Basic Immunology Flashcards
Define the innate and adaptive immune systems, and what the main components of each are.
Innate = Rapid, non specific reactions. Involves macrophages, neutrophils, NK cells, and complement proteins
Adaptive = Antigen specific reactions that can recognise pathogenic organisms both in initial reaction and in subsequent contact. Involves T and B cells, antibodies.
What are the humoral components of the innate and adaptive immune systems
Innate = Complement
Adaptive = Antibodies
Define a phagocyte, and what are the 2 main basic types of phagocyte
Phagocyte = Anything that ingests infectious agents and cellular debris
1) The monocyte/Macrophage lineage
2) Granulocytes = Which can be further divided into neutrophils, Mast cells, basophils, and eosinophils
What is the difference between monocytes and macrophages
These are both basically the same. They are both one of the types of phagocyte
Monocyte = Short lived cells that circulate in blood for a few hours then migrate into tissues and turn in mature macrophages
How do macrophages work
Remember these are the long lived tissue macrophages.
They have receptors for Fc region of IgG
They bind to organisms via these Fc receptors if =
1) pathogen is coated with Ab
2) Or if bacteria has been opsonised by complement
Macrophages can then phagocytose and process pathogen. Can then present peptides to T cells and therefore trigger adaptive arm of immune system
What are dendritic cells, and what is their role?
These are a type of additional phagocytic cell derived from monocytes.
Sole function = Capture, process and present antigens to T cells. They are also called antigen-presenting cells
What is the most common immune cell in the blood? And what %
Neutrophils = 50-70% of all immune cells.
How do neutrophils work?
Remember these are granulocytes, which makes up the second type of phagocytes.
Neutrophils = Activated through Fc or complement receptors. Can phagocytose or release granules that are cytotoxic
What are mast cells, and what role do they play. Where are they located?
They are located in skin, mucosal surfaces, and around blood vessels
They are also phagocytic, and express Fc receptors for IgE.
Activation = Causes release of wide range of molecules including histamine, heparin, PGs, cytokines, and chemokines.
Outcome = These can all cause and control inflammation in sorrounding tissues
How about basophils. What cell are they similar to?
These are phenotypically similar to mast cells.
Also have receptors for IgE
How about Eosinophils? Where do they reside and what is there function
Location = Resp and gut subepithelia
Function = Attach to surface of parasites such as schistosomes. They attach then degranulate that damage the parasite membrane.
Describe what NK cells are, and what part of the immune system they are in
System = They are sort of a bridge between the innate and adaptive arms
NK cells = They are large granular lymphocytes that are a morphologically unique population.
Functino = They have cytotoxic activity against a wide range of tumour cells and virally infected cells.
What are the 2 receptors that NK cells use? and what are they for?
1) CD16 receptors = Attach to specific antibodies on tumour cells or on virally infected cells. This is therefore an antibody-dependant cell-mediated toxicity
2) KIR Killer cell immunoglobulin-like receptors = Heterogenous group. Contains both activating and inhibitory receptors that bind with MHC class 1 molecules on target cells.
Healthy cells that express MHC class 1 are protected from NK cell lysis. But tumour cells cause a downregulation of MHC class 1 = So NK cells can attack.
What are the three consequences of activation of the complement system?
1) lysis of microorganisms = Including enveloped viruses and infected cells (by damaging the plasma membrane)
2) Opsonisation = Coating of all foreign particles with complement protein fragments. Then phagocytes have receptors for these = So can phagocytose it all up (via their Fc receptors)
3) Triggering the complement cascade Forming a bridge between innate and adaptive responses.
REMEMBER complement = The humoral component of the innate immune system
Briefly describe complement protein nomenclature
They are called C1-C9. And they are activated in a cascade so that a small initial stimulus can activate and cause a large effect
Minor fragments = Have the suffix a like C3a. These diffuse from the site of activation and can initiate a local inflammatory response by binding to receptors
Major fragments = Have the suffix b like C3b. These bind to target cell membrane
What are the 3 pathways that complement can be activated by. And what does the activation of all three pathways start with?
1) Classic pathway
2) Alternative pathway
3) Lectin pathway
Central to all three pathways = Cleavage of C3 (the most abundant complement protein), followed by activation of the lytic sequence.
But the three pathways differ in how it is initiated
Describe the classic complement pathway
Initiation = Binding of Ab to antigen. Ab has to be either IgG or IgM bound to surface of pathogen.
This antibody-antigen complex causes a conformational change in the Fc portion of the antibody which exposes a binding site for C1q (the first complement protein)
Classic pathway = Therefore means complement is activated through adaptive immunity, because Abs are used here. Therefore can only be activated in situation where immune system already knows the pathogen.
Describe the alternative complement pathway
Initiation = Binding of C3b to hydroxyl and amine groups on surface of pathogens which includes many gram -ve and +ve bacteria.
This pathway is inefficient = As requires high conc of various components
Innate = Alternative pathway does not require Ab. It is activated through innate immune system
Describe the lectin complement pathway
Initiation = Binding of lectin to glycoproteins or carbs on surface of pathogens, which again includes many gram -ve and +ve bacteria.
Lectin is more efficient then alternative pathway
Innate immune system = Again no Abs required, so initiation through innate immune system
What do all three of the complement pathways eventually lead to?
They all lead to activation of the final lytic sequence = After C3b. There is activation of C5,6,7,8,9 sequentially.
This eventually forms the membrane attack complex = Binds to membrane forming a transmembrane channel which allows salt/water through causing lysis of the target cell.
What is the main limitation of the innate immune system?
