An overview of immunology Flashcards
Aim of the Immune system
The main role of the immune system is to protect from infection.
- The immune system responds to antigen.
- An antigen is anything that the immune system responds to. Usually protein and not necessarily ‘bad’.
- the immune system is set up to respond to naturally occurring proteins.
- The immune system recognises antigen through antigen receptors
- the antigen receptor is the receptor on a cell that recognises antigen
Innate immune system
recognises antigen using germline-encoded pattern recognition receptors.
Adaptive Immune system
Antigen-specific T and B cell receptors. T and B cells recognise antigens specifically to antigen-specific receptors.
Effector mechanisms of the immune system
When we recognise an antigen, and we want to do something about it, we need mechanisms to help us.
- The difference between innate and adaptive immunity is in the way that the cells recognise their antigens not in the way they respond to remove the problem.
Immune system summary
Immune cells are produced in the bone marrow and form pluripotent stem cells and then go on to form myeloid and lymphoid progenitors.
Neutrophil
big, multi-lobed nucleus, it’s one nucleus but its multi-lobed.
its main function is phagocytosis, eating up other cells.
Eosinophil
Large granular cell. role not fully understood. may be important is parasitic infection, we find lots of them about when someone has a parasitic infection. Also important in allergic diseases.
Monocyte (circulating)
Macrophage (tissue)
Macrophages are tissue-resident cells and always the first cells to meet any infection that has penetrated into the tissue. they have a big role in phagocytosis and also do antigen presentation.
Dendritic cell
Specialised cell for antigen presentation. it has the long pseudopodia to sample the external environment, bring things into the cell, process them and present them to T cells on the surface.
Basophil (tissue-resident counterpart= mast cell)
they are thought to be important in parasitic infections but in practice, the main role is in disease which is an allergic disease in industrialized countries. they are the chemical that release histamine and other chemicals during hay fever season.
Lymphoid lineage
- lymphocytes are smaller cells, they are similar to the erythrocytes in size
- their nucleus is much bigger
- Little cytoplasm with few granules
B cells: make antibody, antigen presentation
T cells:
CD4: help other components of immunity
CD8: kill infected cells
*you can’t easily tell T and B cells apart on microscopy, they all look the same. you have to abuse special stains to discriminate what type of lymphocytes they are.
T cells and B cells=ADAPTIVE IMMUNITY
NK cells: are actually INNATE lymphocytes as they don’t have antigen-specific receptors like T and B cells.
NK cells do Direct lysis of infected cells and antibody-dependent cellular cytotoxicity
Macroscopic anatomy of the immune system
- We have the bone marrow in large bones such as the femur where all the cells are produced
- the cells are produced during foetal genesis but they are also produced throughout life, although the output gets slower
- T cells actually go somewhere outside of the bone marrow to mature
- Early T cells go out of the bone marrow and actually mature in the thymus. the rest of them all mature in the bones marrow.
- once the cells are generated, they are released into the blood vessels
- once in the blood vessels, they may traffic through the tissues. particularly to sites of infection and they may also come to reside in the collection of lymphoid tissue known as lymph nodes.
- in some places, you can see and feel them easily such as in the groin and axilla, tonsils. In other places, the lymph nodes are a bit more dispersed for example in the small intestine, we have PAYERS patches that run through.
- the cells may want to leave the tissues and lymphoid organs and they do that through the lymphatics and the lymphatics all merge together and come back into the blood street through the thoracic duct.
Communication of immune cells ; intercellular signalling
- they may secrete soluble mediators, things that are released into the bloodstream that act on another cell or even on the same cell
ENDOCRINE: signalling like a hormone at a distant eg in severe infection where people develop systemic infections and fever. cytokine is released into the systemic circulation that acts on the brain etc.
PARACRINE: signalling to nearby cells
AUTOCRINE: the soluble mediator put out by the initiator cell actually put out a receptor on the same cell. (from me to me)
JUXTACRINE: cells can also come together to signal with one another. rather than releasing a soluble mediator, they do it themselves.
cytokines
•Cytokines are small proteins released by cells that have an effect on another cell
–They are important for communication between cells of the immune system and between immune system cells and other cells and tissues
- cytokines are given a specific nomenclature; they are known as INTERLEUKINS or IL and then they have a number. the number just refers to the order of discovery. i.e IL 1 was the first to be discovered.
….but some cytokines are now named differently eg TGF-β, IFN-g TNF-α
Chemokines
•Chemokines are similarly defined like cytokines, but they have a Different structure, receptors and nomenclature and they do slightly different things.
–Its Main role is temporal and spatial organisation of cells and tissues
Manose binding ligand (MBL)
Manose binding ligand (MBL) is an example of a pattern recognition receptor.
MBL recognises and mannose and fucose residues on the surface of cells. It is predominantly a circulating protein.
- it has a stalk and a globular head. it is recognising the mannose and fucose residues on the surface of the cell.
- lower organisms such as bacteria and fungi have their mannose and fucose residues in a particular conformation
- the globular heads of the mannose-binding molecule are fixed in that particular configuration to recognise the lower organisms mannose and fucose configuration.
