Immunology Flashcards
Why might asthma prevalence be increasing?
Too clean an environment so we produce an overreactive response
examples of anti-inflammatory/immunosuppressive drugs
antihistamine, aspirin, ibuprofen, cortisol steroids
what are the two branches of immunity?
innate (natural) and acquired (adaptive)
examples of innate (natural) immunity?
physical barriers, soluble factors and immune cells
examples of soluble factors that are innate
cytokines, acute phase proteins, inflammatory mediators, complement proteins
examples of acquired (adaptive) immunity
soluble factors and immune cells
examples of soluble factors that are acquired (adaptive)
cytokines and antibodies
pathogens points of entry
digestive system, respiratory system, urogenital system, skin damage
when is innate immunity induced and how long does it take to respond?
present from birth rapid response (mins-hrs)
when is acquired immunity induced and how long does it take to respond?
induced by the presence of foreign materials slow response (days)
is innate immunity specific or non-specific?
non-specific
is acquired immunity specific or non-specific?
specific for each antigen encountered
three modes of ingestion of bacteria and fungi by macrophages?
pinocytosis, receptor-mediated endocytosis and phagocytosis
what is pinocytosis?
ingestion of fluid surrounding cells
what is receptor-mediated endocytosis?
molecules bound to membrane receptors are internalised
what is in lysosomes that allow them to break down cells?
acidic Ph and enzymes
what is a macrophage?
a type of phagocyte
what are mast cells full of?
granules rich in histamine and heparin
what is opsonisation?
the coating of pathogens by soluble factors (opsonins) to enhance phagocytosis
examples of opsonins
C3b
C-reactive protein
IgG/IgM
where are low levels of inactive complement system proteins found?
in the extracellular fluids
what activates complement system proteins?
pathogens
what does the activation of complement system proteins trigger?
a fast and powerful cascade of chemical reactions
what does the cascade of chemical reactions promote?
opsonisation of pathogens, direct pathogen killing, acute inflammation and leukocyte recruitment
what is the inactive precursor of the two active products, C3b and C3a?
C3
why does selective activation of the Mannose-binding lectin arise?
mannose expression is unique to certain pathogens and it is not expressed on human cells
what happens when an unstable C3b molecule binds to a pathogen?
it is stabilised, allowing a series of downstream events of the complement system
what happens once a C3b is generated?
an amplification loop stimulates more and more C3 cleavage via the alternative pathway
what cleaves inactive C5 into active C5a and C5b?
active C3b
what happens when active C5b associates with other complement system proteins?
it produces a pore-forming channel which inserts into the pathogen membrane/cell wall. This is the MAC
what does MAC stand for?
membrane attack complex
a key response to local change of the vasculature during infection/injury?
the recruitment of innate immune cells such as neutrophils and monocytes into the infected/inflamed tissue
how does vascular permeability increase?
tight junctions between epithelial cells break apart
what do neutrophils use to bind to and phagocytose pathogens?
pattern recognition receptors
what two types of cells can mediate phagocytosis?
macrophages and neutrophils
what type of cell is better at killing via phagocytosis, macrophages or neutrophils and why?
neutrophils are better because they have a second way to kill internalised pathogens via a ROS-dependant mechanism
the three neutrophil killing mechanism are…
phagocytosis, degranulation and NETs (neutrophil extracellular traps)
what can neutrophils do after phagocytosis??
degranulation
what is degranulation?
when neutrophils eliminate extracellular pathogens by releasing residual enzymes/toxins
downside to degranulation
it can lead to tissue damage and potential systemic inflammation
what do NETs do?
they immobilise pathogens so stop them from spreading but also facilitate subsequent phagocytosis of trapped microorganisms
what are nets composed of?
genomic DNA, histones, granular proteins and enzymes
two subdivisions of acute inflammation
local and systemic
what is the systemic acute phase response driven by?
pro-inflammatory mediators released by activated macrophages
what proteins are part of the systemic acute phase response
C3, MBL and C reactive protein
what do virally infected cells produce?
they release small proteins called interferons (INFalpha and beta)
interferons…are…. specific but not….. specific
host specific but not virus specific
what type of protection do IFNs produce?
general anti-virus protection
what three things do interferons do?
prevent replication of viruses, signal to cells to produce anti-viral factors that interfere with viral multiplication and activate immune cells (NK cells)
what do NK cells specifically kill?
infected cells and abnormal cancer cells
what are NK cells?
lymphocytes that can recognise and destroy viral or cancerous cells
what makes up an antibody complex?
2x light chain and 2x heavy chain. Complex of four polypeptide chains
what on the antibody binds to one specific antigen?
a unique variable region
what induces the active immune response?
an antigen
other name for antigens
immunoglobulins
individual antigens can contain many different …….
antigenic epitopes
what do B cells use as antigens?
antibodies
what are the 5 different classes of antibodies?
IgM, IgG, IgE, IgA and IgD
what receptors are used in non-specific regulation?
