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321 Cards in this Set
- Front
- Back
Epithelial cells exhibit what hair-like structure on their surface? |
Cilia
|
|
What antimicrobial molecules do epithelial cells secrete?
|
defensins
|
|
What is TcR? |
T cell receptor |
|
What cells secrete mucus |
goblet cells |
|
What is the use of mucus |
- trap microbes - prevents adhesions |
|
What are the 3 key players of the innate immune system |
mast cells, tissue resident macrophages, dendritic cells |
|
How are mast cells, macrophages and dendritic cells distributed? |
embedded through virtually all tissues form an immunological early warning system mast cells near vessels |
|
A mast cells granular appearance is caused by what? |
granules are bags full of potent substances such as: - histamine - leukotrine B4 (LTB4) - cytokines such as TNF alpha - cheekiness such as CXCL2 |
|
Why is rapid reaction of mast cell degranulation important + how is it achieved. |
How - pre-synthesis of the antimicrobial molecules Why - fast response to pathogens |
|
Histamines + LTB4 cause what effect to nearby blood vessels |
Vasodilation to increase blood flow to area - more leukocytes in the region to combat infection Increased permeability of vessels - for white blood cells and fluid to leave. |
|
What cell is the first responders to the mast cells signal? |
neutrophils |
|
What are the steps of the trans-endothelial migration |
1. Rolling 2. Firm Adhesion 3. Trans-migration |
|
What happens in the rolling phase of transendothelial migration
|
weak interactions between neutrophil and endothelial cell results in a slow rolling motion along the surface |
|
What happens in the firm adhesion phase of transendothelial migration |
the cytokine action upon the endothelial cell produces upregulation of proteins. These proteins have a stronger interaction with the neutrophils causing them to come to a stop |
|
What happens in the transmigration phase of trans-endothelial migration |
the neutrophils follow chemotactic gradient and squeeze between the cells of the endothelial cells. |
|
Three signs of immune reaction are yellow tinged flesh, redness and swelling. What causes this? |
Yellow - myeloperoxidase (anti-bacterial) and pus from neutrophils Redness - vasodilation Swelling - leaky vessels |
|
What is the difference of prevalence of neutrophils in humans compared to mice. Why is this important? |
50-70% of circulating leukocytes in humans 10-25% in mice Mice are the key model organism for immunology |
|
What is significant about the nucleus of the neutrophil? |
trilobed / segmented |
|
What are the three tools that neutrophils can use in an infection? |
1. degranulation 2. phagocytosis 3. netosis |
|
What is released from neutrophils in degranulation? |
nucleotides, bioactive amines, bioactive ions, adhesion molecules, PMPs, kinocidins, mitogenic factors, coagulation factors, protease inhibitors, proteases and glycosidases |
|
What are the basic steps of phagocytosis |
bacterium binds to receptor on cell cell surface membrane extends and surrounds the pathogen by fusing together. pathogen encased in phagosome phagosome fuses with lysosome pathogen dies neutrophil apoptoses |
|
What is netosis |
Netosis is the process of self destruction of the neutrophil to destroy pathogens |
|
How does netosis kill pathogens |
neutrophils "explode" their DNA and granules DNA gets coated with antimicrobial enzymes as exploded when hits pathogens they are in turn coated with antimicrobial proteins |
|
What are the three granulocytes |
eosinophils basophils neutrophils |
|
What is the precursor to macrophages and dendritic cells? |
monocytes |
|
What causes neutrophils to exit a vessel in the same direction? |
chemotactic gradient |
|
What two type of cells can secrete cytokines? |
stromal cells & immune cells |
|
What behaviours do cytokines affect? |
life span motility killing capacity repair programmes proliferation |
|
What is meant by cytokine "cross talk" |
cytokines work in many directions simultaneously creating an interactive network |
|
What is a chemokine? |
