Lymphocytes Flashcards
What is immunological memory?
Antigenic presence is recognized and responded to by the immune system, contributing towards immunological memory through the mitotic division of antigen-specific lymphocyte B and T cells, by clonal selection
Stimulates secondary immune response.
Why is the secondary immune response faster and more effective in comparison to the primary response?
-B memory cells are stimulated to divide and rapidly produce a greater quantity of antibodies in a shorter time interval
-Antibodies have a greater affinity to antigen
-There is no lag period, thus suppresses the pathogenic proliferation and preventing onset of symptoms
Where are T cells produced?
Produced in the bone marrow
Where do T cells mature?
Become biologically active in the thymus gland
What is present on t cells?
T-cell receptors (TCRs)
What are T killer cells?
Produce chemicals to destroy infected body cells
What are T helper cells?
Activate the plasma cells+CD8 cells to produce antibodies against the antigens on particular patogen and also secrete opsonins
What are opsonins?
Chemicals which bind to pathogens and label, them, making them easily recognizable by phagocytes
What are T memory cells?
Long-lived cells formulate part of the immunological memory.
When an identical pathogen is re-encountered, the memory T cells rapidly divide, forming a large clone of T killer cells.
Which complexes display antigenic peptides on the cell surface membrane?
Major histocompatibility complexes.
What is the humoral response?
Results in the production of antibodies which are not attached to cells but are carried in blood and tissue fluid
B cells produce antibodies, by are activated by T cells, the humoral response includes the T helper activation and effector stage
What two main stages form the humoral response?
T helper activation and effector stage
What is the first function of CD8+ T cells?
Secretion of cytokines, primarily TNF-alpha and IFN-gamma, which have anti-tumor and antiviral microbial effects
Which cytokines are released by CD8+ T cells?
TNF-alpha
IFN-gamma
What is the second primary function of CD8+ T cells?
Release of cytotoxic granules contains perforin and granzymes
Perforin forms pore in the membrane of the target cell, attributing similar mechanisms to the membrane attack complex of complement
Pore enables granzymes also contained in cytotoxic granules to enter cells
What two cytotoxic enzymes are found within cytotoxic CD8+ granules?
Perforin and granzymes
What are granzymes?
Serine proteases cleave proteins intracellularly, inhibiting viral protein synthesis and resulting in apoptosis of the target cells
How are cytotoxic granules released to prevent unwanted non-specific damage?
Released only in the direction of the target cell, aligned along the immune synapse to avoid non-specific bystander damage to healthy surrounding tissue
What is serial killing?
CD8+ T cells release granules, kill infected cell and move to new target
Which types of cell surface interactions do CD8+ T cells cause to target cells?
Fas/FasL interactions (L = ligand)
Upon FasL interactions with Fas receptors on target cells what happens?
Fas molecules on target cell surface to trimersise, aggregate signaling molecules - activates caspase cascade, results in target cell apoptosis
What is fratricide?
Eliminates immune effector during the contraction phase, terminating immune response
What are the main dendritic antigen-presenting immune cells?
Macrophages
What is the initial stage of T-helper activation?
Macrophages and phagocytes engulf pathogens during internalisation , at the rough endoplasmic reticulum, the antigenic proteins are fragmentized into a specific sequence of antigenic peptides, these are associated with major histocompatibility complex
Complexes move to the surface of the macrophage cell outer membrane = BECOMES antigen-presenting cell
How do CD4+ cells recognise MHC-II?
Specific TCRs bind to the MHC-antigen peptide complex on the APC. This triggers intracellular signals, causing the release of cytokines (interleukin-2 from Th)
Which interleukin is released upon TCR-MHC binding?
IL-2
What effect does IL-2 have on T helper cells?
Autocrine and paracrine effects stimulate mitotic cell division into active t helper cells, proportion into memory cells
Activation of b and cd8 cells.
Which receptors are located on B cell surface?
B-cell receptors (BCRs)
These are complementary to the antigenic peptides presented.
Upon antigen recognition, what occurs within the B cell?
Internalization of the pathogen by endocytosis. Vesicle forms around fuses with lysosome and enzymes digest the pathogen, resulting in remaining fragments of processed antigen.
These fragments become attached to MHC proteins within the cells forming an MHC-antigen complex which is transported to the cell surface membrane, where the antigen is displayed
B cell is considered as an antigen-presenting cell
How are b cells activated?
An activated T helper cell with a complimentary receptor binds to the antigen-presenting cell, producing cytokines that stimulate B cell.
Which cells do b cells divide into during activation?
B memory and effector cells.
The B effector cells differentiate into plasma cells
Which specific cells secrete antibodies?
Plasma cells
What term describes the process of plasma cells producing large amounts of antibodies that are identical to the immunoglobulin of the originate parent B cell.
Clonal selection
What is agglutination?
When antibodies bind to the antigens, the micro-organisms agglutinate together; preventing spreading and easy phagocytosis
What is opsonization?
Antibody acts as an opsonin- a chemical which makes an antigen more easily recognized by phagocytes
What is neutralisation?
Antibodies neutralize the effects of bacterial toxins by binding to them
What is lysis?
Breaking open of bacterial cells.
What is the Cell-mediated response?
Involves T killer cells, these cells have specific receptors in their cell surface membrane which respond to specific antigens
T lymphocytes respond to altered cells including antigen presenting cells, mutated cancer cells or transplanted cells.
How are T killer cells activated?
