Immunology 03. Adaptive Immunity Flashcards
Which part is the Light chain
Which part is the Light chain?
The one in green.
Tbh **abit ambiguous cuz diff pic is slightly diff but whatever. **
Are isotype switching reversible?
Are isotype switching reversible?
Nope. irreversible
IMPT!!
Note that the structure (light & heavy chains) is different from functional regions (Fab & Fc)
Fab = Fragment for Antigen Binding = Variable (V) region
Fc = Fragment Crystalizable = Constant (C) region
A typical antibody has ___ light chains and ___ heavy chains.
They are joined by __ bonds
A typical antibody has ___ light chains and ___ heavy chains.
They are joined by __ bonds
2 light chains and 2 heavy chains
disulfide bonds
Activated B Cells become either ___ or ___
Activated B Cells become either ___ or ___
plasma cells or memory B cell
Adaptive cellular defence and adaptive humoral defence involves?
Adaptive cellular defence and adaptive humoral defence involves?
CD4/CD8 T cells
Humoral: antibody produced by B cells
Affinity maturation descibes?
Affinity maturation descibes?
The qualitative improvement in the strength of binding between AB and their ligands over time
Affinity maturation is correlated to?
Affinity maturation is correlated to?
Isotype switching
Affinity maturation refers to?
Affinity maturation refers to?
Increase in average Ab binding affinity with prolonged exposure to Ag
Affinity of an Ab is defined as?
Affinity of an Ab is defined as?
Strength of monovalent binding of Fab to antigen
ALL the functions of specific antibodies? (IMPT!!)
ALL the functions of specific antibodies? (IMPT!!)
Formation of an immune complex (IgM and IgG)
Complement activation (IgM)
Opsonization (IgG)
Neutralization (IgG, IgA (only at mucosal sites))
ADCC (IgG)
Mast cell degranulation (IgE)
Are B cells a form of APC?
Are B cells a form of APC?
Yes! They are a form of APC as they can present antigens on their cell surface MHC-II complex to Effector T cells
B cells that make antibodies are called?
B cells that make antibodies are called?
Plasma cells
The other lineage is called Memory B cells
Class I MHC are present in all nucleated cells, but class II MHC are only present in (IMPT!!!)
[…]
Class I MHC are present in all nucleated cells, but class II MHC are only present in (IMPT!!!)
APCs (DCs, Macrophages, B cells)
Compare Th1 and Th2 in terms of cells they activate + what they secrete
Compare Th1 and Th2 in terms of cells they activate + what they secrete
Th1: Activate macrophages to kill pathogens by secreting** IFN-y**
Th2: activate B cells and allergy (IgE) by secreting IL-4 (major B cell growth factor)
TLDR
Th1 Macrophages
Th2 B cells
Describe ADCC?
Describe ADCC?
AB binds to antigen on target cells
NK CD16 Fc receptors recognize the AB
Crosslinking of CD16 triggers degranulation into lytic synapse
Tumour cells die by apoptosis
(Abit similar to opsonization just that it is mediated by NK Cells instead of macrophages)
Describe briefly the clonal selection theory?
Describe briefly the clonal selection theory?
Basically, mature APC such as dendritic cell will “sample” a large number of T cells in the lymphoid nodes
It will identify the one with the specific antigen receptor that recognize the said pathogen derived peptide on their MHC molecules
The DCs/APCs will then stimulate the clonal expansion and differentiation of the T cells-> numerous daughter cells
Describe briefly the concept of immunological memory:
Describe briefly the concept of immunological memory:
Bascically, second or third exposure to the same antigen will allow us to mount a much stronger immune response. (applied in vaccination)
This is mediated by memory B and T cells that can respond in much greater numbers than before
Antigen-specific cells can be recruited faster and respond with more vigour!!
Describe how a Naive CD4+ T cell could be activated? (IMPT!!!)
Describe how a Naive CD4+ T cell could be activated? (IMPT!!!)