chemotactic cytokine |
|
What is a PAMP |
pathogen associated molecular patterns |
|
What does TLR1 & TLR2 detect? |
lipoprotein, unconventional LPS, bacterial |
|
what does TLR 2 detect? |
peptidoglycan |
|
What does TLR 2 & TLR 6 detect |
mycoplasmal lipoprotein |
|
What does TLR 4 detect? |
enterobacterial LPS |
|
What does TLR 5 detect? |
flagellin |
|
What does TLR 11 detect? |
profilin (protozoa)
|
|
What does TLR3 detect? |
dsRNA - viral |
|
What does TLR7 detect? |
ssRNA - viral |
|
What does TLR8 detect? |
ssRNA - viral |
|
What does TLR9 detect? |
CpG DNA (bacterial) |
|
What does DAMP stand for? |
damage associated molecular patterns |
|
TLR 9 detects what DAMP |
genomic and mitochondrial DNA |
|
What DAMPs do TLR 4 and TLR 2 detect? |
histones |
|
Define innate immunity |
non-specific |
|
How can we tell that innate immunity is conserved? |
it is found in plants, fungi, insects |
|
Describe the physical properties of defensins |
Small Cysteine Rich Cationic |
|
What produces defensins |
Epithelial cells |
|
How do defensins harm pathogens |
integrate into microbial membrane group disrupt memrane form pores |
|
What is complement |
biochemical cascade that clears pathogens |
|
Are complement proteins active or inactive in blood? |
inactive |
|
Where are complement proteins activated? |
bacterial surface |
|
What processes can complement cause? |
chemotaxis MAC opsonisation |
|
What is MAC |
membrane attack complex |
|
What is an anaphylatoxin |
the smaller "a" consituents cleaved from proteins during complement signalling molecule |
|
What form of complement is part of the adaptive immune system? |
classical pathway |
|
How do innate cells detect PAMPs? |
Pattern Recognition Receptors (PRRs) |
|
What is the difference between external PRRs and internal PRRs? |
internal ones detect intracellular viruses |
|
Recognition of a PAMP by a PRR will cause what? |
activation mediator release inflammation |
|
How did Toll Like Receptors get their name? |
Drosophila irradiated and lost Toll gene Unable to synthesis receptor Over run with fungal infection |
|
Give an example of TLR in plants. What does it detect? |
FLS2 in arabidopsis thaliana flagellin sensitive 2 |
|
What enables TLR 2 to detect peptidoglycan and TLR 5 to detect flagellin |
both PDG and flagellin are made of repeat monomers, the individual monomer triggers the response |
|
After detection of PAMP by the TLR what is the cascade of proteins that follow? |
MyD88 IRAK TRAF6 NF-kappaB |
|
The cascade of proteins after PAMP detection by the TLR will lead to an increase of what in the nucleus? |
transcription factors |
|
Increases of transcription factors in the nucleus after PAMP detection by TLRs leads to increase production of what? |
cytokines |
|
How does inflammation control itself? |
with the initial response healing of injury and tissue repair is also initiated |
|
What proteins in particular are upregulated during the emmigration of leukocytes from blood to tissues |
ICAM-1 |
|
What does ICAM-1 stand for? |
Inter cellular adhesion molecule 1 |
|
What proteins on leukocytes stick to ICAM-1 on endothelial walls? |
integrins |
|
What is the name for leukocytes moving across the epithelium? |
diapedesis |
|
How do leukocytes penetrate the basement membrane during emigration from blood to tissues |
proteolytic enzymes |
|
What is the mechanism of chemotaxis
|
2. First contacts with chemokine on one side of cell. 3. Receptors triggered 4. Cytoskeleton reorganizes which polarizes cell to move in that direction. 5. Reinforced by further receptor hits |
|
Complement C5a, N-formyl methionine, arachidonic acid metabolites are all examples of what?
|
Chemokines |
|
How does inflammation induce it's own resolution?
|
1. Short half life of cytokine mRNA and protein 2. pro-inflammatory cytokines induce cortisol to inhibit their own production 3. IL-1Ra and sTNFR interfere with IL-1 and TNF 4. IL-4 and IL-10 down regulates TNF, IL-1, IL-8 but upregulates IL-1RA |
|
What are the two types of inflammation?
|
acute and chronic |
|
What's the difference between acute and chronic inflammation?
