Week 7 - Active and Passive Immunization + B cells Flashcards
Prequisites to successful Immunization
Appropriate antigen - Epitope, MHC Bound, Correct Size
Optimal Dose
Efficient adjuvant
Best route of Administration
What is the importance of evidity in the Immunization?
Tregs have high evidity for Low amount Ag
Leads to Tolerance
Neutralization
Giving the antibody (Passive) for stoping the toxin (Antigen) damage in the short term - Days.
Elimination Immunization
Giving Ab for the specific antigen - Weeks or Months Ahead.
Too high dose given in Immunization will cause…
Anergy and Deletion of the Antigen - NO IMMUNIZATION
Adjuvant
Increasing the Immunization, E.g - Low amount of Oils or Aluminum salts
Different Administrations possible - Characteristics
Intraperitoneal - to Spleen, Only in Rodents
Subcutaneous - Prevent Anaphylactic Shock, 7 days to lymph nodes
Intramuscular - Large Amount
Oral - M cells in gut take up, Specific viruses (Tolerance and Deletion possible)
Immunization against HBV- Cell responsible
Cytotoxic T cells dependent
Incubation period of HBV
60-150 Days
What Ag of HBV is not a target for Immunization
HBeAg
Ag for Immunization in HBV
HBs - Surface
HBc - Core
HBV Vaccinated Person, Immune Molecule Present in blood
Anti-HBs IgG
Examples for Use of Active Immunization
Smallpox, Rotavirus, Polio, HiB, HPV, Yellow Fever
What is the Latency of Vaccination (Active Immunization)
Days to Weeks
2 Perquisites for the Memory of The Active vaccination
1 - Adequate Immune System
2 - Enough time for the response
What Antibodies are present in the first and second encounter?
First - IgM
Second - IgG
Examples for use of Passive Immunization
Tetanus, Rabies, Snake Bite, HBV
No Memory
Options for Content of Active Vaccine
Live/Attenuated Live, Killed, Epitope, Recombinant Epitope, Toxoid
Why is it important to have T cell Dependent B cell activation in Immunization?
T-Dependent - More Robust production of Antibodies and more Memory cells
Why use Aluminium salts and not oil for example as adjuvant?
Aluminum salt - Microliposopmes like activity- Storage effect for Antigen
Oils - Immune effect is enhanced by danger signal
Where are B cells formed? Matured?
Bone Marrow
Bone Marrow
BCR - which Ig
IgM and IgD
Processes of the Development of B cells after Antigen meeting?
Ending in a Plasma cell
Activation
Affinity Maturation
Differentiation
Isotopes Switch
B cell mRNA possible composition - why?
V33D3J2 - Miu
V33D3J2 - Delta
(IgM or IgD through alternative splicing of PremRNA)
Negative Selection of B cells - Outcomes
1- Apoptosis of Auto-reactivity B cells
2 - Central tolerance:
Receptor Modification,New Light chain expression
Ultimately - No auto-reactivity
Mechanisms Responsible for Full diversity of Antigen Receptors
(6)
1 - Germline diversity 2 - Combinatory Diversity 3 - Junctional Diversity 4 - Receptor Editing 5 - Somatic Hypermutation 6 - Receptor Revision
Classical B cells in cortex Follicles - which response kind?
TD - Require T cells
For Protein antigens
Log Lived Plasma cells, Isotype switched
Marginal area B cells response - what kind?
TI - No T cell
Lipids and Polysaccharides antigens
Short lived plasma cells - IgM
Where do DC and B cells interact?
Secondary Lymphoid organs
Paracortical Area With T cells
What allows the intracellular signaling from the BCR?
ITAM motif
What are the co-stimulatory molecules on TH2 and B cells?
TD, B cell Activation - 3 By order
BCR+Antigen - TCR
CD40 - CD40L
IL21R - IL21
Germinal center cells - Surrounding, Clonality
Surrounded by Follicular DC and Follicular TH cells
Monoclonal from TD interaction proliferation
Affinity (Immunogenic)
Binding Force of Receptor to ligand - Never covalent but all other bonds.
Affinity Maturation
By clonal expansion mutation there is better and better chance to relieve better and more surfaced interaction between the expressed B cell receptors and the Antigen.
(Point Mutation overtime - Somatic Hypermutation)
What happens to B cells clones with weak Antigen Interaction?
