Humoral immunity and B cell effector mechainsm Flashcards
what are the types of B cell activation?
T dependent activation : which basically agianst protien ag and has more class switching and affinity maturation
T-independent activation: against non-protein protien antigen like polysaccharides, multivalent ag and lipids and nucleic antigens
What are the types of B cells?
Follicular B: in lymphoid organ follicle and make long-lived plasma cells
Marginal Zone B cells: in periphery of splenic white pulp and outer follicle of LN and it recognize blood-borne antigens and sacchrides antigens and mainly produce IgM
B-1 Cell: against multivalent antigen and mostly produce IgM
mechanism of activation of B cell by antigen
A B cells with agR recogize 2 or more ag presented by APCs; this causes the 2 adapter proteins IgAlpha and IgBeta which contain ITAM to activate Syk tyrosine kinase and it phopshrylates tyrosine residues on adaptor protiens which activates TF for B cell
How innate immunity activate B cell
1- by complement fragment C3d recognized by CR2 which activates ITAM and Syk tyrosine kinase
2- PAMPs which activates ITAMs and syk tyrosine kinase
what are receptors found on B cell
1- TLR
2- Complement R( C3d)
3- IgR
4- MHC1 and MHC2
5-FcR
6- CD19 and CD20
Antibody feed back inhibtion
when Ig for example IgG binds to FcyR2B receptor on B cell causing activation of ITIM which block B cell receptor signaling
how does the Th cell help in HMI?
when DC present an antigen in the T cell zone in LO, to Th cells it migrates to the parafollicular areas and it decreases the secetion of CCR7 and increase secretion of CXCR5 and at the same time when B cell is activated by an Ag it increases secretion of CCR7 but inhibits CXCR5 making an attraction force and closing to each other
How Th cells activate B cell
by binding the CD40L of T cell to CD40 on B cell and Cytokine from Th cell to cytokine receptor on B cell and i will induce affinty maturation, class switchig and profiration
Class switching Function
it is induced by cytokines and CD40L-CD40 interaction
1- forming IgG1 and IgG3 which bind to fcyR1 activating B cell causing phagocytosis and opsinization and secretion of IFNy, IL4 or IL17 and IL21 and IL10
2- against helminth by secretion of IgE which has FceR whicn eosinophil bind to
3- IgG bind to FcRn in placenta
Class switching mechanism
Cu heavy chain bind to ligh chian and make IgM and thn by AID enzyme transfering Cytosine to uracil in the DNA it makes DNA with nicks and the DNA repair and by help of Tfh cells it make different Igs
what interlukines make IgG
IL4
IL10
IFNy
TGF-B
what interlukines make IgA
TGF-B and BAFF
what interlukines make IgE
IL4 from TfH cells which are activtaed by IL5
How does B cell neutrlize pathogen
1- Block entry
2-Block transmission
3- neutrlize endo and exotoxins
What is the mechanism of opsinziation and phagocytosis
when an encapsulated bacteria is surrunded by Ig mainly IgG the IgG bind to FcyR1 on neutrophil and macrophage (CD64) when ingest the bacteria and make phagolysosome and cause destruction
and it inhibited with Ig bind to FcyR2B (CD32)
where does FcyR1 and FcyR2 present
FcyR1 on macrophage and neurotphil
FcyR2 on neutrophil, macrophage, DC, mast cells and B cells
what is the mechainsm of Antibody dependent cellular cytotoxicity
enveloped virus surrouned with Ig mainly IgG binds to FcyR3 CD16 on NK cells causes secretion granzymes and perforins causing killing
machanism of defense against parasites and helminth
eosinophil has FceR1 where IgE will bind causing it activation
eosinophil secretion is increased by IL5 from Th2 cells
eosinophil will secrete MBP. eosinophil peroxidase and eosinophil derived neurotoxin
Mast cell will have FceR1 receptor where IgE will bind whci will cause IL secretions
what IL are secreted from Mast cell
IL4 increase IgE and Th2
IL5. activate eosinophil
IL13 attract eosinophil
TNFalpha increase permeability and migration
IL33 increase Th2 cytokines
chemokine recruitng leukocytes
what will C3 deficincy cause
increase suscpetibility to bacterial infection
what will C2 and C4 deficincy cause
increase infection and SLE% due toaccumlation of immune complexes
what will C9 and MAC deficncy cause
increase Neisseria infection
what will happen to complement system due to spleenctomy
decrease macrophagoe phagocytosis and decrease in IgM causing inhibiton of classical pathway causing recurrent infection by encapsulated bacteria
what will deficincy in C1 inhibitor cause
Heredatory angiodema
what is the pathology of heredatory angiodema caused by C1 INH def
increase in complement activation and kallikrein breakdown to bradykinin causing edema
what is the pathoglogy of paraxyma nocturnal hemoglobinemia
increase in complement activate on eyrthorcytes causig thier lysis and it is due to decrease DAF and CD59what
what will Factor I and Factor H deficncey cause
Atypical hemolytic uremic syndrome
increase in complement activation
age related macular degenration
what will decrease of properdin do and why
properdin stablizes C3 convertase so when it deficinet there will be no MAC formed so will increase susceptibility to nisseria infection