Flashcards in Principles Immunology Deck (140):
What is Hashimoto's thyroiditis?
Autoimmune disease with antibodies to normal thyroid tissue causing chronic inflammation.
What is vitiligo?
Autoimmune disease causing white areas of depigmentation that is usually symmetrical.
What method of small pox exposure used to be used to try and prevent the disease?
Dried pustules either intranasally or intradermally.
What are the constitutive barriers to infection?
Skin - physical barrier, slightly acidic pH 5.5 and low oxygen tension.
Skin sebaceous gland - hydrophobic oils, lysozymes and ammonia.
Secreted mucous - IgA stop bacterial attachment and penetration of epithelial cells.
What are the two arms of the immune system?
What are the differences?
Innate immune system. Rapid response which is the same general response to all pathogens.
Adaptive immune system. Slow response that is unique to each pathogen. Generates immunological memory.
What cells are phagocytes?
Neutrophils, monocytes, macrophages and dendritic cells.
What are the lymphocytes?
T cells, B cells and natural killer cells.
What is the complement system?
Cascade system triggered by certain pathogens.
Family of 30 proteins produced in the liver and circulate in blood.
Critical role in inflammation and healing.
Where do mast cells reside?
Reside in tissues and protect mucosal surfaces.
What is Graves' disease?
Autoimmune disease of the thyroid giving a goitre.
Where do basophils, neutrophils and eosinophils reside?
Circulate in blood and are recruited to infection site.
What are neutrophils also known as?
What is the relationship between monocytes and macrophages?
Monocytes circulate in the blood and then become tissue resident macrophages.
Where are T and B cells found?
Circulating constantly through blood, lymph and secondary lymphoid tissues.
What are primary lymphoid tissues and what do they produce?
Site of leukocyte development. They are red bone marrow and the thyroid gland.
What are secondary lymphoid tissues and what do they do?
Lymph nodes, tonsils, spleen etc.
They are the sites where the adaptive immune responses are initiated.
What are the cells of the adaptive immune system?
B cells, antibodies and T cells.
What are the two mechanisms of communication in the immune system?
Direct contact by receptor to ligand interactions.
Indirect contact by production and secretion of cytokines from injured cells and activated immune cells.
How long to cytokines last and where do they act?
They have a short half life and act both locally and systemically.
What is an autocrine signal?
Substances are released from and then attach to the same cell and causing a change in cell behaviour.
What is a paracrine signal?
Substances are released from a cell and then attach to the cells nearly or at a distance causing a change in cell behaviour.
What are 4 different types of cytokines?
Interferons, tumour necrosis factor, chemokines and interleukins.
What do interferons do?
Have anti viral functions.
What does IL-2 do?
T cell proliferation.
What does IL-10 do?
Anti inflammatory function.
What is the job of the cells of the innate immune system?
To create acute inflammation and kill the pathogen.
What are the three phases the mast cells, neutrophils, Nk cells and neutrophils are involved in?
Recognition phase, activation phase and effector phase.
What are pattern-recognition receptors?
PRRs. Receptors on innate immune cells that are either on their surface to bind to extracellular pathogens it intracellular for intracellular pathogens.
What are pathogen associated molecular patterns?
PAMPs. Common structures in the surface of pathogens that re recognised by cells of the innate immune system.
What are three types of PRRs?
What does toll like receptor 4 recognise?
Lipopolysaccharide on gram negative bacteria. It is on the outside of the cell.
What does toll like receptor 7 recognise?
SsRNA of viruses. It is on the inside of the cell.
What does Dectin 1 recognise?
Beta-glucans of fungi. It is on the cells surface.
What does NOD 2 recognise?
Muramyl dipeptides. M.tiberculosis. Is on the outside of the cell.
What happens during the recognition phase?
PRRs recognise PAMPs.
What are the activation and effector phase involved in?
Inflammation and pathogen killing.
What happens when physical barriers are breached by a pathogen?
Tissue resident innate immune cells are activated.
Mast cells and macrophages.
What happens to mast cells when they come in contact with a pathogen?
PRR binds to pathogen PAMP.
Mast cell degranulates releasing histamine and tryptase.
Cell also starts expressing genes - TNF, chemokines and leukotrines.
What do mast cells have a key role in protection against?
What pro inflammatory effect do histamines have?
Increase vascular permeability, vasodilation, activation of endothelial cells and causes pain.
What pro inflammatory effect does tryptase have?