|
A = short duration, protein exudate, neutrophils predominate C = long duration, macrophages and lymphocytes, few neutrophils |
|
What can cause chronic inflammation
|
repeated attempts at healing cause progressive fibrosis |
|
What percentage of lymphocytes are T cells |
70% |
|
What % of T cells are alpha-beta T cells |
95 |
|
Aside from alpha beta T cells, what is the other group called?
|
gamma delta |
|
What are T cells called before they have recognised an antigen? |
naive |
|
What two processes occur once a T cell has been activated? |
clonal expansion (proliferation) and differentiation |
|
What has to happen to an antigen before a T cell can recognise it? |
- phagocytosed by antigen presenting cell - processed and cleaved into short peptides - presented on APC surface with a MHC molecule |
|
What is the name for the receptor on a T cell that recognises an antigen presented on a APC? |
T Cell Receptor |
|
The two external "processes" from a TcR bind to different things, what does each part bind to |
1 to the MHC 1 to the peptide |
|
How many amino acids are involved between an antigen on a APC and a TcR? |
1 or 2
|
|
Is the bond between a TcR and an antigen on a APC weak or strong? |
Weak |
|
What can you say are the two general functions of costimulatory molecules? |
- induce intracellular response - form a stronger bond between T cell and APC |
|
What is the name for the structure that forms around the TcR when it binds to the antigen and MHC on the APC? |
immune synapse |
|
What adhesion molecules can form the immune synapse? |
ICAM-1 LFA-1 |
|
true or false Costimulatory molecules are specific to one antigen? |
FALSE |
|
true or false Costimulatory molecules are invariant from cell to cell |
TRUE |
|
What two costimulatory molecules are present on EVERY T cell? |
CD3 CD28 |
|
How many proteins form the complex that is CD3? |
5 |
|
What structure on the T cell is the CD3 costimulatory molecule attached to? |
TcR
|
|
What happens to the CD3 costimulatory molecules once TcR binds to an antigen? |
long cytoplasmic tails bind + activate tyrosine kinases initiate intracellular signalling |
|
Which MHC class do CD4+ cells bind to? |
MHC 2
|
|
Does the CD8 or CD4 bind to the MHC at the same place as the peptide or a different place? |
Different |
|
What is the function of CD4? |
increases binding between APC and T cells links to Lck enzyme |
|
Once attached to the Lck enzyme, what does CD8 or CD4 on a T cell do? |
drags Lck enzyme to CD3 so CD3 can begin to recruit signalling enzymes within the T cell |
|
What class of MHC do CD8+ cells bind to? |
class 1
|
|
CD8, like CD4 also increases binding to the APC and links the Lck enzyme. True or false?
|
TRUE |
|
CD8+ cells are what kind of T cell? |
Cytotoxic T cells |
|
CD4+ cells are what kind of T cell? |
Helper T cells |
|
What costimulatory molecules form the secondary immune synapse? |
CD28 ON THE T CELL CD80/86 ON THE APC |
|
CD 28 is only present on certain T cells? True or False |
False Present on ALL |
|
Ligation between CD28 and CD80 triggers what additional sequence within the T cell? |
signals essential for IL2 transcription |
|
Which costimulatory molecules are responsible for stronger binding between the T cell and APC? |
CD4 + CD8 |
|
Which costimulatory molecules are responsible for forming an intracellular response? How does each do it? |
CD3 - tyrosine kinase activation on cytoplasmic tail CD4 + CD8 - link to Lck enzyme to CD3 - recruit further signalling enzymes CD28 - IL2 transcription |
|
Which interleukin is associated with autocrine signalling in the helper T cell, the absence of which would leave to tolerance? |
IL 2 |
|
After recognition of the antigen-peptide complex on the APC by the T cell, both IL2 and it's receptor are expressed. What does this trigger? |
clonal expansion |
|
If a CD4+ cell which had recognised it's specific antigen but had costimulatory molcules, what would be the outcome |
tolerance to the antigen |
|
After clonal expansion CD40ligand affects the T cell. What is the effect and what other molecules are involved? |
OX40 ICOS differentiation |
|
What is the only cell that can process and present an antigen capable of activating a T helper cell? |
Dendritic cells? |
|
How do Dendritic cells sample their environment? |
pinocytosis endocytosis phagocytosis |
|
If a dendritic cell encountered an antigen what would it do? |
Leave the tissue
through afferent lymphatics To T cell area of lymph nodes |
|
What receptors found on a DC surface enable it to detect tissue damage or pathogen presence? |
TLR (toll like receptors) |
|
What does an activated TLR lead to in a dendritic cell?
