Infection and immunity (Roger Booth lecture 5) Flashcards
B cell ontogeny and immunoglobulin genes
- Development in bone marrow (primary lymphoid organ)
- Multiple V, D and J axons recombine = V region
Recombination indépendant of antigen
Variable region diversity arises from this
B cells become committed to one Vh and one Vl
Single constant region axons for each class
Negative selection to remove strong self reactivity
Class switching retains V-region, changing C region
T cell ontogeny
TCR genes re arrange from uncommitted thymocyte to a this T cell now begins to express both CD4 and CD8 (helper T cells use CD4 plus their TCR, and the cytotoxic lineage use CD8 and TCR)
need to make sure developing thymocytes can recognise HLA, so these cells are tested against some of the antigen presenting cells in the thymus to see whether they’re able to recognise HLA class I or II, using their TCR or CD4 or CD8. Then each cell down regulates the CD4 or CD8 that they don’t need.
Negative selection process: Before they head to the secondary lymphoid organs, this is to test whether they recognise HLA with self peptides very strongly, and if they do they’re gonna be strongly self reactive and potentially dangerous
Whats left: cells that recognise HLA but HLA that is associated with a foreign peptide, now these cells start expressing CD3
Export to secondary lymphoid organs
Thymus structure
T cell differentiation starts at the periphery / cortex and matures as they move inward towards the medulla
Important points: T cell ontogeny and T cell receptor genes
Development in the thymus (primary lymphoid organ)
Multiple V, D and J axons recombine = V region
Recombination indépendant of antigen
T cells become committed to one V alpha and one V beta
Positive selection for HLA class I or II recognition (requires CD8 or CD40
Negative selection against strong self reactivity
* even genetically identical twins won’t have the same B and T cell repitore
Hyper IgM syndrome
CD40 ligand mutation
High IgM but no antigen specific IgG
Inability to switch from the IgM class to the later classes
Class switch from IgM to IgG controlled by T cells, needs CD40-CD40ligand interaction
Microbial factors
type of organism induces different response (virus, bacteria, parasite)
Dose (degree of exposure)
Virulence
Route of entry
Host factors
Integrity of innate barriers (if broken a bit then expect to see an increase in infectious processes) Captive immune competence HLA, Ig and TCR genes Previous exposure Other infections
Antigens seen in viral infections
Lytic or integrated cycle Capsid antigens Internal structural components (HLA I) Metabolic products (HLA I)
antigens seen in bacterial infections
Extracellular (e.g. S aureus)
or intracellular (e.g. M tuberculosis)
Structural components
Metabolic products and toxins
parasites
Large (multicellular) (slower)
Life cycle changes
Radicle changes in antigenicity
Immune factors, what can the immune system do?
- soluble factor mediated effects
Direct neutralisation by antibodies
Opsonisation and phagocytosis
Complement mediated effects
Inflammatory and immnuregulatory cytokines esp antiviral cytokines (interferons)
Other non-soluble functions of the immune system?
HLA restricted T cell mediated cytotoxicity
NK cell mediated cytoxocitiy
Antibodies that are effective against antigens extraceullarly
Viruses (IgA, IgM and IgG)
Toxins (IgM IgG)
Extracellular bacteria (IgA, IgM, IgG)
Parasites (IgE, IgA)
Cytotoxic T cells: effective against intracellular protein antigens?
Virus infections
Timor cells
Transplanted organs
X linked agammaglobulinaemia
few detectable B cells and no tonsils