What pro inflammatory effect does TNF have?
Increases vascular permeability and activates endothelial cell. Is also pro inflammatory.
What pro inflammatory effect does leukotrienes have?
Smooth muscle contraction and increased vascular permeability.
What do macrophages do?
Ingest and kill extracellular pathogens.
Tissue repair and wound healing
How do a macrophages destroy substances?
Recognises, binds, engulfs, forms a phagolysosome, kill and releases debris.
What do macrophages display in their surface to present an antigen?
MHC-II (class II).
What are the pro inflammatory cytokines?
IL-1, IL-6 and TNF.
What do the proinflammatory cytokines do?
Promote liver production of acute phase proteins.
Cause activation of endothelial cells, neutrophils mobilisation and increased vascular permeability. This results in increases phagocytosis.
Signal hypothalamus to make fever resulting in decreased pathogen replication.
What acute phase proteins does the liver make?
C3, C4, CRP and mannose binding lectin.
What does a serum CRP level of under 10 mg/L mean?
What does a serum CRP level of 10-40 mg/L mean?
Mild inflammation and viral infections.
What does a serum CRP level of 40-200 mg/L mean?
Active inflammation and bacterial infections.
What does a serum CRP level of over 200 mg/L mean?
Severe bacterial infections and burns.
What is happens in the innate immune system in the first 4 hours?
Mast cells and macrophages bind to pathogen.
Cause pro inflammatory mediator release.
Results in fever, oedema and swelling (vasodilation and permeability) and raised CRP.
How do pro inflammatory mediators recruit other innate immune cells after the first four hours?
Increase capillary permeability, activate endothelial cells and chemotaxis.
What innate immune cells do proinflammatory markers recruit?
Neutrophils, NK cells and complement proteins.
What do proinflammatory mediators stimulate the bone marrow to do?
Produce monocytes and neutrophils.
What molecules to activated endothelial cells display?
ICAMs and selectins.
What do endothelial selectins do?
Allow weak binding of leukocytes giving rolling adhesion.
What do ICAMs do and what activates their partner receptors on leukocytes?
ICAMs allow strong adhesion of leukocytes to endothelial cells.
They bind to integrins on leukocytes which are stimulated by chemokines.
What is leukocyte adhesion deficiency?
Very rare genetic disease caused by loss or reduced amounts of beta 2 integrins. Prevent leukocytes transendothelial migration and infections can't be cleared.
What are neutrophils and what three ways can they kill?
Short lived professional killers.
1. Phagocytosis - lysosomes containing toxic oxygen reactive species (ROS), hydrolysic enzymes and acidic pH.
2. Release of antimicrobial peptides and degradation proteases into extracellular environment.
3. Generate extracellular traps (NETs).
What do activated neutrophils release that promotes positive feedback?
What is chronic granulomatous disease?
A deficiency in phagocytes causing recurrent bacterial and fungal infections.
What do natural killer T cells do?
Large granular lymphocytes that specifically kill abnormal cancer cells and virally infected cells. They also kill antibody bound pathogens.
What happens when a NK cell meets a cell infected by a virus?
The cell displays stress signals on its receptor which the NK cells can detect.
This makes the NK cell release interferon gamma which increases macrophage Killing activity.
What three pathways can activate the C3 complement cascade?
The classical pathway
The lectin pathway
The alternative pathway.
What are the effector functions of complement?
Opsonisation, chemotaxis, formation of membrane attack complex and clearance if immune complex and inflammation.
How does complement mediate opsonisation?
C3b coats micro-organisms and then binds C3b opsonise to receptors on phagocytes.
What is an immune complex?
What part of complement dissolves it?
Why is this important?
Clumps of Antibody antigen complexes.
C3b, stops the clumps forming and just leaves a single antibody bound to an antigen for destruction.
Allows clearance by phagocytosis. Important as the complexes when formed can precipitate out of the vessels into the tissues leading to damage, inflammation and disease.
What are the components of the membrane attack complex?
C5b binds to pathogen surface.
C6-9 assemble onto it.
It inserts into the membrane making a funnel shaped hole, causing osmotic lysis of the pathogen.
How does complement cause inflammation and chemotaxis?
They bing to receptors on mast cells which degranulate putting out vasoactive substances (histamine) and chemokines.
Why is the complement cascade so potent?
It only takes a small initial stimulus to activate a large cascade.
There is also a powerful amplification loop.
What regulates the complement system?