PAMPs
what does PAMPs stand for?
pathogen-associated molecular pattern molecules
what are PAMPS recognised by?
PRR molecules (pattern recognition receptor molecules)
where do antigen-specific T cells and B cells develop?
in primary lymphoid tissues such as bone marrow and spleen
where do adaptive immune responses occur?
in secondary lymphoid tissues
how do t and b lymphocytes activate?
they activate when they meet their specific partner antigen within a secondary lymphoid tissue
where do mature T and B cells go?
they constantly re-circulate between different tissues in the blood, secondary lymphoid tissues and lymphatic vessels
secondary lymphoid tissues
lymph nodes, spleen and mucosal-associated lymphoid tissues
what process do naive T cells and B cells use to enter lymph nodes from HEV?
Transendothelial migration
what are HEV?
high endothelial venules
what do B cells and T cells flow through to get into lymph nodes?
the HEV
where do the B cells go when they enter the lymph node?
B cell zones called lymphoid follicles
where do T cells go when they enter the lymph node?
T cell zones where they mix with dendritic cells
how can B cells encounter antigens in lymph nodes?
specialised cells within B cell zones can ‘trap’ opsonised antigens
what two signals do specialised B cells need in the B cell zone in the lymph node to become fully activated?
BCR binding to antigen and help from helper T cells
what happens when the B cells become fully activated?
B cells clonal proliferate producing daughter cells with the same antigen-specificity as their parent B cell
what is the name of the secondary follicle within the B cell zone?
the germinal centre
what do cells within the germinal centre differentiate into initially?
short-lived plasma cells
what is initially secreted by short-lived plasma cells?
low affinity antigen-specific IgM antibodies
later on, what is produced in the germinal centre with the help of helper T cells?
IgG antibodies
why are IgG antibodies better than IgM antibodies?
they have a higher affinity antibody production and IgG can act as an opsonin
what else does the production of IgG antibodies allow?
B cells to be differentiated into long-lived plasma cells and the production of antigen-specific memory B cells
what is the first type of Ig produced during an immune response?
IgM
what is IgM present in?
plasma and secretory fluids
what is agglutination?
the action of an antibody forming cross-links with multiple antigens producing clumps of antigens
what does agglutination do?
it increases the efficacy of pathogen elimination by enhancing phagocytosis
what do IgE antibodies do?
Trigger allergic reactions such as allergy, asthma and anaphylaxis
what is the most abundant antibody in normal human serum?
IgG (70-85%) of the Ig pool
functions of IgG (6)
angulation, complement system activation, foetal immune protection, neutralisation, opsonisation and nk cell activation
babies don’t produce IgG antibodies until they’re adaptive immune system develops fully (6 months). How are they protected?
IgG antibodies are transported across the placenta directly into foetal circulation
what does neutralisation do?
it prevents viruses from infecting host cells and prevents microbial toxins from disrupting normal cell function
what high affinity antibodies can neutralise viral infectivity?
IgG and secretory IgA (sIgA)
what antibody type is not well understood?
IgD (don’t know)
what is the second most abundant Ig type?
IgA
function of monomeric IgA? what is it present in?
Neutralisation
present in serum
function of dimeric sIgA? what is it present in?
neonatal defence
neutralisation
present in secretory fluids
how are the GI tracts of neonates protected?
sIgA antibodies are transported into the colostrum and breast milk
what are the only things that T cells can recognise?
peptide antigens
what region is formed by the tips of alpha and beta T cell antigen receptor?
a hypervariable region
each T cell expresses………. that can bind to ……
a unique TCR that can bind to only one specific peptide antigen
in what form must the peptide antigen be presented to their TCR ?
In a complex with major histocompatibility complex (MHC molecules)
do b cells or t cells present antigens in a complex with MHC?
T cells
another name for the major histocompatibility complex
human leucocyte antigens
two classes of MHC
Class 1 MHC and class 2 MHC
what do all Class 1 MHC do?
expressed on all nucleated cells
what do class 1 MHC present?
Present peptide antigens to CD8+T cells
what are class 2 MHC only expressed on?
only on professional antigen presenting cells (APCs)
what are professional antigen presenting cell examples
dendritic cells, macrophages and B cells
what do class 2 MHC present?
peptide antigen to CD4+T cells
what is the bridge between the innate system and the acquired immune response?
dendritic cells
what is the function of dendritic cells?
to process (phagocytosis) and present antigens on their cell surface to T cells
dendritic cell function once activated in inflamed tissue
they phagocytose antigenic debris
what stimulates immature dendritic cells that are in tissues to increase the expression of co-stimulatory molecules?
pro-inflammatory mediators such as TNFalpha
what signals do T cells require to fully activate?
peptide antigen/MHC complex and co-stimulatory molecules expressed by dendritic cells
what do CD4+T cells differentiate into?
different types of effector T cells
what do CD4+T cells start to secrete?
a growth hormone interleukin 2 (IL-2) and express the IL-2 receptor
what induces autocrine mediated production of cd4+ and CD8+ cells?
TH0 cells
