Lymphocytes Flashcards
Why do you need adaptive immunity?
Need adaptive immunity as absence results in inability to fight infections
- Improves efficacy of the innate immune response
- Focuses a response on the site of infection and the organism responsible
- has memory
- Needs time to develop
What is immunological memory?
- Once the immune system has recognised and responded to an antigen, it exhibits “memory”
- Immunological memory is also a consequence of clonal selection
- Antigen-specific lymphocytes (B + T) are the cellular basis
- Memory responses are characterised by a more rapid and heightened immune reaction that serves to eliminate pathogens fast and prevent diseases.
- It can confer life-long immunity to many infections
- Basis for Vaccines
What are the two types of adaptive immune response?
- Humoral B cells e.g. antibodies
- Cell mediated T cells e.g. cytokines, killing
What are antigens?
Molecules that act induce an adaptive immune response (mostly protein)
What is an epitope?
- The region of an antigen which the receptor binds to
- T cells recognise linear epitopes in context of MHC
What is clonal selection?
- Each lymphocyte bears a single, unique receptor
- Interaction between a foreign molecule and that receptor leads to activation
- Differentiated effector cells of that lineage will bear the same receptor
- Self specific receptors are deleted early in development
What is the problem of antigen diversity?
- We are exposed to an incredibly large amount of different microbes and other antigenic determinants – no predicting which ones
- Immune system must be able to respond to them all.
- But - the adaptive immune system is exquisitely specific
- To respond to all these different antigens, we need to have a very large pool of cells with specific receptors that can recognise these huge array of antigens
Why is antigen receptor diversity needed?
-To deal with antigen diversity we encode a massive Repertoire
-10^10 different antibody molecules can be generated
-Each antibody is produced by a B lymphocyte
expressing a specific BCR
-This would be impossible if 1 gene per antibody: We only have 25,000 genes total for all functions!
How is antigen receptor diversity generated?
- Diversity generated through a piece of genetic sleight of hand
- Functional genes for antigen receptors do not exist until they are generated during lymphocyte development
- Each BCR receptor chain (kappa, lambda and heavy chain genes) is encoded by separate multigene families on different chromosomes
- During B cell maturation these gene segments are rearranged and brought together
- This process is called Immunoglobulin gene rearrangement
- Immunoglobulin gene rearrangement generates the diversity of the lymphocyte repertoire
What is the T cell receptor?
- The T cell receptor part of a complex of proteins on the cell surface.
- The variable region made by gene reassortment (1015 – 1020)
- Recognises antigen fragments presented by other cells
What is the major histocompatibility complex?
- The Major Histocompatibility Complex (MHC) plays a central role in defining self and not self
- Encoded by HLA genes in humans
- Presents antigens to T cells
- Critical in surgery- and donor matching
What is MHC gene expression?
- The MHC is polygenic: several class I and class II loci
- Expression is co-dominant (maternal and paternal genes both expressed)
- MHC class I: all nucleated cells, although at various levels: levels may be altered during infection, or by cytokines
- MHC class II: normally only on “professional” antigen presenting cells: may be regulated by cytokines
What are the two flavorous of T cell? What is it defined by? Are they functionally different?
- CD4 (helper) and CD8 (killer)
- Defined by cell surface molecules CD4 (which binds MHCII) and CD8 (which binds MHCI)
- Functionally different
What are CD8 (cytoxic T lymphocytes)?
- Cytotoxic T cells (CTL) kill their targets by programmed cell death = apoptosis
- Apoptosis is characterized by fragmentation of nuclear DNA
- CTL store perforin, granzymes, granulysin in cytotoxic granules released after target recognition
- Perforin molecules polymerise, form pores
What are the CD4 T helper cells classes?
- T Helper cells produce cytokines (a family of inflammatory mediators).
- Cytokines have diverse actions on a wide range of cells
- Cytokines influence the outcome of the immune response