Key phases of infection
- establishment of infection
- induction phase - adaptive threshold
- effector phase
- Memory - threshold lowered when reencountered
Why does adaptive immune response take time
requires cell to move, interact & produce cytokines: effector.
APC takes up antigen, travels from site of infection to lymph node: activates T cells -> activate B cells. Both return to site of infection via circulation
where does T/B precursor rearrange receptor genes
Thymus: -ve & ive selection of naive cell
Immature T cells can be
receive survival signals - if recognise MHC
clonal deletion: interact strongly w/self
where do mature T/B cells encounter antigen
peripheral lymphoid: are activated
MHC-I recognises which kind of cells
CD8+ intracellular antigens e.g. virus (endogenous)
- all of self except RBC can present to CD8+
MHC-II recognises which kind of cell
CD4+ extracellular: extracellular bacteria, soluble antigens, virus particles. e.g. dendritic cells/ pinocytosis
How does MHC polymorphism affect antigen recognition by T cells through
influencing peptide binding & contacts between T cell + MHC
Th1 induces & is induced by
Macrophage activation & delayed type hypersensitivity
induced by: IL-12, IFNy, IL-18
Th2 induces & is induced by
antibody production & allergic response.
induced by: IL-4, IL-5
what signals do APC deliver to naive T cells
- activation 2. survival 3. Differentiation
B cell activation
Antigen recognised by BCR -> antigen internalised via receptor mediated endocytosis -> peptides presented to MHC
if CD4 also recognises antigen will provide help via CD4 & cytokines
what provides flexibility to antibody
Hinge region of Ig when binding to multiple antigens
what happens when IgE recognises antigen
variable region of IgE binds antigen & constant region binds FCeR1 - crosslinks receptors = degranulation of mast cells
3 main functions of antibodies protection
- neutralisation: antibody binds & blocks toxin from
cell receptor - opsonisation: antibodies bind to bacterium, label it foreign. Fc region antibody binds Fc phagocytic cell & is digested.
- complement: recognises certain features of microbial surfaces allowing it to be lysed and ingested.
Central tolerance involves
occurs at young age
+ve selection: cells lacking affinity - dont receive survival signals
-ve: removes T cells which bind too strongly, ensure autoreactive deleted by apoptosis: clonal deletion
Fates: 1. death by neglect 2. +ve selection 3. clonal deletion
describe Peripheral tolerance
occurs throughout lifetime in periphery
ensure self-reactive T&B cells which escaped central tolerance don’t cause autoimmune disease
e.g. antigens not present in thymic selection: sex hormones & food antigens, autoantigen, good bacteria
which mechanisms of peripheral tolerance exist to ensure mature T cells don’t activate inappropriately
- co stimulation signal & specific signals: activates T cell
- specific signal alone (MHC bound) - T cell becomes anergic
- co stim signal alone - no effect on T cell (no antigen)
B. CTLA-4 binds to B7 more than CD8: inhibits T activity
C. Treg: IL-10 & TGFb: inhibit self reactive T cells
What happens if T cells escapes clonal deletion
can become activated
- to non harmful antigens: allergy
- to self antigens: autoimmunity
What happens when tolerance fails
immunodeficiency (immune evasion by pathogens)
1y - genetically acquired
2y - infections, metabolic dysregulation, therapeutically induced
