Sensing Microorganisms - Adaptive Immunity Flashcards
Properties of adaptive sensing?
Can recognise almost any microbial or non mocrobial molecule with high specificity
Adaptable due to somatic recombination of gene segments used to make receptors
Each cell has one unique receptor highly specific for one antigen
What is an antigen?
Molecule recognised by adaptive immune cells (T and B cells)
Will either bind T cell receptor or antibody (b cell receptor)
What is an epitope?
Precise part of antigen recognised by receptor - one Ag can have multiple epitopes
What is a paratope?
Part if antibody or T cell receptor that binds the epitope
How does a B lymphocyte (B cell) recognise an antigen and what is its following effector functions?
Produces antibodies, which bind antigens - often ones still on the microbe.
Effector functions:
-Neutralisation of microbe
-Phagocytosis
-complement activation
How does a Helper T lymphocyte (Th cell) recognise an antigen and what is its following effector functions
Senses microbial antigen presented by antigen presenting cell APC.
Releases cytokines:
-activation of macrophages
-inflammation
-activation (proliferation and differentiation of) of T and B cells
How does a cytotoxic T lymphocyte (CTL) recognise an antigen and what is its following effector functions
Senses antigen expressed on infected cell
Effect: kill infected cell
What is the effector mechanism of a regulatory T lymphocyte (Treg cell)?
Suppression of immune response
What is the main difference between antigen sensing in B and T cells?
B cells recognise Ag on its own (via antibodies)
T cells only recognise Ag presented to them by Antigen presenting cells (APC)
Difference between B and T cell antigen receptors?
B cell receptors:
-Membrane bound AND secreted
-Secreted form has immune effector functions
T cell receptors:
-Only membrane bound (called T cell receptor (TCR))
Differences between membrane bound and secreted B cell receptors?
Membrane bound:
-called B cell receptor (BCR) or surface immunoglobulin (sIg)
Secreted:
-called antibody (Ab) or immunoglobulin (Ig)
Properties of Ag recognised by T cells?
-Proteins
-linear peptide sequence
-8-25 AAs long
-presented on APC
-proteins have to be broken down into peptides
Properties of Ag recognised by B cells
-pretty much anything organic
-native molecule (not processed)
-conformational (can still be linear)
-epitope can cross loops (isn’t continuous, requires proteins conformation in order to be recognised- processing can break up proteins loops and cause epitope to no longer be recognised)
What is the structure of an antibody?
Two longer chains in middle are the heavy chains
Two sorter ones at top on the outside are the light chains
Chains joined by disulfide bonds
Upper region (contains light chains ant top half of heavy chains) makes up the antibody binding region (Fab)
Lower region (contains the bottom half of heavy chains) makes up the Fc region - remains constant and allows interaction with other cells
Hinge region in middle allow for flexing💪
T cell receptor structure?
Made up of two chains (alpha, equivalent to light chain, and beta, equivalent to heavy chain)
One Ag binding site compared to Ab’s two sites
How does the antigen binding region (Fab) of an antibody allow high variation?
Somatic recombination of gene segments (which code for the variable region of the Ab)
What is used to recombine variable region gene segments?
VDJ recombinase
Permanently alters the cell’s DNA
What is junctional diversity?
Rearrangement of V, D and J segments gives only a few million antibody specifities - not enough
Increased by fact that the segments are not joined perfectly
Can be off by a base or two causing variation
What is the second step of junctional diversity?
Addition of nucleotides:
After junctional diversity is created by imperfect alignment of gene segments:
RAG complex cleaves heptamer RSSs from the gene segments to create DNA hairpins
RAG complex then opens up hairpins by nicking one strand of DNA in each hairpin - generating palindromic P nucleotides
N-nucleotides then added by TdT (terminal deoxyribonucleotidyl transferase)
Doesn’t make much sense without lecture 5 diagrams but knowing the words is good ig 🐮
Third step of junctional diversity?
Deletion of bases:
After random addition of N nucleotides, unpaired nucleotides are removed by exonuclease
Gaps are then filled in by DNA synthesis and ligation to form coding joint between gene segments
Results in new DNA at borders of gene segments changing the AA sequence and upping variation
Fate of B cells with non functional sequence on Ab?
Death by apoptosis
Majority of rearrangements don’t result in functional protein
What is allelic exclusion?
VDJ genes on chromosome 14
2 of each chromosome so 2x sets of VDJ genes
2 chances to make a productive rearrangement
Each B cell specific for one Ag
Only room for one Ab on each cell
Thus a successfully rearranged chain will block gene rearrangement on the other chromosome
What is clonal expansion?
T/B cell senses antigen and becomes activated
Divide
All daughters have same Ag specificity
Time required to activate and expand Ag specific T/B cells to an effective number makes adaptive response slower
IL-2 cytokine drives T cell clonal expansion
What is antigenic variation?
1 or 2 amino acid change in antigen can cause T/B cell to no longer be able to recognise or recognise more slowly :(
Different strategies of different microbes to achieve antigenic variation?
Influenza:
Have surface proteins haemagglutin and neuraminidase
Trypanosomes and malaria:
Switch between multiple versions of same molecule
HIV:
High mutation rate
Antigenic variation occurs in the host
Prevents effective adaptive immunity
V difficult to make vaccines
What problems are caused by adaptive sensing’s ability to detect almost any organic molecule?
Body is made of them
Also food and other innocuous molecules we’re exposed to
T and B cells can’t tell what they’re recognising
Can lead to allergy and autoimmunity
Central tolerance?
Mechanism by which T and B cells capable of recognising self are deleted before they are released systematically to fight infection
T cells removed in Thymus
B cells removed in bone marrow
Not perfect - still possibility for self reactive cells to make it through
Also doesn’t stop recognition of outside innocuous molecules (eg food)
How can the adaptive immune system tell if an Ag is from a pathogen?
The innate system can tell if something is a pathogen (PAMPs)
Innate cells (eg DCs) tell T cells whether to respond or not
How do Th cells sense antigens?
Antigen presented by MHC class II (expressed by professional APC)
Express CD4 on surface which stabilises class II interactions
How do Treg cells sense antigens?
Antigen presented by MHC Class II
(Expressed by professional APC)
Express CD4 on surface to stabilise class II interactions
How do CTL sense antigens
Antigen presented by MHC class I (expressed on all nucleated cells)
Express CD8 to stabilise class I interactions
Oral tolerance?
The active process by which the immune system does not respond to an orally administered soluble antigen
Celiac disease vs food allergies
In celiac Th1 cells produce IFN-gamma
Activated Macrophages and B cell activity
In food allergies Th2 cells produce IL-4
B cell production of IgE, Mast cell activation
