The adaptive immune system Flashcards
What is an adaptive immune response?
Specific recognition of pathogens forming memory, through activation of antigen specific lymphocytes
How is the adaptive response escalated?
On activation of the lymphocyte receptor, the cells divide to produce daughter cells expressing the same receptor
Why are lymphocytes so diverse?
Due to somatic recombination of the receptor coding region in the germ line cell. BCRs can also hypermutate.
Why do TCRs require APC to break down the antigen before presenting?
T cells can only recognise short linear AA sequences at its single antibody domain.
How do APCs present antigens to T cells?
Via MHC or HLA complexes.
What do CD8 T cells recognise?
MHC I / HLA A, B, C - recognise shape and peptides from endogenous proteins.
Induces apoptosis of infected cell, followed by phagocytosis by macrophage
What do CD4 T cells recognise?
MHC II / HLA DR, DP, DQ - recognise pattern. Can bind longer exogenous peptides.
What do B lymphocytes recognise?
Can recognise whole antigens by binding to cell surface molecules or patterns.
What is an antibody / immunoglobulin?
A secreted B cell receptor from a terminally differentiated plasma cell. Effective at presenting antigens to T cells.
What proteins are involved in processing antigens of MHC I?
TAP protein - controls movement into ER
Calnexin and Calreticulin - stabilise MHC folding
Tapasin - Retain pool of MHC in ER for rapid increase in surface peptides on T cell binding
Which cells are most likely to present MHC II?
DC, monocytes/ macrophages and B cells as they can internalise exogenous proteins and process them in ER.
What is CD4?
A coreceptor of TCR
What determines the function of a T cell?
cytokine environment
How is a full immune response achieved and why is it important?
A full antibody response can only occur if both T and B cells recognise the antigen via their independent mechanisms to protect from AI.
Where is a B cell developed?
Firstly within the bone marrow and then within secondary lymphoid organs on antigen exposure.
What are the bonds linking heavy and light chains of BCR?
Disulphide bond
What is the Fab fragment?
Fragment of antigen binding. Composed of heavy and light chain. Highly variable region that determines binding specificity.
What is the Fc fragment?
The area containing the constant heavy chain which is accessible to effector ligands following formation of antigen complexes.
What is the difference between a naive B cell and a plasma cell?
A naive cell has had no antigen exposure and uses its antibody as the receptor for an antigen.
A plamsa cell is an effector molecule that sheds Ig in response to an antigen
Ig of a naive B cell cannot signal itself because its cytoplasmic tail is too short. What accessory molecule is involved?
CD19
Where is the variability of a BCR present?
Variable patterns of AA are present with V region but concentrated into the CDR of this region.
Which chains form the constant regions of both heavy and light chains?
Light chain constant sequence - Kappa or lambda
Heavy chain constant sequence - determines the type and function of the antibody. Mu = M, Gamma = G, Delta = D, Epsilon = E, Alpha = A
What is the structure of a TCR?
Contains two non-identical polypeptide chains, that both have a constant and variable region linked by disulphide bond, forming the antigen recognition site.
What is the accessory molecule of TCR?
CD3
Which chains form the two types of TCR?
Alpha + beta is most common
Lambda and delta
Why is somatic recombination important?
Allows diversity in lymphoctyes to evolve with continuously changing pathogens.
What genes make up the genetic segments of a receptor?
Variable domain
Diversity genes
Joining genes
Constant genes
Which enzyme is involved in gene recombination?
RAG (recombinase activating genes) 1 and 2. Ensures rearrangement in a specific order
What condition results from absence of RAG?
SCID as B and T cells cannot develop. An early BM transplant is curative.
What is the purpose of allelic exclusion?
An antigen receptor can only express a single specificity, but during recombination both chromosomes can be recombined to produce different specificity. Once one chromosome has successfully rearranged, the second chromosome will be prevented.
How does a virus interfere with antigen processing?
Can block protein synthesis of MHC I and can block TAP to prevent formation and evade detection.
How do NK cells detect suppression of the immune system by an antigen?
Normally NK bind to HLA-E to inhibit its activation. A virus that blocks MHC synthesis will downregulate HLA-E as the peptides from specific MHC are no longer available to bind to HLA-E and allow surface expression. If no HLA-E is present, NK cells are active and the infected cell is killed by cytotoxic products.
What is the inheritance of MHC genes?
Co-dominant = allows variation in offspring
How are lipids presented to T cells?
DC and monocytes express CD1 that can bind lipids on mycobacteria. CD1/lipid complex is presented to T cells to activate macrophages.
What are the consequences of polymorphism?
Diverse antigen responses in an outbred population, binding different spectrum of peptides.
Rapidly mutating pathogens can escape MHC molecules as some are ineffective.