Upon binding onto antigen-MHC complexes on the surface of the body cell. Activated T helper cells produced through T helper cell activation release cytokines, consequently stimulating a series of rapid cell divisions to produce a clone of identical active T killer cells, and T killer memory cells
What is the function of porins?
Porins form pores within the cell surface membrane of target cells, therefore this increases the permeability of the cell surface membrane, enabling free entry of water and ions, causing the cell to swell and burst.
Which part of the antigen is recognized by t cells?
Epitopes in the context of MHC
What are antigens?
Proteins or molecules that induce an adaptive immune response
What is an epitope?
The region of an antigen that the antibody binds to. Antibodies recognize structural properties.
Which lymphocyte type detect epitope sequences?
T cells identify the sequence
Which lymphocyte type detects the tertiary structure of antigen?
B cells
How is antigen diversity maintained?
A repertoire of specific BCRs
What is a repertoire?
Range of genetically distinct BCRs or TCRs, present in a given host
Larger the repertoire the greater the number of recognizable threats.
How many genes encode for all antibody functions?
25,000 genes, 10^10 different molecules
What happens to BCRs during B cell maturation?
These gene segments are rearranged and brought together
Immunoglobulin gene rearrangement results in diversity of lymphocyte repertoire.
What is post-transcriptional modification?
Primary RNA transcript is complimentary to the exons & introns present in the base sequence of the template strand.
Intron sections removed from pre-mRNA and the exons are combined together through MRNA splicing.
Spliceosomes involved; exons of the pre-MRNA molecules can be spliced together in varying orders, coding for a different polypeptide sequence, variants of multiple proteins
Immature B cells in bone marrow have ____DNA:
Germline
Which recombinase enzyme enables DNA recombination?
VDJ recombinase encoded by RAG genes
Which genes encode for the light chain of antibodies?
V + J
Which genes encode for the heavy chain of antibodies?
V, J + D
Which region determines the type of antibody?
The constant region, alpha constant region gives rise to IgA
How are TCRs formed?
Gene reassortment
Which antibody region interacts with the antigen?
Variable region, recognizes antigenic fragment presented by antigen-presenting cells (epitope)
Which types of cytoplasmic chains within T cells interact with opposite residues in the transmembrane region of CD3 polypeptides?
Alpha and beta charged residues
What is CD3?
CD3 is present on all T lymphocytes (forming the constant region of the TCR)
What is the function of CD3 polypeptides?
Essential in the delivery of intracellular signal to the T-lymphocyte upon antigen-recognition
CD3 polypeptides have longer cytoplasmic tails, consists of motifs containing tyrosine residues.
Upon antigen recognition what happens to the tyrosine residues?
Phosphorylation of tyrosin proceeds in the motifs, when the TCR encounters the antigens, triggers a chemical cascade/
What is ITAM?
Immunoreceptor Tyrosine based activation motif
Which gene encodes for MHC?
Human leukocyte antigen (HLA)
What is the function of the MHC?
Presents processed peptide antigenic fragments to T cells
Where are MHC I and II found and what is their structure?
MHC I: On all nucleated cells and has a single variable alpha chain plus a common beta-microglobulin
MHC II: Only on professional antigen-presenting cells, has 1 alpha and 1 beta chain
Through what process is our lymphocyte repetoire produced?
Immunoglobulin gene rearrangement
What kind of MHC epitopes do T cells recognise?
Linear
What kind of MHC epitopes do B cells recognise?
Structural
How is lymphocyte antigen diversity 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
What is the structure of a T cell receptor like and what is its purpose?
To recognise pathogenic antigens in the context of an MHC
How is MHC gene expression coded?
Co dominant
3 loci for class 1
3 loci for class 2
Up to 6 different proteins-Over 17000 variants
What is the purpose of Tfh
Pro-antibody
What is the purpose of Th17
Pro-inflammatory
Boost bacterial+fungal infection
What is the purpose of Th1
Pro-inflammatory
Boost cellular immune response
What is the purpose of Th2
Pro-allergic
What is the purpose of Treg(T0)
Anti-inflammatory
Limit the immune response
What are the 3 core roles of antibodies
Neutralisation
Opsonisation
Complement activation
What is the difference between thymus dependent and independent B cell activation?
Thymus dependent produces all IgG classes(1-4) and produces memory cells
Thymus independent only produces IgM and produces no memory
How are B cells activated without T cells?
Often polysaccharide, needs to have a repetitive structure, e.g. bacterial surface sugars
The second signal required is provided by a microbial PAMP, e.g. LPS
How are B cells activated with T dependent antigens?
The membrane bound BCR recognises antigen
The receptor-bound antigen is internalised and degraded into peptides
Peptides associate with “self” molecules (MHC class II) and is expressed at the cell surface
This complex is recognised by matched CD4 T helper cell
B cell activated
How can naive B cells be activated?
First needs antigen, then either:
- Directly from microbial constituents
- From a T helper cell
Outline the distribution of antibodies
IgA in GI tract
Everything else in circulation
Which class of antibody forms dimers with a J chain after its secreted?
IgA
Which class of antibody forms a pentamer?
IgM
Which antibody class has the highest neutralisation and opsonisation activities and has 4 subclasses
IgG
Which antibody is produced first on antigen contact?
IgM
Which antibody class is present in mucosal tissues?
IgA
What are the major cells in the innate and adaptive immune response?
Innate: Macrophages, neutrophils
Adaptive: T/B lymphocytes
