L1 - Acquired immunity: Ag recognition systems Flashcards
What are the sources of infection?
Pathogens
What are pathogens?
Organisms that cause disease • Bacteria • Viruses • Fungi • Parasites
What must the immune system be able to do for an effective immune response?
Be able to recognise & respond to any invading organism
Not over react to benign or self
Be able to direct different effector mechanisms against different pathogens
Difference between innate & adaptive immunity?
Innate is activated very quickly
Adaptive takes over if innate doesn’t completely control the pathogen
Specific/adaptive immunity
Induced by exposure to a particular infection
Shows a high degree of specificity
Exhibits memory
Features of specific immunity
Clonally distributed receptors
Large repertoire
Response takes time to develop
Memory cells produced
Clonal selection
- Removal of potentially self-reactive immature lymphocytes by clonal deletion
- Pool of mature naïve lymphocytes
- Proliferation & differentiation of activated specific lymphocytes to form a clone of effector cells
Followed by clonal expansion
What are the 2 lymphocyte receptors for antigens?
B lymphocytes
T lymphocytes
B lymphocytes
BCR expressed by B cells
Membrane anchored protein on the surface of B cell
Binds free antigen
Is subsequently secreted with B cell is activated = an antibody
T lymphocytes
TCR expressed by T cells
Membrane form only - stays on the surface where it functions
Recognises a peptide fragment of antigen bound to MHC expressed by APCs
What do antibodies do?
Activation of complement
Activation of effector cells
What are antibodies formed of?
Formed of 4 polypeptides
• 2 heavy chains & 2 light chains
Formed by domains - variable & constant
Held together by covalent & non-covalent bonds
What do the variable & constant regions do?
Variable regions form the antigen-binding sites - specific for a given Ab
Constant regions are responsible for antibody structure & interacting with other molecules
What are the 2 types of light chain?
Lambda and Kappa
What are the 5 classes of antibody?
IgM, A, D, G, E
Isotype determined by the heavy chain
Differ in structure & function
What are epitopes?
The part of an antigen molecule to which an antibody attaches itself
What are the 2 types of epitope?
Continuous
Discontinuous/conformational
TCRs
Binds/recognises processed antigens (peptides)
Heterodimer of alpha & beta chain (sometimes gamma & delta)
Each chain has a V & C region
Each chain contributes 3 CDRs to Ag binding
What are CDRs?
Complementarity-determining regions (CDRs)
Part of the variable chains in immunoglobulins (antibodies) and T cell receptors, where these molecules bind to their specific antigen
What are MHC?
Major Histocompatibility Complex molecules
Type I or II - related but different structures
Class I MHC
Expressed on all nucleated cells
Heterodimer – 3 alpha chains & beta2-microglobulin
Alpha1 & alpha2 domains fold to form beta-sheet structure known as the peptide binding site (groove/cleft)
Alpha3 & beta2-microglobulin fold into Ig-like domains
What are the 3 different MHC I molecules?
HLA-A
HLA-B
HLA-C
Encoded by separate alpha chain genes
A single gene encodes beta2-microglobulin so same in all 3
Class II MHC
Expression limited to APC (& cytokine-activated cells)
Heterodimers – 2 alpha & 2 beta chains & both transmembrane
Alpha & beta chains encoded by separate genes encoded within MHC
Both alpha2 & beta2 domains are Ig-like
Polymorphic alpha1 & beta1 domains form peptide binding sites
What are the 3 different MHC II molecules?
HLA-DP
HLA-DQ
HLA-DR
What makes up the peptide binding site in MHC I?
Alpha1
Alpha2
What makes up the peptide binding site in MHC II?
Alpha1
Beta1
What makes up the Ig-like domain in MHC I?
Alpha3
Beta2-microglobulin
What makes up the Ig-like domain in MHC II?
Alpha2
Beta2
A TCR expressed by a T cell that co-expresses CD8 can bind what MHC?
Class I MHC
A TCR expressed by a T cell that co-expresses CD4 can bind what MHC?
Class II MHC
MHC I binds what length peptides?
Binds peptide 8-10 AA to present to TCR
MHC II binds what length peptides?
Binds peptide 13+ aa to present to TCR
Define the Fab and the Fc regions of an antibody?
Fab - fragment antigen binding
Region on an antibody that binds to antigens
Fc - fragment crystallizable
Tail region of an antibody that interacts with cell surface receptors
The Lamda and Kappa chains form the …. chain of an antibody?
Light chain
Does beta 2 microglobulin bind to the processed peptide?
No
How many transmembrane domains does an MHC class I and an MHC class II molecule have respectively?
MHC I - 1 transmembrane domain
MHC II - 2 transmembrane domains
What does HLA stand for?
Human Leukocyte Antigen