Lymphocytes Flashcards
(37 cards)
What are the 4 properties of the adaptive immune system?
- Improves the 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 and what is it based on?
Once the immune system has recognised and responded to an antigen, it exhibits “memory” as 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. Can confer life-long immunity to many infections and is the basis for vaccines.
What are the 2 types of adaptive immune response?
Cell-mediated immunity uses T-cells where cytokines and killing cells are the effector molecule and function respectively. Humoral immunity uses B-cells where antibodies are the effector molecules.
How are antigens recognised by different lymphocytes?
T-cells recognise linear epitopes in the context of MHC while B-cells recognise structural epitopes.
Antigens: Molecules that act induce an adaptive immune response (mostly protein)
Epitope: The region of an antigen which the receptor binds to.
What is the process of clonal selection?
- Each lymphocyte bears a single, unique receptor
- Interaction between a foreign molecule and that receptor leads to activation
- Clonal Selection//Expansion
- Differentiated effector cells of that lineage will bear the same receptor
Self-specific receptors are deleted early in development
How is diversity of antibodies produced?
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.
Describe the TCR
The T cell receptor part of a complex of proteins on the cell surface. The variable region made by gene reassortment (1015 – 1020). Recognizes antigen fragments presented by other cells.
What is the MHC?
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.
Describe 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
Which cells bind to the different MHC molecules?
There are two types of T-cells: CD4 (helper) and CD8 (killer). CD4 cells bind MHC II while CD8 binds MHC I - defined by cell surface molecules. MHC is encoded by HLA genes: genes controlling MHC I are A,B and C. Genes controlling MHC II are DP, DQ and DR. Thus, with three MHC class I genes and a possible three sets of MHC class II genes on each chromosome 6, a human typically expresses six different MHC class I molecules and eight different MHC class II molecules on his or her cells.
What are the differences in the distribution of MHC I and MHC II?
MHC I is present on almost all nucleated cells including platelets. MHC II has a restricted tissue distribution and are chiefly found on macrophages, dendritic cells, B cells, and other antigen presenting cells only.
What are the differences in the encoding genes of MHC I and MHC II?
MHC class I proteins are encoded by the HLA-A, HLA-B, and HLA-C genes. MHC Class II proteins are encoded by the genes of HLA-D region.
What are the differences in the nature of presented antigens of MHC I and MHC II?
Antigens presented by MHC class I molecules are of endogenous origin. Antigens presented by MHC class II molecules are derived from extracellular proteins.
What are the differences in the presented antigens of MHC I and MHC II?
MHC I presents cytosolic proteins; they sample peptides generated within the cell or those that may enter cytosol from phagosomes. Class II molecules sample peptides outside the cell such as lysosomal proteins mostly internalized from extracellular environment.
What are the differences in the enzymes involved in peptide generation of MHC I and MHC II?
MHC I uses cytosolic proteasome. MHC II uses endosomal and lysosomal proteases.
What are the differences in where peptides are loaded and the peptide loading complex of MHC I and MHC II?
Peptide loading of MHC I occurs in the ER. Peptide loading complex includes the ER transporter associated with antigen processing (TAP1/2), tapasin, the oxidoreductase ERp57, and the chaperone protein calreticulin. Peptide loading of MHC II occurs in a specialized vesicular compartment. Peptide loading complex includes chaperones in ER; invariant chain in ER, Golgi and MHC Class II compartment/Class II vesicle.
What are the differences in the recognising co-receptors of MHC I and MHC II?
MHC I is recognized by CD8 co-receptors through the MHC Class I β2 subunit. MHC II is recognized by CD4 co-receptors through β1 and β2 subunits.
What are the differences in the structure and amino acids of MHC I and MHC II?
MHC class I molecules consist of one membrane-spanning α chain produced by MHC genes, and one β chain produced by the β2-microglobulin gene. Possess 8-10 amino acids. MHC class II molecules consist of two membrane-spanning chains, α and β both produced by MHC genes. Possess 13-18 amino acids.
What are the differences in the peptide binding domains and invariant chains of MHC I and MHC II?
α1 and α2 are peptide binding domains in MHC I molecules. Has no invariant chain. α1 and β1 are peptide binding domains in MHC II molecules. Has a variant chain.
What are the differences in the functional effect and detection method of MHC I and MHC II?
Presence of abundant antigens detected by MHC I targets cell for destruction. Detection method is serology. Presences of foreign antigens detected by MHC II induces antibody production. Detected by serology and mixed lymphocyte reaction.
What are the differences in processing of intracellular pathogen vs Extracellular pathogen
IC pathogen is processed in the cytosol and presented on MHC I molecules to CD8 T-cells. CD8 binds the alpha-3 domain of MHC Class I on the target cell. EC pathogen is processed in endosomes and presented on MHC II molecules to CD4 T-cells. CD4 binds the beta-2 domain of MHC Class II on the target cell.
Provide an overview of how CD8 T-cells act?
Cytotoxic T cells (CTL) kill their targets by programmed cell death. 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 three major functions CD8+ T-cells carry out post activation?
The first is secretion of cytokines, primarily TNF-α and IFN-γ, which have anti-tumour and anti-viral microbial effects. The second is the production and release of cytotoxic granules. These granules, also found in NK cells, contain two families of proteins, perforin, and granzymes. The third major function of CD8+ T cell destruction of infected cells is via Fas/FasL interactions.
Describe the role of perforin and granzymes
Perforin forms a pore in the membrane of the target cell, similar to the membrane attack complex of complement. This pore allows the granzymes also contained in the cytotoxic granules to enter the infected or malignant cell.
Granzymes are serine proteases which cleave the proteins inside the cell, shutting down the production of viral proteins and ultimately resulting in apoptosis of the target cell. The cytotoxic granules are released only in the direction of the target cell, aligned along the immune synapse, to avoid non-specific bystander damage to healthy surrounding tissue. CD8+ T cells are able to release their granules, kill an infected cell, then move to a new target and kill again, often referred to as serial killing.
