cate lymphocytes Flashcards
when is an adaptive immune response initiated?
when a pathogen overwhelms innate defence mechanisms
how is the adaptive immune response triggered?
as pathogen replicates and antigen accumulates, sensor cells of the innate immune system become activated to trigger the adaptive immune response.
what does the adaptive immune response involve?
expansion of antigen specific lymphocytes
formation of memory cells for long lasting immunity
what major event occurs in peripheral lymphoid organs/tissues to initiate the adaptive immune response?
B or T lymphocytes encounter antigens specific to their receptors
what is an antigen?
molecule (mostly protein) that is recognised by highly specialised lymphocyte receptors, and induces adaptive immune response
what are the hallmarks of the adaptive immune response
highly specific
long-lasting protection
whats the problem with specificity?
the problem of antigen diversity
need very large repertoire of lymphocyte receptors to recognise huge array of antigens
how is diversity generated in the adaptive immune response?
immunoglobulin gene rearrangement
what are the different chains on the BCR receptor?
lamda, kappa, heavy chain genes
explain immunoglobulin gene rearrangement
each BCR receptor chain (lamda, kappa, heavy change genes) is encoded by separate multi-gene families on different chromosomes
during B cell maturation (in bone marrow) these gene segments are rearranged and brought together
how could autoimmunity occur?
during immunoglobulin gene rearrangement (to create many different lymphocytye receptors) you are rearranging gene segments and them bringing them back together.
you may accidentally make a receptor that reacts against your own self antigens
what are the primary cells of the adaptive immune response?
B cells = humoral/antibody response
T cells = cell-mediated response
list differences between T and B cells
how is a T lymphocyte produced?
antigen binds to receptor, cell proliferates and differentiates into effector T lymphocyte
what are the 3 types of t cells?
cytotoxic- kill other cells infected with viruses of other pathogens
helper: produce cytokines, activate other cells such as B cell production of antibodies and macrophage killing of engulfed pathogens
regulatory: suppress activity of other lymphocytes, help limit possible damage of immune response
why do B cells have gene rearrangement and T cells don’t?
there is no class changing in T cells
T cells dont make antibodies
primary function of t cells is activation of macrophages, cytokine release, activation of B cells
TCRs dont need to recognise everything like BCRs, they only recognise peptides presented by MHC.
B cells produce antibodies specific to a specific pathogen
T cell just looks at proteins expressed on surface of infected cells, doesn’t need pathogen specific antibody
which molecule distinguished T helper and T killer cells?
CD4= T helper
CD8 = T killer
what do T helper cells produce?
interleukins
what are the 5 kinds of T helper cells?
Treg- antinflammatory, limits immune response
IL-10 is the IL that limits the immune response
Th2 = proallergenic
boost multicellular response
Th17: proinflammatory
control bacterial and fungal infection
Tfh: pro-antibody
Th1: pro-inflammatory
boost cellular immune response
IL12
what is Th1 involved in?
B cell class switching
some roles in macrophages and inflammation
what is Th2 involved in?
allergies and worms
help control infections by extracellular parasites
what is Th17 involved in responding to?
neutrophils, bacteria, fungi
what do Tfh (T follicular helper) cells do?
B cell support
interact with B cells to regulate antibody production
what do Tregs do?
limit immune response
anti-inflammatory
produce IL-10
what do Tregs do?
limit immune response
anti-inflammatory
produce IL-10
what are interleukins?
type of cytokine
essential role in activation and differentiation of immune cells
how do T helper cells contribute to B cell activation?
T cells express surface molecules and cytokines needed to support B cells to proliferate and differentiate into plasma cells and into memory B cells
how do CD8 t cells kill pathogens?
by apoptosis
cytotoxic t cells (CTLs) store perforin, granzymes and granulysin in cytotoxic granules, released after target recognition
perforin goes into target cell and creates a pore, perforates
granzymes = enzymes that trigger apoptosis
how do T cells recognise pathogens?
