Humoral Immunity Flashcards
Antibodies are also called
Immunoglobulins
Function of antibodies
Opsonization pathogen
Neutralized and eliminate pathogen
Majority of mature B cells reside in
Lymphoid follicles of lymph node and spleen
B lymphocyte end goal
Antigen recognition and presentation to T cells
Antibody production
When B and T cells interact with antigen they’re called
Effector cells
Where are antigens in tissues transported and delivered
Transported to blood
Delivered to follicles via lymphatics and conduits
____ captures the antigens and takes them to adjacent follicles in the lymph
Macrophages or Dendritic cells
___ do not need to be processed for B cells to recognize them
antigens
Where does VDJ recombination happen on immunoglobulin/bcell receptor
Fab
First heavy chain of B cells
μ
μ means what immunoglobulin is on the surface of B cells
IgM
What does the light chain provide
κ και λ
B cell receptors can bind to _____ types of antigens
T cell receptors mainly binds to _____
All
Peptides
B cells recognize which antigens the best
Polly: proteins - best
Pockets: polysaccharides
Nose: Nucleic acids
Lips: lipids
Hair: haptens
And Ass: amino acids - worst
Recognition of antigen by surface BCR triggers _____
INTRACELLULAR signaling pathways
Tyrosine kinase
Protein kinase C
Change in gene transcription
What is the first signal for B cells
Antigen binding
What is the purpose of having a second signal for B cell activation
So if B cell does recognize antigen it only gets activated when it needs to not when it binds to any old antigen
Peripheral tolerance
What has to be activated first before second signal is activated
Innate immune response
B cells express ___
CD21 aka complement receptor 2 - CR2)
CD21 recognizes
Complement proteins during complement activation
CD21 associated with ___ virus
Epstein Barr virus
What’s another second signal for B cells
PAMPs binding to TLR
When a B cell is activated what’s next
Clonal selection
a bunch of B cells made that are specific for the pathogen
Antibody secreting B cell is called a
Plasma cell
Why are plasma cells bigger than B cells
Because producing tonnnns of antibody’s
Polysaccharide antigens can engage
Multiple receptors on B cell
Early phase involves Ig_ and is T- _____
M
Independent
Protein antigens
Need T cell help
IgM is a ___ lived antibody and ___ affinity Ab
Short
Low
T cells get ____ from APC
Protein
What does T cell produce during t-dependent B cell activation
Cytokines and CD40 ligand
Activated B cells move towards T cells from a ______
Chemokine gradient
B cells produce _____ during t dependent B cell activation
CD 40
CD40-CD40L interaction stimulates
Antigen specific B cell proliferation and differentiation
Heavy chain isotype switching
affinity maturation
Making memory cells
Antibody secretion
T dependent is ideal b/c
Memory, isotype switching etc.
For B and T cells to come together both cells need to be
Activatec
How is B cell activated by T cells
CD40-CD40L interaction
What activates Tcells
B7-CD28 interaction
Who presents B7
Dendritic cells
Who presents CD28
T cells
What does B7-CD28 interaction do
Enhances T cell proliferation and differentiation
Where do B cells start making antibodies with low affinity
Extrafollicular region
Where does a fully developed humoral immune response occur
Germinal center of B cell
Where does all action happen for B cells
Germinal center
Affinity maturation occurs in
Germinal centers of lymphoid follicles
___ is a result of somatic hyper mutation of Ig genes in dividing B cells
Affinity maturation
Low affinity Ab———> high affinity Ab by
Somatic mutations
With _____ a host will produce antibodies of successively greater affinities
Repeated exposures to the same antigen
What drives process of low aff Ab to high aff Ab
Cytokines
What is the OG, initial Ab
IgM
Switching of Ab ___ = isotype switching
HEAVY CHAIN
CD40-CD40L is ____ cell ____
T
Dependent
What 4 things does CD40-CD40L do
Isotype switching
High aff Ab
Memory B cells
Long-lived plasma cells
Isotype switching occurs in response to
CD40-CD40L interaction
AND
Cytokines
Cytokine for IgG
IFNγ
cytokine for IgE
IL-4
Cytokine for IgA
TCF-β
Why are there specific Ab
Because some are more affective against different pathogens
IgG good for
NeoNatal immunity
Opsonization + phagocytosis
Complement activation
When you think IgG think
Gomp, comp, Nomp
Gomp = Opsonization and phagocytosis
