Adaptive immunity Flashcards
adaptive immunity basic
specific to a pathogen
slower
humoral immunity within adaptive
proteins dissolved in serum, plasma nd tissue fluid
antibodies
cells involved in adaptive immunity
b cells
antibodies
t cells
effector t cells
memory t and B cells
where do the 3 main types of lymphocyte originate from
common lymphoid precursor
lymphocytes that make ups the adaptive immune system
T and B cells
recognise specific antigen
proliferate and differentiate to mediate effector function
provide immunological memory
antigens
parts of pathogens (often proteins or parts of proteins) to which T and B cells respond
they respond via their antigen receptor
which is highly specific i
lymphocyte antigen receptors
unique antigen receptor on each lymphocyte
large diversity of specificities in T and B cell populations
what is antigen recognition by a specific lymphocyte linked to
activaiton
proliferation
differentiation
results in many specific cells with effector function
T cell responding simple
cytotoxicity
help of other cells
regulation
B cells responding simple
antibodies (neutralisation, opsonisation, activation of complement)
memory T and B cells
long-lived and triggers a quicker and more effective immune response on second infection with the same pathogen
primary lymphoid organs
bone marrow and thymus
where lymphocytes develop and mature from bone marrow-derived stem cells
secondary lymphoid organs
lymph nodes, spleen, MALT
site where adaptive immune responses are coordinated
T cells
originate in the bone marrow
mature in the thymus
express antigen receptor known as T cell receptor (TCR)
TCR recognises peptides presented to it
in the right conditions, T cell breaking TCR recognising the presented peptide becomes activated, proliferates and differentiates into lots of cells which have effector function
5 steps of T cell immune response
diversity
specific recognition
activation
proliferaiton and differentiation
response by effector cells
TCR diversity
genetic mechanism evolved to create diversity of specificities in the adaptive immune system
schematic structure of the T cell receptor
heterodimeric receptor
2 different chains, alpha and beta
with diversity why are many TCR not suitable
some useless: don’t bind peptides presented by molecules on your cells
dangerous: bind self-peptides very strongly
cells bearing these TCR die during T cell development in the thymus
T cell specific recognition
antigen must be broken down into peptide fragments
epitope peptide binds to a self molecule, MHC molecule
TCR binds to complex of MHC molecule and epitope peptide
2 main types of T cells
helper T cells
cytotoxic T cells
helper T cells: MHC, co-receptor and function
MHC 2 (presents antigen only on professional antigen presenting cells)
CD4
produces cytokines to activate others immune cells
express surface molecules to affect other cell types
cytotoxic T cells: MHC, co-receptor and function
MHC 1 (presents antigen on all body cells)
CD8
]kill virus-infected cells directly
which T cell is in the image
CD4 T cell
which T cell is in the image
CD8 T cell
example of an antigen presenting cell
dendritic cell
it is professional
key role in initiating adaptive immunity by linking innate to adaptive
key features of dendritic cells
specialised for antigen uptake and presentation
mature when stimulated by PAMPs and DAMPs
how are dendritic cells specialised for antigen uptake and presentation
dendritic cells present antigen open both MHC class 1and 2
sp they can activate CD8 and CD4 T cells
how are dendritic cells matured when stimulated by PAMPs and DAMPs
cause them to express high levels of molecules required to activate naive T cells
migrate to secondary lymphoid tissue which is a specialised structure for initiation of adaptive immunity
how are professional APC specialised to initiate adaptive immunity
provide all the signal necessary to activate naive T cells
express MHC 1 and 2 so can activate CD8 and CD$
nucleated cells, MHC class?
all express MHC class 1
means when infected they can present pathogen-derived antigens and be targets of CD8 cytotoxic T cells
other examples of professional APC
macrophages and B cells
what are MHCs and HLAs
MHC: major histocompatibility complex
HLA: human leukocyte antigens
large proteins antigens
digested into small peptides, epitopes of the antigen
where are peptide epitopes bound to
in the peptide-binding groove of the HLA encoded by MHC genes
HLA in MHC class 1
A,B and C
HLA in MHC class 2
DP, DR and DQ
which MHC class is this
class 1
expressed by all nucleated cells
binding groove holds short peptides, 8-10 amino acids
which MHC class is this
class 2
expressed by APCs
binding groove holds larger peptides, 13-17
mhc genes
polygeny
polymorphism
polygeny
several MHC genes
polymorphism
variation in population- protection at population level
MHC 1 presentation
infection of body cell by virus
virus is chopped up by the proteasome
new viral particles are synthesised in the ER
antigens landed onto the MHC 1 in the endoplasmic reticulum
activates CD8 cytotoxic T cells
MHC 2 presentations
phagocytosis of pathogen by antigen presenting cell
pathogen is chopped up by phagolysosomes
antigens loaded onto MHC 2 in the phagolysosome
activates CD4 helper T cells
signals that naive T cells need to be activated
antigen binding to the T cell receptor
costimulation
cytokines
first signal of T cell
peptide-MHC : TCR
if there is a recognition then an immune synapse forms
second signal of the T cell
costimulation
B7: CD28
third single of T cells
cytokines
APC produces cytokines that instruct the T cell to differentiate into the right type of effector T cell to destroy the pathogen
outcomes of the activation of T cells
T cell activation, proliferation and differentiation
