Lecture 25 - Infection and immunity Flashcards
Thymus involution
- Immature thymocytes will start at top and then will work their way down
- move from cortex to the medulla
T cell ontogeny
TCR gene rearrange
- First starts as an uncommited thymocyte
- then it will rearrange its t cell receptor genes ( 2 sets of genes coding for each of the chains - alpha and beta)
- There are V, D, J, regions, and these are all rearanged to form new t cell receptors (on antigen bindign site) (all differnet)
Positive seleciton
THese cells express both CD4 and CD8 - need to check if these can regonise HLA, so these cells are tested against some of the antigen presenting cells in the thymus, and if they cannot regonise the HLA, then they die
-they then will downregulate either cd4 or cd8 depending on what htey recognise
Negative selection
-test weather they recognise self HLA + self peptide , so dont want the ones that can regonise these so need to stop these cells - they get deleted
then these are exported to secondary lymphoid organs when they are mature
Hyper IgM syndrome
-Inability to switch from igm class to other classes
-linked to co stimulator CD40 and CD40 ligand and usually is due to a mutation in CD40 ligand gene to stop it working
(need this to swtich form Igm to igg)
How does our body respond to different types of infections
Microbial factors
- e.g differnt types of organisms will make differnt responses
- also degree of exposure - where it is exposed ect.
- virulence
- route of entry
Host factors
- integrity of innate barriers
- adaptive immune system
- HLA, Ig and TCR genes
- previous exposure
- other infections
Pathogens and antigens
Viruses
Bacteria
Parasites
Immune factors
- Nuetralisation (antibodies)
- Opsonisation and phagocytosis
- Complement-mediated effects
- T cell mediated cytotoxicity
- NK cell mediated cytotxicity
- inflammatory and immunoregulatory cytokines
- antiviral cytokines
Antibodies -
Antibodies
Effective against antigens outside cells of body
viruses (IgA, IgG, IgM) toxins (IgG, IgM)
extracellular bacteria (IgA, IgM, IgG)
parasites (IgE, IgA)
Cytotoxic T cells Effective against antigens outside cells of body virus infections (cytoplasmic peptides) tumour cells transplanted organs
Response to PAMPs
Local inflammation
- vascular permeability changes
- phagocyte recruitment
- acute phase protein induction
- local temp change
- -> leads to phagocytosis, complement activation
Complement cascade
relisten
classical pathway
- antigen-antibody immune complexes
- this activates C1, C4, C2 to form an enzyme that acts on the central C3 component to chop it into two pieces
Alternative pathway
-becomes activated form PAMPs this also activates a pathway to activate C3 converatse
complete pathway - convertase enzyme will chop C3 into C3b and c3a
C3b - binds things, neutrophils have a high affinity receptor for it and it enhances phagocytosis
C3b also forms late components to attach themselves, and to form membrane attack complex , and other molecuels are made to help change vasuclar permeability ect.
-mast cells are also activated
How to treat bacterial infecitons
Antibodies and complement
- prevent adherence or reduce mobility
- enhance bacterial destruction (complement)
- enhance phagosytosis (opsonisation)
Avoid antibody effects of bacteria
- capsule resists opsonisation
- intracellular growth
mucosal immunity
In mucous can have igA and igE antibodies
- these serve as a blocking thing and stops bacterial adherence
- often in resp tissues there are mast cells and these have a high affinity for igE, so are often coated in igE material and antigen/pathogen that associate with these lead to degranulation and releasing molecules that affect blood vessel permeability and are chemotactic for neutrophils and other cells
- this stops things going in, and also helps the recruitment of non specific mediators through mast cell degranulation
ADCC killing
-antibody dependent cell mediated cytotoxicity
this is mediated by antibodies binding to material, e.g bacteria or other mateiral in a way that fc is pointing outwards, then we get NK cells and these use fc receptors to bind, and then release factors to kill those targets
- NK cells bind to targets that have antibody around them
- call this antibody dependent cell mediated
NK cells
They have FC receptor (for above slide)
-also have 2 other receptors
Killer activating receptor -
Killer inhibiting receptor -
- these allow them to interact with cells in our body that might have changed their expression of HLA
- sometimes virally infected cells will downgrade their HLA receptors, to avoid getting recognised by cells of immune sytems - this is called natural killing activity
NK recognition and killing
- ubiquitosu molecuels and hla will be found on normal cells and are recognised by the killer activating receptor nad hte killer inhibitory receptor - and if the inhibitory signal is matched - then doesnt kill cell
- however in virally infected cell with downregulated HLA, then get recognition of this through the receptors, and get activated to release some non-specific molecules they are attached to
Dealing with viral infections
- First thing made is interferon (released by virally infected cells to signal to other cells to induce as state to become less able to be infected by viruses)
- these up regulate NK activity
- also then get cytotoxic T cells - to kill these cells infected with viruses
- then we have the antibodies developing later on and these can prevent re infection and viruses from spreading from cell to cel
