imm 4 Flashcards
Name the 3 mechanisms our body implements to increase antibody diversity
1, Germ line diversity 2. Combinatorial diversity3. Junctional diversity
What is are antibody repertoire a part of?
Part of our adaptive immune system
What does The random generation of coding joints generate?
Lots of diversity
How many progenitor B cells will not produce a functional immunoglobulin?
2/3| ie only 1/3 will be functional
What do we need to make sure the B cells produces?
Only one type of antigen receptor
Why do we need to make sure B cells only produce one type of antigen receptor?
So that we can screen out any self reactive b cells more efficiently
How do we regulate and make sure each B cells only produce one type of antigen receptor?
Rearrangement is regulated by allelic exclusion.
What does the generation of immunoglobulin diversity all generate?
Some self reactive B cells
Where does a non self reaction B cell go?
It migrates to the periphery to form a mature b cell
Where does a multivalent self molecule go?
It undergoes clonal deletion of receptor editing (this is more likely)ORUndergoes receptor editing generating a non auto reactive mature b cell (This option Is rare)
Where does a soluble self molecule go?
It migrates to the periphery to from an anergic B cell
What are the 4 functions of antibodies?
- Neutralization2. Opsonization3. Activation of Complement4. Binding to TRIM21 intracellularly, targeting virus to proteosome
What does the function of different antibodies classes determined by?
Determined by the Fc region
What are the difference between different antibody classes ?
Different Ig classes have different functions and distributionDetermined by C regions (Fc).
When B cells first reach maturity which class of antibodies do they ALL produce?
IgM and IgD
Name the 5 different classes of antibodies?
IgM (μ)
IgD (δ)
IgG (γ)
IgE (ε)
IgA (α)
What makes the different classes of antibodies discrete from one another?
Each class has a different constant regions on their heavy chain
When does class changing of antibodies occur?
During clonal expansion when the B cells are proliferating in response to a specific antigen
Can one B cell clone produce different classes of antibodies?
YES and they will all have the same specificity to the pathogen
name the 2 forms all antibody classes can be produced as
Secretes form| Transmembrane form
How are both the secreted and transmembrane form transcribed?
They are both transcribed in the same primary RNA transcript
What determines whether the antibody will be produced in the secreted form of the transmembrane form?
Alternative splicing of carboxy exons determines use of either the hydrophilic secretory sequence or hydrophobic transmembrane domain (membrane bound).
When is IgM produced?
It is procured first prior to class switch
In what form is IgM secreted?
Secreted form is a pentamer
What does having a pentamer structure increase
It increases avidity BUT decreases affinity
Where is IgM present?
In the blood stream but not in tissues (as it is very big)
Describe the structure of IgM
Has 3 C regions but not hinge
Describe the structure of IgM
Has 3 exons in its Constant region but no hinge
What functions can IgM carry out?
- Neutralisation 2. Opsonisation 3. Can activate the compliment system
When is the IgD produced?
It is co expressed with IgM on B cells
Do we know what IgD do?
We don’t know as it doesn’t perform any of the antibody functions well
What can IgG, IgE, IgA all do?
They can all readily diffuse from blood to tissues
Where is IgG found?
It is the principal antibody found in our blood and extracellular fluids
What functions can IgG perform?
- Neutralisation 2. Opsonisation 3. Sensitisation for killing by natural killer cells 4. Very good at activating the compliment system
What does IgE defend us against?
Multicellular parasites functions in allergy.
What does IgE antibodies bind to?
Mast cells which can induce pathogen expulsion by coughing, sneezing, vomiting
What function can IgE perform?
Sensitisation of mast cells
What is the main role of IgA?
IgA is the principal antibody in secretions| It is found In our epithelial cells
Which antibody is responsible for allergies?
IgE
What functions can IgA do?
Neutralisation| Opsonisation
What does IgG exist in?
Exists as subclasses
Where are IgG found?
In the blood stream and tissues
What does IgG do?
It strongly activates compliment It is an effective neutraliserIts an efficient opsonin and binds to phagocytes
What happens when IgG binds to phagocytes?
Triggers engulfment
How can IgGs cross the placental barrier?
Via binding to neonatal FcR (FcRn)
What can IgG do when it crosses the placental barrier?
and give passive maternal derived protection to newborns.
What do we describe babies as?
they are not fully immunocompetent
What is passive immunity
When you have gained immunity from a different source| You have not produced the antibodies yourself
Give some examples of passive immunity
Mothers to babies| Anti toxins when people have been poisoned
Where is IgA secreted?
Secreted at mucosal surfaces in the gut and respiratory tract Can be secreted into breastmilk
What is the major function of IgA?
Major function as neutralising antibody.
In what form is IgA usually found?
Monomeric or dimeric form
Where can the dimeric form be transported?
Can cross the epithelia to our outside mucosal surfaces
How can the dimeric form be transported across the epithelia?
We have a receptor called polymeric Ig receptor that binds to the dimeric form of IgA IgA is then transported across the epithelia cells to the outside apical surfaces of the mucosaThe receptor is then cleaved and this process releases the IgA
Where does clonal expansion of B cells to fight off infection occur?
Occurs in the secondary lymphoid organs
What steps have B cells taken before they can be activated to produce antibodies?
- B cells at immature stage 2. B cells produce their specific antigen receptor 3. Made sure B cell isn’t reactive 4. Made sure each B cell is only producing one the of antigen receptor (allelic exclusion)5. Cell exit bone marrow and go our to secondary lymphoid organs
What are the 2 different types of antigens?
- T independent antigens| 2. T dependent antiegns
How do T independent antigens activate B cells
Can activate B cells alone, without T cell help.| They engage a lot of different B cell receptors and other receptors at the same type (Like toll receptors)