APC phagocytoses a pathogen and undergoes antigen processing of the pathogen proteins
APC then presents the pathogen antigen peptide on its MHC-II complex
antigen peptide-MHC II complex then binds to the TCR of the Naive CD4+ cells
Activation of CD4+ cells to become a T helper Cell
Note: CD4+ so its MHC II!! Not I.
Describe how a person stung by a bee once during childhood can die from a second sting?
Describe how a person stung by a bee once during childhood can die from a second sting?
1st Bee sting -> pathogen-> presented to CD4 cells-> effector t cell-> memory T cell-> 2nd Bee sting (activated again by same pathogen) -> stronger immune response than before (immune memory) -> cytokine storm -> death from anaphylaxis
Describe how a T helper cell can activate a naive B cell?
Describe how a T helper cell can activate a naive B cell?
Naive B cell captures antigen from pathogen and presents it on its MHC II complex
peptide antigen-MHC II complex then binds to TCR of the T helper cell
Activation of naive B cell-> proliferation and differentiation
B cell-> plasma cell (BLIMP1) or memory B cell (default)
Describe how Dendritic cells travel?
Describe how Dendritic cells travel?
Immature DC: Periphery such as our skin (langerhans cell)
-> captures antigens from pathogens -> becomes mature DC while migrating to local draining lymph nodes where they present the antigenic peptides to the circulating lymphocytes
Describe the mechanism of Opsonization by AB and which Ig subclass does it
Describe the mechanism of Opsonization by AB and which Ig subclass does it
Opsonization of microbe by IgG (surrounds it)
Binding to phagocyte via Fc receptors
Fc receptors signals activate phagocytes
Phagocytosis of microbe
Killing of ingested microbes
Difference between Adaptive and Innate immunity response? (IMPT!!!!)
Difference between Adaptive and Innate immunity response? (IMPT!!!!)
1st:
Innate immunity: low specificity but very fast
Adaptive: highly specific but takes time to develop
2nd:
Innate immunity: response does not improve on second exposure to the same antigen
Adaptive immunity: response improves to become much stronger to the same antigen on subsequent exposure
TLDR think about specificity, onset and immune memory
Diffference between affinity and avidity?
Diffference between affinity and avidity?
Affinity: Strength of a monovalent binding event between an AB and its target antigen
Avidity: binding strength when an AB uses more than one of its binding sites simultaneously to bind to a target antigen
Each B cells only makes antibody of ____ specificity
Each B cells only makes antibody of ____ specificity
One specificity
Fab region of AB does?
Fab region of AB does?
Basically binds to antigens
Fab = Fragment for Antigen Binding
Fc = Fragment Crystalizable
Need to know how to spell in exams!!
Fc region of the Ab, what does it bind to? What does it do?
Fc region of the Ab, what does it bind to? What does it do?
Constant region that binds to Complements, Mast cells, NK cells etc, sends signals, effector
Fc regions of IgM antibodies can bind to?
Fc regions of IgM antibodies can bind to?
Classical pathway-c1q (essentially a C1q protein) to activate a complement cascade that results in the formation of a MAC
Forms holes through outer membrane -> kills it by osmotic lysis
TLDR, bind to c1q for complement activation
For heavy chain gene, what are the segments involved in somatic recombination?
For heavy chain gene, what are the segments involved in somatic recombination?
V D J C
V and D are far and J and C are close together
Function of IgA?
Function of IgA?
Specialised for secretions in mucosal sites.
Prevents colonization of mucosal sites by pathogens
Function of IgE?
Function of IgE?
IgE binds to antigen on worm/fluke-> mast cells then bind to Fc part of IgE molecule-> induction of mast cells to granulate.
essentially for mast cell degranulation to protect against parasites
heavy chain gene locus is found on which chromosome?
heavy chain gene locus is found on which chromosome?
heavy 14!!!
How are mast cells activated?
How are mast cells activated?
