ICS - Immunology Flashcards
what is innnate imunity
instinctive, non specific does not depend on lymphocytes, it is presant from birth
what is adaptive immunity
specific and learned. it requires lymphocytes and antibodies
noth innate and adaptice immunity are made up of cells and soluble factros (humoral)
what is teh main purpose of eh immune system
to distuingish between self and non self
when you centrifuge a blood sample, what 3 layers are presant
plasma, tehn teh buffy coat of leukocytes, then teh lower layer of erthrocytes and platelets
what is serum
plasma witjout fibrinogen and other clotting factors
what are the three polymorphonucleur leukocytes
eosinophil. neutrophil, basophil
what are teh mononumcleur leukocytes
monocytes, t cells, b cells
what do monocytes turn into
macrophages whihc are static in tissues
what do b cells turn into
plasma cells
what do t cells turn into
t regulator, t helper, cytotoxic, th17
what are the three immune cells whihc are in a catogry by themselves
mast cells, natural killer cells, dendritic cels (macropgages in teh skin)
what are teh 4 soluble factors
complement, antibodies, cytokines and chemokines
what are complement factors
serum priotines secreted by the liver that need to be activated to be functional
what are teh modes of action for complement factors
direct lysis, attract more leukocytes, coat invading organism
how do antibodies work
bind to antigens, are soluble
what are teh 5 classes of imunoglobulins
GAMED
what is teh structure of an antibodies
it is Y shaped, with an Fc (commen end) and then FAB ends which are specific to teh antigens, it is made of a heavy chain and a light chain
what is teh most commen tyrp of antibody
IgG, it can go anywhere
infomation about IgM
it is a large molecuke and is resticted the blood
what is IgA
it is secreted in everything - saliva, breastmik, vaginalk fluids. It is important for killing things outsode of teh body
wha are teh functions of antibodies
act as opsiion
agglutination
anti toxin
what is a cytokine
protiens secreted by the immun and non immune cells
what are teh 5 groups of cytokines
interferons
interluikins
colony stimuluating factors
tumour nectosis factor
chemokines
what is an interferon
a cytokine whihc induces a state of antiviral resistance in uninfected cells
what are interleukins
produced by many cells, can be proinflamitory
causes cells to divide, differentiate and relaese factrs
what are colony stimulating facros
involved in teh division and differentiation of bone amarrow stem cells and are precurosrs to leukocytes
what is tumour necrosis factor
medicate the inflamitory response - are pro inflamitry and cytotoxic reactions
what are chemokines
leykocyte chemoattractants
what is innate immunity composed of 3 main parts
physical and chemicla barries
phagocytic cells (neutrophilss and macrophages)
blood protiens ( complement and acute ohase)
what are physical and chemicla barriers
lysozomes in tears
skin as a physical barrier
mucus n lungs
acid in gut
low vaginal ph
wha is teh bodys response to a cut
Stop bleeding (coagulation)
Acute inflammation (leukocyte recruitment)
Kill pathogens, neutralise toxins, limit pathogen spread
Clear pathogens/dead cells (phagocytosis)
Proliferation of cells to repair damage
Remove blood clot – remodel extracellular matrix
Re-establish normal structure/function of tissue
what are teh three steps of inflamaiton
Increased blood supply
Increased vascular permeability
Increased leukocyte transendothelial migration ‘extravasation’
which cells sense micorbes in the blood
monocytes and neutrophills
whihc cells sense microbes in teh tissues
macrophages, dendritic cells
what does PRR and PAMP stand for
PRR – Pattern Recognition Receptors (on cells)
PAMP – Pathogen-Associated Molecular Patterns
(on microbe)
what do tehe complement facotrs do
lyse microbes directly, chemotaxes, opsoniation
what is teh process of extraavasion
(diapadesis)
endothelial cell becomes sticky,
teh neutrophills strat to rolll instead of flowinf past
they begin to get fully stuck
they tehn squeeze though teh gaps and move to teh sight of infection
what is MHC
major histocompatibility complex
what are antigen presenting cells
macrophages, dendritic cells, b cells
how do t cells work
respond to presented antigens
t cell receptor recognises forign antigens in association with major histocompatibility complex
how are t cells made in childood
in the feotus, teh t cells kill all of the self recognising t cells
what are intrinsic antigens
- are for viruses and kill teh cell infected by the pathogen, this is down by teh t killer cells
what are extrinsic antigens
MHC class 2, they t helper cells help teh b cells make extrcellular pathogen and can help to kill it directly
what are teh tyes of t cells
naive, undifferentiaeted
CD8 - T killer cell
CD4 - (teh precursor one that divides itno TH1 and TH2)
TH1 - helps to kill intracellular pathpgens
TH2 - T helper cell antibody production helper
what is humoral immunity
b cell based, this is teh antibodies
what are the three t cells taht do the work
TH1 - macrophage activation
TH2 - b cell activation
CTL - cytotoxicity
what are teh primary lymphoid organs
bone marrow - all immune cell origins and teh B cell maturation site
thymus - t cell maturation sight
what is seconday lymphoid organs
They provide a space for teh forign antigens to inteact with the lymphocytes
lymph nodes - site of DC, B and T cell interactions
spleen - removal of RBC and Ab coated bacteria
there are alos muscosal associated lymphoid tissues in teh gut such as peyers patches in teh gut
what is teh tertiary lymphoid organs
transiet formation of genminal centres, usulaly pathplogy related
they form ectopicallt at sights of chronic inflamation such as in multiple sclarosis there are TLOs in teh brain whihc stop teh mylenation.