|
1. increased expression of MHC 2 2. increased antigen presentation and processing ability 3. expression of CCR7 4. expression of costimulatory molecules |
|
What is CCR7 and what does it do? |
Chemokine receptor Allows dendritic cells to make way to lymph nodes after antigen detection |
|
Which costimulatory molecules are expressed when dendritic cells detect PAMPs or DAMPs? |
CD40 CD80 CD86 |
|
What is the definition of tolerance? |
"a state of antigen specific unresponsivness to an antigen which under other circumstances can stimulate an active immune response" |
|
Why is tolerance necessary |
prevent immune response to self or harmless antigens from food proteins, commensals and foetuses |
|
Which diseases can be caused by a lack of tolerance? |
Type 1 diabetes Rheumatoid arthritis Crohns disease Coeliac disease |
|
In Crohn's disease, what is the immune response responding to? |
harmless commensal bacteria |
|
In coeliac's disease, what is the immune response responding to |
gluten - a wheat protein
|
|
Why does the body create T and B cells capable of reacting with self (autoimmunity) or harmless foreign antigens? |
receptors produced through random genetic processes needed to create the many thousands of possible receptors we may need |
|
What is the difference between central and peripheral tolerance? |
Central = tolerance to self antigens in primary lymphoid organs affects development of immature T and B cells Peripheral = tolerance to harmless foreign antigens, or tissue specific self antigens in secondary lymphoid organs affects mature T and B cells |
|
What are the 4 mechanisms for tolerance?
|
ignorance clonal deletion clonal anergy active regeneration |
|
What is ignorance, in terms of tolerance? |
occurs when lymphocytes are normally not exposed to tissue antigens - can't make immune response - i.e. lens of eye or testis |
|
What is clonal deletion? |
maturing lymphocytes encounter self antigen during development either in thymus (t) or bone marrow (b cells) leads to death of reactive cell |
|
What is clonal anergy |
when a mature T cell encounters a self or foreign antigen in periphery which is presented on an APC without costimulatory molecules. Anergic T cells remain present but unresponsive for the antigen |
|
What is active regulation? |
1st encounter with antigen results in T cell differentiation into a T regulatory cell. Generated by self antigens in Thymus or foreign antigens in periphery. |
|
Comment on the level of B cell production through life |
generated through life production decreases with age |
|
Development of B cells occurs... a) before birth b) after birth |
foetal liver
bone marrow |
|
What is BcR and what does it recognise |
B cell receptor recognises antigens |
|
What type of antigen can a BcR recognise? |
protein carbohydrate lipid DNA |
|
What is the antigen binding component of the BcR made of? |
membrane bound antibody (mIg) Ig alpha Ig beta |
|
What does clonal selection prevent?
|
autoimmunity
|
|
What is antigen independent B cell development? |
Ig gene rearrangment
generates functional BcR |
|
Where does B cell development take place? |
Bone Marrow |
|
What is antigen dependent B cell development, and where does it take place
|
Bone marrow + periphery
BcR recognition of antigen drives it |
|
What happens to Immature B cells expressing a BcR recognising self antigen. Thus B cell repetoire is,.. |
they are eliminated SELF TOLERANT |
|
What happens in clonal deletion |
apoptosis driven by multivalent or membrane-bound antigens |
|
Clonal anergy is driven by... |
soluble antigens B cells remain but BcR down regulated B cells become unresponsive |
|
How does necrosis cause inflammation? |
Necrosis leads to -chromatin clumping -swollen organelles -flocculent mitochondria WHICH LEADS TO -disintegration -release of intracellular contents -triggers inflammation |
|
What is SLE |
systemic lupus erythematosus autoimmune disease pathogenic anti-nuclear antigen autoantibodies associated with defects in apoptosis, clearance of apoptotic cells and B cell tolerance |
|
What happens to immature B cells which don't undergo clonal deletion/anergy? |
Fully differentiate in spleen within a few days become mature B cells recirculate through lymph nodes |
|
Why is T cell tolerance enough to ensure tolerance of B cells |
T cells activate most B cells. |
|
Which type of T cell activates B cells?
