What are components of the adaptive immune system?
- T lymphocytes -> cellular immunity
- B lymphocytes -> humoral immunity
- Antibodies
- Cytokines
Classes of T lymphocytes: What are Th (helper) cells?
- Express CD4
- Activate macrophages
- Help B cells to produce antibodies
Classes of T lymphocytes: What are CTL (cytotoxic) T cells?
- Express CD8
- Kill cells infected with microbes
- Kill tumour cells
Classes of T lymphocytes: What are Treg (regulatory) cells?
- Inhibit function of other T cells
- Control of immune responses
Where are antigen receptors found?
- On B and T cells
- Ig on surface of B cells; TCR = T cell receptor
- Can virtually recognise any microbial structure
- Distinguish antigens on different microbes and on same microbes
- When self-non-self discrimination fails -> autoimmune disease
How do both B and T cells recognise antigens (in general terms)?
- B cells recognise antigen directly (as they have antibodies on surface)
- T cells - the antigen is processed + presented by APC (eg macrophages, dendritic cells)
How do antibodies work?
- Bind to extracellular microbes + toxins
- neutralise (prevent binding of antigens to receptors or cells ; block antigen entry or effects on cells)
- eliminate microbes: opsonisation + complement activation
What is meant by intracellular microbes? Examples?
- Cell-mediated immunity fights intracellular microbes
- Intracellular bacteria in phagosomes of phagocytes
- viruses: cytoplasm of cells (phagocytes or non-phagocytes eg. epithelial cells)
- parasites (helminths) - both intra- and extra-cellular
- Main effectors: T cells
Can B and T cells both recognise soluble and cell-bound antigens?
- B cells recognise soluble or cell-bound antigens
- T cells recognise cell-bound antigens, peptides from foreign antigens only bound to MHC
What is the mechanism of T cell antigen recognition?
- T cells recognise antigens processed + presented by APC
- APCs process antigens to peptides (for most T cells)
- Peptides bind to MHC molecules
- peptide-MHC complexes are presented on APC surface
- -> activation of T cells specific for antigenic peptide
What is the most common type of T Cell Receptor?
alpha-beta TCR
What is meant by MHC restriction of antigen recognition by T cells?
- CD4+ helper T cells: antigens (peptides) displayed by MHC class II
- CD8+ cytotoxic T cells: antigens (peptides) displayed by MHC class I
T cells cannot recognise peptides unless they are combined with MHC molecules. MHC restricts antigen recognition by T cells
How does the T cell receptor actually bind to MHC?
- MHC has polymorphic residue which binds to T cell receptor
- There is a peptide which fits into both the T cell receptor and MHC grooves
- Anchor residue of peptide fits into “pocket” of MHC
- T cell contact residue of peptide also
Describe structures of both MHC I and MHC II
MHC molecules display peptides from processed antigens
- MHC I: a chain + B2-microglobulin ; present peptides to CD8+, short peptides can fit into the groove between a1 + a2 (same chain)
- MHC II: a chain + B-chain ; present peptides to CD4+, larger peptides can fit into groove between a1 and b1 (2 diff chains)
Where are MHC I and MHC II expressed?
- MHC I : all nucleated cells
- MHC II : antigen presenting cells (dendritic cells, macrophages)
Cells that are important for presenting antigens to CD4 T cells are macrophages and dendritic cells (APCs) - What are key features of dendritic cells?
- sentinel cells
- skin, mucosa, tissues
- capture microbes
- phagocytosis
- process pathogens + present Ags to T cells
- link innate + adaptive immune response
What are the 3 signals APCs send out for T cell activation?
- Signal 1: antigen recognition -> present antigen on MHC, bind to TCR
- Signal 2: co-stimulation, upregulation on surface of APCs, ligate receptors on T cells
- Signal 3: cytokines, produced by APC, tell T cell what kind of effector T cell to differentiate into
All 3 result in T cell activation, all are important as just 1/3 wouldn’t be enough for sustained activation
So why does CD4 specifically bind to MHC II and CD8 specifically to MHC I?
Eg. You can see that the CD4 T cell forms a complex with the peptide:MHC II structure but also the CD4 directly attaches to a portion of the MHC II molecule.
This is important as in the absence of the CD4 T Cell contacting the MHC II, the T cell will need 100x more MHC:peptide complexes on the surface of the APC in order to get activated. The binding of CD4 to the MHC II allows for a lower threshold for activation.
Describe antigen processing and presentation to CD4+ T cells
Exogenous antigens (eg bacteria) taken up in cells, processed + presented by MHC II to CD4 T cells
- uptake of extracellular proteins into vesicular compartments of APC
- processing of internalised proteins in endosomal/lysosomal vesicles
- biosynthesis + transport of class II MHC molecules to endosomes
- association of processed peptides w/ class II MHC molecules in vesicles
- expression of peptide-MHC complexes on cell surface
tl;dr phagocytosis occurs, then antigen is presented on surface bound to MHC II
Describe antigen processing and presentation to CD8+ T Cells
Cytosolic antigens (eg virus) are processed + presented by MHC I to CD8+ T cells
- prod of proteins in cytosol (as opposed to extracellular)
- proteolytic degradation of proteins
- transport of peptides from cytosol to ER
- assembly of peptide-class I complexes in ER
- surface expression of peptide-MHC class I complexes
What is the difference of role between the following types of T cells?
- Th1
- Th2
- CTL
- Th1 (CD4+) - help phagocytes to kill ingested microbes
- Th2 (CD4+) - help eosinophils/mast cells to kill helminths
- CTL (CD8+) - kill cells infected by microbes that grow freely in the cytosol
What is the main cytokine of Th1-mediated immune responses?
IFN-γ (gamma)
What is the main role of Th1-mediated responses?
- Activate phagocytosis
- To increase destruction of intracellular pathogens
- Stimulate production of IgG from B cells -> inc phagocytosis of microbes (complement + opsonising)
Examples of Th1-mediated diseases?
- granulomas
- autoimmunity
