lymphocytes Flashcards
- What type of immunity are T cells a part of?
- What type of immunity are B cells a part of?
- What is specificity of B and T cells due to?
Cell mediated
Humoral
respective BCRs and TCRs
- Define epitope
- What structure of epitopes do T cells recognise?
- What structure of epitopes do B cells recognise?
Region of an antigen which the receptor binds to
Linear epitopes in the context of an MHC molecule - Primary structure Structural epitopes - the 3D structure of the antigen in space
- Explain the process of clonal expansion
Each lymphocyte bears a single, unique receptor
Interaction between a specific foreign molecule and that receptor leads to activation and clonal expansion (multiple copies of same cell) Differentiated effector cells of that lineage will bear the same receptor
- Explain the antigen receptor diversity problem
- How is antigen receptor diversity generated?
We need to encode a large Repertoire of lymphocyte receptors
We need 10^15 different genes for each different antibody, but we only have 25000 genes total for all functions
Each BCR chain is encoded by separate multi-gene families on different chromosomes.
During B cell maturation these gene segments are brought together.
This process is called Immunoglobulin gene rearrangement
what are the three types of chain that form BCR?
- What is the role of an MHC?
kappa, lambda, gamma
To bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells
Critical in surgery and donor matching
defines self and non self
- Describe the structure of MHCI and where are they found?
- Describe the structure of MHCII and where are these found?
Single variable alpha chain plus a common beta- microglobulin
On all nucleated cells
2 chains - alpha and beta Normally only on "professional" antigen presenting cells
- What gene in humans encodes for MHC?
- How are MHC genes expressed?
HLA genes
MHC is polygenic - 3 class I and 3 class II loci Co-dominant (maternal and paternal both expressed) Each person can have up to 6 of the variations of the gene if completely heterozygous
- What are the 2 T cell families?
- Which MHC is presented to CD8 T cells?
- Which MHC is presented to CD4 T cells?
CD4(helper) and CD8(killer)
MHC1
MHC 2
Where are intracellular MHC/TCR interactions processed?
what are they presented on
what are they presented to
which domain of MHC molecule does CD8 cell bind to
Cytosol
MHC1
CD8 T cells
alpha 3 domain
Where are extracellular MHC/TCR interactions processed?
what are they presented to
what is it presented on
which domain on MHC?
endosomes
CD4 T cells
MHC2
beta 2
- Explain what CD4 T helper cells do
They produce cytokines (family of inflammatory mediators)
Influence the outcome of the immune response.
- List all 5 CD4 T helper cell classes
Th1 - boosts cellular immune response
Th2 - boosts multi-cellular response Th 17 - controls bacterial and fungal infection Treg (Th0) - limits immune response Tfh - pro-antibody
- Which CD4 T helper cell class are pro-inflammatory?
- Which CD4 T helper cell class includes interleukins 4,5 and 13?
- What CD4 T helper cell class is pro-allergic?
- Which class of CD4 T cells includes interleukins 6, 17 & 23?
Th1 and Th17
Th2
Th2
Th17
what cytokines are released by a:
- TH1 response
- Tfh response
- Treg response
IL-12
TNF- tumour necrosis factor
INF- Gamma
IL-21
IL-10, TGF-beta
- How do cytotoxic T cells (CTL) kill their target cells?
- How is apoptosis characterised?
Apoptosis
Fragmentation of nuclear DNA
- What do Cytotoxic T Cells store and then release after target recognition?
- How is apoptosis carried out by CD8 T-cells?
Perforin, granzymes, granulysin (all in cytotoxic granules)
CD8 T cell makes Perforin hole in the infected cell Injects granzymes into the cell Granzyme triggers cascade of events within target cell which leads to cell death and kills anything within inside of target cell
- Outline the process of how CD8 cells kill cells once they are infected
- Virus infects the cell and releases its contents
- Cell now starts making viral proteins
- Displays these as non-self MHC
- CD8 cell detect non-self MHC and attacks
- CD8 cell kills the virally infected cell
- What is the main purpose of B cells?
- What are the 3 core protective roles of B cells?
To make antibodies
- Neutralisation - antibody prevents bacterial adherence to host cell - Opsonisation - promotes phagocytosis - Complement Activation - enhances opsonisation and lyses some bacteria
- List all of the antibody classes
- IgG: highest opsonisation and neutralisation activities
classified into four sub classes (IgG1, IgG2, IgG3, IgG4)- IgM: Pentamer, produced first upon antigen invasion, increases transiently
- IgA: form dimers after secretion
expressed in mucosal tissues - IgD: unknown function
- IgE: Involved in allergy
- Which antibody class is involved in type I hypersensitivity?
- Which antibody class is expressed in mucosal tissues?
- Which antibody class has highest opsonisation activity?
- Which antibody class has highest neutralisation activity?
IgE
IgA IgG IgG
- Where does B cell generation and maturation occur?
- What do mature B cells migrate into from the bone marrow?
In bone marrow in the absence of antigen
Circulation and lymphoid tissues
- What do naïve B cells require to be activated?
- Describe the Thymus Independent activation of B cells
Accessory signal:
1. Directly from microbial constituents (thymus independant) 2. From a T helper cell
Thymus independent antigens directly activate B cells without help of T cells- usually polysaccharide
Second signal required is provided by a microbial PAMP eg LPS from gram negative bacteria
- Outline the process by which B cells are activated by T cells (Thymus Dependent antigens)
- Membrane bound BCR recognises antigen
- 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 that was activated by dendritic antigen presenting cell
- B cell activated
