adaptive immunity 2 Flashcards
(37 cards)
Adaptive Immunity – Key players
two types of cell?
what kind of response?
from?
key cells?
B lymphocytes – Humoral response (antibody-mediated response)
From bone marrow
Antibodies (Immunoglobulins)
T lymphocytes – Cellular response (cell-mediated immune response)
From thymus
Helper T cells (CD4+)
Cytotoxic ‘Killer’ T cells (CD8+)
T lymphocytes – Lineage and classes
lineage of T cells? what does it form?
how is CD4 and CD8 formed?
different CD4
Pro T (CD4- CD8-) -> AB cell (CD4+ CD8+) and Yd cell (CD4- CD8-)
AB cell (CD4+ CD+) -> CD4+ (CD4+ CD8-) and CD8+ (CD4- CD8+)
CD4+ -> TH1, TH2, TH17, Treg
T lymphocytes - Classes
what are the 3 classes of T cells?
what do they express?
what are the main functions of these cells?
Helper T cells (Th)
Expresses CD4 (CD4+)
Secrete cytokines for signalling
Activate macrophage, B cells & CTL
Regulatory T cells (Treg)
Inhibit (suppress) function of other T cells
Control immune response and immune tolerance
Cytotoxic T cells (CTL)
Expresses CD8 (CD8+)
Kills virus-infected cells, cancer cells, graft cells (organ transplant therefore take immunosupressant)
Adaptive immunity brief overview of cell mediated and humoral response
how can CTL be activated? what will happen after it is activated?
How can TH be activated? what happens once they are activated?
how do you fully activate a B cell?
CTL can be activated by foreign antigen on nucleated cell. Once activated, it seeks out cells presenting similar peptides, destroy cells via chemical warfare. Subset of activated CTL will differentiate into memory T cells.
T-helper cells are activated when they recognise foreign peptides presented on antigen presenting cells like monocytes, macrophages and B cells. Once they are activated, they release cytokines to signal other immune cells which will proliferate and make more clones.
To full activate a B cell, you need cytokines from T-helper cell therefore B cells present antigen to T-cell to activate it. Cytokines released and more B cells can differentiate into plasma cells + memory B cells
Antigen recognition by B and T lymphocytes
what do they have?
what do they recognise?
Receptors on surface (BCR or TCR)
Recognise different structures on pathogen
Antigens from different pathogen
Different areas of same antigen
Distinguish non-self from self – autoimmune disease if fail
BCR
B cell receptor
how do they recognise it? type of response?
BCR recognise antigens directly
Antibody-dependent response
Humoral immunity
TCR
T cell receptor
how do they recognise it? type of response?
TCR requires cells to process and present antigenic peptides
Antibody-independent response
Cell-mediated immunity
MHC and BCR/TCR
what response is antigen presenting immune cell part of?
Antigen presenting immune cell is part of the innate immune response which will present the antigenic peptides on the MHC (I or II) which will present to TCR
MHC and TCR bridge gap betweem innate + adaptive immunity
MHC
class I present where? what does it do? what is it recognised by?
class II where?
how is this presented?
recognised by?
MHC Class I
Present in all nucleated cells (including professional APCs)
Continuous sampling of peptides from within the cells (cytosol) -> will make sure cells are normal + healthy, in case cells are infected or cancerous
Recognised by CD8+ CTL
MHC Class II
Present on professional APCs only (e.g. mononuclear phagocytes, dendritic cells)
APCs engulf and breaks-up pathogens from outside the cell, presents broken-up peptides on MHC Class II
Recognised by CD4+ Th cells
MHC
exemptions to the rule
what engulfed material can be presented on MHC class I? why?
when will intracellular proteins be present on MHC class II? why?
Extracellular peptides presented in MHC class I in cross-presentation -> this means that engulfed extracellular proteins can be presented on MHC class I to ensure not only humoral arm of adaptive immune resposne is activated but also Killer - T cells activated too
Intracellular peptides presented by MHC class II during autophagy -> cells will degrade a part of itself to get rid of misfolded protein + damaged organells which will be displayed on MHC class II
Important structures: MHC Class I
how many chains? sub units of aplah chain? what makes up the peptide-binding cleft? what does this do? where is disulfide bonds? why? what will a3 have? why?
units of B?
why does it have a disulfide bond?
where does B2 bind? what present the peptide?