IgE floats around body
Binds to parasites or allergens
Mast cells use a specialise Fc receptor specific for IgE (FCER1) to bind
Mast cell activation and degranulation
***Mechanism for type 1 HS is abit diff.
FCER1 = Fragment Crystalizable Epsilon Receptor 1
How does CD8+ CTLs kill infected cells? (IMPT!!!!)
How does CD8+ CTLs kill infected cells? (IMPT!!!!)
Degranulation, release vesicles containing Perforin + granyzme B + Granulysin into infected cells. Activates apoptosis of target cells via CASPASES
or
FASL. Also activates apoptosis of target cells (rmb CD8 is called CTLs, so FASL is on Cd8)
Immune complexes are associated with which type of HS?
Immune complexes are associated with which type of HS?
III
Kappa and Lambda light chain locus are found on which chromosomes?
Kappa and Lambda light chain locus are found on which chromosomes?
Kappa 2 Lambda 22
Light chain gene does not have which segment?
Light chain gene does not have which segment?
Light chain no D!! Purely VJC.
Heavy have diversity region so its VDJC
V = Variable
D = Diversity
J = Joining
C = Constant
light chain gene somatic recombination only involves?
light chain gene somatic recombination only involves?
V J C segment
Main function of IgG is?
Main function of IgG is?
1) Bind to pathogens or toxins and neutralize them: prevents binding between pathogens and receptors to host cells and tissues
2) Can also induce ADCC by binding to Fc receptors for IgG that are expressed on NK cells.
Opsonisation, Neutralization and ADCC.
Main function of IgM antibody?
Main function of IgM antibody?
Recruitment of Complements (and Complement Activation), which are membrane attack complex found in our blood.
Extremely important in anti-bacterial immunity
Main importance of having IgM immunity?
Main importance of having IgM immunity?
Important against bacterial invasion
Maturation of Dendritic cells involve? (IMPT!!!)
Maturation of Dendritic cells involve? (IMPT!!!)
Basically transformation of DC from one that is very good at phagocytosizing pathogens (antigen-capture) to one that is very good at presenting antigens (antigen presentation)
Physical changes include
1) Increase in costimulatory molecule such as B7 and CD40
2) Increase synthesis and presentation of MHC molecules on cell surface
3) Decrease endocytic capacity
MHC I presents […] microbes to CD[…] T cells
MHC II presents […] microbes to CD[…] T cells
MHC I presents cytosolic/endogenous **microbes to CD8+ (CTL) T **cells
MHC II presents extracellular/exogenous microbes to CD**4+ (helper) **T cells
Just remember I x 8 = II x 4 Ezpz :))
Probably the most basic yet impt knowledge in immuno
Neutralization of pathogens basically involves:
Neutralization of pathogens basically involves:
Abs binding to surface of viruses/pathogens etc and blocking them and their binding activity for host cell receptors
A crude but effective way to remember this is that ab neutralization = cockblock
lol. Sorry kids
Positive selection and negative selection for B cells involve?
Positive selection and negative selection for B cells involve?
Positive: select for B cells expressing pre-BCR
(pre-BCR becomes BCR through light chain gene formation and expression)
Negative: select against B cells whose BCR binds to self antigens (autoreactivity)
EXTRA DETAILS
B cell selection
Early B cell development involves production of a fully folded antibody heavy chain. This is expressed in combination with a surrogate “light” chain
Positive selection of B cells who express pre-BCR
Subsequent light chain gene formation and expression follows. Successful expression results in surface BCR (IgM always first)
Negative selection of B cells whose surface BCR binds to self antigen on stromal cells
The final stages of B cell development take place in secondary lymphoid organs (spleen, lymph nodes)
T cell selection
Positive selection of T cells whose TCRs bind to MHC mildly
- Binding provides developing T cells with survival signal
- Failure to bind results in apoptosis of developing T cells (death by neglect)
Negative selection of T cells whose TCRs bind to MHC too strongly
- Negatively selected cells die within thymus (elimination of self-reactive T cells)
B cell selection and T cell selection are some what analogous, especially for the negative selection part.
