Immunology Flashcards
Where are B cells produced?
In the bone marrow
Where are T cells produced?
In the thymus
What are examples of barriers to pathogens?
Skin
Mucous
Commensal bacteria
What cells are tissue resident innate immune cells?
Macrophages
Dendritic cells
Mast cells
Natural killer cells
What do natural killer cells do?
Kill infected cells and abnormal cancer cells - help get rid of virus
How are natural killer cells activated?
By a lack of interaction between its peptide link and the abnormal cell
What does C3b do?
Cleave more C3 to produce C3b and C3a in an amplification loop
Produces C5 convertase which cleaves C5 into C5a and C5b to form a MAC - direct killing
Is a powerful opsonin so aids in phagocytosis (indirect killing)
Wht does C5b do?
Produces a MAC - membrane attack conplex
What do C3a and C5a do?
Promote acute inflammation by activating MAST cells (degranulate producing pro inflammatory mediators) and by acting directly on blood vessels
What is an antibody?
A protein produces in response to a particular antigen
List the antibody types
IgG IgA IgD IgE IgM
What are dendritic cells?
Antigen presenting cells (present to T cells)
The bridge between the innate and acquired system
How do NK cells destroy virally infected cells?
By releasing cytotoxic granules to destroy the cells
What is the first antibody to be made in infection?
IgM
What is the function of IgM?
Clumps together pathogens and activates the complement system (by being bound to pathogens)
Which antibody is most abundant in the plasma?
IgG
What does IgG do?
Is the secondary response to infection
Is transported across the placenta into the foetal blood stream
What is the least abundant antibody?
IgD
What does IgA do?
A monomer in serum that helps with the neutralization of pathogens
Is a dimer in secretary fluids : tears, saliva, breast milk
What does IgA do?
Allergic reactions
Which MHC class is expressed on all nucleated cells?
Class 1
On what cells are MHC class 2 presented on?
Antigen presenting cells
Eg: dendritic cells, macrophages
Which class presents antigens to CD8+ cells?
MCH class 1
Which class presents to CD4+?
MHC class 2
What do CD4+ T cells differentiate into?
T helper cells (ThO cells)
Which differentiate into either Tfh cells (aids proliferation and differentiation of B cells) OR Th1 cells (increases macrophage killing)
What do CD8+ T cells do?
Cytotoxic T cells - recognise pathogen antigens attached to MHC class 1 and kill the infected cell
what can you do to manipulate the immune system?
immunisations
anti-inflammatory and immunosuppressive drugs
cancer immunotherapy
which immune cells are part of the innate immune system?
macrophages
natural killer cells
mast cells
neutrophils
what soluble factors are involved in the innate immune system?
cytokines
acute phase proteins
inflammatory mediators
complement proteins
which soluble factors are involved in the adaptive/acquired immune system?
cytokines
antibodies
which immune cells are involved in the acquired/adaptive immune system?
B cells
T cells
what role does IgA play as a barrier to infection?
It is secreted in mucous to prevent bacteria and viruses attaching and penetrating epithelial cells
what are the different ways that natural barriers can prevent pathogens from entering the body, and give examples?
physical barriers (skin) traps (mucous) elimination (coughing) unfavorable pH (stomach acid) lysozyme enzyme (tears) commensial bacteria
describe differences between the innate and acquired immune systems.
Innate is present continuously whereas acquired is induced by presence of foreign materials.
Innate produces a generic response whereas acquired is unique for each pathogen.
Innate is rapid, acquired is slow (days)
Innate has no immunological memory whereas acquired does.
what are the secondary lymphoid tissues and what do they do?
Lymph nodes and spleen.
Lymph nodes filter lymph, removing dead cells, pathogens and antigens - and activates the adaptive immune response as a result of this.
Spleen filters blood, removed old and damage RBCs, infectious pathogens and uses them to activate the adaptive immune response
which immune cells are present in the blood and are recruited to inflamed tissue?
Neutrophils, eosinophils, basophils
which cells are present in the blood and go to secondary lymphoid tissues?
B cells, T cells and NK cells
which cells are present in the blood and recruited into normal AND inflamed tissues?
Monocyte
describe what mast cells, eosinophils and basophils do.
