B-Cells and Complement Flashcards
What type of immune response is used in vaccines?
T-dependent B cells responses
T-dependent B cell responses
form memory B cells
this response takes 10-14 days to manifest
can use Ig class switching and affinity maturation
T-independent B cell responses
respond to polysaccharide or LPS signals
mostly IgM response
fast (3-5 days)
What type of antibody activates the complement cascade?
IgM
T-dependent B cell response steps
Signal 1- B-cell binds antigen through it’s cell surface BCR. Crosslinking the BCR transmits activation signal to the nucleus
Signal 2- T helper cells and cytokines release signal to activate B cell
Where does T-dependent B-cell maturation occur?
Secondary lymphoid tissues
Examples of secondary lymphoid tissues
spleen
lymph nodes
CD40 and CD40L
costimulatory molecules that strengthen adaptive immunity response
between B-cells (CD40) and T-cells (CD40L)
Signal 1
B-cell binding to polysaccharide antigen
Signal 2
B-cell binding to other things like T-cell or cytokine
What is the end product of T-independent B cell response?
plasma cells
Plasma cells
acutely secrete antibodies
Memory B-cells
can be reactivated to become plasma cells to secrete antibodies
CD40
on B cells
CD40 L
on T cells
Is 2 signal system also found in T-independent B cell responses?
yes
Signal 1 - polysaccharide
Signal 2- TLR, complement receptors, cytokines
Affinity maturation
process by which antibodies gain increased affinity for the target antigen
result of somatic hypermutation of Ig genes in B cell regions
What is the primary mechanism of Ig diversification?
VDJ rearrangement
VDJ rearrangement
antibody gene segment rearrangement
occurs before antigen exposure
occurs in bone marrow
Where does affinity maturation occur?
Secondary lymphoid tissue
When does affinity maturation / isotype switching occur?
After antigen exposure
B-cells migrate to germinal centers of spleen and lymph node and undergo somatic hypermutation
Somatic hypermutation
uses enzyme activation induced deaminase to generate mutations in the antibody’s variable region
What is the result of somatic hypermutation?
some mutations improve Ab-antigen affinity
higher affinity B-cells will survive more
Affinity
strength of binding
Avidity
of binding sites available
(similar to valence)
What 2 isotopes do all new B cells produce?
IgM and IgD
How do B-cells produce IgG, IgA and IgE?
hav to isotope switch
Where is IgG?
mostly in the blood
Where is IgA?
mucosal surfaces
also in secretory fluids
IgM
can activate the complement cascade system
How does the complement system kill pathogens?
inserts pore structures in the microbe that cause lysis and death
IgG antibodies
uses phagocytosis to uptake pathogen
Fc region
(staph aureus uses Protein A to get around)
IgE
provide immunity against parasites (helminths)
plays major role in allergies
IgA
protect mucosal surfaces
IgD
works in the gut
dampens the immune system
Hyper IgM syndrome
helper T-cells cannot provide adequate assistance to B cells, therefore cannot make antibodies to T-dependent antigens
what is inheritance pattern of Hyper IgM syndrome
X-linked recessive
bonus: inheritance pattern of hemophilia
X-linked recessive
Manifestations of Hyper IgM syndrome
suspectibility to pyogenic bacteria
pyogenic bacteria examples(4)
H. influenzae
Strep pneumo
S. pyogenes
Staph aureus
What do pyogenic bacteria normally require in order to kill them?
normally need to coat them in antibodies
(to make effective, long term antibodies you need T-cell dependent B-cell activation)
How do you treat Hyper IgM syndrome?
IVIG therapy
patients with deficiences in C5-C9 are suspectible to what?
Neisseria infection
Graves disease
thyroid-specific autoimmune disorder that causes the thyroid gland to produce too much thyroid hormone
not a systemic autoimmune disease
ANA protein
high sensitivity
low specificity (15-20% of women have ANAs)
Genetic polymorphisms and lupus
genetic polymorphisms can affect general pathways of immune regulation, including type I interferon production
Type I IFN-alpha
normally produced by dendrictic cells
something viral can trigger IFN-alpha
then, if you have a genetic mutation IFN-alpha might really amp up ?
What are 3 roles of complement system?
opsonin (tag pathogens)
anaphylatoxin
MAC (lyses microbes)
What does complement deficiency lead to?
makes you suspectible to encapsulated bacteria infection
Deficiencies of C1, C2 and C4 lead to …
infection by strep pneumo and H. influenza type B
these are all early complement components
Deficiencies of late components (C5-C9) leads to?
increased Neisseia infections
deficiency of C3 leads to
severe recurrent pyogenic infections in early life mostly by streptococcus
What is most common deficiency of complement?
C2 deficiency
Hereditary angioedema
C1-INH deficiency (regulatory complement protein)
classic pathway is chronically activated
increased bradykinin leads to swelling and smooth muscle contraction
Factor H and DAF
examples of inhibitors that protect you from overactivation of complement system
What are the 3 pathways of complement activation?
Alternative
Classical
Lectin
Hyper IgM syndrome results in what antibody not being produced ….
IgG
(no CD40L for T-cell dependent B-cell activation)
Why does Hyper IgM make you more suspectible to pyogeneic infection?
normally IgG will tag something for phagocytosis (opsonization) and this cannot occur
Where does IgM class switching occur?
in germinal centers
What antibodies do mature, naive B-cells express?
IgM and IgD
What is the beginning of B-cell activation?
antigen presented to B-cell through MHC-II
What causes hereditary angioendema?
C1 esterase deficiency
How does C1 esterase def. cause angioendema?
C1 esterase normally breaks down bradykinin
having less C1 esterase means you will have more bradykinin which causes edema
What is the inheritance pattern of C1 esterase def?
autosomal dominant
