L3 - adaptive response Flashcards
innate mechanisms
rapid response to a broad range of microbes
innate external defences
skin, mucus membranes and secretions
Innate internal defences
phagocytic cells, antimicrobial proteins, inflammatory responses and natural killer cells
Adaptive mechanisms
slower responses to specific microbes
Adaptive humeral responses
antibodies
adaptive cell-mediated response
cytotoxic lymphocytes
difference between innate and adaptive
innate = cobstant adaptive = for when there is a breach
Respiratory infections account for more than ?% of the global burden of human disease
6%
Adaptive immunity is a …
protective response to antigens from pathogens
but overactivity can cause excessive inflammation
Antigens
molecule usually made of proteins or carbs
capable of inducing an adaptive immune response
pathogens
covered in a myriad of unique antigens which are recognised as foreign
antigen-presenting cells are AKA…
aka dendritic cells!!
Antigen-presenting cells
raise the alarm, sends processes out to ‘taste’ the environment and phagocytose foreign material, process and present the antigen
then migrate to lymph nodes so T lymphocytes may recognise the antigen which activates them
lymphocytes
adaptive effector cells
T cells
cytotoxic T cells and T helper cells
Cytotoxic T cells
killer cells
T helper cells
produce cytokines
B cells
produce antibodies
(3) properties of adaptive immune response
ability to mount specific responses to a huge range of pathogen-derived antigens
avoids reacting to self-antigens - self-tolerance
development of immunological memory
Constant region
anchors receptor to the cell (B or T)
Variable region
only acts with a specific antigen via lock and key method
somatic hypermutation
Subsequent exposure to an antigen during infection triggers lymphocyte proliferation with inaccurate DNA replication, generating further replication
DNA-encoding B and T cell receptors contain..
multiple different variable, diversity and joining segments
in every lymphocyte all but one of each region is deleted, the remaining segments are all linked together
VDJ recombination
variable-diversity-joining recombination
breakages do not occur when a region is deleted, therefore increasing diversity
When a receptor recognises an antigen…
the lymphocyte expressing the receptor is triggered to proliferate
Variable region DNA
is unstable and prone to mutation during rapid cycles of cell division therefore further diversity - somatic hypermutation again
Affinity maturation
clones recognising the antigen more effectively are selected to survive above those which bind less effectively
Immune tolerance
state of unresponsiveness of the immune system to antigens that normally have the capacity to elicit an adaptive immune response
Tolerance can be..
to self and the foetus during pregnancy
can develop to pathogens through chronic infections and cancers
Failure to establish tolerance
can lead to autoimmune disease
B cells are from
bone marrow
T cells are from
thymus
Central tolerance
contains tissue specialist cells which display all our self antigens - cells which recognise self-antigens may undergo apoptosis which can lead to clonal deletion
Tregs
T cells that react with self-antigens are deleted or develop into suppressor Tregs
Tregs migrate to peripheral lymph nodes and mediate periphery tolerance
Tregs and tolerance
mediate periphery tolerance by preventing B and T cells emerging or proliferating if they recognise self
Peripheral tolerance
In lymph nodes, auto reactive clones escaping central tolerance are deleted or suppressed by Tregs
Immunological memory
allows rapid immunological response on subsequent exposure
following activation a small proportion fo high affinity B and T cells differentiate into long-lived memory cells
memory cells
distinguished from naive cells by an increased lifespan, faster stronger response to stimulation and high affinity receptors
Memory cells location
reside in lymph nodes or tissues
Antigen presentation form
APC ingests pathogen and presents it on surface with major histocompatibility complex, both must be recognised
CD8 T cells
activated by recognising antigen and become cytotoxic
CD4 T cells
Bind the antigen and MHC releases cytokine
differentiate into a range of T helper subtypes based on the cytokines
Activated cytotoxic T cells
APCs activate these to kill the pathogen-infected or tumour cells by pore formation
Cytotoxic T cell mehcanism
bind to infected cells and use perforin to make holes in the cell membrane, causing it to lyse –> kills them
Defective cytotoxic T cell responses
increase viral infections and may promote cancer progression
Th cell activation
cytokines activate different T cell transcription factors leading to differentiation into different Th cell subsets
Th cell defects
leads to many opportunistic infections
Th17
fungal
Th2 and Tfh
help B cells - they can interact with antigens directly but most need input from th2 and Tfh cells
activated B cells
proliferate and become antibody-producing B cells
antibody they produce is the same as the receptor, so recognises and binds the inciting antigen
inmate plasma cells
express IgD and secrete low affinity IgM
Isotope switching
where the variable antibody region is unchanged but becomes attached to a different constant region, altering its properties and increasing affinity
IgM
used in initial early immune response
IgG
secrets by plasma cells as they mature
specialist lung and gut plasma cells
produce IgA antibody
IgA antibody
works on mucosal surfaces in the gut and respiratory secretions
IgD
B cell receptor
IgE
binds mast cells and mediates allergic reactions
neutralisation
antibody covers biologically active portion of microbe or toxin
complement reaction
Fc region of antibody binds complement proteins so complement is activated
Agglutination
antibody cross-links cells to form a clump
Opsonization
Fc region fo antibody binds to receptors of phagocytic cells, triggering phagocytosis
Variable region binds…
target antigen
constant region interacts…
with effectors
antibody for neutralising and agglutinating
IgM
Antibody good at opsonising
IgG and IgA
Vaccination
augments adaptive response to induce secondary responses and prevents infection
Immune suppression
reduce the adaptive response
Monoclonal antibodies
Many applications in infection, inflammatory disease and malignant disease
Adjuvants
used in vaccinations to enhance immunogenicity
Booster vaccines
help to generate high affinity antibodies
Influenza vaccine antigens
neurominidase and hemagluttin
Influenza mutations
occur due to antigenic drift, occurs in all flu viruses
can reduce antibody affinity so affects proleration
genetic reassortment
with viruses in can affect other specifics leading to pandemics
Corticosteroids
modulate transcription and suppress both innate and immune responses with multiple side effects
Antimetabolites
suppress DNA synthesis, mainly T cells e.g. methotrexate, purine analogues and Mycophenolate
Methotrexate
Prevents folic acid synthesis
Mycophenolate
inhibits guanosine synthesis
Calcineurin inhibitors
prevent G0-G1 cell cycle progression
MAB
engineered for specific targets
fuse myeloma cells with spleen cells immunised mice
can now be used using recombinant technology with viruses or yeast and make chimeric or even humanised to reduce allergic responses
Presentation fo tumour antigen
with MHC and co-stimulation should lead to an activated T cell response
Checkpoint receptors
expressed by T cells, tumours may express ligands to engage these checkpoints in order to inhibit the immune response
