immune system 3 Flashcards
what is the process of B cell activation and antibody production
- Mature B cells enter a secondary lymphoid tissue
- In absence of its specific antigen, the B cell leaves the lymph node and recirculate
- Naive B cells encounter an antigen in a secondary lymphoid tissue
- When this happens the antigen-specific B cells are further activated by helper T cells
- Some of the activated B cells proliferate in the primary follicle and differentiate in plasma cells which secrete IgM antibody and fight the infection (primary response)
- Other activated B cells migrate in a
secondary lymphoid follicle where they
mature more slowly. Once they complete
their differentiation, they transform into
plasma cells secreting high-affinity
antibodies (IgG, IgA etc) - As the primary immune response subsides, B cells in the secondary lymphoid follicle also develop into memory B cells, which possess high-affinity isotype-switched antigen receptors
- At a second encounter with the same antigen, these memory B cells will rapidly activate and develop a secondary quicker and stronger antibody response
t cell receptors
- Made of 2 polypeptide chains α and β (core TCR) (sometimes gamma and sigma )
- Each chain have a variable and constant region as for antibodies
- Each V chain contains 3 CDRs
- The TCR complex also include proteins of the CD3 complex and the ζ chain, required for signal transduction
what are MHC molecules
Major Histocompatibility Complex molecules T cells use TCR to recognise short peptide fragments bound to MHC (not free antigens like BCR)
differences between class I and class II MHC molecules
Two types, MHC class I and II
* Related, but different structures
* Different expression patterns
* Present peptides from different sources
* Many genetic variants (polymorphic)
* Role in transplant rejection
class I MHC molecule
expressed on all nucleated cells
made of the transmembrane heavy chain (alpha) which has 3 extracellular domains and one transmembrane domian bound to a small protein beta macroglobulin
8-10 amino acids short peptides bind between alpha 1 and alpha 2
binds TCR and CD8+ T cells
MHC class II
mainly expressed on antigen presenting cells (macrophages, dendric cells)
made of 2 chains (alpha and beta) each with a transmembrane region and 2 extracellular domains
more than 13 amino acid peptides bind between alpha 1 and alpha 2
binds TCR of CD4 T helper cells
endogenous antigen presenting to CD8+ T cells
proteins from pathogens are made in the cytoplasm (intracellular endogenous antigens) are presented by MHC class I molecules)
proteins must be processed to peptide before binding MHC
all nucleated cells have MHC class I molecules, so any cells infected by the virus can be killed by cytotoxic CD8 T cells
exogenous antigen presentation to CD4 T helper cells
exogenous (extracellular) antigens are internalised and presented by MHC class II
just like endogenous protients must be processed to peptides before binding MHC
only a limited number of cells express MHC class II: these include professional antigen presenting cells that activate CD4 T cells
T cell development and B cell development similarities
originate from bone marrow
rearrange receptor genes
express pre-T receptor
elimination of self reactive T cells
negative selection (doesn’t eliminate non functioning cells)
T cell development B cell development differences
undergo development in thymus
alterative lineages
(CD4+ or CD8+) must be able to interact with self MHC
positive selection (eliminate non-functioning cells)
what can immature t cells recognize when they leave the bone marrow and migrate to the thymus
can recognise self MHC and respond to foreign peptides (defense)
can recognize and respond to self-MHC plus self-peptide (danger)——- negative selection
no recognition of self MHC (useless) —– positive selection
positive selection
- Positive selection of cells which recognise self MHC (+ self peptide)
- It selects T cells with a TCR able to bind molecules
- Occurs when the TCR of double-positive (CD4+CD8+) T cells recognise MHC molecules expressed on cortical epithelial
cells
– Only 1 - 2% capable of recognizing own MHC will be selected
– Vast majority of T cells with non-binding TCR die via apoptosis
– Double-positively selected cells move to medulla and mature to single positive cells (expressing CD4 or CD8
negative selection
- Negative selection of cells that recognise self MHC (+self peptide)
- It removes cells with a TCR binding tightly to self peptides
- Occurs when the TCR of CD4 or CD8 T cells recognize MHC molecules expressed on dendritic cells/macrophages with high affinity. These cells undergo apoptosis (high risk if survive)
- Dendritic cells present variety of self peptides with MHC class I and II to T cells
- T cells with moderate binding to MHC-self peptides complexes are allowed to survive
effector T cells
activated T cells acquire effector functions in the secondary lymphoid tissue after encountering an antigen presented by dendric cells and after the interaction of co- stimulatory molecules
function of CD8+ T cells and CD4+ T cells (helper Th cells)
mainly function by secreting cytokines –> effects on other cell types (they help other cells)