Principle driver of asthma amongst the antibodies? (vvvv IMPT!!!)
Principle driver of asthma amongst the antibodies? (vvvv IMPT!!!)
IgE
Serum immunotherapy brief concept?
Serum immunotherapy brief concept?
Using immune serum from immunized animal or recovered patients to treat newly infected
Somatic hypermutation of B cells happen where and involves?
Somatic hypermutation of B cells happen where and involves?
Dark zone of germinal centers and involves introducing many point mu**tation in the V (variable) regions of their antibody genes
The Fc part of the antibody is made completely from ____ chain
The Fc part of the antibody is made completely from ____ chain
Heavy chain!
We can only make a function B cell/Antibody response to a pathogen if ________ ?
We can only make a function B cell/Antibody response to a pathogen if ________ ?
We make a concurrent T helper response against the same pathogen AS we need the T helper to activate the B cell and for Isotype switching
What are B cell zones called in the lymph nodes?
What are B cell zones called in the lymph nodes?
Follicles
What are the 2 cells that B cells interact with in the light zone? What does these interactions do?
What are the 2 cells that B cells interact with in the light zone? What does these interactions do?
FDC: Provide iccosomes for B cells with the correct BcR to bind and rip the iccosomes off, and then process and display the iccosomes as antigens on MHC-II
CD4+ helper T: Interaction of B cell CD40 with CD40L on CD4+ Th cells provides B cells with proliferation and differentiation signals into memory B (default) or plasma cells (BLIMP1 signal)
What are the 6 Ab functions mediated by?
What are the 6 Ab functions mediated by?
Mast cell (IgE)
ADCC (IgG)
Neutralization (IgG and IgA (only at mucosal sites))
Opsonization (IgG)
Complement activation (IgM)
Formation of immune complex (Agglutination) (IgG and IgM)
In another words,
IgG does Opsonization, Neutralization, ADCC & Formation of immune complex
IgM does Complement Activation, Formation of immune complex
IgE does Mast Cell degranulation
IgA does Neutralization (mucosal sites only)
IgD does B cell activation
What are the secondary lymphoid organs?
What are the secondary lymphoid organs?
Mainly the spleen and lymph nodes
What are the two antigen receptors in adaptive immunity called?
What are the two antigen receptors in adaptive immunity called?
TcR and BcRs
What are the two subtypes of light chain on an antibody?
What are the two subtypes of light chain on an antibody?
Kappa and Lambda light chain, each with its variability
Kappa 2 Lambda 22
What costimulatory molecules does B cell have? (IMPT!!!)
What costimulatory molecules does B cell have? (IMPT!!!)
CD40 which binds to CD40L on CD4+ T Helper Cell
Signalling provides survivial growth and differentiation signals to both CD4 and B cell
Recall that DCs also have CD40, which makes sense that CD4+ will have the CD40 Ligand!
What does a DC do in the lymph node to identify the right lymphocyte?
What does a DC do in the lymph node to identify the right lymphocyte?
Forms transient contact (touch and go) with the lymphocytes to identify the one with right antigen receptor
Macam like…online dating??? The correct term to use is “sampling”….
What function does Antibody secreted by Plasma cells have?
What function does Antibody secreted by Plasma cells have?
- Complex formation
- ADCC
- Mast cell degranulation
- Complement activation
- Opsonization
- Neutralization
CAMCON
All 6. Just that diff Ab isotypes does diff ones.
What happens to the B cells in the dark zone and the light zone of the germinal center respectively?
What happens to the B cells in the dark zone and the light zone of the germinal center respectively?
Dark zone: Somatic hypermutation
Light zone: competing with each other for the iccosome binding by FDC + class switching with help from CD4 T helper cells + proliferation and differentiation signal from CD4 T helper cells
What is agglutination (in context of immuno)?
What is agglutination (in context of immuno)?
