immunology - processes, subdivisoons Flashcards
describe the different layers of the immune system
innante - first layer that forms barriers to prevent pathogen entry
cellular and soluble components - second layer comes into action if the barrier is broken (backup). Either neutralises threat immediately or COMMUNICATES threats to other immune cells via chemo/cytokines
adaptive immune system - this elicits a SPECIFIC TARGETED response to different threats
briefly name the functions of the immune system
recognise - threats and non-threats
react - destroy, remove or repair
regulate - turning on and off these responses
remember - allows an effective and swift response to previous threats
where do the cells of the innate immune system derive from/
all immune cells derive from hematopoietic cells
innante immune cells come from the MYELOID lineage
> macrophages/monocytes, neutrophil, eosinophil, basophil, mast cell
> also dendritic cells that link innate and adaptive immune system together by phagocytosing and antigen presenting to these cells
which immune cells are involved in parasite defence
parasites to large to be engulfed but neutrophil, eosinophil and basophils can release histidine + other mediators by degranulatons
where do the cells of the adaptive immune system arise from
all immune cells derive from hematopoietic cells
adaptive immune cells come from the LYMPHOID lineage
> B and T lymphocytes which can form immune memory, re`cognize antigens
> also there are INNATE lymphoid cells like NK that defend against viruses and cancer
describe the dange model of immuniy
immune system will respond to different threats using different chemicals and cells at their disposal
so each issue will have its own specific immune response
what is the difference between adaptive and innate immunity
innate - we are born with and involved the first and second layer of immune repsodne (barrier and cells and solbuble compentns). has a fast response
adaptive - develops and adapts to the enviroment. can form immune memory making up the third layer of immunity. makes use of lympoid lineage cells. has a specific and targeted response so slower
can you name some phsical barriers and organs in the innate immune repsosne
skin, mucous lining and cilia are physical barrier and can secrete antimicrobial elements or expel pathogen by wafting (mucocicilary escalator)
hostile environment is stomach acid as well as sweat and urine to expel the pathogen or at least weaken it due to low pH
lungs we can cough and sneeze to expel pathogen
can you name some chemical barriers in the innate/early induced phase of immunity
lysozymes in tears and sweat can degrade the bacterial cell walls and also skin secretes antimicrobial factors
> e.g psoriasin and protectin
lysosomes are part of the oxygen independent degrafation pathways
how is the skin adapted to protect us from pathogens?
so the epithelial cells can produce alpha and beta defensins and s100 proteins which can target invading pathogens
also epithelial cell are dead and keratinised and regualrly shed so helps with removal of pathogen
what is the role of surfactant in immunity?
surfactant is secreted by type2 alveolar cells and contain proteins like surfactant protein A.B,C which can mark pathogens (act as. Opsonins) making them easier to engulf
lungs also have alveolar macrophages too which can phagocytose to elimiate pahogen
can you name some soluble mediators
cytokines, chemokines , mucins antimicrobial peptiles like s100, defensins and
histidine is a chemcisl mediator, how does it help in immunce cell recruitment?
histidine can dilate blood vessels so more WBC can be recruited from the circulation
Secreted by basophils via granule degradation
what is acytokine and what is a chemokine
cytokines are secreted proteins which are invovled in cell growth, differentioation and can help to traffick cells and develop immune tissue in immunity
chemokines are a subtype og cytokine which is invovled in chemotaxis to recruit immune cells
how do macrophages respond in an immune respinse?
they can become inflammatroy macrophages so are larger, express hydrolytic enxymes, have an enhanvced phagoctyotic abiblity.
this dissipates as the inflammation is resolved
describe features of cytokines. how do they work?
they are pleiotrpic so can act on more than one cell type but also show redundancy as mutliple ones can have the same effect
act synergisitcally or antagonisisically with each other
they will activate signal transcution cascades to activate, regulate or amplift the immune resposne
besides chemotaxis, what else can cytokines do?
well they can promtoe wound healing, angiogenesis, metastasis and cell trafficking too!
