adaptive immune system Flashcards
MHC class 1
CD8
MHC class 2
CD4
MHC peptide
only can present a limited repertoire
MHC 1 antigen processing
- Proteins degraded by proteasome into peptides in cytoplasm
- Peptides pumped into endoplasmic reticulum (ER) by TAP, binding to MHC 1
MHC 1/peptide transported to cell surface
- Peptides pumped into endoplasmic reticulum (ER) by TAP, binding to MHC 1
MHC 2 antigen processing
- Extracellular proteins are phagocytosed, degraded by lysosome
- MHC II generated in ER, invariant chain puts MHC II into MIIC vesicle
- MIIC fuse with lysosomes, peptides loaded onto class II in MIIC vesicles
MHCII/peptide is exported to cell surface
how many major classes of MHC are there
3 class 1 3 class2 = polygenic
CD4 cycle
- a naïve t-cell receives antigen recognition
- Release cytokines (e.g. IL-2)
- Cloning
Differentiation
Th1 summary
cytokine release - IFN-gamma
target cell - macrophages
host defence - intracellular pathogens
Th2 summary
cytokine release - IL-4, IL-5, IL-13
target cell - eosinophils
host defence - parasite
Th17 summary
cytokine release - IL-17, IL-22
target cell - neutrophil
host defence - extracellular pathogens
Th0
- drives clonal expansion
- Have a choice for differentiation
Determined by signal 3 (cytokine secreted by dendritic cells)
- Have a choice for differentiation
Th1 process
- IL-12 and IFN-gamma drive Th1 differentiation
- Dendritic cells and natural killer cells = good source of IFN-gamma
- Macrophages have receptors for IFN-gamma
- IFN-gamma activate macrophages into M1 macrophages (good killers of intracellular organisms)
Th1 cytokine promote IgG isotype switching
Macrophages affected by th1
- Th1 secrete IFN-gamma, macrophages have IFN-gamma receptor
- Th1 express CD40L (macrophages have CD40)
- Causes release of cytokines (TFN-a, IL-1, IL-12)
○ Induces production of antimicrobial agents (NO and O2-)
Increase expression of MHC
th17 process
- IL-1, IL-6, IL-23 and TGF-B drive Th17 differentiation
- Dendritic cells and macrophages = good source of these cytokines
- Mobilise neutrophils
○ Acts on epithelial and endothelial cells to secrete chemokines - hey attract neutrophils - killing extracellular bacteria
IL-22 acts on epithelial cell layers to increase integrity
CTL
- Contain: ○ Perforin ○ Granzymes - Perforin allows Granzymes to enter cells Granzymes activate apoptotic pathway
Th1 on dendritic cells
Th1 cells activate dendritic cells to become better activators of CTL differentiation
CTL secrete IFN-gamma - promoting Th1
Intracellular bacteria
- Th1 activate macrophages to kill microbes in phagolysosomes
- CTL kill infected macrophage
Both important
- CTL kill infected macrophage
virus prevent MHC1 processing and presentation
Natural killer cells kill downgraded MHC1 viruses - NK cells activated by type 1 interferon - NK cells have two types of receptors ○ Activating receptors recognise stress ligands on infected cells ○ Inhibitory receptors recognise class 1 MHC If NO MHC class 1 - inhibitory receptor not engaged = killing cell
B Cells
- Recognise free antigen
- Differentiate into effector B cells (plasma cells)
Plasma cells secrete antibody
- Differentiate into effector B cells (plasma cells)
what region of the antibody determines if the isotype can interact with Fc receptors or complement
the constant region
IgM
- Pentamer
- Receptor for naïve b cells
- First antibody response
- Low affinity
- High avidity
- GOOD for complement - only one IgM is needed to bind to complement
○ Opsonisation
○ Inflammation
Lysis
IgG
- Activated complement
- High affinity - good for neutralisation
Neonatal immunity - can cross placenta
- High affinity - good for neutralisation
IgA
- High affinity - good for neutralisation
- Found in milk
- NO complement
- 2 types:
○ IgA1
§ 15%
§ Pro-inflammatory
○ IgA2
§ Mucosal secretions
non-inflammatory
IgE
- Good for fighting helminths
- Causes allergy
- Found on surface of eosinophils and basophils
- No complement
No neutralising
IgD
- Receptor for naïve B cells
Function obscure
Evasion strategies against antibodies
- Cleave antibodies
Bind antibodies
how do antibodies neutralise viruses
by binding to them, preventing them from bind to host cell - REQUIRES HIGH AFFINITY (IgG, IgA)
Antibodies can fight infections in 3 ways
- Neutralisation - high affinity (IgG, IgA) - blocks binding
- Opsonisation (IgG and IgA, IgM with complement)
Lysis (complement IgG, IgM)
- Opsonisation (IgG and IgA, IgM with complement)
opsonisation
- Classical complement pathway deposits C3b on cell surface
○ Phagocyte recognises C3b - phagocytosis- Phagocytes express Fc receptors specific for heavy chain constant region
○ Antibody binds to pathogen
○ Phagocyte recognises Fc receptor on antibody
Phagocytosis
- Phagocytes express Fc receptors specific for heavy chain constant region
lysis
- Binding of C3b to microbe
- Membrane attack complex creates pores in microbial membrane
Induces osmotic shock - lysis
- Membrane attack complex creates pores in microbial membrane
what antibody is initially produced
IgM produced with no T cell help
IgM + T cell help
IgG, IgA, IgE produced
time of antibody production
- First antibody produced is IgM (low affinity), peaks at around day 7
- IgM diminishes as B cells switch to other isotypes (IgG) - affinity increases
- Primary response peaks at day 14
If re-exposure secondary response is greater and quicker (memory cells)
b cell stimulation
B cells present antigen to t cells on MHC II
T cells stimulate b cells with CD40L and cytokines
antibody differentiation
IgM is default
IgG driven by IFN-gamma
IgE driven by IL-4
IgA driven by TGF-B
