Lecture 15: B lymphocytes and antibodies Flashcards
What are the four cytokine properties?
Pleiotropic (multiple targets) -> B cell proliferation, Th proliferation, Mast cell activation
Redundant (overlapping action) -> B cell proliferation
Synergistic (Assist one another) -> AB class switch to IgE
Antagonistic (inhibits others) -> Block IL-4- IgE class switch
What are the affects of interferon alpha and beta?
- Transient viral resistance in viral infected cells
- Attract natural killer cells
What are the innate Interferons?
IFN alpha, beta, gamma
- Inhibit viral infections
What are the functions of IL1,6 and TNF-alpha?
- Proinflammatory (Esp. bacterial infections)
- Wound healing and tissue repair (non-infected related trauma)
- > Fibroblast proliferation
- > Bone reabsorption
- > Prostaglandin and collagenase synthesis
- > Neuroendocrine effects
What are some adaptive cytokine examples and what do they do?
IL-1
-> T and B cell activation
IL-2
-> T cell proliferation and NK cell activation
IFN-gamma
-> Antiviral, macrophage activation, NK cell activation, MHC upregulation
IL 4,5,6 -> B cell differentiation, antibody class switching
What are some chemokines and their functions?
IL8 (Alpha chemokine)
- Neutrophil migration
MCP-1, MIP-1a (Beta chemokine)
- Allergic inflammation
What are some heamopoetic chemokines?
G-CSF, M-CSF, GM-CSF
- Lineage specific control
IL3
- Proliferation of many lineages in bone marrow
IL5
- Eosinophil growth and activation (Allergy)
IL7
- Erythroblast and megakaryocyte growth
- B cell ontogeny in bone marrow
Describe antibody structure
Insert picture
What are antibody classes defined by? what are their heavy and light chain isotypes?
Heavy chain isotypes
- Alpha, delta, gamma, delta, epsilon, mu
Light chain isotypes
- Kappa, lambda
Describe antibodies in relation to their levels at birth:
- Mostly maternal IgG in utero, this declines at birth
- At birth Bubba IgG levels increase
- Over time IgM and IgA slowly rise around 6 months
Hence insufficiencies may not present till 10 moths post birth. Also antibodies transferred in breastmilk
Describe the role of cytokines in B cell clonal activation:
B cell recognize antigens and Th cells produce cytokines and this causes proliferation and differentiation
What are the effects of antibodys?
- Blocking and neutralisation
- Agglutination
- Opsonization
- ADCC (K-lymphocytes)
- Complement activaiton
Write some notes on antibody blocking and neutralization:
- Attatchment and entry (virus, parasites etc)
- Main protective effect of secretory IgA
- Toxins
- Immoblising bacterial flagella
In agglutination what happens over time?
- Antibodys form cross links and become complex, forming larger immune complex sizes (Under constant antibody concentration)
Describe IgG opsonisation:
IgG binds antigen, Phagocytes contain receptors for Fc region of IgG and for C3b complement component.
Because IgG Fc region can also bind C3B
What happens in ADCC in relation to K cells?
K cells FcR recognize Ig Fc region and kills them.
Whats the relation of Ig and complement activation?
Ab binds bacterium and compliment binds Fc region leading to:
- Lysis
- Opsonisation
- Chemotaxis
- And or anaphylaxis
- C5b, 6, 7, 8, 9 form membrane attack complex.
Review compliment classic and alternative pathways and affects
Slide 25
Describe the classic and alternative pathway of compliment cascade:
Classic pathway - Antigen-antibody complexes i.e C1,2,4 OR Alternative pathway - Pathogen surface, C3b, Factor B, Factor D
leads to:
C3 convertase and this in turn:
-> splits C3 and C5 into C3a and C5a = Vasodilation, mast cell activation and chemotaxis
It also leads to membrane attack complex formation
What are the antibody complexes involved in the secondary response (memory)?
IgG and IgA
IgM is minor
Write some notes on IgM:
- Largest, pentamer
- 10% AB pool
- First in primary response
- VERY EFFECTIVE AGGLUTINATOR
- Efficient complement activator b/c shape
- Important against blood-borne disease
Write some notes on IgG:
- 70-75% immunoglobulin pool
Good:
- Antitoxin antibody
- Effective barrier against virus infections
- Compliment activator
- Strongly bound by phagocytosed cells = enhanced opsonisation
and
Crosses the placenta
Write some notes on IgA:
- Predom class in sero-mucous secretion
- Main role is protection of external body surfaces - Gut, resp and genitourinary tracts
Write some notes on IgD:
- Trace amounts in blood and secretions
- Found on the surface of antigen sensitive naive B cells
- Receptors for antigen binding to activate naive B cells.
Write some notes on IgE:
- Trace amounts in blood
- Binds strongly to mast cells (differentiated basophils)
- Important in parasitic infections and allergies
- Allergens binding to mast cell associated IgE, activates processes that leads to symptoms of allergy or asthma.