Lecture 1- 6 Flashcards
What must the immune system do for an effective response?
- be able to recognise and respond to any invading organism
- not over react to benign or self
- be able to direct different effector mechanisms against different pathogens
What are the features of specific/adaptive immunity?
- mediated by lymphocytes (B/T cells)
- clonally distributed receptors = recognise different pathogens
- response takes time but memory cells are produced
What do antibodies do?
- activate the complement system = opsonisation -> classical pathway activation -> activation of effector cells
What is the role of TCR ( T-cell receptors)?
recognizes peptide fragments of antigen bound to MHC expressed by APC
What is the role of BCR (B-cell receptor)?
membrane form of Ig that binds free antigens = secreted when B cell is activated
What is the structure of antibodies?
- formed from 4 polypeptides
- 2 identical heavy chains and light chains held together by covalent and non-covalent bonds
- 2 types of light chain = lamda and kappa
- each chain has a variable region and a constant region
What is the function of the V and C region in antibodies?
- paired variable region (V) = form 2 identical antigen-binding sites
- constant (C) region = responsible for Ab structure and interacting with other molecules
What are the 5 antibody classes and how is the isotope determined?
- IgM
- IgD
- IgA
- IgG
- IgE
isotype is determined by the heavy chain (C region)
How many domains does the H and L chain on an antibody have?
L chain = 2 domains
H chain = 4 or 5 domains
What are antibody domains and what do the comprise of?
domains = patterns present in many other proteins in the immune system
comprises of two beta sheets linked by disulphide bridge
What is an epitote?
the piece of antigen that antibodies recognise
What are the characteristics of MHC class I?
- expressed on all nucleated cells
- heterodimer: alpha chain (42 kD) and b2-microglobulin (12 kD)
- 3 different types of MHC class I molecules
What are the 3 MHC class I molecules?
HLA-A
HLA-B
HLA-C
What are the characteristics of MHC class II?
- expressed only on APC and cytokine-activated cells
- heterodimer: alpha chain and and beta chain
What are the 3 MHC class II molecules?
HLA-DP
HLA-DQ
HLA-DR
What is the process by which enough cells expressing receptors for the correct pathogen is known as?
clonal selection
What are the 2 chains of an antibody called?
heavy chain and light chain
Which part of an antibody interacts with the epitope of an antigen?
two identical antigen binding sites mainly CDRs
Define the Fab and the Fc regions of an antibody?
Fab is (VH/CH1+ VL/CL1) domains (artificially generated with papain)
Fc is ((CH2/CH3/+ (CH4 sometimes)) x2 regions of antibody that binds to FcRs;
(also artificially generated with papain)
What is the antigen binding site of an antibody made up of?
variable domain of H and L chains
The lamda and kappa chains form what chain of the antibody?
light chain
How many hypervariable regions are involved with antigen binding in a single antibody molecule?
12
What type of proteins are TCR?
heterodimeric proteins
What are the most common T cells?
T cells that express gamma and delta TCRs
What class of MHC binds smaller processed peptides?
Class I MHC in the endoplasmic recticulum
What are the H chain and TCRb encoded by?
V region encoded by 3 gene segments = V, D and J
What are the L chain and TCRa encoded by?
V region encoded by two gene segments: V and J
When and why do genes rearrange?
genes rearrange during B cell development to form a functional gene
What is the gremline organisation of L and H loci in the human genome?
lamda light chain = one of the variable genes on the light chain locus randomly joins to the J region and then joins to constant region
kappa light chain = V region genes and J region genes randomly join together
heavy chain = take a D and J and then a gene segment and bind randomly with a B region and constant region
Which gene segments encode the variable region of the Ig heavy chain?
VDJ
Which gene segments encode the variable region of the light chain of an
antibody?
VJ
How are the heavy (H) chain of an antibody and the beta (b) chain of the TCR
similar?
Similar gene fragments (VDJ)
When does rearrangements of Ig genes occur?
during their development in the BM when they are termed pro and pre-B cells
Does the heavy or light chain constant region determine an antibody’s isotype?
heavy
What guides DNA rearrangement?
guided by special sequences flanking the V, D and J regions = recombination signal sequences
What do the recombination activating gene encode?
RAG-1 and RAG-2 genes encode lymphoid specific components of the recombinase
What are the 5 distinct mechanisms that allow for antibody diversity?
- Families of gene segments that re-arrange i.e. combinatorial
- junctional diversity (not precise joining)
- N region addition
- heavy and light chain pairing
- somatic hypermutation
What is allelic exclusion?
In a single B cell, only one allele of H and L chain is expressed to produce a cell with specificity to a certain antibody
What is somatic hypermutation?
AID acts on DNA to de-aminate cytosine to uracil = is recognised by error-prone DNA repair pathways leading to mutation
What is the difference between the arrangement of B and T cells?
T cells = occurs in thymus
B cells = occurs in bone marrow
What are the most abundant T cell receptors?
TCR-alpha and TCR-beta
How does MHC polymorphism affect their function?
occur in the domains that fold to form
the peptide-binding groove so will increase the no. of possible peptides that are suitable for
binding, allowing the human population to be able to bind as many different peptides as
possible