Lecture 35 Flashcards
Which Immunoglobulins are determined by Alternative RNA splicing
IgM to IgD
Which Immunoglobulins are determined by Class switching
IgA, IgE, and IgG
(from IgM or IgD)
Function of antibodies
Mediate the clearance and destruction of pathogen in a variety of ways (depending on each antibody isotype)
Key antibody functions
1) Neutralization
2) Opsonization
3) Complement fixation/initiated complement
4) Antibody-dependent cell-mediated cytotoxicity (ADCC) (including NK cells inducing apoptosis)
5) Degranulation similar to ADCC
6) Transport
How do Igs opsonize, act on cells, and get across cells
By Fc receptors (FcR)
Which cells are transmembrane receptors that bind to Fc portions of Igs found
Expressed on macrophages, granulocytes, dendritic cells, mast cells, B cells, epithelial cells
How do transmembrane receptors bind to Fc portion of Igs
In a Class specific manner
FcgammaRI binds to IgG1
FcepsilonRI binds to IgE
Which effector function of antibodies do Fc receptors mediate
Crosslinking FcR to trigger signaling
What is crosslinking
When more than 1 Fc receptor binds to an antibody that is bound to an antigen
No crosslinking–>no intracellular signaling
Functions of Fc receptors
1) Degranulation
2) Opsonization
3) Transportation and maintenance of serum levels
4) ADCC
Benefit of using FcRs
Allows non-specific immune cells to take advantage of antigen-specific antibodies
Main action of Opsonization
Promotes and/or enhances the engulfment of antigens by phagocytes
IgG different subclass effector functions
1) Effective complement fixation
2) Good at mediating ADCC by NK cells
Effector function shared by ALL IgG variants
Enhance phagocytosis by macrophages–>opsonization
Main action of antibody-dependent cell-mediated cytotoxicity (ADCC)
Activates the killing activity of several types cytotoxic cells (ex. NK cells)
Which Fc receptors do NK cells
NK cells have FcgammaRs (recognize Fc region of IgG antibodies)
Pathway of ADCC
FcgammaRs on NK cells bind to Fc region of IgG antibodies–>crosslinking triggers signaling–>NK cell releases toxic granules (same in ADCC and innate)–>target cell dies by apoptosis
Which immunoglobulin is best known for role in allergy and asthma
IgE
Which Immunoglobulin plays a role in protection against parasitic helminths and protozoa
IgE
IgE effector function
1) Degranulation of eosinophils/basophils
2) Release of molecules such as histamine to damage large pathogens
Main action of Neutralization
Protects against viral or bacterial infection, or against the damaging effects of toxins
Targets for Neutralization
Toxins, Viruses, Bacteria
Which antibodies/Igs are most important for neutralization
IgG and IgA
Mechanism of Neutralization
Bind antibodies to toxins or pathogen to prevent them from binding their targets and exerting their effects
Where is IgA found
Secretions and mucosal tissues
1) Mucus in gut
2) Milk in mammary glands
3) Tears
4) Saliva
Outcome of Complement activation
Generation of membrane attack complex (MAC), inflammation and/or opsonization
What does C1q bind to
C1q binds pathogen surface
1) Can bind pathogen directly
2) Can binds antibodies that are bound to pathogen surface
What does C1q binding trigger
Signaling cascade on pathogen surface
C3 convertase is generated
C3 cleaved–>C3a and C3b
Which Igs trigger the complement cascade
IgG and IgM, but IgM is the most effective
What is IgM effective at
1) Activating the complement cascade
2) Forming dense antibodies pathogen complexes that are efficiently engulfed by macrophage
Where is IgE found
Near epithelial surfaces
Where is IgG found
Widely distributed
In newborn circulation (maternal IgG, passive immunity)
Where is IgD found
Blood but at higher levels in secretion of upper respiratory tract
Effector functions of IgD
Binds basophils and mast cells promoting them to release antimicrobial peptides (AMPs), cytokines, and chemokines
