B cell activation #2 Flashcards
What is allelic exclusion?
one allele of a gene is expressed while the other is silenced (It makes one LC + one HC)
Without it you will have Ab with multiple specificities.
What is heavy chain rearrangement?
@ B cell
Heavy chain –> is productive –> could be maternal mui or paternal mui
if second time doesnt work: apoptosis
What is light chain rearrangement?
@ Pre- B cell
Heavy chain –> isnt productive –> made again
Can be rearranged x4
paternal: kappa + mui
maternal: kappa + mui
What is isotype switching?
Changing from IgM to another isotype (IgE + IgA + IgG)
Does switching isotypes change specificity?
No (even if you rearrange it can bind to what it needs)
What does isotype switching need?
switch regions + T helper cells
Where does isotype switching take place?
germinal centers of secondary lymphoid organs
What enzymes needed for isotype switching?
AID –> activation-induced cytidine deaminase
Where is the switch region found?
in front of mui + in front of gamma
Why is there no switch region in front of delta?
Because when making mui you need delta
What are the 2 T cell signals needed to get cytokines for isotypes?
- SIGNAL 1: MHC signaling with APC B cell
* SIGNAL 2: CD28 – B7
What cytokines released to make IgG?
IFN gamma
What cytokines released to make IgE?
IL4
What cytokines released to make IgA?
Tgf-beta/APRIL/BAFF
How is diversity generated?
Random assortment
What are examples of diversity? (3)
Permutations in V-D-J genes for H.C and V-J genes for L.C. (You have rearrangement of heavy + light chains)
Pairing of different H.C. and L.C.
Recombination process by imprecise joining junctional diversity
What is junctional diversity?
Joining of V,D and J (small no. nucleotides can be added/ deleted)
What is somatic hypermutation?
Mutations that occur in the V, D or J segments
What is the affinity maturation in primary + secondary response?
o Primary response: Antibodies have a lower affinity
o Secondary response: there is somatic hypermutation and affinity maturation which means= > Ab + Ab has higher affinity for antigen
What segments are found in alpha, gamma, delta and beta TCR?
Alpha + gamma: VJC
Delta + beta: VDJC
How is alpha chain made?
- Joining: V+ J joining
- Transcription -> Primary RNA transcript made
- Splicing -> mRNA made
- Joining: VJ put together + C
- translation
- Then protein made: alpha chain
How is beta chain made?
- Joining: V+ J joining
- VDJ formed
- Transcription -> Primary RNA transcript made
- Splicing -> mRNA made
- Joining: VDJ put together + C
- translation
- Then protein made: beta chain
What is immunization? And how do we do it?
Provide individual with long-lasting immunologic protection again infectious agents
They slightly from infected -> put in healthy -> immunity (slightly infected called Inoculated)
What is components of natural acquired passive immunity?
IgG –> placenta
IgM –> after birth
IgA -> breast milk
IgG > as we grow + IgA (
What is artificially acquired passive immunity?
Ig/ immune cells (based on MHC) -> injected artificially
is artificially acquired passive immunity Injected pre/post exposure? What are examples of artificially aquired passive immunity?
Post exposure
Diphteria + Tetanus + Measles + Rabies
What type of hypersensitivity is artificially acquired passive immunity?
3
What is the benefit of artificially acquired passive immunity?
Immediate protection
What is the disadvantage of artificially acquired passive immunity?
o no long term production + chance of serum sickness (immune system react to foreign proteins -> immune complexes)
o Donors must be properly screened: HIV + hepatitis
o Graft versus host disease when immune cells are injected
Describe + give examples of this active immunization: Killed whole organism
Entire organism -> killed to be harmless
example: typhoid
Describe + give examples of this active immunization: Attenuated bacteria
Culture organism to reduce pathogenicity but retain antigen of virulent form
example: Tuberculosis
Describe + give examples of this active immunization: toxoids
Bacteria toxins proteins denatured -> no longer dangerous -> has epitopes for protective antibodies
example: Diphtheria + tetanus
Describe + give examples of this active immunization: Surface molecules
Purified surface molecules isolated from various pathogens
example: Influenzas + hepatitis B + S. pnemonia
Describe + give examples of this active immunization: Inactivated virus
Virus treated so it wont infect host cell -> has epitopes for protective antibodies
example: Salk vaccine for polio
Describe + give examples of this active immunization: Attenuated virus
Live viruses weakened to be nonpathogenic
examples: Polio vaccine + measles + mumps + rubella
Describe + give examples of this active immunization: recombinant virus proteins
Major capsid proteins
HPV + hepatitis B
What are live vaccines?
attenuated organisms –> These organisms are able to cause mild undetectable infection but not disease
What is the immune response in live vaccines? What is the dosage?
Immune response: Immune response similar to natural infection
Dosage: One dose is effective except in those administered orally
What is the disadvantage of live vaccines?
o virulent: The organism may mutate & revert to virulent form + severe reactions possible
o Cause disease: Risk of causing disease in immunocompromised persons
o Pregnancy: May cross placenta & damage foetus: Should be avoided in pregnancy
o Temperature: Must be kept at optimum temp from production to use (cold chain)
What are adjuvants? What are adjuvant examples?
Weak antigen + adjuveant -> make it more immunogenic
Adjuvant example: Aluminum salts (alum) is approved in humans
What are the immune responses to vaccines: Live attenuated vaccine ?
CD8+ & CD4+ & B cells
What are the immune responses to vaccines: inactivated vaccines?
B cells & CD4 T cells
What are the immune responses to vaccines: Polysaccharide vaccines induce only B cells without the aid of CD4 positive T cells ?
T- cell independent immune response (repeated on surface) + primary + secondary response is the same. (NO MEMORY)
What is idiotype?
the distinctive sequence and region that makes any immunoglobulin/TCR unique from others of the same type (which is its variable region.)
What is allotype?
each immunoglobin has unique sequences particular to the individual’s genome that manifest in its constant region
What is isotype?
refers to the slight phenotypic variations within the immunoglobulin gene family that encode for variant immunoglobulin heavy chains and immunoglobulin light chains.
