Lecture 45 - Tolerance Flashcards
haematopoiesis
to make blood
positive lymphocyte selection
Need to recognise pathogenic antigens (non-self)
= bacteria, viruses…
negative lymphocyte selection
Need to ignore autologous (self) antigens to prevent auto-immune disease
tolerance lymphocyte selection
need to tolerate harmless non-self antigens to prevent damage/disease
Celiac disease = intolerance
damaged villi in the intestine due to gluten intolerance
leads to inflamed intestine and impaired food uptake
T cell maturation
- Lymphoid precurser cell in bone marrow matures to…
- immature T cells = go to thymus = cortex
- immature B cells = migrate to lymph nodes
immature T cells in cortex of thymus
- proliferate and express both CD4 and CD8
- means can bind with both MHC I and II
positive selection = immature T cells in medulla, determines which co-stimulator remains on surface
encounter antigens presented by both MHC I and II, if they recognise any antigen = positively selected = survive
cytotoxic cell specialisation = medulla
cell recognised a peptide presented via MHC class I = keeps CD8+, loses CD4+ receptors
t helper cell specialisation = medulla
cell recognised a peptide presented via MHC class II = keeps CD4+ and loses CD8+ receptors
negative selection = middle of medulla of t cells
cells presented with self antigens = if the new T cells bind to any of these they get negatively selected = die
what percentage of T cells leave the thymus
5% = 2 million out of the 60 million that are produced in lifespan in cortex of thymus
non-self antigen presentation
- macrophages
- dendritic cells
- cortical thymic epithelial cells (cortex
self antigen presentation
- medullar thymic epithelial cells
medullar thymic epithelial cells
controlled by Aire gene = auto-immune regulatory gene,
Aire gene
mTECs = produce, breakdown and present proteins specific for cells in all organs of the body = self recognition by mature T cells outside of the thymus is prevented
acquired tolerance = Eu-FEDS
Eutherian fetoembryonic defence system = foetal material (foetus, sperm, eggs, gametes) don’t express MHC molecules
reproductive system acquired tolerance
cells = overproduction of glycoproteins = suppress immune system = because even if antigen presentation occurs, the lymphocyte activation is suppressed as the antigen cannot be reached
t lymphocyte activation requires…
- receptor-antigen recognition
- co-stimulation
anergy
lack of co-stimulation means t cell won’t to antigen
two regions on an anitbody
Fc and Fab
Fc region on antibody
swappable region = class switching
purpose of class switching
makes antibodies better suited for their location and function
immature B cells produce mainly…
IgM (and some IgD)
IgM
pentamer = low affinity = circulating first defence, binds many antigens to one antibody
activated B cells…
switch Ig class depending on location and function = high affinity
functions of the different immunoglobulins
IgM = circulating first defense IgE = histamine relesase mast cells = allergy IgA = mucose, tears, saliva, breast milk IgG = crosses placenta = foetus protection
monoclonal antibodies
all have same target and same target sequence
polyclonal antibodies
all have same target pathogen but not same target sequence, more than one activated b cell as antigen receptors recognise different antigens of the same pathogen
somatic hypermutation
high rate of mutation, 1 in 1000, in VJD gene segments =
benefit of somatic hypermutation
mature B cells continuously need to be activated in order to proliferate there will be a positive selection of the B cells with a higher receptor affinity for the pathogen
when does somatic hypermutation occur
after first b cell activation in lymph node
B cell maturation in lymph node
- b cells mature in germinal centre of lymph node
- divide and form clones
- somatic hypermutation changed affinity
- either positive or negative selection
virus mutations
- antigenic shift = genetic shuffling
- antigen drift = random mutations