what are the two pulps of teh spleen
red pulp - miltratio of RBC
white pulp - active immune response trhough humoral and cell mediated immunity. rich in t cells and teh lymphoid follicules are rich in b cells
what is teh storage function of teh spleen
stored 25% of lymphocytes and 30% of red blood cells, it can also store platelets
it also produces red blood cells
what is teh initial blood cell called
heamocytoblast
how do neutrophills kill the pathogens though phagocytosis
contian 2 granule types containg enzyme and lowerd pH but this onyl kills 2% of pathogens
they take loads of pathogens into the cell
they then do teh respiritory burst whihc kills teh pathogens and also teh neutrophills tehmelsves, it is a suicide bomber!!
what is teh respitiory burst
teh releae of free radicals in neutrophils using the free radicas superoixede nd hydrogen peroxide
teh enzyme myloperoxidase is used to produce CL.
what is teh role of dendritic cells
they are antigen presenting cells that take teh antigen to teh lymph node, where it can select teh correct T cell, thsi is caled T cell priming
T cells can only recognise antigens presented on MHC
Whats do natural killer cells do
kill cells infected with viruses r cancer by injecting toxins or causing apoptosis
What is teh B cells role with antigens
They can react to both presented and non presented antigens
tehy can also phagocytoese and present themsleves onto MCH2
How does a B cell react to being shown an antigen
phagocytose it if its a pathogen and become antigen presenting by putting it on the MHC2
Become activated whihc helps it turn into a mast cellk
mast cells release antibodyes (whihc are really just the antigens on teh B cell but floating free)
Whast are teh two types of T cell
CD4 - the T helper cells which secrete cytokines to help teh cells coordinate via chemotaxis, They can only see antigens on MCH2
CD8 - these are teh cytotoxic t killer cells, very similar to teh natural killer cells but only see antgens presented on the MCH1 complex not all of them
what are the two types of receptors found on the T cells
phagocytotic - allow it to bind and then phagocytose, thsi allows for teh investigation of teh pathogens
Signalling - toll like receptors which are all teh complicated (or not so much hahaha) T thingys whihc are inside and out side of teh cell
what re teh two gruanel tyes found inside of the ohagolysosome
specific - protease and hydrolse enzyme whihc are activated at a neutral ph (so first)
nect teh ph is lowerd
thsi causes teh azurophilic granusls to be reale whihc are hydrolases and oxidative eenzymes
describe the different signalling PRRs
TLR = toll like receptor
TLR 1 2 4 5 6 - work extracellularly and respond to PAMPs such as peptidoglycan and lipolysaccorise and teh flagella protines
TLR 3 7 8 9 - on teh inside of teh cell and respond to virus RNA, work intrinsically, cause a release of proinflamitory cytokines, whihc cass vasodilation, fever and increased leukocyte prescne
it will also produce interferon alpha a and b whihc stop teh virus from replicating in other cells
which receptors are cytolysic
NOD-Like Receptors and RIG-Like receptors are cytosolic
what us pyroptosis
Pyroptosis is an inflammatory programmed cell death in response to bacterial infection.
what attracts neutrophills to teh sight of infection
chemokine IL-8 (CXCL8)
how do neutriphills get teh teh infected tissues
- E-selectin (an adhesion molecule on the capillary endothelium), is activated by IL-1 and TNF-α from damaged cells and binds to the glycoprotein CD15 on neutrophils in blood.
- This causes neutrophils in the blood to slow down and roll along the endothelium lining.
