How does the Immune System Recognise Pathogens? Flashcards
what is an immunogen?
what is an epitope?
immunogen: anything that elicits an immune response - most (but not all) antigens are immunogens
epitope: portion of antigen that is recognised and bound by a receptor on an immune cell
what is v basic overview of how antigen recognition occurs?
what is the capacity of innate immune cells, compared to adaptive immune cells, in no. of antigens recognised?
- *innate**: recognise a few common microbrial structures that are present in microbes but not humans = few antigens can be recognised.
- *adaptive (**lymphocytes - T/B cells): recognise millions of antigens. each individual T/B cell in body recognises different antigens - will be specific for single antigen
how do innate immune cells recognise antigens?
how do u describe innate immune cells’ response to self?
have Pattern Recognition Receptors (PRRs) recognise Pathogen Associated Molecular patterns (PAMPs) (structures found in microbes but not people - limited no. of structures)
- can be on surface, in lysosomes or cytoplasm
inherent lack of response to self (tolerance) - antigens arent present
what are Toll like receptors?
which TLR recognise flagella and LPS?
what happens as a response to TLR engagement?
- *Toll-like receptors: examples of PRRs:**
- TLR-5: recognises flagella
- TLR-4: recognises LPS (on gram-negavtive bacteria)
get both them on plasma membranes and in lysosomes.
- *TLR engagement:**
- dimerization of receptor
- activation of kinases
- activation of TF
- causes production of cytokines
wha
how do `T and B cells recognise antigens? - what does this mean with specificity?
- each new lymphocyte only expreses one type of receptor and recognises only one type of antigen: means specificity is rare
- *antigen introduced:**
- only activates lymphocytes with correct receptor
- lymphocytes clonal expansion -> expresssing same receptor
- causes lots of daughters cells
how do B cells recognise antigens?
- B-cells have recognition molecules called immunoglobins (Ig): often the eptiope is conformational
- B-cells recognise antigens directly (without help of other cells)
- activated B cells differentiate into plasma cells: secrete immunglogulin (‘antibody’)
what is the structure of an antibody?
- *constant region:** same between different antibody molecules
- *variable region:** differentates between the antibodies.
what are different classes of antibody?
what is specif
- B-cells –> plasma cells: can make different classes of antibody (isotopes):
- each antibody class can mediate different biological functions:
- *antibodies**:
- IgM
- IgG
- IgE
- IgA
the specificity of these are identical (still recognise the antigen that was bound to B-cell), but the constant parts vary:mediating different biological functions
- B cell always initially makes IgM - made in first in immune response but then swtiches to making IgG
- IgG decreases but then increasees massively when have secondary response
- antibody specificity remains constant - whilst biological effector functions are varied
how is the great number of receptor diversity generated on antibodies?
- each developing B cells expresses a distinct receptor
- not different genes for millions of different receptors
- INSTEAD: diversity is generated by mixing and matching gene segements within the heavy and light chain loci:
- Immunglobin heavy chain has:
a) V segments (40); b) D segments (25); c) J segments (6)
- get splicing of each of ^ to make lots of different genes: combinatorial diversity
- also: additional nucleotides can be added at the joints of ^^ to make more variation: junctional diversity
THEN:
any of immunoheavy chain stuff can associate with any of the light chains: more diversity: combinatorial diversity
how do t cells recognise antigens? what are the distinguishable features?
- use **TCR - T cell receptor
- T cells are presented antigens byantigen presenting cells (APCs):recogniselinear antigens
- **The APC presents the antigen to the T cell using the major histocompatability complex (MHC)
how does antigen recognition differ between T cells and B cells?
- T cells: use APCs, B cells do not
- T cells recognise short, linear peptide antigens, B cells recognise conformational epitopes
what is the structure of T cell receptor like?
- two chains: alpha and beta chains
- both chains have a constant (same between all TCR) and a variable region (different: recognises different antigens)
- antigen recognition with the peptide and MHC happens at the top
what are the two types of T cells? what are their roles?
- *CD4 T cells:** helper cells
- *CD8 T cells**: cyotoxic cells
how do we get such a wide variety of TCR diversity?
somatic DNA recombination (like in B cells)
get multiple variable regions (see slide) and get variable splicing
which is the most potent APC?
dendritic cell
what are the two types of MHC cells? which cells express each type?
- *MHC Class 1:** expresed by all cells. made from:
- alpha chain with 3 domains
- peptide-binding cleft between a1 and 2 (see slide)
- alpha chain is encoded by MHC.
- alpha chain associates with B2 microglobulin
- *MHC Class 2:** expressed by APC cells only
- alpha and beta chains (both formed by cell)
- peptide-binding cleft: formed from B1 and alpha1
Both have peptide-binding cleft: but the fit between the amino acid side chains inthe peptide and the grove of MHC molecule determine binding
MHC Class I presents antigens to X?
MHC Class 2 presents antigens to X?
are they specific to one type of peptideS?
MHC Class I presents antigens to CD8 T cells
MHC Class 2 presents antigens to CD4 T cells
peptide binding by MHC molecules is promiscious - multiple peptides can be accomodated in the groove
what are the properties of MHC that ensure the maximum number of peptides can be presented?
- *1. MHC genes are polygenic:** more than one type of MHC class I and MHC class II molecule - can present slightly different range of peptides
- *2. MHS genes are highly polymorphic:** multple alleles in the population mean that most people are heterozygous for MHC genes. (as a result - mother and father MHC genes are likely to be different - its this what is a barrier to organ transplant)
polygenic and polymorphic of MHC genes ensures mutlple different MHC molecules expressed, increasing the reportoire of peptides that can be presented
how does coeliac disease occur
- coeliac diease people undergo T cell response to gluten
- only occurs in people carrying particular MHC class II molecules (HLA-DQ2 or HLA-DQ8)
- only these MHC molecules can present gliadin peptides (in gluten) to T cells
- gliadin peptides also acts as a substrate to tissue transglutaminsae (enzyme in GI): increases further the ability to bind to HLA-DQ2 or HLA-DQ8.
- although necessary, if you have HLA-DQ2 or HLA-DQ8, don’t necessarily have CD.
what is immunlogical tolerance?
immunlogical tolerance: the immune system attempting to eliminate self reactive cells that recognise self as antigens
removal during development: central tolerance
control when out in the body: peripheral tolerance
