Adaptive Immunity Flashcards
(40 cards)
What is adaptive immunity?
‘Specialised’ immune response with set tasks to give a more powerful response
Occurs when innate immunity can no longer cope or has failed to remove infection - After the initial ‘innate’ defences are either compromised or overwhelmed
Highly specific
Can distinguish between closely related pathogens
Delayed initiation
Executed by specialised cells / molecules
Powerful elimination tool
Memory Recall function
What is the order of lymphocyte Generation and where do each cell type mature?
Haematopoietic stem cell (HSC)
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Multipotent Progenitor (MPP)
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Common lymphoid progenitor (CLP)
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B cell T cell NK cell
B-cells
Production site – Bone marrow
Maturation site – Bone marrow
T-cells
Production site – Bone marrow
Maturation site – Thymus
What happens when lymphocytes encounter antigens?
Naive lymphocytes [B+T cells] circulate via the blood and lymphatic system, but up until this point they have never encountered an antigen. In circulation they continuously survey the host for invaders.
Antigen encountered in the secondary lymphoid organs:
lymph nodes, spleen, mucosal lymphoid tissues [gut, respiratory, nasal & urogenital tracts]
Naive cells see an antigen and can go through two stages upon activation. They can either mature into their effector form, most often, or they can go on to become memory cells that are able to remember that specific pathogen is that if there is ever a second exposure the immune response is faster and more effective.
What is the colonial selection hypothesis?
Colonial selection hypothesis: The lymphocyte precursor allows generation various different types of immune mature cells with different receptors on their surfaces.
Once the antigen is encountered only the cell that recognises it is gets selected and activated by a cycle of rapid proliferation (this is why this stage takes days - lag phase), as this is the cell required to mount the adaptive immune response.
This gives us a large abundance of effector cells that either kill organism/cells infected with organism or produce molecules such as antibodies.
Colonial selection states that you have a large pool of cells with different receptors but only after an antigen is encountered and a specific receptor cell selected will this rapid proliferation take place in order to generate effector cells.
How does B cell differentiation occur?
Plasma cells (soluble form) Produce antibodies which: - Neutralise the microorganism - Coat the pathogen for destruction - Activate complement (classical pathway)– to kill the pathogen
Memory B-cells
- Provide long-term protection against the same exact pathogen - not
mutated forms
- Critical for reinfection with the same pathogen = very specific!
What do T cells differentiate into?
Cytotoxic T cells (CD8+): - Kill virus-infected cells - Release toxic granules from cytoplasm that can kill the target (infected cell) - They then undergo apoptosis - CD8 marker that allows lab detection
Helper T cells (CD4+):
- Provide ‘help’ to the B-cells which then make antibodies
(the humoural side)
- Secrete messengers (cytokines) that direct B cells to develop into
plasma cells
- If macrophages get infected so can’t kill effectively they are able to
activate the macrophages and enhance their intracellular killing
- Main type - CD4 marker allows lab detection
What is the difference between an antigen and an epitope?
Antigen – any molecule capable of inducing an immune response.
Foreign part of the pathogen that is recognised by immune system. But the immune cell’s defined receptors can’t recognise the whole large antigen which can be a:
Protein, glycoprotein, polysaccharide, chemical.
Epitope – part of the antigen [short peptide] which is recognised by the immune cells.
Many diff cells (receptors) can recognise one molecular antigen, but at different epitope sites - how you can mount different immunological responses to one antigen.
E.g. a football is an antigen but each hexagon on it is an epitope. Each epitope (hexagon) is different, therefore the same antigen (football) can be recognised by lots of different immune cell receptors from different angles.
What is the difference between direct and indirect antigen recognition?
Directly recognising different parts of the antigen:
e.g. Polysaccharide antigens are recognised by B-cell receptors (b cells are recognition cells and effector cells)
In-direct antigen recognition:
the microbe has already been processed by different cells in the immune system (APCs), but is presented as a small peptide to the T cells
Eg mainly with proteins, so viruses infect host cells and use host cell machinery to produce proteins which are then degraded the immune cells and are then presented on the host cell surface and recognised by T cells which mount a response against the infected cell.
e.g. Microbial peptide bound to host protein and presented to T-cells by specialised cells
What are antigen presenting cells and how do they allow indirect antigen presentation?