|
Th2 |
|
what does B cell activation lead to? |
proliferation differentiation into memory or plasma cells |
|
What kind of B cell produced antibodies
|
B plasma cells |
|
Which kind of B cells produce immunological memory
|
B memory cells |
|
How are B cells activated? |
1. Foreign antigen detected 2. Cross linked with BcR 3. Induces internalisation of antigen 4. Antigen processed internally 5. Peptide produced on B cell surface 6. Presented to Th cell |
|
What do activated B cells form in medullary cords? |
Foci |
|
What occurs in foci? |
differentiation of B cells |
|
What is the first type of antibody to be produced by B cells? |
IgM |
|
What is the location of class switching antibodies of B cells? |
B cell follicles - germinal centres |
|
What occurs in germinal centres?
|
- rapid B cell proliferation - somatic mutation - class switching IgM to IgG - differentiation |
|
How common is a naive B cell for 1 particular type of antigen? |
rare/ low frequency |
|
B cells entering the follicle have a half life of how long? |
3 - 8 weeks for naive cells that don't encounter antigens Memory cells can persist for years |
|
Compare the affinities of initial IgM produced by B cells and the isotype post class switching. |
IgM = low affinity but rapid IgX (post class switch) = high affinity |
|
What is the benefit of adaptive memory B cell response? |
response will be faster stronger |
|
What is the typical lag phase of primary and secondary responses? |
1 = 4-7 days
2 = 1-3 days |
|
What is the typical peak phase of primary and secondary responses? |
1 = 7-10 days 2 = 3-5 days |
|
What is the main antibody secreted in the primary and secondary responses? |
1 = IgM 2 = IgG |
|
Does the level of IgM get bigger or smaller in the secondary response compared to the primary?
|
Smaller |
|
The initial response is dominated by which part of the immune system? |
innate |
|
What is Coryza |
inflammation of nasal linings produce nasal discharge |
|
What is on the outside of influenza which aids it's virulence? |
Haemagglutinin Neuraminidase |
|
How does hemaglutinin aid influenza's virulence? |
binds to sialic acid receptor on cell triggers endocytosis virus enter's cell |
|
How does neuraminidase aid influenza's virulence? |
aids exocytosis |
|
What are the host defences for influenza? |
mucus + cilia interferons innate antimicrobial proteins such as defences antibodies cytotoxic T cells |
|
Where are antibodies present? |
serum and other body fluids |
|
What is anti-serum |
serum which contains antibodies against more than one antigen |
|
What is an antigen |
any molecule that can be bound by an antibody |
|
Can antigens be from the host? |
Yes, (although we usually think of antigens as foreign matter, they can be from self) |
|
What are the biological effects of antibodies? |
-opsonisation - aids phagocytosis via Fc receptors -neutralise bacterial toxins -immobilisation - flagella of motile bacteria -cytolysis - complement fixation |
|
What are the stages of clonal selection?
|
1. Each B cell has a different BcR 2. Antigen binds to the cognate BcR 3. Activation results in cell division and differentiation 4. Plasma cells secrete Ab of the same specificity |
|
How many light chains does an antibody have? |
2 |
|
How many heavy chains does an antibody have?
|
2 |
|
What grew letters can be assigned to the different types of light chains? |
kappa or lambda |
|
What are the two regions of an antibody? |
Fab and Fc regions |
|
What bonds hold the two sides of the antibody together? |
disulfide bonds |
|
Which region of antibody is the antigen binding site |
tips of the Fab region |
|
What are the domains of the antibody? |
VL, VH, CL, CH1, CH2, CH3
|
|
What are 4 shapes of antigen binding sites? |
Groove Shallow surface Protrusion |
|
Give an example of what binds to a pocket binding site on an antibody
|
Haptens, such as ferrocene |
|
Give an example of what binds to a groove binding site on an antibody |
HIV peptide |
|
Give an example of what binds to a shallow surface binding site on an antibody |
HEL |
|
Give an example of what binds to a protrusion binding site on an antibody |
HIV gp120 |
|
What domains of an antibody don't change during class switching? |
VL CL VH |
|
Where are the CH3 and CH2 domains of an antibody?