lots of cells ready to destroy pathogen directly or indirectly
what do effector cells not need
co-stimulation to exert their function
what are the types of t helper cells
Th1
Th2
Th17
Tfh
T reg
Th1
polarising cytokine: IL-12
transcription factor: T-bet
cytokine produced: IFN gamma
primary function: activate macrophages
Th2
polarising cytokine: IL-4
transcription factor: GATA3
cytokines produced: IL4,5 and 13
primary function: activate eosinophils and mast cells, alternative macrophage function
th17
polarising cytokine: IL-6 and 21
transcription factor: ROR gamma T
cytokines produced: IL-17 and 22
primary function: enhance neutrophil response
Tfh
polarising cytokine: IL-6, TGF beta, IL-23
transcription factor: Bcl6
cytokines produced: IL-21 (and IL-4 or IFN gamma)
primary function: activate and mature B cells
T reg
polarising cytokine: TGF beta
transcription factor: FoxP3
cytokines produced: IL-10, TGF beta
primary function: suppress other effector T cells
what can CD8 cytotoxic T cells do after recognition
can kill virus infected cells
cytotoxic T cells killing mechanism
killing is specific, requires the specific peptide-MHC: TCR interaction
killed by: perforin/granzyme or Fas:FasL interaction
fas:FasL interaction
FasL is expressed by cytotoxic T cells and Fas is expressed by the target cells
FasL- Fas interaction activates FADD then pro-caspase 8 in the target cell
during apoptosis, caspases are activated
activation of cascades results in orderly destruction of the target cell
what are caspases
cysteine proteases that cleave aspartic acid
granzymes/ perforin
exocytosis of lytic granules at the immune synapse
attack of the target membrane: perforin polymerise forming cylindrical pores in the target cell, granzymes enter
triggering of caspase cascade, leading to DNA cleavage and cell death
CD4 T cell help of CD8 T cell ctivaiton
activated CD4 T cells expresses CD40L ligand on its surface
induces expression of IL-2
cross primes CD8 by enhancing APC activation
stimulation of APC through CD40 increases B7 and CD40, co-stimulate naive CD8, increase APC production of IL-12
cross presentation
how antigen taken up by phagocytosis gets loaded onto MHC 1
important for anti-tumour and anti-viral immunity
b cells
produced in the bone marrow and exit with the recombined antigen
antigen receptor is the B cell receptor
B cells with BCR specific to the antigen become activated, proliferated and differentiate into effector cells
plasma cells make antibodies
stages of B cell immune response
diversity
specific recognition
activation
proliferation and differentiation
effector cells and memory cells
what is in the image
surface antibody
what is in the image
soluble antibody
rearrangement of immunoglobulin genes
rearrangement at heavy and light lg chain loci
nucleotides are added or removed at random between the segments as they come together in the recombined gene
B cell receptors
bind directly to the antigen even if they are still attached to the pathogen
B cell 3 signals
BCR signalling and uptake
co-stimulation
cytokines
B cell first signal
antigen activates the B cell via the BCR
it is taken up, processed and presented on MHC 2 to a specialised CD4 t helper cell
B cell second signal
CD40: CD40L
B cell third signal
cytokines produced by the T cell intersect the B cell to produce certain antibody type
B cell activation
B cell is activated, proliferates and differentiated into plasma cells and memory cells
IgM is the first antibody class type to be made
what is the first antibody class type to be made
IgM
plasma cells
produce and secrete antibody
cytokines produced by the T cell direct class-switching of B cells
what must the classes of antibodies have
a different heavy chain constant region, region linked to the function
variable region q
determines antigen specificity
constant region
determines antibody class
finds Fc receptors
what are the 5 types of antibodies
IgG
IgE
IgD
IgA
IgM
IgG
multi-purpose
high affinity
crosses the placenta
IgE
parasite responses and allergies
IgD
basophils
IgA
secreted at mucus sites
IgM
first to be made on encounter with antigen
IL-4 role of regulating expression of antibody classes
inhibits: IgM, IgG3 and IgG2a
induces: IgG1, IgE
IL-5 role of regulating expression of antibody classes
augments production of IgA
IFN- gamma role of regulating expression of antibody classes
inhibits: IgM, IgG1, IgE
induces: IgG3, IgG2a
TGF- beta role of regulating expression of antibody classes
inhibits: IgM, IgG3
induces: IgG2b, IgA
IL-21 role of regulating expression of antibody classes
induces: IgG3, IgG1, IgA
what are the functions of antibodies
neutralisation
opsonisation
complement activation
NK cell sensitisation
mast cell, eosinophil and basophil sensitisation
neutralisation
IgA and IgG
antibodies that bind bacterial toxins and virus particles
stop them binding receptors on host cells and prevent damage to tissue
opsonisation
IgG
antibodies that bind to pathogens
phagocytes recognise bound antibody via Fc receptor
trigger phagocytosis and killing
complement activation
IgM and IgG
antibodies that bind pathogens and activate the complement pathway
trigger formation of membrane attack complex and killing of pathogen
NK cell sensitisation
IgG
antibodies binds antigens on the surface of target cells
Fc receptors on NK cells recognise bound antibody
cross-linking of Fc receptors signals the NK cell to kill the target cell
target cell dies by apoptosis
mast cell sensitisation
mast cells express Fc receptors recognising IgE
crosslinking of the antibodies by antigen causes mast cell degranulation
releasing mediators such as histamine
eosinophil sensitisation
regonise UgE bound to parasites and release granules to kill the parasites
basophil sensitisation
recognise IgD
activating anti-microbial and pro-inflammatory mechanisms