Less interaction with TH cells - Less survival signals released for its favor
Follicular DC to Follicular TH cell signal upon antigen sign
IL6 (Many others are possible but this was in the slide)
Follicular TH cells to B cells signal upon antigen sign
IL21 (Many others are possible but this was in the slide)
Follicular DC function
In Germinal center Light zone
Traps for Antigens - FC receptor and Complement receptors
Promoting Opsonization
Promoting B cell interaction with it
Isotype (Class) Switch - Signals leading to which Antibody constant regions by B cell
IFNgamma - IgG
IL5 - IgA
IL4/IL13 - IgE
Process of Isotype switch
Deletion of Regions between S (Switch Regions)
Different signals cause formation of different loops of Excision
Key Enzyme of Somatic Hypermutation and Isotype switch
AID - Activation-Induced Cytidine Deaminase
Plasma cells production of Ab in the Peripheral and Germinal centers
Peripheral - IgM for Initial response
Germinal centers - IgG (week 3)
Survival signal for Plasma cells
Change with aging
IL6 and BAFF from Stromal cells of Bone marrow
Secretion of these factors is lowered by Bone marrow with years
FCgammaR (CD32) Function and Motif
Feedback inhibition for B cells (Surface) on interaction by IgG pathogen bound.
ITIM (Inhibitory )
Localization of Memory cells
Mantle zone of the Secondary Lymphoid organs
Principle Effector Functions of Ab Isotypes
IgM - Complement activation
IgG - FC receptor opsonization, Placental Transfer.
IgE - Helminths Immunity and Mast Degranulation (Hypersensitivity 1)
IgA - Mucosal Immunity (could transport along Epithelia)
Poly FC receptor
Binds the Dimer IgA FC portion
Expressed only on basal surface of Epithelial cells allows for endocytosis and translocation to the mucosal surface.
Why do we need another proteolytic remnant portion of PolyFC receptor on the Lumen IgA dimer?
Protection from Digestive Enzymes
FCR3A function
NK cell Antibody dependent cellular cytotoxicity
ADCC
TI-1 - B2 cells response
Carbohydrates reaction - Non specific Ab response Polyclonal
TI2 - Marginal zone (Spleen) B
Sugar antigen recognition
MZB - Low Affi. IgM , Short life span for them
TI2 - B1 cells reaction
Cells marker
Autoactivation - self reacting antibodies as well as when Ag present - High spontaneous Production of Ig
CD5+
T-dependent response of B cell in Lymphoid organs:
by which kind of B cells? What type of Antigen? and What is the consequence?
TD Response:
Follicular B cells with Protein Antigen and TH cell.
Result: Isotype switch, High affinity Antibodies of Long lived Plasma cells.
T-independent response of B cell in Lymphoid organs:
by which kind of B cells? What type of Antigen? and What is the consequence?
TI Response (Lymphoid): Marginal Zone B cells with Sugars/Lipids the result is IgM secreting short lived plasma cells.
T-independent response of B cell in Mucosal linings:
by which kind of B cells? What type of Antigen? and What is the consequence?
TI Response (Mucosal): B1 (CD5+) B cells with Sugars/Lipids the result is IgM secreting short lived plasma cells.
What is the main advantage of the (relatively primitive) B1 cell?
High degree of Spontaneous production of Ig
What are the two functions of Adjuvants in order to increase Immunogenicity?
Danger signals - PRR Response
Depot Signals - Storage of Ag, Longer effect
Causes of inefficiency of introduction of antigen without an Adjuvant? (3)
- Antigen brakes down by enzymatic lysis over time
- without costimulation there is anergy
- It is highly unlikely that the antigen meet with recirculating antigen specific T or B cells.
Complete the T cell Differentiation Result for the cytokine:
IL 12 - ___
IL4 - TH2
IL 23,( also TGF-beta, IL 6)- TH17
IL 12 - TH1
IL4 - TH2
IL 23,( also TGF-beta, IL 6)- TH17
Complete the T cell Differentiation Result for the cytokine:
IL 12 - TH1
IL4 - ___
IL 23,( also TGF-beta, IL 6)- TH17
IL 12 - TH1
IL4 - TH2
IL 23,( also TGF-beta, IL 6)- TH17
Complete the T cell Differentiation Result for the cytokine:
IL 12 - TH1
IL4 - TH2
IL 23,( also TGF-beta, IL 6)- ___
IL 12 - TH1
IL4 - TH2
IL 23,( also TGF-beta, IL 6)- TH17
