Humoral Immunity Flashcards
Ag bind on what in B cells?
Hypervariable regin or paratope or idiotype
What is the chemical difference of CH (Constent regions of heavy chain )
Chemical: change in amino acid
What is the chemical component of Abs or immunoglobulins ?
Gamma globulins in all blood fluids
What is the function of humoral response ?
Eliminate of extracellural microbe and their toxins
Abs are formed of 4_______
polypeptide
Abs is a Y shape monomer differentiate into to 2 identical H and L chain , name their domains
H chain consist of 4 domains each chain :
1 VH and 3 CH
——————-
L chain contains 2 domains each chain :
1 VL , 1 CL
What are the 3 fragments of Abs?
There are 3 fragments
2 FAB ( fragments ag binding ) also called bivalent
1FC (Fragments crystallizable) function is effector function
Variable region in contain
1 VH and 1 VL —-> has hypervariable (idiotype or paratope ) interacts specifically with one epitope ( complementary)
Produced by one specific clone of b cell
Name the constant region of heavy chain and name its function
CH1 , CH2 , CH3
Function:
# classify Ab into isotypes
G(gamma)
A(alpha)
M(mu)
E(epsilon)
D(delta)
#Fc (CH 2 , CH3 ONLY)–> biological (effector) example–> binding to Fc R on immune cells
+ complement
A plasma cell secret all kind of Ab , what is the different between lgG of this cell and the lgG of another cell
بمعنى آخر b cell clone 1 and b cell clone 2
Variable region
TGF beta
From MQ and DC _____
FROM Treg ______
FROM submucosa _____
Th17
inhibitions(more details: block + of MQ and DC —>anti inflammation)
IgA
When we use polysaccharides as vaccine ?
I don’t know , but when I do I will say
Direct stimulation of B cell is thymus depending or independing ?
Thymus Independing
How b cell is activated?
second path : if the Ag was formed from repeating multi same epitope ( t cell independent ) b cell will +directly by cross-linking without interaction of t cell ,this is faster but indeed this is a bad news :(
There is two ways to + B cell according to the Ag it self
# the first path : if the Ag was protein or hapten carrier conjugated, b cell couldn’t stimulate because proteins doesn’t contain more forms of the specific epitope
So b cell will do something interesting, it will internalize (receptor mediate endocytosis and its not a form of phagocytosis ) the epitope and associated with MHC class2 and work as APC .
It will Interact with T helper cell to gane the two signals
1) MHC CLASS 2 bind with TCR and CD4 and Ig alpha and beta will + B cell (first signal)
2) CD40 L on + t cell will bind to CD 40 (2nd single)
T cell will stimulate b cell by producing its cytokines
First Ab produced by plasma cell is
Secreted IgM
What is the function of IgD ?
It work as BCR and it doesn’t have any functions as secreted IgD , in serum it only 0.2%
Each Ab molecule (monomer or basic unit ) is
Y shape
What are the 3 things that prove IgM is the highest weight monomer ?
Most efficient in complement and agglutination
Mostly intravascular
Contain 10 Ag binding sites
Pentamer
Who is the cytokine responsible for IgA in submucosa ?
TGF-beta
What are the function of secretory component?
Play as lgA receptor for lgA Ab
Facilities IgA transport across mucosa
Protect IgA from digestion by enzymes
Name Abs that do neutralization
IgG(most effective)
IgM
IgA( in mucosa )
Name IgA chains
J chain
Secretory components
Name function of IgA?
Neutralization
Prevent there adherence in mucosa
Present in milk ,Protect newborn from infection
Definition of neutralization
Prevent microbe and their toxics adherence and preventing them from interning tissues (lgA)
Prevent viruses and extracellular bacteria and their toxins from binding to target cells(lgG)
There are 2 Ab forms , name them and define them too
Membrane bound : receptors of Ab
Secreted form : secreted by plasma cell
Name 3 structure on the surface of b cells
BCR : lgM , lgD
2 signaling molecules : lg alpha and LG beta
MHC class 2
What is the function of lg alpha and lg beta
Transmit intracellular activation signal
Name the function of b lymphocytes
A. Responsible for humoral immunity by producing Abs
B. Professional Ag presenting cell –> activate T helper cell
B cell % in blood before being + is ( naive )
30 %
The regin that recognize Ag in b cells is
Variable region
When Ag interact with b cell it differentiate into to kind , name them
Plasma cells
Memory cells
A naive b cell is
Dr : without processing
What are the characteristics of Ags that bind to b cells
Free ( soluble ) in its native form , which means no processing
Protein, polysaccharides, lipid , DNA Ag
In t cells it should be pressed and protein
No MHC ???