Comp = complement activation
Nomp = neonatal immunity
IgE good for
Against helminths (parasites)
Mast cell degranulation
When you see IgE think
Eeeeeeew a worm MAST (de)go
Worm = parasite
Mast (de)go = mast cell degranualtion
IgA good for
Mucosal immunity
When you see IgA think
AAAAAchoo
Sneezing is from mucosa epithelial
AID
Activation induced cytosine delaminase
Enzyme for recombination of class switching
Key points for class swithcing
Recombination involved
Through AID enzyme
Heavy chain is switched
What kind of cells do not secrete antibodies and are very long lived
Memory cells
Antibody isotype for primary immune response
IgM>IgG
Antibody Isotype for secondary isotype
IgG or IgA or IgE
T independent antigen
Polysaccharides
IgM
Little affinity maturation
Plasma cells are short lived
No memory cells
T dependent antigen
Proteins
IgG, IgE, IgA
There is affinity maturation
Long lived plasma cells
There are memory cells
Antibodies us Fab for
Binding and blocking harmful effects of microbes/toxins
Antibodies us Fc to
Activate diverse effector mechanisms
What does it mean that a antibody can be flexible
One Ab can bind to two antigens
looks like its doing the splits
Affinity vs avidity
Aff = 1 interaction
Avidity = sum of interactions
Look up pics if need be
What forces does an Ab bind to an antigen
Non covalent reversible ones
What are the 2 subcategories of Antibodies
Direct Ab mediated
And
Complement mediated
Direct antibody mediated includes
Neutralization of microbes
Opsonization and phagocytosis of microbes
Antibody-dependent cytotoxicity
See pics - humoral immunity - week 8 - slide 50
Complement mediated Ab funcitons
Lysis of microbes
Complement activation
Inflammation
Phagocytosis of microbes opsonized with complement fragments
How does Ab neutralize microbes/toxins
1: binds and blocks from entering epithelial barrier
2: binds and blocks microbe from infecting
3: binds and blocks toxin from binding to cellular receptor
Describe direct Ab mediated opso. And phago.
- Ab binds by IgG
- Fc finds to phago cell
- Fc sends signals to activate phago
- Phago eats microbe
- Death to microbe
Describe antibody dependent cellular cytotoxicity (ADCC)
- Ab bind to microbe on Fab region
- Those Ab Fc regions are recognized by NK cell
- The NK cell is activated and now kills
See pic - week 8 - humoral - 54
NK 2 receptors are
Activation receptors - antibody coated cells
Inhibitory receptors - recognizing MHC I on cells
___ region of the Heavy chain determines Ab
C
IgM can exist as
Monomer - found on B cell surface as antigen receptor
pentamer - usually secreated version
A pentamer of IgM has
5 antibody molecules
10 antigen binding sites per molecule
Which Ab activates complement and through what pathway
IgM
Classical
First complement protein to bind to IgM
C1
Pentamer of IgM is good for classical pathway bc
It offers C1 multiple ways to bind
IgG exists as
Monomer
IgG can easily move to tissue bc
Of specialized endothelial receptor
IgG functions
Longest 1/2 life - cuz associated with memory
Most abundant in blood
Can weakly activate complement classical path
Neutralize
Opsonization
Ab dependent cellular cytotoxicity via NK cells
IgG Fc receptor on phagocyte
FcγR
IgM Fc receptor on phagocyte
FcμR
IgE Fc receptor on phagocyte
FcεR
IgA Fc receptor on phagocyte
FcαR
What Ab can cross placenta
IgG
The long half-life of IgG is bc of its ability to bind to
Neonatal Fc receptor (FcRn)
Which IgG isoforms activate complement system
IgG1 and IgG3
Odd bois
Why does IgM have a low affinity but a high avidity
It naturally has a low aff BUTT combined all those low affinities together with the pentamer structure and it = high avidity
IgA exists as
Monomer or dimer
Monomer IgA function vs dimeric IgA function
M = combine with IgM and IgG to protect all tissues reached by the blood
D = protects mucosal surfaces
in breast milk
Function of IgE
Clear parasites
Involved in allergy and asthma
IgE activates eosinophil which
Helps kill parasites
Where are FcE receptors
Mast cells (CT)
Basophils (blood)
Eosinophils (mucosa)
What causes sneezing, vomiting, diarrhea
IgE
Specifically the cross-linking of receptors leads to release of mediators
It acts on smooth muscle to cause “violent” expulsion of pathogen
Binding of ligand to IgD receptor on B cells _____ activation of B cells
Does not lead to
Which Ab activate classical complement
IgM, IgG1 and IgG3