Immuno - Lymphocytes Flashcards
What is the adaptive immune system made of?
Lymphocytes coming form the common lymphoid progenitor
Where is the adaptive immune system found?
Only in vertebrates
What is the role of the adaptive immune system?
Clear infection and re-infection of a pathogen, improve the efficacy of the innate immune system and reduce the severity of re-infection of a pathogen
What is immunological memory?
Long lived memory of lymphocytes so that once they have been exposed to a pathogen, they will develop memory so that upon reinfection, they will recognise the antigen and rapid produce an immune response, which is therefore quicker and much less severe.
What responses make up the adaptive immune response?
Cell mediated response
Humoral response
What is responsible for the cell mediated response?
T cells - CD4 and CD8
What is responsible for the humoral response?
B cells which produce antibodies
How is the specificity of T and B cells generated?
Through the T cell receptor or B cell receptor
What does the TCR bind to/recognise?
The TCR binds to the linear, primary structure epitope of an antigen which is bound to via the MHC molecule
What does the BCR bind to/recognise?
The BCR binds to the structural 3D tertiary structure of the antigens therefore could potentially recognise 2 different parts of the antigen.
How many receptors does each lymphocyte have?
T cells only have one TCR specific to one antigen however B cells can have up to a 1000 BCRs which are all identical with respect to their specific antigen.
What occurs upon antigen binding to a receptor?
This causes activation of the lymphocyte and thus subsequent clonal expansion of the cells which go on to produce cytokines and recruit other immune cells to attack the pathogen.
How does recombination generate adaptive diversity?
The BCR is made up of many different components which are encoded for by multi-gene families. This allows for recombination of the genes to give different BCR combinations. The segments are rearranged via immunoglobulin gene rearrangement, thus generating a massive repertoire and thus adaptive diversity.
What is the role of helper T cells?
They are activated via a specific antigen presenting cell, they then undergo clonal expansion and then divide to form a variety of T helper cells which activate other cells such as B cells and help activate cytotoxic T cells.
What is the role of cytotoxic T cells?
Once these are activated in the presence of activating cytokines and the specific antigen, the cells go on to become powerful killers that kill not only pathogens and their antigens, but also the cells that have been infected.
What is the TCR made out of?
Made up of an alpha chain and a beta chain, each with a variable and a constant region which bind to their specific antigen in the context of the MHC
What is the MHC?
Major histocompatibility complex
What is the role of the MHC?
Presents antigens to T cells therefore has a central role in defending self cells from the not self.
What are the 2 classes of MHC?
MHC 1 and MHC 2
What is the difference between MHC1 and MHC2?
MHC 1 is expressed by all nucleated cells and has a single alpha chain with a common beta microglobulin. MHC 2 on the other hand has one alpha chain and one beta chain
How is there lots of variability between people’s MHC make up?
Encoded for by HLA genes and is polygenic, determined overall by 6 loci therefore in theory one person can have up to 6 copies of MHC if they were to be completely heterozygous.
What MHC do CD8 cells interact with?
Class 1
What MHC do CD4 cells interact with
Class 2
What is the role of T helper cytokines?
Although they all have diverse outcomes they overall influence the outcome of the immune response
What are Tfh cells?
Pro antibody,
releases IL-21
What are Th17 cells?
Pro-inflammatory, controls bacterial and fungal infection.
Releases IL-17, IL-6, IL-21
What are Th2 cells?
These are pro-allergic cells which boost the immune response via IL-4, IL-5 and IL-13
What are Treg cells?
Otherwise known as Th0 cells. They are anti-inflammatory cells which limit the immune response via IL-10 and TGF-B
What are Th1 cells?
Pro-inflammatory which boost the cellular immune response via IFN-gamma, TNF and IL-12
What cells initiate apoptosis?
CD-8 cytotoxic T cells
How do cytotoxic lymphocytes initiate apoptosis of infected cells?
CD8 cells when they detect an infected cell, will release the protein perforin which will form a pore in the membrane of the infected cell, and will subsequently exocytose a granule contain granzyme and granulysin which will enter the infected cell via the pore and then initiate apoptosis
How do cytotoxic T cells initially recognise virally infected cells?
The MHC 1 of nucleated cells will express self peptides if uninflected however when they become infected, the virus will take over the machinery of the cell and will display viral protein as non-self MHC. The CD8 cells will then recognise this and thus initiate the sequence to give apoptosis
What is the role of B cells?
B cells bind to specific antigens via the BCR which they then internalise and then display to T helper cells to lead to their activation, allowing them to proliferate into B cells with the same specificity.
What can B cells develop into following activation and proliferation
They can either develop into plasma cells which secrete antibodies or to memory cells which are specific and will retain memory to that specific antigen.
What are the 3 core protective roles of antibodies?
Neutralisation
Opsonisation
Complement activation
What is neutralisation?
When an antibody binds to an active site on bacteria or virus e.g. the spike protein to stop the pathogen from entering or binding self-cells
What is opsonisation?
The process of marking the pathogen therefore making it more attractive and likely to be phagocytosed
What is complement activation?
Enhances the opsonisation and can lyse some pathogens e.g. bacteria through the formation of the membrane attack complex.
What are the 5 classes of antibody?
IgG IgM IgA IgD IgE
What are IgG antibodies?
Highest opsonisation and neutralisation activates
What are IgM antibodies?
Produced first upon antigen invasion and then increase transiently depending on whether there are antigens present or not
What are IgA antibodies?
Expressed in mucosal tissues, once they are secreted they will join to form dimers
What are IgD antibodies?
These have an unknown function in the body
What are IgE antibodies?
These are involved in allergy responses e.g. type I hypersensitivity.
How is the class one antibody determined?
Via the variable region of an antibody
Describe the structure of the BCR
It is a surface bound antibody therefore has a constant region and a variable region which will undergo antigen binding directly, without the MHC
Explain the plasticity of the BCR response
BCR is made before the B cell ever encounters the antigen therefore cannot change upon binding - it is a plastic response not an elastic response
How many BCRs are found on each cell?
We can 1000s of BCRs on a cell however they must all be of the same specificity
What does the BCR not require but TCRs do require?
MHC
Explain the need for an accessory single for activation of naive B cells
This is the need for a secondary signal to allow for the activation of naive B cells, thus preventing autoimmunity through B cells acting against self antigens
What are the 2 forms of accessory signal?
Directly from microbial constituents
From a helper T cell (more common)
How are B cells activated via microbial constituents?
This is done independent of the thymus as T cells are not involved - the B cell will bind directly to the antigen and then the antigen polysaccharide or large receptive strut of the bacteria will bind and induce activation. Only IgM antibodies are formed via this route
How are B cells activated via T helper cells?
This is the thymus dependent route by which al IgG antibodies are formed. The membrane bound BCR binds to an antigen which will the be internalised and broken down to peptides. Peptides are then displayed via the MHC 2 of the B cells which allow it to associate to CD4 helper T cells. These then activate and produce cytokines and co-stimulatory markers which allow activation of the B cell and secretion of antibodies.