Types of epitope:
1 Ag may have
Different epitopes on the same Ag which case _____
Repeating (identical) epitopes stimulate one b cell clone , e.g ____
Simulate different b cell clone
Polysaccharide
The main BCR is
Igd
What is the difference between phagocytosis and receptor mediated endocytosis
Dr : لازم تكون اخذتوا الفرق بينهما في الهستولوجي
When b cell receptor bind to Ag epitope and receptor mediate endocytosis occurs, will it process all the Ag or just the epitope specific to it ?
Only epitope specific to it
When Ag coat with b cell , the lgd and lgM will inter with antigen
What we call this process?
Internalized or receptor mediated endocytosis
Can b cell activate t cell when b cell it self want to be activated ?
Yes , at the end it is an APC
What is class switch and what does it require?
Is the change of amino acid of constent heavy chain which case producing of different Ab with same variable region
It requires 2 signals
1/ CD40 L of + t cell bind to CD40 on b cell
2/ the producing of cytokines from t cell to bind with b cell
Don’t forget lg alpha and beta
Mention 3 characteristics about memory cell
Remain inactive ( quiescent) for long period
Express surface lgG as it’s Ag receptor
Activate rapidly and quickly upon reexposure of the same Ag
Which Ag case no memory cell ?
T cell independent ag
Why independent b cell produce only lgM
Due to absence of cytokines and CD40L activation
In 1ry immune response the b cell is ______ and long lag period from __ to __ or ___
Naive
5
7
10
Low affinity found in
First immune response
Most abundant ( وفير ) Ab in serum is
IgG , 80%
Half life of lgG is
Long
Dr: 20 to 25 days
IgG the the lowest molecules weight , what is the benefit
To expand fast in the body
IgG bind to ____ on phagocytes and NK cells
Fc Gama R
Concentration of secerted lgM in serum is
5 to 10%
The heavy chain of lgM is
μ chain
Subtypes of lgG
G 1 , 2 ,3 ,4
Effector function of lgG
Opsonization (enhancements of phagocytosis) –> bind to Fc Gama R on MQ and neutrophils –> facilitate intracellular killing
IgG coats with infected cell and tumor cells –> binds to Fc Gama R on NK and phagocytes( who can kill Extracellular )–> release of granular toxic mediator حسب تعبير الكتاب وللمعلومية، ADCC ليست قاتلة
+ complement by classic pathway?
Agglutination or clumping of pathogens
Neutralization (most efficient)
دي هي الوظيفة ل depend FAB
Placental passage by umbilical cord case immunity to fetus and neonates
What is neutralization?
Ab binds to viruses, Extracellular bacteria and toxins –> prevents their binding to target cell
How can lgG cross trophy trophoblast cells ?
By Fc gama R on trophoblast membrane
Function of lgM
+complement classic pathway –> opsonization & cells lysis ???
Most efficient
Agglutination of microbe
Most efficient
Neutralization
Yes
If the fetus was infected by microbe from maternal , the b cells of fetus will produce ____ Ab ,
This case is called _____
IgM
Intrauterine infection
it is the first Ab to be produced in 1st immune response
IgM
Nk
Cytotoxicity : without IgG Ab _____
“ : with lgG _____
Direct Cytotoxicity (innate)
ADCC
Eosinophil: killing worms
Cytotoxicity: without Àb _____
With IgG ______
Direct Cytotoxicity
ADCC
Concentration of lgA in serum
10 to 15%
IgA is the main Ab secretion in
Saliva and tears
Mucus of RT and GIT
Breast milk ( 2ed Ab mother transmit to fetus )
Saliva, tears … are synthesized by _____ under effect of ____
Submucosal cells
TGF-beta
Subtypes of lgA
A1 ,A2
Secretary IgA is monomer
No it is dimer
The lowest concentration of Ab in serum is
IgE
IgE bind to Fc elipsoid R on
Mast cells
Basophiles
Eosinophil
Function of IgE
A. ADCC (Ab dependent cellular cytotoxicity)
IgE coating helminths binds to Fc elipsoide R on eosinophils
→ Releases toxic protein to kill parasite (helminths)
IgE is the main host defense against parasites
B. VD & inflammation in skin and mucosa of RT & GIT
Binds to Fc&R on mast cells & basophil
→ Degranulation & release of histamine
C. Type I hypersensitivity (allergy) In case of excess IgE
Ab responsible for opsonization
IgG
Ab responsible for ADCC
IgG,IgE
Source of complement protein
Liver
Site of complement protein is ____&_____ except _____&____
Serum
Tissue fluid
Cerebrospinal fluid
Urine
Complete circulate in inactive form than they’re + in ______
Cascade manner
What are the importance of complement protein
defence against microbe
# removal of immune complex
What are the 3 pathways of complement activation
Classic pathway
Lectin pathway
Alternative pathway
Classical pathway is a shape of _____ immunity
By ______ complex
Humoral
Ag-Ab
What kind of microbe, lectin pathway deal with and why?