APCs are specialised cells; e.g. dendritic cells, macrophages
and B-cells. Their function is to take up any antigen that is not a self antigen and present it to cells of the immune system.
Macrophages phagocytose the microbe then go through processing of antigen peptides then present them on their surface. In order to do this they must have a specific mechanism so that other immune cells then know to act on that cell in an in-direct immune response.
To do this they present the antigen alongside an MHC molecule, this is the self molecule but what it presents is the foreign peptide.
Hence the process is:
- Micropinocytosis/Phagocytosis /Endocytosis
- Degrade / process into peptides
- Assembly into a complex
- MHC + Peptide
What is a major histocompatibility complex (MHC)?
AKA Human Leucocyte Antigen (HLA)
Germline encoded on chromosome 6
Highly Polymorphic
Responsible for graft-rejection
Two forms:
- MHC class I – on all nucleated cells (All uncleared cells need the
ability to present an antigen if they are infected)
- MHC class II – on professional APCs (Only present on certain T cells
that are professional antigen presenting cells, such as B cells,
macrophages, dendritic cells. They have class one and two)
Present antigen to different T-cell types. So CD4 and 8 both recognise antigens but in the context of different classes of MHC -
What are the features of MHC class I?
HLA-A, HLA-B, HLA-C: Basic structure is an alpha 1, 2 and 3 chain that spans the transmembrane region and an associated beta-2 microglobulin.
The associated β-2 microglobulin protein is not highly polymorphic, unlike the other regions
Expressed on all nucleated cells
Presents endogenous antigens: hence displays internal status of a cell - if infected this may mean viral antigens
- e.g. Viral derived peptides: presents antigens to CD8+ T cells because
their main job is to fight viral infections.
What are the features of MHC class II?
HLA-DP, HLA-DQ, HLA-DR - but there are other subtypes
Expressed only on APCs: Macrophages, B-cells, Dendritic cells
Presents exogenous peptides - anything taken up by cell, degraded and loaded onto MHC
2 transmembrane regions - alpha 1, 2 and beta 1,2 chains, al together they form the peptide binding groove where the peptide is expressed.
- e.g. Bacterial toxins derived peptides: Presents antigen to CD4+ T cells
How does each MHC class interact with T cell subgroup?
Two ways peptides are recognised - these peptides could be on each MHC class on one cell.
Class 1 activates CD8 T cells that then release their granules to target and kill the infected cell. They also release cytokines that have an effect on other cell types, signalling that other neighbouring cells require immune response.
The same, or different, cell can also express MHC Class 2, activating CD4 T cells that can mature into effector cells and help B cells develop into plasma cells and produce antibodies against the organism, or cytokines that help macrophages phagocytose or NK cells get rid of the organism, etc. So depending on which cell types are activated it can have various different results, all with the end goal being to get rid of the infectious organism.
What happens after the infection has been eliminated?
To keep homeostasis, the effector cells undergo apoptosis leaving only the memory cells.
Memory cells survive in order to provide a quicker response in the future
Why is regulation important?
Don’t want immune response constantly activated, need a way to dampen the immune system and end the response.
Regulatory cells do this, eg reg T cells block B cells from proliferating/producing antibodies/releasing cytokines which in turn prevents the continuation of inhibit other areas of the immune response eg the complementary pathway.
Otherwise would lead to tissue injury.
What is the humoral mechanism?
Humoral Immunity is the soluble immune response: e.g. antibodies produced by plasma cells (hence, B-cell mediated) Basic structure of BCR BCR Diversity Antibody classes Affinity vs avidity Antibody production Effector functions Role in Disease
What is the nature of a B-cell receptor/antibody?
Y shape protein with two identical heavy chains (mainly 5 diff types) and two identical light chains (two different types). Both chains have domains (regions)
The hinge region:
Provides flexibility to recognise epitopes on the antigen surface
The outermost region is variable:
Recognises the antigen and forms the antigen-binding sites
Innermost region is constant:
elicits and performs the effector function
For one B cell receptor (BCR) there are two antigen recognition sites - can recognise two epitopes at once.