- ICAM-1 on endothelium (induced by LPS, IL-1, TNF-α) binds to integrin on neutrophil; the neutrophil stops.
- Diapedesis: neutrophil squeezes through endothelium (holes caused by C3a, C5a, chemokines, histamines, prostaglandins, leukotrienes (causing smooth muscle contractions in the bronchioles))
what are eosinophills important for
Important cells in dealing with parasitic infections.
Release cationic granules such as major basic protein.
Release ROS, eicosanoids, leukotrienes, elastase among other molecules.
whay are basophills importnat for
Can be thought of as circulating mast cells that release histamine upon IgE crosslinking Fcε receptors.
They also secrete serotonin and heparin
Important in asthma, anaphylaxis, atopic dermatitis, and hay fever.
Key point; They do not egress into tissues and become mast cells .
what are yeh three granulomacytes (polymorphonuclar cells and whta does this mean)
BEN; Basophil, Eosinophil, and Neutrophil.
pmn cells - tehy have multiple nucelues
what are mast cells important for
Important in parasitic infection and allergic reactions.
At mucosal surfaces.
Stem cell factor is essential for development.
Main source of histamine.
Activated by immune complex IgE crosslinking FcεR1
What are teh 5 antobodies for
G - teh main antibody, can cross teh placenta, beinds to phagocytes
A - secretes into mucous saliva teads, tags pathogens for destruction
M - fixes complement, main antibody of primary response, B cell recepor and important for the immune memnorry
E - bainds to mast cells and basophil allergy and hypersensitivity
D - b cell receptor, stimulates release of IgM
how do natural killer cells work
ADCC is an independent mechanism that does not require complement and uses only one cell type. It is classically NK cells that do this. Typically IgG will bind surface antigens on the pathogen-infected or cancer cell. NK have Fc receptors (CD16) that recognise the antibody Fc region. This cross-linking triggers degranulation and cell apoptosis. Viral proteins are expressed on the surface of cells during viral replication can become antibody targets.
whihc cells can present MCH1 and whihc can present MCH2
MCH1 - all nucleated cells - this means red vblood cells dont!!
MCH2 - macrophages, B cells, dendritic cells
what has to happen between a dendritic cella and t cell for a response to occur
When immune cells come together they form what is know as an immune synapse. For a response to occur 3 things are essential 1. Binding of primary receptors e.g. TCR to MHC II. 2. Binding of co-stimulatory molecules e.g. CD28/CTLA4 to CD80/CD86. 3. A robust release of the appropriate cytokines. MHC binding without other stimulation leads to anergy (lack of response as a form of peripheral tolerance).
what are teh markers on T cells
Naïve T cells are identified by being CD45RA+ whereas memory T cells are identified by being CD45RO+. The general marker for T cell activation is CD25 expression.
what are the t types of T helper cells
Th1 - cell mediated immunir=ty regulation, regulation of monocytes and macrophages
Th2 - hummoral immunity, regulators of eosinophil, basophils and mast cells
what are the 4 hypersensitivty reactions
Type I (allergy)
Primarily IgE dependent
Type II
Primarily IgG-dependent cytotoxicity
Type III
IgG/IgM-dependent immune complex formation
Type IV (delayed type hypersensitivity, DTH)
Cell dependent (Th1/cytotoxic T cells/macrophages)
which antibodies corspond to whihc reaction
1= IgE - Eleanor is having an allergic reaction
2 = IgM and IgG - myself im attacking
3 = IgG - gathering of antibodies
4 = T cells - go cray cray but it’s a bit delayed
what are the 7 allergic diseases
Anaphylaxis
Allergic asthma
Allergic rhinitis (hay fever)
Atopic dermatitis
Allergic conjunctivitis
Oral allergy syndrome (food allergy)
Angioedema (not idiopathic)
what cells are invoved in allergic reactions
eosinophills, mast cells and basophills
defien atopy
Atopy = a hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens.
what are teh CD4+ cells for tolerance and inflammation
TREG - T regulation causes tolerance - IL10 cytokine has mass antiinflamitory actions
Th17 - importnat in muclsal mucosal membranes it promtes inflamation, teh princilple cytokine is IL17!
where does B cell regulation take place
secondary lympohid organs (lymph nodes)
what is teh structure of an antibody
FAB regrion - antigen binding fragment binds to e antigen and are the effector regtions
Fc region - constant regeon
what are teh functions of antibodies
Neutralisation of toxins, agglutination, precipitation, opsonisation of pathogens, complement activation via the classical pathway 🡪 cell lysis and chemoattraction.
what are teh 4 hypersensitivoty reactions (PTS defornitions)
Type 1 is a fast reaction occurring in minutes. Cross-linking of antigen to IgE on mast cells and basophils causes massive degranulation and therefore massive release of histamine.