Only cleaved proteins are active.
They have a short half life.
Complement inhibitors: C1 inhibitor, factor I, factor H and C4 binding protein.
What deficiency causes hereditary angioedema?
What does deficiency of early Complement proteins cause?
(C1, C4 and C2).
SLE, glomerulonephritis and polymyositis.
What is an antigen?
Any substance which causes an adaptive immune response by activating B and T cells. Individual cells can have many different antigens. Individual antigens can have several different parts that can be recognised by the immune system (antigenic epitopes).
What is a T cell antigen receptor?
It is a membrane bound protein heterodimer with and alpha chain and a beta chain.
What is a B cell antigen receptor?
Membrane bound antibody IgM or IgD.
What are antibodies?
Produced by B cells and expressed on their surface. They will bind to an antigen.
Describe the structure of an antibody?
Y shaped proteins.
The middle long parts of the Y are the heavy chains.
Attached to these by disulphides bonds are the light chains. One on each short open part of the Y.
They have variable regions on the two top tips of the Y, which bind to antigen epitopes.
The rest of it is called the constant domain.
What five different types of antibody do we have and what is the difference between them?
IgM, IgG, IgA, IgE and IgD.
They have different heavy chain constant regions.
Whats the difference between PAMPs and antigens?
PAMPs are non specific common structures recognised by the innate immune system.
Antigens are unique structures recognised by adaptive leukocytes.
How are heavy and light chain coded from genes?
Heavy have 4 sections and each of the first three will have one of a selection of a type gene in it. The last is a constant gene.
Light have the same but 2 variable parts and a constant part.
How are TCRs coded?
In a similar way to BCRs with random gene arrangement.
What are the implications of random gene arrangement in B and T cells?
Gives rise to a hugely diverse population of cells.
Where do adaptive immune responses occur and why?
In secondary lymphoid tissues.
Antigens and debris are trapped in secondary lymphoid tissues e.g. Lymph nodes.
B and T cells constantly circulate between them and so can come into contact with antigens there.
What are the two different zones in lymph nodes?
T cell zones and B cell zones.
What happens to T and B cells in secondary tissues if they don't encounter an antigen?
After several days they leave and renter the blood system via the efferent lymphatics.
What are the 5 steps in antigens entering the lymph nodes?
1. Particles and antigens derived from pathogens are released from phagocytes.
2. Inflammatory TNF stimulates immature tissue resident dendritic cells producing B7 expression (PRR).
3. Dendritic cells phagocytose the pathogens released by phagocytes which bind to their B7 receptors.
4. Dendrites then display small peptides from the pathogen on their surface MHC proteins (antigen presentation).
5. These then travel to local draining lymph nodes.
What do stromal cells in lymph nodes do?
Trap opsonised antigens, through C3b receptors on their surface.
What does a B cell require to activate?
What are examples of these?
BCR and an antigen combined with T cell help.
BCR and an antigen and a PRR and PAMP.
Signal 1 and 2 can be an antigen with multiple epitopes attaching to multiple BCRs.
What is the only way T cells can recognise antigens?
If they are presented by MHC.
What are the human leukocyte antigens?
They are able to present many different peptides and are encoded for by highly polymorphic genes.
What are the two classes of MHC proteins?
Class I and II.
What is MHC class I?
Expressed on all nucleated cells. They present peptide antigens to cytotoxic T cells.
What is MHC class II?
Expressed only on professional antigen presenting cells e.g. Dendritic cells, macrophages and B cells. They present peptide antigens to helper T cells.
What is required to activate T cells?
How do dendrites do this?
Two signals just like B cells.
Dendrites can supply both of these, one from the pathogen and MHC and one from the B7 expressed on its surface.
What happens to activated B and T cells?
What is the timescale?
They are activated by a specific antigen and co stimulation.
They enter into the cell cycle and undergo mitosis.
Then they undergo differentiation.
What do B cell differentiate into after activation?
Memory B cells and antibodies.
Where are the low affinity, antigen specific antibodies I.e. IgM made?
In the B cell zone of lymph nodes.
What are the high affinity, antigen specific antibodies?
Where are they made?
IgM initially, IgG, IgA, IgE and IgD.
Made in the germinal centre of lymph node.
Where are memory B cells made?
In the germinal centre of lymph nodes.
What is IgG?
Most abundant Ig in plasma. It is actively transported across the placenta and is divided into 4 subtypes Ig 1-4.
