Acquired immunity B cells and antibodies Flashcards
What type of cells secrete antibodies?
Only B cells or immunoglobulins
antibody function
- bind to extracellular bacteria and viral particles and inactivate/prevent adherence/infection
- antigen-antibody complex is recognized by macrophages
- bind to toxins and neutralize them
- toxin-antitoxin antibody complex cannot bind to target cell
- can activate complement system
- bind to aged/damaged cells so they can be phagocytosed
coating of antigen by antibody is a type of opsonization
pathological role of antibodies
- antibodies against self antigens (autoantibodies) destroy self tissue = autoimmune disease
- antibodies provoke exaggerated/inappropriate response= allergies
- B cells become tumorgenic, cancer = myeloma
myeloma
- plasma cell tumor
- arise from single precursor cell (starts in bone marrow)
- secrete single Ig of any class called myeloma protein (antibodies)
- way too much of one antibody is produced
- causes immune suppression becuase B cells cant react to other antigens
autoimmune hemolytic anemia
autoantibodies against RBCs
RBCs are destroyed= jaundice
Lupus
antibodies against skin and joints
arthritis, rashes
Rheumatoid arthritis
antibodies against synovial membrane and joint tissue
arthritis
Type I sensitivity
allergic response
IgE and eosinophils
for IgE antibody generation, Th2 and IL-4 is essential
B cell development
- stem cell in bone marrow
- pre B cell in marrow with cytoplasmic u chains
- immature B cell in marrow with membrane bound IgM, IgD
- mature B cell in marrow, lymph node, spleen with antibodies
- differentiation into plasma (Ig secretion) or memory cell
primary lymphoid organs
development occurs
no antigen interaction
Bone marrow (B cells, primary and secondary), thymus (T cells), peyers patches
B cell functions
- secrete Antibody (or immunoglobulin) production
- Antigen processing and presentation
only effective against extracellular pathogens, antibodies cannot enter cells
2 forms of antibodies:
- Secretory: Detected in the fluids such as serum, peritoneal cavity, mucosal fluids (“humors”) etc.
* They neutralize antigen and assist in their removal. - membrane bound: Important for specific binding to antigens
* B cell receptor (BCR) 200,000 to
500,000 identical antigen receptors (T cells have around 30,000 TCRs), Each BCR is specific to only ONE antigenic epitope.
- Antibodies recognize Free Antigens (i.e. do not require
combination with MHC unlike T cells) - Antibodies are Specific: Bind specifically to the antigen, which
induced antibody production - Cannot Penetrate the cell!
antibody structure
- They are glycoproteins made of 4 polypeptide chains.
- Have a flexible Y shaped structure
- amino end: where antigen binds, has variable V region
- carboxy end: bind to membrane
- 2 heavy and 2 light chains
- hinge region
antibodies recognize SHAPE/SEQUENCE of antigen
antibodies recognize SHAPE of antigen
Fc region
for complement binding on antibody
receptors expressed on surface of innate immune cells
IgM
-
First antibody (Ab) to appear in circulation
(predominant in primary antibody response) - Largest in size
- Membrane bound form is a monomer, Secretory form is a pentamer
- Seen primarily in the blood stream
- Has a J chain
- Second highest in serum immunoglobulin levels
Functions: - Agglutinate antigen
- Neutralize antigen
IgG
- Most abundant
- Monomer
- Smallest
- Can cross placenta in some species
- Can move out of blood stream and is
- Found in tissue, blood vessels, and other secretions
Functions:
* Agglutinate antigen
* neutralize antigens
* Important in inflammation
IgA
- Has a “Secretory Component” (sIgA) which allows IgA to appear in secretions and protected from digestion by proteases.
- Prevents adherence of pathogens and antigens in general to mucosal surface and agglutinates
- Tends to be synthesized under intestinal, respiratory, reproductive and other mucosal surfaces.
- Only one that can survive in harsh environment
IgE
- monomer
- heavier than IgG
- binds to mast cells (in tissue, very inflammatory) and basophils (in blood) through Fc receptor
- important in allergic reactions, helminth infestations
- IL-4 dependent like eosinophils
IgD
- (dont worry too much about this one)
- monomer
- similar to IgG
- BCR bound
- secretion is negligable
- found in humans, rats, mice
primary vs secondary immune response antibody differences
primary: short peak, IgM
secondary: tall peak, other antibodies
IgM to IgG class switch
IgG is the only Ab which can penetrate placenta and blood vessels
IgM to IgA class switch
IgA is the only Ab that survive in mucosal sites that is
enzyme rich and acidic
IgM to IgE class switch
IgE induces allergic Type 1 hypersensitivity reaction
Th1/Th2 and class switching
Th1 and Th2 cytokines trigger the switching of IgM to IgE/IgA/IgD/IgG
B cell receptor (BCR) recombination
BCR determines specificity of B cells
(ex: BCR for salmonella antigen is different than BCR binding e. coli)
recombination of genes for BCR leads to variable region of BCR
all B cells express:
- B cell Receptors: binds specifically to antigen
- CD19: binds to C3d-decrease the threshold for B cell receptor signaling pathways
- CD40: receptor for CD40 L (or CD154) on activated T cells
all B cells express:
- B cell Receptors: binds specifically to antigen
- CD19: binds to C3d-decrease the threshold for B cell receptor signaling pathways
- CD40 and CD86: costimulatory
- MHC class I and II
- Th2 cytokine receptors
Th2 cytokines acting on B cells
Th2 cells secrete cytokines that initiate B cell activation and differentiation.
* IL-4 Induces class switch (IgM-IgE). Enhances MHC class II and Fc receptor expression.
* IL-5 acts on activated B cells to differentiate into Plasma cell (Ab secreting cells, not present in plasma).
* IL-13- similar function as IL-4
* IL-6 final differentiation of activated B cells into plasma cells
