Lymphocytes Flashcards
Why do we need adaptive immunity?
Only evolved recently
Protects us from repeat infections
Absence of it results in an inability to clear infections
Not without costs- autoimmunity
What does the adaptive immune system do?
Improves efficacy of the innate immune response
Focuses the response on the organism responsible and at the site of infection
Had a memory
Needs tome to develop
What is the characteristic of the memory response (secondary)?
More rapid
Heightened immune response
Therefore a severity on re exposure
Basis of vaccines
The memory is incredibly long lived
What are the two parts of the adaptive immune response?
T cells: cell mediated. Produces cytokines (CD4) kills infected cells (CD8)
B cells: humoral. Produce antibodies
How do T and B cells recognise pathogens?
BCR - B cell receptor
TCR
What is an epitope?
The region of an antigen which the receptor binds to
What part of an epitope do B and T cells recognise?
T cells: Linear epitopes in the context of MHC (primary structure)
B cells: recognise structural epitopes (the tertiary structure)
How specific is the adaptive immune response?
Very
Each antibody only recognises one antigen
What is clonal expansion?
Interaction between a foreign molecule and a unique receptor leads to the activation of the cell and causes it to undergo clonal expansion
This forms multiple copies of the same cell
Each of the clones express the same receptor
How is the diversity of lymphocyte repertoire generated?
Each BCR chain receptor is encoded by separate multi gene families on different chromosomes
During B cell maturation these gene segments are rearranged and brought together
This is called
Immunoglobulin gene rearrangement
What is the T cell receptor?
Part of a complex of proteins on the cell surface
The variable region is made by gene Reassortment
Recognised antigen fragments presented by other cells in the context of MHC
They are semi similar to antibodies, as they are coded fro by the same family of genes
What is the MHC?
Major histocompatibilty complex
Plays a central role in defining self and non self
Presents antigens to T cells
Critical in surgery and donor matching
What are the two families of MHC molecules
MHC class I: Present on all nucleated cells (at various levels)
Has a single variable alpha chain plus a common beta microglobulin
MHC class II: Normally only present on professional antigen presenting cells
Has and alpha and a beta chain
How does MHC gene expression work?
Encoded by HLA genes
Polygenic: 3 class I loci and 3 class II loci
Expression is co dominant (maternal and paternal genes both expressed)
Therefore a person can have up to 6 of each gene
There are more than 17000 variants of the genes
How do MHC complexes and T cell receptors interact?
MHCI:
Intracellular pathogens/antigens
Processed in the cytosol
Presented to CD8 (cytotoxic) cells
MHCII:
Extra cellular pathogens/antigens
Processed in endosomes
Presented to CD4 (helper) cells
What is the role of T helper cells?
Produce cytokines (a family of inflammatory mediators)
Cytokines have a wide range of actions over a wide range of cells. They influence the outcomes of the immune response
What are the classes of t helper cells?
Th1: pro inflammatory, boost cellular immune response
Th2: pro allergic
Th0: anti inflammatory
Limit the immune response
Th17: pro inflammatory
Control bacterial and fungal infection
Tfh: pro antibody
What do Cytotoxic T cells do?
Kill their targets by apoptosis
(Characterised by fragmentation of nuclear DNA)
T killer cells contain perforin, granzymes and granulysin in granules that are released after they reach their target site
Perforin forms pores in the membrane of the pathogen and the granzymes are released triggering a cascade that leads to apoptosis
What is the main purpose of a B cell?
To make antibodies?
What is the structure of an antibody?
Made up of two light chains and two heavy chains
Had a variable and a constant region
They have a huge potential for diversity in the variable region
What are the main functions of antibodies?
Neutralisation - an antibody binds to an active site in a virus or bacteria, thereby stopping the pathogen from doing its job
Opsonisation - the antibody makes the pathogen more attracted to being phagocytosed
Complement activation - esentially leads to the death of anything the antibody is bound to
What are the 5 classes of antobodies?
IgG - Highest opsonisation and neutralisation activity
IgM - the pentamer that looks like a snowflake
IgA - expresses on mucosal tissues
IgD
IgE - involved one allergy
What is the relationship between the BCR and the antibody?
The shape of the antibody is identical to that of the BCR the pathogen binds to
How do B and T cells differ in binding antigen?
B cells bind to soluble antigen
Whereas T cells need to bind to antigens associated with MHC
How is antibody production regulated?
Can’t be activated solely by antigen
Requires accessory signals either directly from microbial constituents or from a T helper cell
What are the two pathways through which Antibody production is achieved?
Thymus dependant:
T helper cells
All Ig classes
Memory
Thymus independent:
Microbial constituents
Only IgM
No memory
How does thymus independent signalling work?
Directly activated the B cells without T cells
Can only be done by pathogens that have molecules with a long repeating structure (eg bacteria with long chains of poly saccharide)
The second signal required is provided by a microbial PAMP
How does thymus dependant activation of B cells work?
Membrane bound BCR recognises antigen
Receptor bound antigen is internalised and degraded into peptides
Peptides associate with MHCII molecules and are expressed on the surface of B cells
This complex is recognised but CD4 t helper cells
The B cell is activated