there are 4 families of cytokines, can you name then>
naming is based on the location of the *conserved cytosinse* aa on the N terminus C C-C CxC CxxxC
describe the actions of the main cytokines
tnf-alpha and IL-beta - can bind to immune and non immune cells. activate vasclar endothelium cells to help migration of immune cells from blood
IL-6 - proinflame but also antiinflame, activates lymphocytes to increase antibody production
> both have a negative feedback effect on hematopoeric cells to increase neutrophil differentiation
whar are interferons? what are their action
another soluble medior, they are a subset of cytokines which csn inhibit viral replication, stimulate antivody procuin enhance phagocytosis of macrophages can slow cell grow enhance cytotoxciity of NK cells
what does C4b2a3b mean?
part of the compliment system
so we had 4b, 2a then bound to it and then after that 3b bound
so 3b was the last to bind!
C5 converstase so will cleave C5 into C5b and C5a - chemoattrsxtant
what is the complement system
Innate immune system
comprised of 30 proteins which can become activated and begin a protein cascade that results in an amplification of the immune repsonse
end result is the membrane attack complex
> MAC is a pore which causes cell to burst as it disrupts osmotic balance of pathogen
the proteisn are synthesised in the liver as zymogens and become activated by cleavage forming large and small fragments
decribe and name regulatiort elemnet sof the compliment system
the proteins themselves are inactive zymogens and have a very short half life too
protectin = prevent C9 binding and membrane attack complex forming
membrane cofactor B = inactivate C3b
delay accelorating factor = displace Bb blocking formation of alternative C3 convertase
how does the C1 protein differ between the other compliemnt protiens?
C1 does not cleave into fragment a and b
instead it exists as indiviaaly portoeins 1q 1r 1s which form the C1 complex (qr2s2) which can then cleave C4 and C2
describe the porterties of C3 a and C3b of the compliemnt system
C3a- potent anaphylatoxin
C3b - opsonin so it can coat pathogen, marking it for phagocytosis
> phagocyte has receptor which can bind to the C3b and C5a can activate phagocytosis
pamp and damp
pathogen asscoiated molecular patterns
damage assoicated moelcualr patterns
these are recognised by Pattern recognition receptors like TOLL like receptors and NOD like receptors
what does Toll like receptor signalling result in
interferon, chemokine, defensin production so efffecrive aginst viral infecitons!
what does TLR6-TLR2 heterodimer detect A flagella B triacyllipopeptide C lipopolysaccharide D diacylipopeptide E ss. RNA
THESE ARE extracellular TLR so good to detect both gram+- bacteria
OPTION D - diacylipopeptide of Gram+ cells
Lipopolysaccharide of gram- cell
so cant’t be ssRNA as thats intracellular
what is the difference between toll like receptors and nod like receptors
both recognise PAMP + DAMP
different families of cells,
both expressed onsimilar cells, both have leucine rich extracellular domains but NOD has caspase recruitment domain too
> caspase can activate IL-1beta
How do neutrophils degrade pathogens
Oxygen dependant pathway
Uses NADPH oxidase to convert o2 to ROS which are toxic to pathogens
Macrophages also use NItroc Oxide to kill pathogens
Oxygen independent pathway
Uses lysosymes which fuse with phagosome and release its hydrolytic enzymes to degrade pathogen
Macrophages are antigen presenting cells as they have (Mac class 2) so can initiate the adaptive immune repsonse and release cytokines and chemiskines
Or when they die they can produce neutrophil extracellular traps which can help kill more bacteria
How dose acute and chronic inflammation differ?
