required for complement fixation
- IgG molecules bind to antigens on bacterial surface = C1q binds to two or more IgG molecules and initiates complement activation
- IgG molecules binds to soluble multivalent antigen = C1q binds to soluble immune complex and initiates complement activation
Immune complexes
Protein complex formed by binding of antibodies to soluble antigens.
- size of immune complex is dependent on the concentration of antigen and antibody
- large complex - often coated with complement and cleared by phagocytes
- small complex - accumulate in small vessel walls where they can activate complement and cause damage
1. renal podocytes, leads to damager of glomeruli (kidney disease)
Patients with deficines in the ealry components of the complement cascade (C1)
cannot coat immune complexes with C4b and C3b, and cannot remove them
Leads to kidney damage.
CR1 on an erythtocyte surface binds C3b tagged immune complex
Erythrocyte carries immune complexe to the liver or spleen where it id detached and taken by a macrophage
Opsonization
Clearing of extracellular bacteria
Important receptor in Opsonization
FcgammaR1
specific for IgG
FcyR1
high affinity receptor for IgG1 and IgG3
- FcyR1 binds the lower hinge and CH2 of IgG3
- IgG3 bound to FcyR1 binds antigen
Allergic and anti-parasite responses
IgE
IgE
IgE binds to mast cells thrrough FcER1 (Fc epsilon receptor)
mast cells are already decorated with IgE on their surface. The interaction between IgE and Fcepsilon = high affinity receptor
granules of mast cells
contain histamine and other inflammatory mediators
- multivalent antigen cross links IgE antibody bound at the mast cell surface causing the release of granule contents
Good way to kill mutlicellular parasites
Eosinophils, mediates by IgE and Fcreceptor expressed on eosinophils
Antibody-dependent cellular toxicity (ADCC)
- NK cells can kill cells coated with IgG1 or IgG3, mediated through FcyRIII (CD16)
- influenza infected cells can express viral glycoproteins which can be recognized by these IgG molecules, lead to ADCC
- this is the mechanism of action of the anti-B Cell tumor drug Rituximab
ADCC pathway
killing of antibody coated cell
Activation
FcyR1
FcyR3-B
High affinity
FcyR1 - binds gamma and is the major receptor for opsonization
Low affinity
FcyR3-B - CD16 (NK cells)
FcyR2-B
Inhibition
FcyR2-B (Naive B cells that prevent them to participiate in secondary responses)
pH dependent
FcRN
Increased Ig half life
FcRN