When antibodies form immune complexes with bacteria, cells or particles!! These complexes are then removed via phagocytosis
What is an epitope?
What is an epitope?
Sites within the antigen that is recognized by the antibody (Fab is also known as paratope)
Epitope is also known antigenic determinant
TLDR we alw think that ab bind to ag but actually it binds to epitope of the ag, not the whole ag!
What is another name for human MHC?
[…]
What is another name for human MHC?
HLA
MHC = Major Histocompatibility Complex
HLA = Human Leukocyte Antigens
Spell out in exams
What is IL-4?
What is IL-4?
- major B cell growth factor
- Induces naive T cell differentiation into Th2
- Induces IgE class switching also
It has over 50+ functions but these are the impt ones
What is the chemokine released by Th cells that decides whether the B cell become a plasma cell or memory B cells?
What is the chemokine released by Th cells that decides whether the B cell become a plasma cell or memory B cells?
got BLIMP1 = plasma cell
no BLIMP1 = default = memory B
What is the enzyme driving the point mutation in somatic hypermutation?
What is the enzyme driving the point mutation in somatic hypermutation?
Activation Induced Deaminase (AID)!!
What is the key molecule involved in CD8 killing of cells?
What is the key molecule involved in CD8 killing of cells?
Caspase Activated Deoxyribosenuclease (CAD) which basically cleaves DNA causing DNA fragmentation and apoptosis
What is the one of the most efficient way to shut down an infection?
What is the one of the most efficient way to shut down an infection?
Neutralization!
IgG and IgA does this.
its da most capable bby in town :)
What is the principal function of the Follicular Dendritic Cell?
What is the principal function of the Follicular Dendritic Cell?
Present protein antigens **to B cells **in the form of an iccosome
iccosomes select for B cells with the correct BcR
These B cells process and present antigen proteins on their MHC II to CD4+ Th cells
CD4+ Th cells provide proliferation and differentiation signals
B cell multiply and differentiate into memory B cell (default) or plasma cell (BLIMP1)
What signal is needed to induce IgE class switching?
What signal is needed to induce IgE class switching?
IL-4!!! from Th2 cells!!!!
“4 from 2”
Where can mature dendritic cells be found in the lymph node?
Where can mature dendritic cells be found in the lymph node?
Deep cortex
Where does affinity maturation in B cells occur?
Where does affinity maturation in B cells occur?
Germinal centers in the lymph nodes
Where does B cell complete development?
Where does B cell complete development?
In the secondary lymphoid organs
Where does somatic recombination happen for T cells and B cells?
Where does somatic recombination happen for T cells and B cells?
Happens in the Thymus for the T cells and the Bone marrow for the B cells
If u didnt realize by now…but seriously???
T cell = Thymus cell
B cell = Bone marrow cell
Which 2 major cell types do activated CD4+ T cells (aka Helper T cell) go on to activate?
Which 2 major cell types do activated CD4+ T cells (aka Helper T cell) go on to activate?
Macrophages (phagocytose the capture pathogen)
B cells (Make antibodies)
Th1 Macrophages
Th2 B cells
Which chain of Ab contributes to the diversity of Fab?
Which chain of Ab contributes to the diversity of Fab?
Both heavy and light chain
Which part of the antibody determines the class of the anitbody?
Which part of the antibody determines the class of the anitbody?
Constant (C)/Fc region which is influenced solely by the heavy chain they contain
Which region of the antibody determines the specificity/ antigen selectivity of the antibody?
Which region of the antibody determines the specificity/ antigen selectivity of the antibody?
The variable (V) region
1.
Why does less antigen result in better antibodies?
Why does less antigen result in better antibodies?
Less antigens-> less iccosomes on FDC -> Higher competition for B cells for a chance to bind to and rip an iccosome from FDC
Only B cells with stronger and more specific BCRs can outbind, outcompete and acquire antigens needed to present to Helper T cell
Costimulation and T cell signal for them to survive
The weaker ones just die of neglect
This is essentially how affinity maturation works