What is IgD?
Extremely low levels in the blood.
It is surface bound BCR.
What is IgE?
Extremely low levels normally.
Produced in response to parasitic infection and allergic responses.
What is IgA?
2nd most abundant Ig type.
Monomer in form found in the blood.
The dimeric form is found in breast milk, saliva, tears and mucosal secretions.
What is IgM?
Surface bound monomer (BCR).
1st type secreted during an immune response.
Present only in plasma and secretions
Is a pentamer.
What antibody protection does a baby have from its mother?
IgG in utero and dimeric IgA in breast milk.
What is the dual function of antibodies?
Have a recognition function - bind to antigens at variable region sites.
Effector function - clearance mechanisms mediated by interaction of Fc region with effector molecules e.g. Complement and Fc receptors.
What is the Fc region of an antibody?
Constant regions of heavy chains.
How is binding of high affinity neutralising antibodies protective?
They prevent viruses from infecting host cells.
Also prevent microbial toxins from disrupting normal cell function by stopping it from binding to cells.
What is agglutination?
Immune complex formation.
How can antibodies activate complement?
They activate the classical pathway.
How do antibodies act as opsonins?
Phagocytes express Fc receptors that can bind to the constant region of Igs, providing the second activating signal of an antigen that already has an opsonins bound.
What is antibody dependent cell mediated cytotoxicity?
It is antibodies activating killer T cells.
How does ADCC work?
Antibodies bind to the surface of a pathogen or infected host cell.
Fc receptors on NK cells recognise the bound antibodies.
Cross linking of the Fc receptors signals the NK cell to kill the target cell.
The target cell dies by apoptosis.
How can antibodies trigger allergic reactions?
By binding to mast cells causing degranulation and onset of inflammatory response.
What are the major antibody classes that act as neutralisers?
Mainly IgG and dimeric IgA.
What are the major antibody classes that cause agglutination?
IgM and IgG.
What are the major antibody classes that act as opsonins?
What are the major antibody classes that activate complement?
IgM and IgG.
What are the major antibody classes that activate NK cells?
What are the major antibody classes that are transferred across the placenta?
What are the major antibody classes that activate mast cells?
What are the major antibody classes that activate B cells?
IgM and IgD surface monomer.
What effector cells do resting T cells (CD4+ and CD8+) differentiate into?
CD4+ - when combined with peptide and MHC II, change into helper T cells.
CD8+ - when combined with peptide and MHC I, change into cytotoxic T cells.
What do helper T cells do?
Help activate other immune cells.
What do cytotoxic T cells do?
Kill infected and cancer cells.
What cells do helper T cells activate?
CD4+, CD8+, macrophages and B cells.
How does interleukin 2 assist in activation of effector T cells?
Th cells release it which stimulates more Th cells and also Tc cells.
How do effector T cells help macrophages?
They migrate from lymph nodes into sites of infection/inflammation. The Th cells are then re activated by macrophages in an antigen specific manner e.g. TCR on the Th cell binds to an antigen loaded MHC receptor on the macrophage.
The Th cells then express CD40L which binds to CD 40 on the macrophages enhancing their killing activities and pro inflammatory responses.
How do effector Th cells help B cells?
Effector Th cells move into B cell zone in lymph nodes where they are re stimulated by B cells carrying an antigen on their MHC II receptor.
They start to express CD40L, this binds with CD40 on the B cell.
This stimulates the B cell to proliferate and survive. The Th cells produce cytokines which further activate the B cell.
What happens in the germinal centre reaction?
B cell proliferation.
Antibody heavy chain switching.
Generation of high affinity antibodies.
Differentiation into plasma cells and memory B cells.
What happens during antibody class switching?
B cells with the antibody heavy chain segment that they use.
What is the aim of somatic hypermutation?
To produce antibodies that recognise the same antigen but with increased affinity.
What happens during somatic hypermutation?
Point mutations made in the heavy/light chain gene segments that encode for the variable antigen binding sites of antibodies.
How do cytotoxic T cells kill cells?
Effector cytotoxic T cells leave lymph nodes and migrate to infection sites.
They recognise and bind to virus infected cell by MHC 1 carrying viral peptide.
The CTL programs the cell for death by inducing DNA fragmentation.
The CTL then migrates to a new target while the last cell dies by apoptosis.
What different types of memory cells do we have?
Memory Th cells, memory Tc cells, memory B cells and long lived plasma cells.