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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
Proteins

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


1. Equal distribution of receptors recognizing chemotactic factors on CSM.


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


persistence of a causative agent


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?

Pocket


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

What is the relationship between the subsets?

Each subset is regulatory of the others

What causes a naive CD4+ cell to differentiate into a Th1 cell?

IL12 produced by dendritic cells

What causes a naive CD4+ cell to differentiate into a Th2 cell?

IL4



Transcription Factor: GATA-3


What causes a naive CD4+ cell to differentiate into a Th17

TGF beta


IL6


IL23

What inhibits differentiation of a CD4+ cell into Th17 cell?

gamma IFN

What causes a naive CD4+ cell to differentiate into a Tfh cell?

IL6


IL21

What role does gamma IFN play in CD4+ cell differentiation?

Enhances IL12 production


> IL12 promotes differentiation into Th1 cells.




Inhibits Th17 production

What enhances the production of IL12 by dendritic cells?

- gamma IFN



- interaction CD40 ligand (t cell) + CD40 (APC)


How is the production of gamma IFN by Th1 cells regulated?

Transcription factor T-bet

What is the purpose if Th1 cells producing gamma IFN

activated macrophages to kill intracellular infections and to release pro inflammatory mediators



What pro-inflammatory mediators does gamma-IFN promote macrophages to produce?

TNF alpha


IL1


IL6

What can inappropriate activation of Th1 cells lead to?

arthritis


inflammatory bowel disease

What is needed from Th2 cells for B cell proliferation and differentiation during antibody production?

IL4, 5, 6, and 13

What affect does IL4 have on B lymphocytes?

class switcher




produce IgE and IgG1

Inappropriate activation of Th2 cells leads to what diseases..?

asthma


hay fever


(IgE mediated diseases)

What type of pathogens do Th2 cells protect against?

extracellular pathogens - parasites etc

What is the purpose of Th17 cells producing IL17

recruit and activate neutrophils



What is the purpose of Th17 cells producing IL22

induces anti-microbial peptides


induces tight junctions in intestine

What type of pathogens do Th17 cells protect against?

extracellular bacteria and fungi

What does inappropriate activation of Th17 lead to?

marked tissue inflammation

What do Tfh cells do after activation by antigen?

migrate to B cell follicles of lymphoid organs

What type of TcR interaction is required by Tfh cells?

high affinity TcR interaction

What transcriptional repressor is required to Tfh production?

Bcl-6

What kind of B cells do Tfh cells interact with?

B cells that are specific for the same antigen


What is the purpose of Tfh cells in the B cell follicles?

drive the formation of the germinal centre

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

What two molecules on the Tfh cell have to interact with their counter receptors on a B cell?

ICOS


CD40 ligand

What additional purpose do Germinal centres have in terms of providing a secondary immune response?

generate memory T and B cells.

Are regulatory T cells mainly CD4 or CD8+

CD4+

What are the two main groups of regulatory T cells?

Natural Treg




Inducible Treg

What costimulatory molecules are present on natural Treg cells?

CD4+


CD25+

What specific transcription factor must Natural Treg cells develop under, in the thymus?

FoxP3

What is the purpose of Natural Treg cells

recognise self antigens


prevent autoimmunity by producing TGFbeta and inhibiting APC

How does a Natural Treg cell inhibit APC

CTLA4 on Treg surface


removes CD80/CD86 from APC

What kind of antigens do inducible Treg cells recognise?

self or foreign antigens

Where do inducible Treg cells differentiate from naive CD4+ T cells?

after recgnition of an antigen in peripheral immune system

inducible Treg cells have many subsets - True or False

True

What do inducible Treg cells produce

- some subsets produce IL10 selectively (Tr1)




Others produce TGFbeta and function as regular Natural Treg cells

What molecule do NK T lymphocytes express?

NK1.1 - natural killer molecule

What do NK T cells recognise?

lipids on pathogens

Do NK T cells bind to MHC class I or II

Both - not MHC restricted

What cytokines are produced in early immune responsed by NK T cells

IL 4



gamma IFN


?

Where are gamma delta T cells rare and where are they more common?

rare in blood + lymph nodes




more common in skin, gut + other surfaces

Do gamma-delta T cells produce CD4 or CD8?

Neither

What MHC class doe gamma-delta T cells interact with?

not MHC restricted

What kind of antigens are recognised by gamma-delta T cells?

conserved, non-peptide antigens


(i.e. components of cell walls)

What is the function of the mediators released by gamma-delta T cells/

promote tissue repair