Discuss the differences between recognition of antigens by T and B cells
T Lymphocytes focus on intracellular microbes.
T cells cannot recognise a antigen directly, need to have it presented to them
CD8+ (MHC1)
CD4+ (MCH2)
Describe the main antigen presenting cells and the signals that they provide to T cells
Triple handshake (signal)
1. Antigen recognition
2. co-stimulation
3.Cytokines
Il12- differentiation into TH1
Il4 - differentiation into TH2
Discuss the main structure of T cell receptors and their role in antigen recognition by CD4+ and CD8+ T cells
2 chains, each having 1 variable and 1 constant region.
generated by re-arrangement of genes
bind to MHC outside of antibody groove, this then decreases threshold for T Cell activation
Describe the exogenous antigen processing and presentation pathway (MHC II and CD4+ T cells)
uptake of extra cellular proteins into vesicles
process of internalised proteins
transport of MHC2 to endosomes (inhibited at this point)
association of processed peptides with MHC2
transport to surface
Describe the endogenous (cytosolic) antigen processing and presentation pathway (MHC I and CD8+ T cells)
proteasome breaks down cytosolic proteins
transported to ER
assembly of peptide- MHC1 complexes in ER
surface expression
Discuss the main structure of MHC molecules and their role in antigen recognition by CD4+ and CD8+ T cells
MHC 1 had Alpha chain and B2 microglobulin
MHC2 has an alpha chain and a Beta chain.
Understand the basic principles of B cell maturation and antibody generation
to be fuly developed need an IgM and an IgD expressed.
Naive B cells populate lymph nodes/ spleen and wait for antigens.
Meet a T Helper cell ‘recognises’ an antigen.
migrate to a primary focus- start prod antibodies- poor affinity.
Some migrate to germinal centre- undergo somatic hyper mutation and affinity maturation- better fit for antibodies.
Describe the structure of antibodies and their role (ie main effector mechanisms) in the immune system.
two identical heavy chains. two identical light chains.
5 types of heavy chains (corresponds to Ig M,G,A,D,E)
2 types of light chain Kappa, lambda
3 hypervariable regions in both heavy and light chain antigen binding sites. These are the sites that make contact.
rest of variable region is the framework.
neutralization of infectivity, phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and complement-mediated lysis of pathogens or of infected cells
Discuss mechanism of isotype switching and describe the role of helper T cells in this process
The Same B Cell is capable of prod different classes of antibody.
IgM–> G,A,E
IgG A,E
THelper (CD40L) cell interact with CD40 on B Cell
Cytokines released
IFN-Gamma switch to IgG1/3
IL-4 –> IGE
TGF-B, IL-5 –> IgA
DNa rearrangement- irreversible, initiated by AID enzyme. removed interveining DNA sequences.
Understand the principles of generation of antibody diversity
limited number of whole genes to code for antibody diversity. BUT
Variable regions = gene segments
Vheavy encoded by 3 segments
Vlight encoded by 2
gene segment recombination makes antibody diversity.
I.E combining different VJD segments on the germ line, before splicing causes different genes all from the same DNA.
Understand the process of affinity maturation
needs continued signals from TH cells.
initial antibodies weak affinity
after somatic hyper mutation- mutations in variable region of immunoglobulins (rearranged VDJ/VJ) increaces affinity (through +ve/-ve selection)
Initiated by AID Enzyme (activation-induced cytidine deaminase)
Define the complement system
an innate cascade complex.
activates small soluble heat sensitive proteins - combine and create proteolytic complexes.
the interface between innate and adaptive immunity. Enhances the ability of the antibodies and phagocyte elements to opsonise and eliminate pathogens.
List the main functions of complement in the immune response
Recognise
Opsonisation
Effector (inflamation, phagocytosis, membrane attack)
other:
chemotaxis, adhesion of inflam cells.
Vascular permeability, contraction of smooth musc cells
disposal of waste (immune complexes, apoptitic waste)
Describe the main pathways of complement and the terminal complement pathway
Classical:
Antibody triggered
results in C3b coating the outer surface of the target cell.
C3 convertase is a pretty important molecule.
Understand the need for regulation of complement activation and outline how this is achieved.
could get spiral of lysis on host cells.
Host cell membranes have mollecules that inhibit actions of important mollecules
Understand how loss control of the complement system can lead to disease and relate to clinical examples.
Describe the main pathways of complement and the terminal complement pathway
Lectin:
Atypical glycosylation
Mannnose binding lectin, N-ac gluc binding Ficolin
Yeast cells + some bacteria have mannose on their surface glycoproteins.
Describe the main pathways of complement and the terminal complement pathway
Alternative:
C3b generated by Lectin and classical
Tick over feedback- spont hydrolysis, amplification loop.
C3 H2o shot phased, splits to C3b. starts the cycle.
Describe the main pathways of complement and the terminal complement pathway
Terminal:
results in C9 molecule forming holes in the target cell, which causes contents to leak out.
Talk about C1 complex
formed from C1q and a two each of C1r and C1s
catalyses the break of C4 and starts cascade.
mannose binding lectin receptors function in a similar way and look the same.
