immunology Flashcards
What is the difference between innate and acquired immunity?
- innate = rapid first response to infection
- no immunological memory
Acquired - lag time from exposure to response
(greater than 96 hours)
- immunological memory, responses are faster and more powerful, basis for protective vaccination against infectious disease
- specific for each antigen encountered
- self regulating through regulatory T cells
What are resident immune response cells (innate) and how do they recognise invading pathogens
- phagocytic (eating cells)- macrophages and dendritic cells
- others - mast cells
- pathogens - signature molecules (pathogens associated molecular patterns (PAMPS)
Innate immune cells - express partner receptors to these PAMPS called Pattern recognition receptors (PRRs)
Detail some modes of ingestion
- pinocytosis - ingestion of fluid surrounding cells
- receptor mediated endocytosis - molecules bound to membrane receptors are internalised
- Phagocytosis - intact particles (bacteria) are internalised whole which is facilitated by ‘opsonisation’
Draw a mental picture of the steps of phagocytosis
- macrophages express a set of PRRs
- Receptor binding to PAMPs signals the formation of a phagocytic cup
- cup extends around the target and pinches off, forming a phagosome
- fusion with lysosomes to form a phagolysosome - killing of pathogens and degradation of contents
- debris (antigens) is released into extracellular fluid
- pathogen-derived peptides are expressed on special cell surface receptors (MHC-2 molecules)
pro inflammatory mediators are released (TNF- alpha)
What is the definition of opsonisation?
coating of the pathogen by soluble factors (opsonins) to enhance phagocytosis
When are mast cells initiated? what is their mechanism?
- something that is too large to be engulfed invades (parasite)
- bind to the pathogen by PRR - PAMP - (degranulation - release of pre-formed pro-inflammatory substances (histamines))
- gene expression - production of new pro-inflammatory substances (leukotrienes and prostaglandins)
What leads to local, acute inflammation?
release of pro-inflammatory mediators - NO, prostaglandins histamines etc
How does inflammation affect healthy tissues?
- vascular changes
- recruitment and activation of neutrophils (transendothelial migration)
- chemicals are produced that attract neutrophils to the site of infection
What are the steps of transendothelial migration?
1 - margination of neutrophils to the endothelium near sites of damage
2 - binding of neutrophils to adhesion molecules on endothelial cells
3 - migration of neutrophils across endothelium via process of diapedesis
4 - movement of neutrophils within the tissues by chemotaxis
5 - activation of neutrophil by PAMPs and TNFalpha
What are the three jobs of neutrophils?
phagocytosis - use PRR to bind and phagocytose, killed using two mechanisms (phagolysosomal killing and Reactive oxygen species)
- degranulation - release of antibacterial proteins from neutrophil granules directly into extracellular environment can also cause tissue damage and systemic inflammation
- Neutrophil extracellular traps
How does reactive oxygen species work?
- NADPH oxygenase-dependant mechanism (repiratory burst) produces ROS
1 - neutrophil activation
2- assembly of the NADPH oxidase complex
3 - production and release of ROS into phagolysosome
How is the acute phase response driven?
- pro inflammatory mediators released by activated macrophages
- mediated by proteins secreted in the liver such as C3 and MBL (complement) and C reactive protein - primes bacteria for destruction by complement system)
How is a virus dealt with by the immune system?
- release cytokines called interferons which:
- signal neighbouring unaffected cells to destroy RNA and reduce protein synthesis
- signal neighbouring infected cells to undergo apoptosis
- activated immune cells such as natural killer cells - recognise and destroy virally-infected cells (and cancer cells)
What is the purpose of the complement system?
- opsonisation
- direct pathogen killing
- acute inflammation
- leukocyte recruitment§
Describe what the different pathways of the complement system to cleave C3?
Classical pathway, mannose binding lectin pathway and the alternative pathway
How does the mannose-binding lectin pathway work? - how does it lead to downstream complement pathway?
- MBL binds to manose on bacterium to activate C3 convertase to cleave into C3b and C3a - c3b turns into an alternative pathway to convert C3
- C3b then binds to pathogen surface and cleaves C5 into C5b and C5a - membrane attack complex is activated by C5b
- C3b is also involved in opsonisation
- C3a and C5a is used for acute inflammation
Why are dendritic cells so important?
bridge the gap between the innate immune response and acquired immune system responses
What are B and T cells involved in?
B cells - antibodies that attack pathogens circulating in the blood and lymph
key role in defence against extracellular pathogens
T cells - cellular immune response - defence against intracellular pathogens
CD4+ T cells - regulators of the entire immune system
CD8 T cells - kill infected body cells
How do B and T cells recognise pathogens?
pathogens have different antigens that are recognised by individual T and B cells
What type of cell is a B cell? what is its structure?
- it is an antibody
- complex of four polypeptide chains - 2 light chains and 2 heavy chains
- each antibody has a unique variable region that binds to 1 specific antigen
- can either be membrane bound or soluble
How does a T cell work?
