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
What is antibody function?
Antibodies extremely important in protection against reinfection 3 Core protective roles: 1.Neutralisation 2.Opsonisation 3.Complement activation
What are B cells?
- White blood cells
- Lymphocytes
- Derived from hematopoietic stem cells
- Effector cells of humoral immunity
- Secrete antibodies
- Memory B cells (ready to prevent repeat infections)
Where doB cells come from?
B cell generation and
maturation occurs in
bone marrow in the
absence of antigen
• Derived from stem cells in the bone marrow
• Migrate into the circulation (blood, lymphatic
system) and into lymphoid tissues
• Mature B cells are specific for a particular antigen
• Specificity resides in the B cell receptor (BCR) for antigen
What is the BCR?
The BCR – Surface bound antibody – encodes the antibody the cell will make
• BCR have a unique binding site which bind to a portion of the antigen called antigenic determinant or epitope
• Is made before the cell ever encounters antigen
• Is present in thousands of identical copies on the surface of the b lymphocyte
What is antibody production by B cells?
General rule: Naïve antigen-specific lymphocytes (B or T) cannot be activated by antigen alone Naïve B cells require accessory signal 1)Directly from microbial constituents 2)From a T helper cell
What are thymus independent antigens?
- Directly activate B cells without the help of T cells
- Often bacterial/ polysachharide, needs to be repetitive structure
- The second signal required is either provided by the microbial constituent or by an accessory cell
What is B cell activation by T cells?
1) The membrane bound BCR recognises antigen
2) The receptor-bound antigen is internalised and degraded into peptides
3) Peptides associate with “self” molecules (MHC class II) and is expressed at the cell surface
4) This complex is recognised by matched CD4 T helper cell
5) B cell activated
