Humoral Immunity Flashcards
Describe what an Ab looks like?
Has 2 heavy chains (Fc) region and inner arms.
Outer arms are light chains.
The bottom half is all constant and the upper paratope regions are variable.
Above the Fc region is the Fab region (Ag binding fragment)
4 polypeptide chains.
5 classes
Th1 helper cells do what?
Th2 helper cells do what?
Th1 activates CD8
Th2 activates B cells
Where are B cells made and mature?
Made and mature in hematopoietic bone marrow. Usually flat bones including the ileac crest of hips, top of femur, sternum, vertebrae and ribs.
B cell receptor complex
Antigen recondition molecule (usually IgD) and 2 accessory intracellular signaling molecules.
B cell clonal selection
- Antigen binds B cell. B cell phagocytes, processes, and presents epitope on MHCII.
2a) epitope + MHCII of B cell will bind with T helper cell receptor.
2b) Additionally, there will be a co-stimulatory signal from the t helper cell.
2c) Cytokines will be released from T helper cell to signal B cell and signal Th2 formation. - Now B cell has received the 3 signals to proliferate, class switch, and produce Ab.
When does class switch occur?
Occurs at time of activity activation of B cell by previously known antigen- only happens once.
If B cell is first activated and has never encountered an Ag before, the B cell will only produce IgM Ab and cannot class switch until later exposures.
Fetal cells cannot class switch
What determines which Ab the B cell class switches to?
Cytokine signals
Type/amount of antigen
What changes during the class switch? and what can the Antibodies class switch to?
Constant regions of the heavy chains change but Ag specificity remains the same.
A, E, G, or M. Cannot switch to D bc thats what is on the surface of B cells.
T-independent antigens
A BIG, repetitive identical antigenic determinant, antigen binding the B cell can activate the B cell without contact to TCR/costimulatory signals/cytokines.
Can you get a class switch with T-independent antigens?
No- due to no costimulatory or cytokine signal from Th2
Indirect and direct antibody functions
Indirect:
Complement activation
Opsonization
ADCC (antibody dependent cell mediated cytotoxicity)
Direct:
Neutralization
Agglutination
Precipitation
Indirect Ab function: Complement activation
Classical pathway is activated by Ab binding antigen. This activates C1 to start the cascade. Will result in MAC and pathogen death
Requires prior Ab response ?
Indirect Ab function: Opsonization
Ab will bind Ag to the Fab region. The Fc region of the Ab can bind the Fc receptors on phagocytes. The phagocytes will eat the Ag that the Ab is bound to
Requires prior Ab response ?
Indirect Ab function: ADCC
Used to destroy large organisms, many viral infected cells, or many cancer infected cells.
FcR on NK/MO/eosinophil cells will bind Fc region of Ab that is bound to Ag. NK will then phagocytose the Ab and large organism or cell it is attached to.
Requires prior Ab response!
Direct Ab function: Neutralization
Ab binds free floating toxins or viruses before they have the chance to bind to cells.
Involved in vaccines. Ex: tetanus vaccine produces Ab against the toxin.
Direct Ab function: Agglutination
ex uses IgM, has high valency. Clumping holds invaders still until immune cells can come in and destroy.
This process is for large, whole cells.
Direct Ab function: Precipitation
Ab bind to small, water soluble molecules floating in solution and makes them insoluble, pulling them out of the solution so other immune cells can come clean it up.
IgM
Largest Pentamer stabilized by J Chain 10 valency First Ab produced during the primary response Synthesized during fetal life
First Ab produced during the primary response and fetal life
IgM
IgG
Most abundant class (80-85%)
Transported across the placenta by active transport to provide passive immunity.
Four classes- IgG1-4
Which Ig can be transported across the placenta?
IgG
Two types of IgA
IgA1: Predominantly in the blood.
IgA2: Predominantly in mucosal secretions.
IgA
Dimers anchored by J chain and secretory piece (prevents bacterial enzymes from degrading Ig)
Which two Ig are stabilized by J chains?
IgM and IgA
Secretory immune system in which tissues and secretions?
Lymphoid tissues throughout the body.
Present in tears, sweat, mucous, saliva, and breast milk.
IgE
Least concentrated Ig class in CIRCULATION
Binds to surface of Mast cells and basophils.
Defender against parasites.
Mediator of many common allergic responses.
Atopic ppl have more IgE
IgE activation starting with APC binding parasite Ag
- APC binds parasite AG and presents to Th2 cell.
- Th2 cell activates B cells to release IgE
- IgE will settle on mast cells. Once the Ag binds IgE fab region, Mast cells will degranulate.
- Degranulation of mast cells releases ECF-1 (eosinophil chemotactic factor-A) and histamine.
- This results in diapedesis of eosinophils that follow chemotactic signals to the parasite.
IgD
Low concentration in blood
Found on the surface of B cells - function as receptor for B cell
Primary humoral immune response
- Exposure
- Long lag period.
- IgM concentration increases
- Then IgG concentration increases (class switch) but doesn’t reach as high of concentrations as Igm.
Secondary humoral immune response
- Exposure
- Short lag period.
- IgG concentration skyrockets
- At about the same time ^^, IgM concentrations increase, but to a much much lower degree.
Immune response is quicker, stronger, and stays on longer.
T cell primary and secondary immune response
Primary:
- Infection
- 1 week until effector expansion occurs (proliferation)
- 7-30 days pass before memory cells are made.
Secondary:
Response is quicker and larger due to memory cells.
Fetal/neonate immunity:
- Ab function is deficient. Passive immunity provided by material Ab
- IgG crosses placenta
- IgA in breast milk
Elderly immunity:
- Decreased T cell activity- thymus atrophies over life.
- Decreased circulating B memory cells.
- Decreased MO activity= more Ab:Ag complexes= precipitations and problematic.
- Tolerance system fails. Increase in auto Ab
Cell that bridges from innate to adaptive immune system
Dendritic. Contacts Ag in epithelium and brings to secondary lymphoid tissues for clonal selection.