MHC
what is an epitope?
region of antigen that is recognised by receptor
what do infected cells/APCs express on their surface?
peptide fragments of the pathogens proteins
the MHC delivers these fragments to the cell surface
what does the MHC do?
presents fragments of antigens to T cells
important in recognising self and non-self
critical in surgery and donor matching
whats the difference between MCHI and MHCII?
MHCII can activate cells more quickly
which MHC do CD8 cells recognise?
MHC I
cd8 cytotoxic t cell is primarily responsible for pathogen surveilance
antigens derived from viruses/bacvteria dividing inside an infected cell are displayed on the cells surface by MHC I
they are then recognised by the antigens receptors of cytotoxic t cells
which MHC do CD4 cells recognise?
MHC II
expressed by APCs (macrophages, dendritic cells, B cells)
CD4 recognise antigens taken up by phagocytosis from extracellular environment (exogenous antigens)
CD4 differentiate into several types of effector T cells that orchestrate dif immune functions
describe briefly, process of MHCI
virus infects cell
viral proteins synthesised in cytosol
peptide fragments of viral proteins bound by MCI in ER
bound peptides transported by MHCI to cell surface
cytotoxic T cell recognises complex of viral peptide with MHC class I
kills infected cell
how is MHC expressed?
co-dominant (maternal and paternal genes both expressed)
so each person can have up to 6 of each gene if completely heterozygous
means its a way of expressing self, hard to transplant organ, body might recognise as non-self and attack it
what is codominance?
when 2 alleles are expressed separately to yield different traits
both alleles at a gene locus are fully expressed in the phenotype
neither phenotype is completely dominant
what properties of the MHC make it difficult for pathogens to evade immune responses?
MHC is polygenic
contains several different MHCI and MHCII genes
so every person has a set of MHC molecules with different ranges of peptide-binding specificities
MHC is highly polymorphic
multiple alleles of each gene within the population as a whole
what gene encodes the MHC molecules?
HLA gene, found on chromosome 6
how are B cells activated?
by T cells, MHCII
what are the 2 pathways by which antibody production by B cells is achieved?
thymus dependent pathway
thymus independent pathway
explain the thymus independent pathway
thymus independent antigens can induce antibody production in the absence of t helper cells
typically highly repetitive molecules
only occurs in IgM: no memory
explain the thymus-dependent pathway
BCR recognises thymus dependent 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 the matched CD4 helper cell
B cell activated (class switched, mature plasma/memory cell)
what happens when B cells are activated?
clonal expansion
explain clonal expansion of lymphocytes
foreign antigen binds to receptor on mature naive lymphocyte
lymphocyte is now activated and starts to divide
produces clone of identical progeny
this is clonal expansion
antigen specificity is maintained as progeny proliferate and differentiate into effector cells
what is a naive cell
mature cell which has matured in thymus but not yet encountered its antigen
stage between maturity and activation
what are the different kinds of antibody produced by B cells?
G M A D E
what is the class of an antibody defined by?
the structure of its heavy chain
IgG, M A D E
IgM has pentameric shape
produced first
only produced with thymus independent pathway
not as specific as IgG so not as strong an immune response
IgG produced after clonal expansion has occurred
label this IgG antibody
Fab = antibody (variable region)
Fc = constant
2 heavy chains, 2 light chains
heavy chains linked to each other by disulphide bonds
each heavy chain linked to a light chain by a disulphide bond
2 types of light chains, lambda and kappa, are found in antibodies
what are the core functions of antibodies?
complement activation
neutralisation
opsonisation
what is neutralisation?
antibodies bind to viruses/bacterial toxins and block their access to cells they might infect or destroy
what is complement activation?
antibodies coat a bacterial cell
C regions* form a platform that more efficiently activate complement proteins (covalent deposition on bacterial surface)
complement proteins on the bacterium can be recognised by complement receptors on phagocytes
this stimulates phagocytes to ingest and destroy the bacterium
what is opsonisation?
antibodies coat bacterium to better enable a phagocytic cell to ingest and destroy it
pathogen is tagged for phagocytosis