Type 2 IgM or IgG binds to self antigen leading to cell destruction by the membrane attack complex and cellular mechanisms.
Type 3 IgG binds soluble antigen forming a circulating immune complex. These deposit in vessel walls especially in the kidneys. Here they kick off an inflammatory response causing complement deposition, opsonisation, phagocytosis etc. RBCs carrying the complement receptor 1 bind complement coated immune complexes and transport them to the liver and spleen for phagocytosis.
Type 4; This is helper T cell mediated. Specifically Th1. Th1 are activated by antigen presenting cells. Memory T cells are formed. When the memory T cells encounter the antigen again, they will activate macrophages leading to tissue damage.
what is teh diffecne between immune tolerance and autoimmunity
Immune tolerance refers to the unresponsiveness of the immune system to self-antigens. This is crucial in order to avoid inflammatory reactions against healthy tissue. Autoimmunity arises when there is a breakdown of immune tolerance.
what are teh features of autoimmunity
Often relapsing-remitting
Organ-specific vs Systemic
Damage to or destruction of tissues
Altered organ growth/function
Generation of autoantibodies
what is a primary and secondary immunodeficancy
Primary Immunodeficiency
Those born with intrinsic defects in their immune system.
Rare and mostly genetic disorders
E.g. SCID
Secondary Immunodeficiency
These are acquired and are referred to generally as immunosuppression
Drug induced e.g. Steroids, azathioprine, chemotherapy.
Cancers of the bone marrow and blood cells
AIDS.
what is tumour necrosis factor
release by macrophages
it induces fever and acts as a neutrophil chemotaxis
what are 4 immuno surpressive drugs
glucocorticoids
Ciclosporin, tacrolimus and rapamycin
Purine analogues.
Alkylating agents.
what is a pyogenic infection and what cell is most liekly to be raised
Pyogenic infections are characterized by local inflammation of skin, soft tissue and bodily parts which are mainly caused by invasion and multiplication of pathogenic microorganism
Neutrophil!
what is teh difference between MC2 and MHC 1
MHC1 - its is shown on all cells and shows endogenous antigens to show that it is part of self
MHC2 - shown on antigen presentic cells such as b ells, macrophages and dendritic cells, its shows exogenous antigens such as from pathogens
what are toll like recepros
they are signalling PRRs cause a cascade of signals to be released
Single polypeptide chain found on all leukocytes, epithelial cells ad endothelial cells as well
what are the two catogries of TRRs
- TLR 1 2 4 5 6
- Are on the cell surface and bind to extracellular PAMPs such as peptoglycan, lipopolysaccoride and flagella
- TLR 3 7 8 9
- Are in the cell, bind to intracellular PAMPS such as viral RNA
- These activate transcription factor NF-kb
- Casing a proinflamitory cytokine secretion
- This causes vasodilation, fever and increase leukocyte prescence
- If it’s a virus the cell will also produce interferon alpha and beta which stops the virus from replicaitng in other cells
what does TLR 2 3 4 respong to
2- gram positive and TB
3- intracellular stuff
4- LPS (lipopolysaccoride on gram negative)
what do TLR 5 7 8 9 respong to
5 - flagella
7 - single strnad RNA
8 - intracellular
9 - non methylated DNA
what is teh comminication of a dendritic cell and t helper cell called
dendritic synapse
what receptors do cd4 and cd8 respond too
cd4 respond to mhc2
cd8 respond to mhc1
the way to remeber tis is that 8x1 is 8 and 2 x 4 is also 8
what is thymic selection and how does it happen
it is when teh thymus gets rid of teh t cells that are self recognising and would causse an autoimmune disease
if it is positivly slected, it responds to mhc1 and 2 and doesnt cause an immune response
what is thymic selection and how does it happen
it is when teh thymus gets rid of teh t cells that are self recognising and would causse an autoimmune disease
if it is positivly slected, it responds to mhc1 and 2 and doesnt cause an immune response
if it is negativly selected it will recognise teh anitbodies but will still cuase an immune reponse
what do interlukins do t helper cells produce
T helper cells release interlukin 4 and 5
* Interlukin 4 incduces clonal expansion of b cells
* Interlukin 5 induces b cell differentiation into a plasma cell to produce antibodies
define somatic mutation and class switching
- Somatic hypermutation - point mutation in Ig as evolutionary measyre
- Class switching - change one Ig into anotehr type