The antigen is in a soluble form, same as an antibody, but in order to be expressed on the B cell surface it must also have an extra transmembrane region which is transcribed, translated and exported to expressed in the surface. Otherwise is in exactly the same form both in secretion and in expression.
How do B cell receptors function?
B cell receptors on the surface allows association with other surface proteins which have further extension into the cytoplasm - this is where signalling takes place.
The antigen is recognised and the signal is transferred through these coreceptor proteins. This is how it is then transferred through the cytoplasm to the nucleus resulting in effector function (proliferation etc…)
How do BCRs and antibodies have such diversity?
Within the genes that encode the heavy and light chains is divided up into segments.
The heavy chain has a variable, diversity and junctional region - of which there are several different types for each.
Then there is the constant region, for which there are also several different types - but only one per chain.
These allow the immune system to generate various different combinations together to get the final product. You only ever have one of each region. Any of the heavy chains then combine with light chains to give further variation.
Genes are on diff chromosomes - heavy chain on humans is on chromosome 14. 2 light chains are on chromosome 2 or 22.
How is antibody diversity achieved?
Antibody diversity occurs when different gene segments come together. Gene rearrangement allows the formation of the variable regions. For example, light chain gene rearrangement forms the variable region of the light chain; these come together to form the antigen binding site. In the constant regions, there are multiple possible gene rearrangements to five variable constant regions c(mew) , delta, etc - which constant region is selected determines which antibody class it is. It's this region that carrier out the effector function (not recognition). For example, if C new is chosen then you produce an IgM, usually the first antibody as it is the first constant region after the VDJ segments within the gene. Whereas if gamma 3 is selected you get aN IgG3 antibody... This can then rearrange into other antibody forms.
How do antibodies form isotypes and what are the differences between antibody types?
Structure may be similar but how they arrange themselves is different, for example IgA forms a dimerise via a J chain and IgM forms a pentamer.
Each isotope has a different effector function:
IgM is a pentamer with 10 binding sites, hence is very good at recognising foreign epitopes - could be different ones on the same antigen.
The pecentage in the serum varies too. Mainly will find IgG, followed by A and M. So only very minute concentrations of IgE and IgD, where D tends to be mainly expressed as the B cell receptor (alongside IgM), so isn’t secreted in large amounts under normal healthy circumstances.
IgG can pass the placenta giving babies immunity before it has its own effective immune system.
IgM and G are the most effective at activating the complement pathway.
How can antibodies switch between classes?
Antibody classes can be produced in different OR the same cells.
You have the VDJ combinations of the variable region (forming the antigen recognition site), then a constant region (determines antibody class - and effector function).
Usually M is made first, as Cmew is the first constant region. But the same cell can then switch to a different class by selecting different constant genes and deleting the previous.
Eg switching from M to G to A. This is a class switching event, important in infection as although M may be the first one produced, a mucosal infection requires A, so it is important to be able to switch. So that the body can adapt and produce the best antibodies against infection.
Which antibodies are necessary in which type of infection?
Depends on the sort of infection and site of infection as to which immunoglobulin is most necessary.
Type of infection:
Primary infection – IgM produced
Secondary infection – IgG produced as you need memory cells and quick activation
Mucosal – IgA is found in secretions – mucous, saliva.
Parasitic – IgE
During pregnancy – IgG crosses placenta
Depending on which Ig is produced will depend on the function that is elicited as each is slightly different.
Effector function:
Activation of complement – IgG
Activation of mast cells in allergic reaction – IgE
Antibody-dependent NK-cell killing - IgG (antibody dependent NK cell cytotoxicity - only IgG can do this)
What is the difference between affinity and avidity?
Affinity:
- Strength of binding
- Lock-key hypothesis (higher affinity increases association and
decreases dissociation)
- IgG usually has high affinity, but isn’t often secreted just remains
on cell surface
Avidity:
- Overall binding capacity
- The more complex the structure the higher the avidity
- No of binding sites /antibody molecule, e.g. IgM pentamer (x5 abs -
each could recognise diff epitopes)