|
Fc region |
|
What molecules are bound to antibody's and don't change during class switching? (not antigens)
|
carbohydrates |
|
What two domains are involved in the antigen binding site? |
VL and VH |
|
In IgM, what is the greek letter assigned to it's heavy chain? |
Mu |
|
What type of cells express IgM |
naive B cells |
|
What type of shaped molecule is IgM |
pentameric |
|
Which immune response is IgM most associated with? |
primary |
|
What is the name of the chain that holds the individual antibody subunits together in IgM? |
J chain |
|
IgM average serum level |
1.5 mg per ml |
|
Half life of IgM in serum (days) |
10 |
|
What is the molecular weight of IgM |
970 kDa |
|
What are the functions of IgM |
Toxin and viral neutralisation by Ag binding Agglutination Fc complement activation Fc phagocytosis/opsonisation |
|
Does IgM cross the placenta? |
NO |
|
Which antibody is mainly membrane bound? |
IgD |
|
What is notable about IgD's hinge region? |
it's longer than usual |
|
What level of IgD is in the serum? |
trace |
|
What are the functions of IgD |
co-receptor for B cells secreted in upper resp tract for defence against rest pathogens binds to basophils |
|
When IgD binds to basophils, what does it induce the secretion of?
|
anti-microbial factors such as LL37 + beta-defensin 3 pro-inflammatory cytokines such as TNF alpha + IL-1beta chemotaxtic factors such as IL8 and XCL10 Ab-inducing factors such as IL4 + BAFF |
|
What greek letter is assigned to the heavy chain of IgD
|
delta |
|
What is the molecular weight of IgD
|
184 kDa |
|
What is the half life of IgD in serum? |
3 days |
|
How many types of IgG are there in humans? Name them |
4 IgG1 IgG2 IgG3 IgG4 |
|
In mice, there are also 4 types of IgG. Name them. |
IgG1 IgG2a, IgG2b, IgG3 |
|
What are the functions of IgG |
toxin + virus neutralisation
-agglutination - Fc complement activation - Fc phagocytosis / opsonisation |
|
do IgG cross the placenta via FcRn? |
Yes |
|
Which list IgG's in order of their ability to activate the classical complement pathway |
3, 1, 2, 4 |
|
Which IgG activates the alternative pathway |
none |
|
List IgG's in order of their ability to be transferred across the placenta
|
1, 3, 2, 4 |
|
Which IgG's can bind to macrophage Fc receptors to aid phagocytosis? |
1, 3 (4 kind of but not well) |
|
Which IgG can bind to mast cells and basophils |
none |
|
What shaped molecules does IgA exist in? |
monomers, dimers and tetramers |
|
In serum, what shape does IgA usually take? |
monomers |
|
In external secretions, what shape is IgA usually? |
dimers or tetramers |
|
What is the function of IgA
|
protection at external surfaces agglutination |
|
How do infants get IgA? |
from their mothers through breast feeding |
|
What is the name of the heavy chain of IgA |
either alpha1 or alpha2 |
|
What is the molecular weight of IgA |
160 |
|
Which form of IgA has a slightly higher presence in serum? |
1 3 mg per ml whereas 2 is 0.5 mg per ml |
|
what is the half life of IgA in days in the serum |
6 |
|
Which antibody has the lowest level in serum? |
IgE 5 x 10^-5 |
|
When is serum levels of IgE increased
|
atopies |
|
What additional domain does IgE have |
C-epsillon-4
|
|
What is the molecular weight of IgE |
188 kDa |
|
What is the half life of IgE in days? |
2 |
|
What is the function of IgE |
interacts with FcepsillonR on mast cells expulsion of parasites at mucosal surface via inflammatory response using eosinophils |
|
What unintended affect does IgE have against non harmful foreign matter? |
allergic response |
|
What are the isotypes of all of the H chains of antibodies |
mu, delta, gamma 1,2,3,4 epsillon and alpha 1 and 2 |
|
What are the isotopes of all of the L chains for all antibodies |
kappa, lambda 1,2,3 or 4 |
|
What is the complexity of the BcR repertoire? |
2 x 10 ^27 |
|