- only recognise peptide antigens
- can express thousands of copies of a single antigen receptor
What condition must be filled in order for a T cell to recognise a peptide
can only recognise peptide antigens presented to their TCRs by MHC molecules
What is the function of Major histocompatibility complex?
display peptide antigens to T cells ( many different peptides to T cells)
What is the difference between class 1 and class 2?
class 1 - on nucleated cells, present peptide antigens to CD8+ T cells
class 2 - only on dendritic cells, macrophages and B cells
present peptide antigens to CD4+ T cells
where do T cells and B cells develop in the body?
primary lymphoid tissue - bone marrow or spleen
where do B cells encounter antigens?
- B cell zone in secondary lymphoid tissues
- soluble antigens and opsonised antigens are transported in lymph to the B cell zone in the lymph zone
Where do T cells encounter antigens?
1 - dendritic cells phagocytose pathogen derived particles and antigens
2 - pro-inflammatory TNFa stimulates immature tissue resident dendritic cells to increase expression of co-stimulatory molecules
3 - dendritic cells digest ingested proteins and display small peptides derived from these on their cell surface
in the T cell zone in the lymphoid tissue
How do B cells become fully activated?
- signal 1 - BCR and antigen
- Signal 2 help from T helper cells
- they then differentiate into plasma cells, into antigen specific antibodies and then can battle pathogens
What is initially secreted by short lived plasma cells?
What is initially secreted by short lived plasma cells?
What is produced after the short lived plasma cells?
- B cells mutate so they change into low to high affinity antibodies
- switch the class of antibody they produce
then differentiate into long lived plasma cells and long lived memory B cells
How does an antibody kill and eliminate pathogens?
- recognition - binding to antigen,
- effector - clearance mechanisms of the heavy chain (Fc region) with effector molecules, complement and Fc receptors
what does an IgM molecule look like when its membrane bound and in its secreted form?
membrane bound - monomeric form, IgM serves as the B cell antigen receptor
secreted - pentameric form is the first!!! Ig types produced during humeral response
What is the definition of agglutination? what is it mediated by?
- the action of an antibody cross linking multiple antigens producing clumps of antigens
- increases efficacy of phagocytosis and prevents viruses from binding to and infecting host cells
- mediated by IgM and IgG
What is the most common type of antibody? detail some functions
- most common type of antibody is IgG and is monomeric form when secreted
agglutination, foetal immune protection, neutralisation (best with IgG and IgA), opsonisation and natural killer cell activation
What is the function of IgD?
- membrane bound monomeric form - IgD serves as a B cell antigen receptor - mediates B cell activation
not well understood
What is IgA good for?
most common in the body
- monomeric form and it is involved in neutralisation
- neonatal defence - transported into colostrum and in breast milk to protect the GI tract of neonates(dimeric form)
What is IgE involved with?
- trigger allergic response
- least abundant type of Ig
- provides immunity to parasites such as helminths
What happens after T cells come into contact with the pathogen in the secondary lymphoid tissue
become active cells,
entry into cell cycle and clonaly expand then differentiate into effector cells and then memory cells
What are cellular immune responses mediated by?
- CD4+ T cells
- naive CD4 T cells proliferates into
- CD4+ Th0 cells
- which differntiate again into CD4 effector TH cells
(Th1, Th2, Tfh and regulatory T cells)
What do Th1 cells do?
Create a super activated macrophage and release pro-inflammatory signals
How can some pathogens evade phagolysosomal killing?
killing macrophages - infect and propagate in macrophage (legionella, mycobacteria)
What do T folicular helper cells fo?
They play a critical role in protective immunity helping B cells produce antibody against foreign pathogens.
What do antigen activated CD8+ cells proliferate and differentiate into?
killer cells - cytotoxic lymphocytes
migrate out of lymph and enter sites of infection in order to kills host cells
How do cytotoxic T cells work?
recognise and bind virus-infected cell
CTL programmes target for death inducing DNA fragmentation
CTL migrates to new target
Target cell dies by apoptosis
When are IL-2 released?
first part of the adaptive response (Th0),
What is involved in the innate immune response
Mast cells, natural killer cells, phagocytes and complement
- responsible for acute inflammation and killing of pathogens
What is pus?
Dead and dying neutrophils + tissue cells + microbial debris
When are cytokines produced?
response to infection, inflammation or tissue damage
What are the local effects of inflammation?
Redness, heat, swelling, pain and loss of function
What does the liver release in response to pro-inflammatory cytokines?
Acute phase proteins - IL1 and IL6, TNF - infection, trauma, chronic nflammation
Why are C3a and C5a important in immunology?
bind onto mast cells and basophils and release granules producing histamine and chemokines
How do T and B cells recognise pathogens?
T cell antigen receptor = membrane bound protein heterodimer
Alpha and Beta chain
B cell antigen receptor = membrane bound antibody (IgM or IgD)
has light and heavy chain disulphide bridges
How do B cells switch their class?
Changing their antibody heavy chain segment
What are some important facts surrounding IgG
Most abundant immunoglobulin in blood serum, most dominant in the memory immune response and is transferred across the placenta into the foetal circulation
What is important in the activation of
the complement system via the classical pathway?
IgG
IgM is also relevant for the classical pathway.