Bacteria because MBL bind only with polysaccharides like mannose on Bacteria surface
Complement protein and other proteins involved in classical pathway
From c1 to c9
No other involved proteins
Complement protein and other protein involved in lectin pathway
C2 to C9
MBL
Complement protein and other protein involved in alternative pathway
C3,C5 to C9
Factor B
Factor D
Properdin
What are the steps of activating complement protein in classical pathway
1/ IgM (most efficient) or lgG bind to Ag surface of microbe
2/ interaction with C1q
3/ C1q + C1r and C1s
4/C1qrs + C4(c4a and c4b) than + C2(c2a and c2b)
5/ c4b coat with c2b forming c4b2b or c3 convertase
C4b coat with c2b which also coat with c3b forming c4b2b3b or c5 convertase
Steps of complement activation in lectin pathway
1/ MBL bind to mannose(polysaccharides) on bacteria surface
2 / + of 2 associated proteases with MBL :MASP1 and MASP2
3/ MASP1 and MASP2 + c4( c4a and c4b) than + c2( c2a and c2b)
4/ c4b coat with c2b forming c4b2b or c3 convertase
C4b coat with c2b which also coat with c3b forming c4b2b3b or c5 convertase ( c3b is stabilize)
Name the steps of activating complement in alternative pathway
1/ Spontaneous cleavage of c3( split of c3 without interaction of c3 convertase)
2/ factor b bind c3b and I clevaged by factor d
3/properdin stabilize c3b
4/ formation of c3bBb ( c3 convertase)
And c3bBbc3b ( c5 convertase)
Steps of formation of MAC or membrane attack complex
1/ c5b binds c6, c7, c8, and multiple Mol. Of c9 (polymerized)
2/ c5b6789 or MAC
Entry of water cases by pores called
Osmotic swelling
MAC is more important in lysis of bacteria with _____ wall like _____
Thin cell
Neisseria
Mac is less effective in lysis of bacteria with ______ wall and ____ as it can’t be inserted easily
Thick cell
Capsule
Simulation of inflammation response
Chemotaxis by
C5a
IL-8 تعمل كيموتاكسس
Anaphylaxis by __,___,____, attach to their receptor on mast cells
C3a,c4a,c5a
IgEتعمل نفس ايشي
Opsonization by
C3b and lgG and acute phase protein
Removal of harmful immune complex from body
C3b
Regulation of complement
Proteins on surface of self-cells
A. Increases levels of sialic acid on mammalian cells(host cells): Rapid inactivation of bound C3b on host cells(ic3b)
B. CD59 (Protectin or protection): decreases C9 polymerization during formation of MAC
C. Decay acceleration factor (DAF): Displaces C2b from C4b(حالة نادرة) Or Bb from C3b→ Dissociation of C3 convertas
Who dissociate c3 convertase?
Decay acceleration factor
DAF
Regulation of complement
Serum protein
II. Serum proteins
A. C1 inhibitor: Binds C1 →decrease activation of classical pathway-
B. Factor I: Cleaves C3b→ Inactive C3b (iC3b)
C. Factor H: Cofactor in Factor I action →ic3b
How MAC lysis microbe
3/ MAC pores in target membrane
4/ entry of water
5/ osmotic swelling
6/ lysis of target or cytolysis