What is the name of the syndrome for people born without thymuses? |
Di George syndrome |
|
What are the groups of effector T cells? |
Helper cells (Th cells) Cytotoxic T cells Regulatory T cells Memory T cells NK T cells |
|
What do Helper T cells do? |
produce cytokines assist B lymphocytes to produce antibodies activate macrophages |
|
What do cytotoxic T cells do? |
kill tumour cells kill infected tissue cells |
|
What do regulatory T cells do? |
inhibit activity of other lymphocytes prevent autoimmunity |
|
What do memory T cells do? |
generate secondary immune response |
|
What do NK T cells do? |
act early in immune responses link innate and adaptive immunity |
|
What do 90% of T cells express |
alpha beta T c R |
|
What are the two subsets of alpha beta T cells? |
CD4+ CD8+ |
|
What percentage of alpha beta T cells are CD4+
|
60 - 70 % |
|
What percentage of alpha beta T cells are CD8+ |
30-40 % |
|
Which subset of T cells recognise MHCII |
CD8+
|
|
What type of antigens are detected by CD8+ cells? |
antigens synthesised in cytoplasm or nucleus of infected cell |
|
What IL is required to prime CD8 cells |
IL2 |
|
Is costimulation required for CD8 cells to kill target? |
no |
|
What enzymes are released by CD8 cells to kill target cells? |
perforin and granzymes from granules in T cell |
|
What does perforin do? |
forms pores in cell membrane and intracellular vesicles |
|
What do granzymes do? |
induce death by apoptosis |
|
Do cytotoxic T cells lead to inflammation when they kill a target cell?
|
no |
|
How many CD8+ cells are needed to kill a target cell? a) 1 b) 5 c) many |
many |
|
What process enables CD8+ cells to kill more than one target?
|
recycling |
|
What cytokine do CD8+ cells produce? |
gamma-interferon |
|
What autoimmune disease can CD8+ cells cause? |
type 1 diabetes |
|
Is costimulation required for CD4 helper cells? |
YES |
|
What infects and kills CD4+ cells? |
HIV |
|
How does HIV kill CD4+ cells? |
binds to CD4 molecule |
|
What are the subsets of CD4+ cells? |
Th1 Th2 Th17 TFH |
|
What differentiates the 4 subsets of CD4+ |
cytokines produced |
|
What cytokines do Th1 cells produce |
gamma IFN TNF beta |
|
What cytokines do Th2 cells produce |
IL 4,5,6,9,10,13 |
|
What cytokine does Th17 produce |
IL17 |
|
What is another name for TFH cells |
Follicular helper T cells |
|
What do TFH cells produce?
|
IL21 |
|
What determines how a naive CD4+ cell differentiates? |
the way in which the foreign antigen is presented the nature of the inflammation which is present |
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What is the relationship between the subsets? |
Each subset is regulatory of the others |
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What causes a naive CD4+ cell to differentiate into a Th1 cell? |
IL12 produced by dendritic cells |
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What causes a naive CD4+ cell to differentiate into a Th2 cell? |
IL4
Transcription Factor: GATA-3 |
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What causes a naive CD4+ cell to differentiate into a Th17 |
TGF beta IL6 IL23 |
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What inhibits differentiation of a CD4+ cell into Th17 cell? |
gamma IFN |
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What causes a naive CD4+ cell to differentiate into a Tfh cell? |
IL6 IL21 |
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What role does gamma IFN play in CD4+ cell differentiation? |
Enhances IL12 production > IL12 promotes differentiation into Th1 cells. Inhibits Th17 production |
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What enhances the production of IL12 by dendritic cells? |
- gamma IFN
- interaction CD40 ligand (t cell) + CD40 (APC) |
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How is the production of gamma IFN by Th1 cells regulated?
