Humoral immunity Flashcards
What molcecules do B cells recognize
BCR recognizes native molcules
- Peptides
- proteins
- nucleic acids
- carbohydrates
- Lipids
- small chemicals
Phases of humoral immune responses
Antigen recognition
Clonal Expansion
Differentiation into antobody recreting Plasma cells
Antigen capture and delivery to B cells
- mature B lymphocytes migrate from one secondary lymphoid organ to the next in the search for Antigen
- naive B cells reside in the follicles of peripheral lmyphoid Organs and circulate through them in search of specific antigens
Primary and secondary humoral immune response
Primary:
- naive B cells are stimulated by Antigen, become activated
- differentaite into antobody secreting cells
- some migrate to bone marrow
- usually IgM>IgG
Secondary:
- elicited when the same Antigen stimulates These Memory B cells
- more rapid Proliferation
- production of greater quantities
- relative increase in IgG (sometimes (IgA, IgE)
Seconary immune Response is typical of T cell dependent antibody Responses to protein antigens
Activation of B cells by helper T
- Antigen-activated helper T cells and B cells move toward one another in Response to chemokine Signals
- make contact adjacent to the Edge of Primary follicles
- B cells presents Antigen to T cell
- B cell recieves activating Signal from T cells
Antigen presentation on B cells to helper T cell
- protein Antigens Bound to membrane Ig are endocytosed and processed
- Peptide Fragments are presented on MHC II
- Heper T cells recognize MHC-Peptide complexes and stimulate B cell Response
- Activated B cells also express co Stimulators that enhance helper T cell responses
Germinal Centers in secondary lymphoid organs
- are involved in T cell dependenet antibody Response
- within the lmyphoid follicle (B cell Zone)
- contain follicular dendritic cells
Processes in germinal centers
- extensive Ig isotype switching
- hypermutation of Ig V genes
- B cells migrate into the light Zone –> Encounter follicular dendritic cells displaying Antigens and TFH cells
- B cells with the highest Affinity Ig receptors are selected to survive
- differentiate into antibody secreting or Memory B cells
heavy chain isotype (class) switching
Isotype switching in Response to different types of microbes is regulated by cytokines
- in activated IgM and IgD expressing B cells
- Induced by CD40 and cytokines
Result: production of antibodies with heavy chains of different classes: γ, α, and ε
Mechanism of heavy chain isotype switching
- in the Absence of helper T Signals, B cells produce IgM
- when there are Signals from helper T cells –> B cells unfergo swithcing to other isotypes
- Stimuli initiate germline transcription through the Iε-SεCε locus
- proximal CH genes are deleted in a circle of DNA, leading to recombination of the VDj exon with the Cε gene
- switch regions: Sμ or Sγ
Affinity maturation
- T-dependent humoral immune Response
- somatic Mutation of Ig genes and selection of high Affinity B cells
- early in the immune Response: low Affinity antibodies
- in germinal Center reaction: mutated B cells with high Affinity Antigen receptors start to produce high afiinity antibodies
- binding of the B cells to Antigen displayed on follicular dendritic cells –> necessary to Rescue B cells from programmed cell death
- B cells may also present Antigen to germinal venter TFH cells –> promotes B cell survival
Antibody Responses to T cell independet antigens
- non-protein Antigens (Polysaccharides and Lipids) stimualte antibody production in the Absence of helper T cells
- antibodies are generally low Affinity and consist mainly of IgM
- Limited isotype swithcing to some IgG and IgA
Effector functions of antibodies (in General, all of them)
- neutralize microbes and other Antigens
- opsonize microbes for phagocytosis
- sensitize them for antibody-dependent cellular cytotoxicity
- induce antibody-mediated helminth killing
- activate complement system
Fc receptors
- -> activation of efefctor mechanisms
- recognize antibodies of different isotypes for optimal defense
Neutralization of microbes and toxins
- antibodies against micorbes and microbial Toxins block the binding of These microbes and Toxins to cellular receptors
Antibody-mediated opsonization and phagycytosis
- IgG antibodies coat microbes and promote their phagocytosis by binding to C phagocytes
Antibody-dependent cell-mediated cytotoxicity
- antibodies of certain IgG subclasses bind to infected cells
- Fc regions of the Bounds antibodes are recognized by Fc-γ receptors on Nk cells
- NK cells are activated and kill the antibody.coated cells
Antibody-mediated clearance of helminths
- antibodies, mast cells, eosinophils function together in killing some helminths
- helminths are resistant to the microbicidal products of neutrophils and macrophages
- can be killed by cationic protein –> Major Basic protein –> present in granules of eosinophils
- IgE, IgG, IgA coat helminths and bind to Fc receptors of eosinophils and cause their degranulation
Antibody-mediated activation of complement
- activation of complement involves: sequential proteolysis of proteins to generate Enzyme complexes with proteolytic activity
- zymogens: proteins that acquire proteolytic activity by the Action of other proteases
- products of complement activation become attached to microbial cell surfaces or to antibodies Bound to microbes
- complement proteins become activated after they are attached to microbes or ti antibodies
Classical pathway of complement activation
- initiated by cibding of the complement protein C1 to IgG or IgM that have Bound Antigen
- igG3 and IgG1 are more efficient activators of complement Systems
Late steps of complement activation and MAC formation
MAC = membrane attack complex
- cell associated C5 convertase cleaves C5 and generates C5b
- C5b, 6, 7 complex is directly inserted into the Lipid bilayer of the Plasma membranes –> then Insertion of C8
- C9 molcules then polymerize around the complex to form the MAC
- Mac creates pores in the mmebrane and induced cell Lysis
- C5a released on proteolysis of C5 stimulates inflammation
Complement-mediated inflammatory responses
- proteolytic Fragments C5a, C4a, C3a –> induce acute inflamation activating mast cells and neutrophils
- Peptides bind to mast cells and induce degranultation
- Peptides are also called anaphylatoxins –> reactions they trigger are characterisitc of anaphylaxis
Regulation of complement activation
regulated by various Plasma and cell membrane proteins that inhibit different steps in the cascades
Pathologic effect of the complement system
- can cause significant tissue Damage
- may be due to complement-mediafed acute inflammatory Responses
- intravascular thrombosis and can lead to ischemic injury to tissues
Protective immunity in neonates
- passive immuity is provided by maternal antibodies transported across the placenta by specialized neonatal Fc receptor (FcRn)
- passive immunization by milk antibodies in newborns
Humoral immunity in mucosa
- prodcution of seceretory IgA by Plasma cells in the lamina propria
- binds to the poly-Ig receptor at the base of an epithelial cell
- Transport of the antibody into the lumen
- Bound IgA is releasd by proteolytic cleavage
- IgA bind to microbes and Toxins to neutralize them
–> process is called transcytosis
Summary on effector functions of antibodies
IgG:
- opsonization of Antigens
- activation of calssical pathway
- antibody.dependent cell-mediated cytotoxicity
- neonatal immunity
- Feedback Inhibition
IgM:
- activation of classical pathway
IgA:
- mucosal immunity
- activation of the lectin pathway
IgE:
- mast cell degranulation
IgD:
- Antigen receptor of naive B lymphocytes
