Exam 2: Humoral Response 1 Flashcards
Antibodies are soluble
BCR
BCR light chain is made up of:
Constant Domain (CL) Variable Domain (VL) Light Kappa Chain (K) Light lambda chain (lambda)
BCR Heavy Chain is made up of:
Variable Domain (VH) Constant Domain (CH) Five different types of heavy chains: alpha, gamma, delta, epsilon, mu
Complementary Determining Regions (CDR)
There are three regions of variable 6-10 amino acids
Framework Regions
Constant regions among hypervariable regions
How many constant domains do alpha, gamma and delta have?
3 constant domains: CH1, CH2, CH3
How many constant domains do mu and epsilon have?
4 constant domains: CH1, CH2, CH3 and CH4
What is the antigen binding site?
Vh and V1
What stabilizes the antigen-binding site?
Ch1 and CL
What is the Hinge Region on the BCR?
creates universal joint around which the immunoglobulin can swing freely (IgM does not have)
What are the BCR signal transducing components?
CD79, Ig alpha and beta
BCR Signal transducing cascade
- Signal initiated by antibody binding
- Receptor clustering
- Phosphorylation ITAms
- activates signalling cascade
Complete Activation of BCR
Stimulation by TH cells and cytokines
B Lymphocytes have 2 roles:
- Respond to antigen by making antibodies
2. Antigen Presenting Cells
The Primary response of co-stimulation of B lymphocytes steps:
- antigen binding -BCR
- BCR internalized and transported where MHC-1 and antigen fragments combined
- MHC1-BCR complex sent to B cell surface and presented to TH cell
- TH cell activates
The Secondary Response of co-stimulation of B lymphocytes steps:
- T cell CD154 binds CD40 on B cell, TCR binds MHC, CD86 and CD28 causes release Il-4
- Stimulation for cytokine release: IL-1, 4, 5, 6
IL-4 functions to
- increase growth and differentiation of B cells
- increase expression of MHC 2
- induces IG class switching
Il-5 functions to
- B cell differentiation into plasma cells
- Stimulates IgM and IgG production
- Il-4 and 5 induce IgE production
- selectively stimulates IgA production
IL-6 functions to
- needed for final differentiation of B cell into plasma cells
- with IL-5 promotes IgA production
- with IL-1 promotes IgM production
Binding of CD40 on B Cells and CD154 stimulates:
binding of CD 86-28, B cell activation, memory cell development, IG class switching
Binding of CD40 on DC Cells and CD154 stimulates:
antigen presentation, cytokine production, cell survival
Binding of CD40 on Macrophage Cells and CD154 stimulates:
Cytokine production, activation
What does the binding of CD21/ CD19 stimulate?
Lowers the the thresh hold for B cell activation 100x
When PAMPs bind to TLRs on B cells causing B cell activation and proliferation, results in:
No participation of Th cells, Only IgM response, No memory cells, No IG class switching
Clonotype
a clone of B cells expressing a capable of responding to a single epitope
Where do B cells originate?
bone marrow
Where are plasma cells found?
Spleen, medulla of lymph nodes and bone marrow
What signifies a typical plasma cell structurely?
Increased rough endoplasmic reticulum activity, typical of a cell dedicated to Ig production of Ig
How many molecules of Ig can be produced per second?
10,000 molecules of Ig per second
Where are long term memory B cells located?
cortex of the lymph node to proliferate to form germinal centers
What cytokine expression protects against apoptosis?
bc1-2
Where are short term memory B cells located?
spleen and lymph node
What are long lived resting memory cellsdependent on?
not dependent on antigen contact
Short lived memory cells are depend on?
antigen contact
What occurs in the lymph node germinal center?
- antigen derived cell proliferation
- somatic hypermutation
- pos and neg B cell selection
IgG is found where?
spleen, lymph nodes and bone marrow
Binding of IgG to bacteria causes:
- agglutinization
- opsonization
- activates the classical complement pathway
IgM is found where?
secondary lymphoid organs
Where is its complement activation site?
CH4
What are the functions of IgM?
- opsonization
- virus neutralization
- agglutinizaiton
- not v. important in inflammation
Where is IgA found?
body surfaces: intestine, respiratory tract, urinary system, skin and mammary gland
What is the major Ig found in external secretions of non-ruminants?
IgA
Where is IgE found?
located under body surfaces
IgE binds which receptor on mast cells and basophils?
FceRI
IgE mainly functions in:
- releases inflammatory molecules from mast cells
- enhances local defense
- immunity against parasites
What has the shortest half life of all immunoglobulins?
IgE
Where is IgD mainly found?
attached to B cells
Which immunoglobulin mediates the link between innate and adaptive immune responses?
IgD
Allotypes
variations in heavy chain genes reflected in structural differences
Idiotypes
variation in aa sequence of light and heavy chains, of each individual animal
What is the sequence of heavy chain series?
IgM-IgD-IgG-IgE-IgA
What are the B lymphocyte Recombination events?
- VDJ recombination
2. antigens activiating B cell class witching of heavy chain
Primary immune response is dominated by which immunoglobulin?
IgM
Secondary Immune response is deominated by which IG?
IgG
Are these CD receptors present on T cells: CD3, 4, 8? T/F
T