Very good first line of defence against bacteria, years, parasites.
But it cannot attack viruses or other intracellular organisms well. Relies on adaptive immune system for this
Briefly describe the role of B cells in the adaptive immune system
They have Abs on their cell surface = These bind to antigens, then antigen is internalised, degraded, and complexed with MHC class 2, then returned to cell surface
Peptide-MHC complex = Can then be presented to antigen specific T cells, which secrete cytokines, and induce clonal B cell proliferation and differentiation into Ab producing plasma cells.
What are the similarities between all 5 classes of Ab, and what differs them
All = Are made up of 2 identical light chains, and 2 identical heavy chains.
But they differ = In size, charge, carbohydrate content, and amino acid sequence
What heavy chains are present in each of the 5 Abs?
IgM = Mu heavy chain IgG = Gamma heavy chain IgA = Alpha heavy chain IgE = Epsilon heavy chain IgD = Delta heavy chain
Which Abs are able to activate the complement pathway. And which one and why is the most potent activator of complement.
Remember this is the classical complement pathway only = Therefore it is only IgM and IgG because these are the ones that are involved in adaptive immune system mainly
IgM = More potent activator, since it has 5 complement binding sites (pentamer)
Which Abs are present on membrane of mature B cells
IgM = Because these are used in actviation of Ab production on B cells
IgD = Also. As far as we are aware this is all IgD does = Acts as transmembrane antigen receptor for mature B cells. Has no effect function.
Which Ab is present in mucosal secretions
IgA
Which Ab induces mast cell degranulation?
IgE
Which Ab is able to cross the placenta?
Only IgG
Which Abs are able to bind to phagocyte Fc receptors?
Remember the Fc receptors can bind to Abs in order to phagocytose pathogens that are covered in Abs.
IgG = Defo can bind to Fc receptor ?IgM = We think this can also bind.
What are the 2 main regions of the Ab, what are they called and what is their function?
Each end of the Ab has a light chain and heavy chain on each side. Meaning that one end will be comprised of both 1 light chain, and 1 heavy chain. (look at pic on p297)
Fab = Antigen-binding region. At this end there is the amino-terminal domains of the heavy and light chains. This is also known as the variable region because it changes for every antigen.
Fc = Constant region = This is the carboxy-terminal domains of the heavy and light chains. The Fc region determines which effector function will be activated.
Note that all Ab types are bifunctional = They are able to bind to antigens, but also the Fc region has an effector function. THE ONLY EXCEPTION is IgD.
How many subclasses of IgG are there, and which ones are more active in 1) crossing placenta 2) activating complement 3) binding to Fc receptors on phagocytes
There are 4 subclasses of IgG
1) IgG 1, 3, 4 = Cross placenta and therefore protect foetus
2) IgG 1, 3 = Activate complement the most
3) IgG1, 3 = Are good at opsonisation, so can bind well to Fc receptors on phagocytes for phagocytosis
NOTE = 134, then 13, then 13.
What is the name of the receptor on T cells, and what are the two main groups of this receptor, as well ass where they are expressed?
T cell receptor = TCR
1) Alpha/beta TCRs = Expressed on more then 95% of circulating T cells
2) Gamma/Delta TCRs = Rarely expressed on blood T cells. But are present on T cells in mucosal surfaces such as small intestine, pregnant uterus, as well as in the liver
Describe how alpha/beta T cells are formed
Alpha/beta T cells (remember this is one of the 2 groups) are generated in bone marrow.
They undergo TCR gene rearrangement in the thymus. And the immature T cells (thymocytes) that recognise self MHC mosulces are selected. The cells that do not undergo apoptosis
Thymocytes then migrate deeper into the cortex = Here they increase expression of TCR, and cell surface molecules, CD3, CD4, and CD8
TCRs that recognise self with high affinity are also deleted here = This process is known as negative selection
Then T cells = Either go on to express either only CD4 or CD8
Descibre the difference between CD4 and CD8 cells
CD4 = T helper cells. These are MHC class 2 restricted
CD8 = Cytotoxic T cells which are MCH class 1 restricted
Describe how gamma/delta T cells are generated
These are also made in the bone marrow.
But these differ from the alpha/beta ones.
Gamma/delta = They have neither CD4 or CD8, and are MHC unretricted
Describe how CD4 T cells (helper cells) interact with APCs/
The CD4 on the T helper cells binds to the MHC class 2 molecules on the APC that has the antigen on it.
Activation = Following this activation the naive CD4 cell produces IL-2 and either turns into Th1 or Th2 depending on what signals it gets after activation.
Describe the 2 subset of CD4 T cells and how they differ
They can be categorised as either Th1 or Th2 based on the pattern of cytokines they release
1) Th1 cells = Produce IFN-y and IL-2. These cytokines activate macrophages and CD8 T cells, therefore promoting cell-mediated immunity. More useful for intracellular pathogens like intracellular bacteria and viruses.
2) Th2 cells = Produce IL-4 and IL-5. These cytokines stimulate B cells to produce antibodies. Therefore promoting humoral/anti-body mediated immunity
After CD4 T cell activation wit APC, what determines whether it becomes Th1 or TH2
1) Th1 = IFN-y and IL-12 cause Th1
2) Th2 = IL-4 promotes Th2
Besides Th1 and Th2, there are 3 other th types of CD4 T cell. What are these and what are there roles
1) Th3 cells = produce high amounts of TGF-beta (transforming growth factor beta)
2) Th0 cells = Express both Th1 and Th2 cytokines
3) Tr1 cells = Secrete IL-10 and little or no IL-2 or IL-4. Which overall leads to immune supression