Pro-inflammatory
parasitic killing mechanisms
linked to allergy and asthma
describe what neutrophils do.
phagocytosis
pro-inflammatory
bacterial killing mechanisms
describe what dendritic cells do.
antigen uptake in peripheral sites
antigen presentation
naive T cell activation.
describe what NK cells do.
Kill virally infected and tumour cells
describe what macrophages do.
phagocytosis pro/anti-inflammatory bacterial killing mechanisms antigen presentation wound healing/tissue repair
what do T cells do?
CD4+T helper cells enhance innate and acquired immune responses.
CD8+ cytotoxic T cells kill virally infected cells and tumour cells.
what do B cells do?
antibody production and secretion
what is an antigen?
A substance which can cause an adaptive immune response by activating B and T cells.
What is an antibody?
A protein that binds to one specific antigenic epitope.
where are complement system proteins produced?
in the liver
what are cytokines?
Small proteins and peptides produced in response to infection, inflammation and tissue damage.
what are the 4 types of cytokine and what do they do?
Interferons = anti-viral
Tumour necrosis factor alpha (TNFa) = pro-inflammatory
Chemokines = control and direct cell migration
Interleukins = various functions
Summarise what the innate immune system’s response to a pathogen is.
Inflammation, complement activation, phagocytosis and destruction of pathogen
Summarise what the adaptive immune response to a pathogen is in chronological order.
Interaction between dendritic cells and T cells: recognition of antigen, adhesion, co-stimulation, T cell proliferation and differentiation.
Activation of antigen-specific B cells. Formation of effector and memory T cells.
T and B cells interact forming germinal centers.
Formation of effector B cells/plasma cells and memory B cells. Production of antibody.
Emigration of effector lymphocytes from peripheral lymphoid organs.
Elimination of pathogen by effector cells and antibody.
The complement system is part of which immune response?
Innate
Describe the different ways macrophages can ingest bacteria and fungi.
Pinocytosis = ingestion of fluid surrounding cells
Receptor mediated endocytosis = molecules are internalized.
Phagocytosis = intact particles are interalized whole, this is facilitated by opsonisation.
Explain how phagocytosis works.
Macrophage expresses PRRs.
PRRs binds to PAMPs signalling formation of phagocytic cup.
Macrophage changes cytoskeleton to surround the pathogen forming a phagosome.
Fuses with lysosomes to form a phagolysosome; killing and degradation.
Debris released into extracellular fluid.
Pathogen derived peptides are now expressed on the macrophage by MHC-II.
Pro-inflammatory mediates are released (eg: TNFa)
what is opsonisation?
Coating of pathogens by soluble factors (opsonins) to enhance phagocytosis.
Give examples of opsonins.
C3b
C reactive protein
IgG/IgM
Describe what happens if a pathogen is too large to be phagocytosed by a macrophage.
Mast cell steps in.
PRR binds to pathogen and danger signals are received from damaged cells causing degranulation (releasing pro-inflammatory substances) and increased gene expression within the mast cell to produce new pro-inflammatory substances
What does PRR stand for?
pathogen recognition receptor
Describe what happens in the early innate immune response.
Pathogens express PAMPs and injured tissue cells release danger signals.
This brings in macrophages and mast cells.
Pathogen is killed, infected cells are killed and production of pro-inflammatory mediators.
Resulting in localised, acute inflammation.
Give examples of pro-inflammatory mediators.
NO
Prostaglandins/leukotrienes
Histamines
Pro-inflammatory cytokines (TNFa)
What does PAMPS stand for?
pathogen associated molecular patterns
How do mast cells work?
They degranulate to kill pathogens and release pro-inflammatory mediators (eg: histamine)
which pro-inflammatory mediators do macrophages and mast cells release?
macrophages release TNFa
mast cells release histamine.
Give an overview of the main things the complement system does.
opsonation of pathogens
direct pathogen killing
acute inflammation
leukocyte recruitment.
What is the initial reaction in the complement system that will begin the cascade?
C3 –> C3b + C3a
What are the three different pathways that facilitate the complement system?
Classical pathway
Mannose-binding lectin pathway
Alternative pathway
How is the alternative pathway activated and what does it do?
It is activated once C3b is generated and it causes an amplification loop which stimulates more and more C3 cleavage
How does the MAC (membrane attack complex) work?
