Lecture 7 Flashcards
Origins of blood cells
all cells in blood come from stem cells in bone marrow
differentiate along different pathways depending on outside signals, telling bone marrow what we need and when we need it
-all originate from primary lymphoid organs
Pancytopenia
Petechial Haemorrhages = micro-bleeds under skin (subcutaneous bleeds)
-due to low platelets, not able to clot as easily, gets little haemorrhages
Pancytopenia: “pan”=extensive/across everything. “cyto”= cells. “penia”=fewer.
-extensively fewer cells in blood
-many blood forming elements decreased
-maybe something is occurring in bone marrow, as stem cells arent producing mature cell types
Immature cells : normally not seen in blood, only in bone marrow. Are part of the differentiation lineages from stem cell –> mature cell.
Cancer/defect in bone marrow, preventing cells from fully maturing
Immature cells end up overloading bone marrow, and spilling into blood
-Effects on immune system: vulnerable to infections. Low granulocyte numbers, not going to be able to phagocytose as easily,, potentially vulnerable to things requiring phagocytosis(e.g. bacteria)
-lacking in lymphocyte numbers, compromised adaptive immunity as well
-range of different symptoms, and likely presentation with someone with lymphomas or luekmias
Connection between Secondary Lymphoid organs
Many connected together, especially lymph nodes between lymphatic vessels
All have blood flowing through them as well
What are the divisions between Secondary Lymphoid Organs?
- Filter and response factories
Filter materials that the immune and adaptive immune system need to recognise and respond
to. Gets antigenic shapes from around the body.
spleen –> blood filter (spleen is most likely to to be responding to thing from blood)
lymph nodes –> tissue filter (from lymph fluid draining tissues)
Peyer’s patches –> gut filter (most common elements of digestive system. Responds to antigens coming through digestive system) - Blood vessels and lymphatic vessels
-Bring in antigens and cells
-Take out immune effectors
3.
What proportion of lymphocytes are located in the blood?
10% lymphocytes in blood
Remaining 90% mostly in 2 Secondary lymphoid organs
-as this is where they recognise antigenic shapes and respond
-some in tissues
How do antigens get to secondary lymphoid organs?
- Lymphatic system- antigens taken directly to lymphoid organs through lymphatic system of blood
- Specialised cells (dendritic/specialised antigen presenting cells) - collected from site of infection
Antigen Transport
Dendritic/Specialised Antigen Presenting Cells
various parts of body. Sentinal cells, that collect antigens and take them to secondary lymphoid organs
large star shaped cells, big dendritic processes.
Can capture antigens from a site, transport through lymphatics, to nearest lymph nodes (where lymphocytes are able to respond). Anitgen specific cells recruited
-Lymphocytes test their receptors against the presented antigens by dendritic cells
-if have correct receptors, proliferate and differentiate into effector populations , leading to swollen lymph nodes (palpatable)
Lymphocyte Subpopulations
Effectors: 4 main populations, allow adaptive immune system to produce an effect to help deal with antigen
-Antigen production (B lymphocytes) exclusively. Highly evolved to recognise antigens and make antibodies against them.
-Antigen-specific cytotoxicity (CD8 T Lymphocytes) CD8 marker on surface. can kill cells will particular surface antigens.
-Antibody-Dependant Cellular Cytotoxicity (ADCC (K Lymphocytes))
-Natural Killer activity (NK lymphocytes)
Regulators: Regulate control of effector populations
-cytokine production (CD4 T lymphocyte) have CD4 on surface “helper/regulator cells” via doing:
a. Producing cytokine hormones
b. cell to cell interactions
Shape recognition
- Common components of many microbes (e.g. bacterial cell wall sugars) -not in own cell walls. recognised as potentially foreign and harmful
Adaptive immune sys recognises more specific things: - Uncommon components of particular microbes (e.g. viral capsid protein) - B lymphocytes try to recognise and neutralise before they reach target cells which they want to infect
- Common components in uncommon context (e.g. myocardium shapes on streptococcal bacteria)
-streptococcal looks like shapes on heart muscle. Responds and Cross reacts with heart muscle antigens and starts to damage aspects of your heart.