- In humans, the mannose and fucose residues are in the wrong configuration for mannose-binding ligand so the molecule doesn’t bind.
B cells antigen receptors
It’s an antibody on the surface of the B cell also secreted into the circulation and found in the plasma.
-Antibodies comprise 2 identical heavy chains. It’s a mirror image. and 2 identical light chains.
-the antigen-binding site interacts with the antigen and the rest interacts with other bits of the immune system.
VARIABLE REGION; its variable because it has to bind to lots of different things.
CONSTANT REGION; conserved between different antibody molecule, it doesn’t need to be different.
The T cell receptor
- T cell receptor is very similar to the B cell receptor
- rather than heavy and light chains, we have alpha and beta chains
- we still have a variable and constant region
- it’s still attached to a cell
- but unlike the antibody, it’s not secreted
- it’s just a surface receptor that you find on T cells and B cells
- the antigens that slots into the receptors are very different from the antibody.
- antibodies recognise big 3 dimensional extracellular molecules and T cells recognise peptides that have been processed.
- Only a surface receptor on CD4 and CD8 T cells
Recognises processed antigen in the form of linear peptides
Generation of adaptive immune receptor by somatic recombination events
somatic recombination.
- We produce diversity in the heavy chain region by having different gene regions. so we have the V, D, J region. each of these gene regions contains lots and lots of genetic material and you can sample at random different gene segments from each of them and swap them together to make a receptor.
- we take a bit of genetic material from V at random, same from D and J. we splice them together, take a bit from V, put it together. transcribe and translate it and we have a new variable region.
- we do the same for the light chain but for light chains we just have V and J regions.
- so we have increased the number of combinations that are possible with a small number of genetic materials.
- The disadvantage of random somatic recombination is that majority of the receptors that we produce are junk. they either just don’t work because you can’t put the amino acids together in that particular configuration or they may not bind to anything useful in the environment or they may be potentially harmful because they recognise their own tissue.
- so we lose a lot of the receptors that we make, it’s a very energy-intensive wasteful process.
- the exact same process of somatic recombination happens for T cells (alpha and beta chains) as well just like it does for B cells.
T CELLS
There are 2 types of T cells.
1. CD4 (helper T cell)
2. CD8 also known as cytotoxic lymphocytes. they kill virally infected cells.
-In the image; we have our virus infecting cells and injecting its genetic material into the nucleus of that cell and the cell will now begin to synthesise viral proteins. in order to synthesise viral proteins, the viral proteins are being handled just like our own protein. they are being transcribed, translated through the endoplasmic reticulum through the Golgi and into the cytoplasm.
some of these viral proteins along with our own protein will go back through the endoplasmic reticulum and will get attached to a molecule called MHC -major histocompatibility class 1.
we’ve got a bit of the viral protein as a peptide on the surface of the cell in combination with MHC Class 1.
-so we have our viral infected cell, the virus was hidden inside the cell bit now we’ve displayed some of it on the surface.
-CD8 cytotoxic lymphocytes recognise that viral peptide and now can kill the viral infected cell.
- in doing this, we are damaging our cells and we can see that macroscopically as a disease
- i.e in a genital ulcer in herpes. the genital ulcer is there because the cytotoxic lymphocytes have stripped off the infected mucosa, leaving an ulcer.
CD4 T cells
- They are helper T cells. they orchestrate everything and tell all the other cells what to do.
- for CD4 T cells to recognise an antigen, it needs to be presented to them by a specialised antigen-presenting cell.
- CD4 T cells only respond to antigen presented by antigen-presenting cells.
- Antigen-presenting cells include - dendritic cells, macrophages and B cells.
- The antigen-presenting cell eg dendritic cell will put the antigen into vesicles and into the vesicles, the antigen is digested into peptides and the peptide gets loaded onto an MHC CLASS II molecule.
-the CD4 T cells is then able to tell other cells what to do.
- there is specificity so it can only bind to specific antigens.
Clonal selection
These are all different types of B cells. the spiky bit on the surface all represent antibody and all these cells have different antibody receptor, they all respond to different things.
we are born with this huge number of different antigen receptors (antibody)and we don’t know which ones we are gonna use and the cell doesn’t know what they are for.
eg if we live an environment where antigen X is very important, we will meet that soon after birth , and we have our B cell that responds specifically to antigen X.
then the antigen X specific B cell will be selected for division, lots and lots of daughter cells and you end up with a big population that will respond to antigen X and produce lots of antigen X antibody.
T and B cell memory
PRIMARY IMMUNE RESPONSE - when you first inject antigen A, nothing happens for a few days because it takes a while to recognise and do all the clonal selection and maturation. After a few days, the response to antigen A starts to go up and it then drops but it never drops all the way down to baseline.
SECONDARY IMMUNE RESPONSE - you meet antigen A again, the 2nd time around, you get a faster response that then goes up to a higher level.
Acute Inflammation
•Inflamito – setting alight
•Cardinal features: hot, painful, red, swollen
•Describes a process, but tells you nothing of the cause
Blood vessel changes underlie the process
- Vasodilatation
- Adhesion molecules
- Increased permeability
The clinical features are therefore defined by an interaction between the pathogen and host immunity