It is a channel insterted into the pathogen cell wall/membrane. This allows extracellular salts and water to enter the pathogen causing it to swell and burst
what do C3a and C5a do?
Promote changes in local vasculature, acute inflammation and leukocyte recruitment.
describe how C3a and C5a carry out their function.
Activate mast cells.
Act directly on local blood vessels.
what are the symptoms of acute inflammation?
Redness, heat, swelling, pain, loss of function and fever
what causes acute inflammation locally?
TNFa
histamine
C3a and C5a
describe the effect pro-inflammatory mediators have on the local vasculature.
Blood flow slow as dilation of post-capillary venules leading to vasodilation and increased blood flow.
Endothelium becomes leaky due to tight junctions between endothelial cells being lost, causing increased vascular permeability.
Endothelium becomes sticky as adhesion molecules are expresses to recruit circulating neutrophils
Describe the 5 steps leading to transendothelial migration of neutrophils.
- Margination (slower blood flow allowing neutrophils to be at edge of vessel)
- Binding of neutrophils to adhesion molecules on endothelial cells
- Migration across the endothelium by diapedesis (stimulated by chemokines and chemical gradients)
- Movement of neutrophils within the tissue via chemotaxis
What is the binding of neutrophils to adhesion molecules on the endothelium mediated by?
Pro-inflammatory mediators promote the expression of adhesion molecules/selectins.
what do neutrophils do?
phagocytosis
degranulation
NETs
what is a disadvantage of degranulation?
It can cause tissue damage and potentially systemic inflammation
what does NET stand for?
neutrophil extracellular traps
what types of pathogen can induce NETs?
Fungi and bacteria
what does a rapid increase in C reactive protein signify?
Inflammation
what does C reactive protein do?
Primes bacteria for destruction by the complement system
what do virally infected cells produce and release and why?
interferons (INFa/b) to alert other cells to stop transcription and translation to stop the virus replicating AND induces nearby cells to express MHC I molecules on their surface so surveying T cells can identify the virally infected cells.
Describe how NK cells work.
Recruited to area in similar way to neutrophils.
Distinguish between healthy and infected by expression of MHC I molecules (infected will have reduced expression)
NK will release cytotoxic molecules causing the cell to undergo apoptosis
how are antibodies composed?
2 light and 2 heavy chains.
Variable region
How do T and B cells enter lymph nodes and once in the lymph nodes where do they move to?
Enter through high endothelial venules.
B cells immediately go into the lymphoid folicle within the node.
T cells stay in the T-cell area in order to interact with dendritic cells
where do lymph, B and T cells leave the lymph node?
Through the medullary sinus
what is the other name for the humoral immune response?
Acquired immune response mediated by B cells
Describe the humoral response.
B cells produce antibodies.
Once activated, B cells clonally proliferate and differential into either plasma cells or memory B cells
what do plasma cells do?
produce and secrete soluble antigen-specific antibodies
what do memory B cells do?
long lived cells which continue to circulate round the body remembering the specific pathogen so a faster approach can occur if it ever returns.
how do B cells encounter antigens?
Phagocytosis releases debris containing soluble antigens, which are opsonised and so can be trapped within the B cell zones of the lymph node
what triggers a change in production of IgM to IgG antibodies from the germinal centre?
T helper cells help switch the production to IgG as it is a better antibody
what are the types of antibody, generally speaking?
Membrane bound
secreted
What does IgM cause (both forms)?
Membrane bound = B cell activator as B cell antigen receptor
Secreted = immune complex formation/agglutination and complement system activation
what is agglutination?
action of antibody when it cross-links multiple antigens producing clumps of antigens
what is agglutination mediated by?
IgM and IgG
what is the purpose of agglutination?
To increase the efficacy of pathogen elimination by enhancing phagocytosis ALSO can prevent viruses binding and affecting host cells
what is the classical pathway of the complement system activated by?
By the Fc region of IgM and IgG antibodies when they are bound to antigens
what are the functions of IgG?
Agglutination complement system activation Foetal immune protection neutralisation opsonisation NK cell activation
what is the function of IgD, IgA, IgE?
IgD = B cell activation IgA = neutralisation IgE = mast cell activation