-illustrates how incorrect context can be damaging
Lymphocyte Activation
Via receptors
BLymph have Surface Immunoglobulins (sIG)/Antibody. similar to blood antibodies, but have extra part on tail that anchors them into membrane. 1000s all look same. Antigens interact with part of these sIG and generate an internal signal (change in some associated surface molecules that tells the inside of the cell that binding has occurred, giving first antigen specific activation signal)- do you want to respond to it? Also have CD70 signal transduction molecules
-become antibody forming cells
T lymph have T cell receptors TCR, No immunoglobulins, have different specificity. Recognised presented antigens. Triggers change in transmembrane molecules, signifying that the cell has recognised something and do you want to respond to it. CD3 signal transduction molecules. If CD8 bearing cells will become cytotoxic cells. Or if CD4 will produce helper cells
Antibodies
(glyco)protein molecules
4x polypeptide chains: 2x identical small(light)chains. 2x identical long(heavy) chains.
folded together and convalently bonded by di-sulfide bonds to hold together
Chains each have 2x components
Light: 2x 1/2s almost identical aa sequence (constant region Cl) + 2x 1/2 highly varied aa sequence (variable region Vl)
Heavy: 3/4 constant aa sequence (CH123)(3x domains) 1/4 top highly variable aa sequence - associated with variable regions of light chain (VH)
-arms have same Vh and VL regions on them
Hinge Region: Middle of heave chain. Area which is quite Prolean rich. More flexible.arm of Y can move in space - important for function
Variable regions: folded together to form Antigen binding site. recognises antigenic epitope (of virus/bacteria) = 3-4 Hypervariable regions short, with huge amount of variablility- intimate contact with recognising antigen
-different variable regions= different shaped antigen binding sites= but same on each arm
CH2 domain = below hinge region = Complement binding region - binds complement components when antibody is in the configuration due to being BOUND to antigens
-FC region = CH2 and CH3 domains (are highly conserved across all antibodies)= High affinity to neutrophil receptors = links the bound antigen to the neutrophil to enhance phagocytosis
6 week check
Postnatal check
Discuss immunisations
In utero: Immune system doesnt develop until first trimester(form immune organs). Havent been exposed to outside world. Antibodies derived from mum(get a sample of antibodies mum is making, as will be born into mums environment). Transplacentally given from mothers blood stream–> placenta –> developing blood stream in utero
Birth: all are Maternal antibodies. Gradually decay, topped up by breast milk antibodies (another class of antibodies, but all protective) absorbed into our blood stream, topping up maternal antibodies during early months
Babies own: Make own antibodies as are exposed to environmental antigens (breath eat etc)
-early phase of mostly mums, developing own.
Decay period where maternal are decreasing and we are developing out own: potential dip in antibodies. potentially Vulnerable to infections. Dependant on rate of decay:Babies development
-Not born with all the antibodies we are likely to make, as we have to be exposed to environmental antigens to make them
-born with a sample of mums antibodies that protect us, until we can develop our own
-try to enhance baby’s antibodies and immune responses against early childhood infections by deliberately immunising with antigens form these illnesses
-Cultural differences:
Antibody responses
born able to respond to antigens, to generate antibodies
- Rabis virus injections
- Rabis antigens get to secondary lymphoid organs. B-lymphocytes there recognise shapes and produce a response
- Initially no antibodies able to recognise rabis shapes
- 3-4 days after vaccination. Primary antibody response. B cells able to recognise Rabis shape, and start to respond and start to pump out antibodies specific to this shape. Wont continue for ever - will reach a peak and decline
- Years time. Rabi’s specific antibodies much lower.
- Repeat injection
- Rapid increase. Much earlier.. Several logs higher 10-1000x. Lasting Longer. Secondary response. Adaptive part of immune system - during primary response, not only did you make antibodies, but you remembered them, and system changed so next response is quicker, more vigorous and in a more sustained way later on
The Principle of Immunisation
Generating a primary response
In order to facilitate generation of Antigen specific memory
-so if later exposed = secondary response
B cell clonal activation
Antigen sensitive B lymphocytes in 2 Secondary Lymphoid organs
-have surface immunoglobulin receptors. Only has 1x antigen binding site shape on its 1000 receptors = B cells committed to 1x receptor shape
Antigens test receptor shape. most wont fit.
Does fit. Signals B cells to highlight that its recognised something. doesn’t respond immediately. Differentiates and expresses additional surface receptors which “ask for help”(is this dangerous should i respond?)
If Helper signals are appropriate, then yes it will respond. - context is important as it is the context which is providing the helper signals
B cell proliferates and differentiates into 2x effector populations (in 2 lymphoid organ).
1. Plasma/Antibody secreting cells: Large metabolically active - initial increase few days after immunisation/ Primary immune response (few days as antigens have to get to organs, find b cells, b cells have to activated, get helper signals, proliferate and produce plasma cells)
2. Memory cells: replacements for original antigen-sensitive b cell. same receptors. 10-1000x. longer lived, recirculate: come from original lymphoid organ and repopulate all other lymphoid organs = distributed protection
-able to respond to much lower concentrations of this antigen
- aren’t as fastidious about help, so can switch on responses quicker, giving rise to Secondary response
-Want to generate alot of memory cells during immunsation