Acute is rapid onset and short duration, can be resolved by apoptosis of neutrophils
Chronic is slower onset and monger duration and driven by lymphocytes. Can be exacerbated by necrosis, fibrosis and angiogeneis
Normally inflammation is resolved by increasing antiapoptopoc cytokines and apoptosis of inflammatory cells which TERMINATES inflammatory response
What are lymph nodes
They are part of the lymphatic system where immune cells can be transported
Act as checkpoint regulations where some lymphatic fluid is checked by macrophages and dendritic cells to assess for any threats
Which of these are Not secondary lymphoid organs Spleen Mucous associate lymphoid tissue Tonsil Bone marrow
Bone amrroe and thymus are primary tissues as its here where the cells are made and mature
Secondary organs is where they are stored
Decribe how a T cell can develop
In the primary lymphoid organ of the bone marrow, T cell progenitor cells are made
They migrsde to the thymus and mature and develop y interacting with xorcial epithelial cells and nice towards the medullary area of thymus
Becoming double postive
Then travel in circulation and enter the paracroticoid area of the lymphatic follicle
How does white and red pulp of spleen differ in function
White pulp filters pathogens and immune complexes
Red pulp filters old RBC
Both filter things from blood, NOT the lymphatic fluid itself (function of lymph nose)
From the spleen, decribe how the different immune cell arises
Spleen has white pulp containing a T cell zone and a B cell follicle giving rise to cells of t and B cell immunity
Also has a marginal zone surrounding these white pulp regions where macrophages and dendritic cells can derive from which can sample the blood fro pathogens
What is Malt why need?
Mucous associated lymphatic tissue. They can store and develop immune cells
This is necessary as mucousal membrane are thinn and an easy target point for pathogens so this can help speed up the immune response by having the immune cells already patrolling these areas
Which cells present MHC class 1 B lymph RBC T lymph Epithelial
All apart from RBC
All NUCELEATED cells express MHC1
Only antigen presenting cells express MHC2 like phagoctes (neutrophils, macrophages)
How do B and TCells differ in recognition
They recognise antigens presented by Antigen presenting cells via the MHC
B cell receptor can recognise free antigens too
How to antibodies help to neurslise threats
They can recruit innate and adaptive immunce cells.
Aid ohsogcyosis by aglutinating and immobilising pathogen
Opsinate and Mark pathogen makinngti easier to remove - igG1+3
Activate compliment system - igG and igM
What is VDJ recombination
Recombination of the variable domains of BCR (VDJ for heavy, vd for light)
Similarly alpha and beta recombination happens in TCR
Allows for many variable Fab/Antigen binding site regions of the B and T cell receptor enabling ma y antibodies to be made!
despite the limits of the genetic material
what changes happen to the antibodies structure in class switching?
class swithcing allow B-cells to change antibody expresion allowing tailoring of immune response depending on what specific pathogen they are targeting
the Fc region (bottom) changes but the Fab (top) stays the same - only naiive B-cells can do this when they have encountered their antigen for first time
which part of antibody stucture allows it to be speicfic
the Fab region
specifically the variable domains as they encode 3 complimentarity determinant regions (CDR) with CDR3 being the most variable
what does a leader protein do (V(D)J)
precedes each variable segment of the variable domain gene of antibody
and directs protein into the cell secretory pathway
how does IgE. IgA, IgM structure differ from the rest of the antibodies
it has 4 constant domains on the heavy+light chains instead of 3
also IgA is a dimer instead of a single antibody
IgM is a pentamer structure and good at agglutination
what is periscoping
way that dendritic cells sample the envrioment and relay into to t-cells
they push thier dendrtic strucutr between cells and protrude into the tissue microenvironment
> thry can phagocytose solids and macropinocytose fluids
what happens when a dendritic cell finds a threat
it will migrate to lymph noe and present antigen to NAIIVE tcell (mhc class 2)
t cell will then differentiate to effector cell and leave ymph node and enter circulation by efferent lymph vessel
and follow chemotaxic gradient to threat
DIFFERENCE between immature and mature dendritic cells
immature - low expression of MHC11, low levels of glycolyss as no need for ATP, low CCr7 expressin but high phagocytic capcity
mature- encounted an antigen, pahgocytic capcty reeuces, glycoslysis increases, MCH11,CCr7 and co stimaltroy mecules increase expression
what does CCr7 increased expression result in?
increased CCR5 chemkine receport on MATURE DENDRITIC CELL =
maturation of DC, chemotaxix and increases migratory speed
cc19 and cc21 can bing to CCr5 receptor (pleiotropic redundant)