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Transcription factor T-bet |
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What is the purpose if Th1 cells producing gamma IFN |
activated macrophages to kill intracellular infections and to release pro inflammatory mediators |
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What pro-inflammatory mediators does gamma-IFN promote macrophages to produce? |
TNF alpha IL1 IL6 |
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What can inappropriate activation of Th1 cells lead to?
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arthritis inflammatory bowel disease |
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What is needed from Th2 cells for B cell proliferation and differentiation during antibody production? |
IL4, 5, 6, and 13 |
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What affect does IL4 have on B lymphocytes? |
class switcher produce IgE and IgG1 |
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Inappropriate activation of Th2 cells leads to what diseases..? |
asthma hay fever (IgE mediated diseases) |
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What type of pathogens do Th2 cells protect against? |
extracellular pathogens - parasites etc |
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What is the purpose of Th17 cells producing IL17
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recruit and activate neutrophils |
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What is the purpose of Th17 cells producing IL22
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induces anti-microbial peptides induces tight junctions in intestine |
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What type of pathogens do Th17 cells protect against? |
extracellular bacteria and fungi |
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What does inappropriate activation of Th17 lead to? |
marked tissue inflammation |
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What do Tfh cells do after activation by antigen? |
migrate to B cell follicles of lymphoid organs |
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What type of TcR interaction is required by Tfh cells?
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high affinity TcR interaction
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What transcriptional repressor is required to Tfh production?
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Bcl-6 |
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What kind of B cells do Tfh cells interact with? |
B cells that are specific for the same antigen |
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What is the purpose of Tfh cells in the B cell follicles? |
drive the formation of the germinal centre |
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What is somatic hypermutation? |
intense proliferation of B cells and rapid mutation of antigen combining regions of the genes coding for their antibody molecules. - B CELL SELECTION FOR THOSE WITH HIGH ANTIGEN AFFINITY |
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What two molecules on the Tfh cell have to interact with their counter receptors on a B cell? |
ICOS CD40 ligand |
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What additional purpose do Germinal centres have in terms of providing a secondary immune response? |
generate memory T and B cells. |
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Are regulatory T cells mainly CD4 or CD8+ |
CD4+ |
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What are the two main groups of regulatory T cells? |
Natural Treg Inducible Treg |
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What costimulatory molecules are present on natural Treg cells? |
CD4+ CD25+ |
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What specific transcription factor must Natural Treg cells develop under, in the thymus? |
FoxP3 |
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What is the purpose of Natural Treg cells
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recognise self antigens prevent autoimmunity by producing TGFbeta and inhibiting APC |
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How does a Natural Treg cell inhibit APC
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CTLA4 on Treg surface removes CD80/CD86 from APC |
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What kind of antigens do inducible Treg cells recognise? |
self or foreign antigens |
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Where do inducible Treg cells differentiate from naive CD4+ T cells? |
after recgnition of an antigen in peripheral immune system |
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inducible Treg cells have many subsets - True or False |
True
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What do inducible Treg cells produce |
- some subsets produce IL10 selectively (Tr1) Others produce TGFbeta and function as regular Natural Treg cells |
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What molecule do NK T lymphocytes express? |
NK1.1 - natural killer molecule |
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What do NK T cells recognise? |
lipids on pathogens |
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Do NK T cells bind to MHC class I or II
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Both - not MHC restricted |
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What cytokines are produced in early immune responsed by NK T cells |
IL 4
gamma IFN ? |
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Where are gamma delta T cells rare and where are they more common?
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rare in blood + lymph nodes more common in skin, gut + other surfaces |
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Do gamma-delta T cells produce CD4 or CD8? |
Neither |
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What MHC class doe gamma-delta T cells interact with? |
not MHC restricted |
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What kind of antigens are recognised by gamma-delta T cells? |
conserved, non-peptide antigens (i.e. components of cell walls) |
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What is the function of the mediators released by gamma-delta T cells/ |
promote tissue repair |