2 chains - a and B
alpha chain has 3 sub units
a1 and a2 will make up the peptide-binding cleft which presents the antigen peptide
disulfide bonds in 2 + 3 to stabilse protein as a chain is large
a3 will have a transmembrane region to anchor cell to cell membrane
B is 1 unit
it has disulfie bond to stabilise unit + inetgrate woth a chain (a3)
B2 and a3 arms support a1 + a2 hands that present the peptide
Antigen processing and presentation in nucleated cells(MHC class I presentation)
what happens to proteins destine dfor degradation?
what will happen to some of them? what happens to rest?
if cells are normal, what happens? if not?
proteins destined for degradation are tagged by ubiquitin conjugation which tells proteosome to chop the proteins into peptides
Some a.a. broken down to be recycled but some will be traffiked into ER where it will be coded into MHC class I . trafikked via golgi body + presented on the cell where they can be recognised by CD8+ cytoxic T cells.
If cells are normal, no CTL can recognise it therefore cells carry on as usual BUT if cells are infected by virus or mutated, CTL will recognise it and kill cell
Important structures: MHC Class II
made up of? is it same of different a chain to MHC class I?
how many disulfide bonds? where?
what makes up the peptide binding cleft?
transmembrane region anchor?
made up by 2 symmetrical chains
a and B chain ( a1, a2, B1, B2)
DIFFERENT a chain to MHC class I
there are 2 domains stabilised by disulfide bonds (b has 2 and a has 1)
a1 + b1 make up the peptide binding cleft
both chains have a transmembrane region anchor
Antigen processing and presentation in APC (MHC class II presentation)
what do apc have the ability to do? which MHC class does this correspond to?
what happens to the pathogen? what about the MHC class II?
what happens before it is presented on the surface of APC?
APCs have the ability to engulf pathogens therefore MHC class II
The pathogen will be uptaken, degraded and processed in endolytic vesicles in APC At the same time, MHC class II will be sent from ER and traffiked away from golgi apparatus to the endolytic vesicle
The MHC class II will associate with the pathogen antigen. Now it will be trafikked and presented on surface of APC where it will be recognised by CD4+ helper T cells
2 step recognition with TCR and MHC
what must the TCR be able to do?
what must the CD4 receptor be able to do?
2 step recognition phase
T cell receptor needs to fit the peptide presented on MHC class II
CD4 receptor needs to bind to appropriate partner to lock in this recognition signal
for killer T cell, it is the CD8+ and not CD4+
TCR lineage
what does the cell lineage depend on?
what can it either differentiate into?
what do both chains have? (3)
the 3 different AB cell
whats the only YD cell?
T cell lineage (classes) depends on TCR glycoprotein chain
It will either differentiate into aB or Yo cells
Both chains have domains, variable + constant region
αβ (alpha beta) T cells
CD4+ or CD8+
CD4+ becomes Th cells
CD8+ becomes CTL
γδ (gamma delta) T cells
CD4- and CD8-
αβ and γδ chains
ab
what is the TCR made up of?
where is the majority of the T cell population?
what does it require of the antigen?
yd what is the tcr made up of? where is the highest abundance? why is it unconventional? what does it recognise?
αβ (alpha beta) T cells
TCR made up of one α chain and one β chain
Majority of T cell population in peripheral blood
Requires antigen presentation on Major Histocompatibility Complex (MHC) – peptide antigens
γδ (gamma delta) T cells
TCR made up of one γ chain and one δ chain
Highest abundance in gut mucosa
‘Unconventional’ - Do not need MHC presentation to work
Recognise non-peptide antigen?
Important structures: TCRs
how are yd and ab similar? what is different?
what are they stabilised by?
what do they have on the chain?
what do they have in the transmembrane region?
γδ TCRs similar to αβ TCRs, but different chains
chains are nearly symmetrical
stabilised by 2 disulfide bonds in each chain
has a cytoplasmic tail in the transmembrane region
has glycocarb groups on the chain
Signals for T cell activation
how many signals needed? why?
what are the signals?
need 3 signals to prevent T cells activating prematurely and damaging healthy cells
signal 1 = binding of the the TCR to the peptides presented on the MHC molecules + the binding of the co-recptor CD4 or CD8 to the MHC
signal 2 = co-stimulation signal as a result of binding of receptors on the antigen presenting cell + T cell
e.g CD80/CD86 is present on cells including APC but CD28 is only present on T cells therefore can confirm identity of T cells
signal 3 = cytokines in the environment. APC secrete cytokines to activate T cells hence tell T cells what to differentiate into
CD8/CD4 and MHC I/II
describe the two interactions
TCR of CD8+ cytoxic T cell interacts with assymetrical MHC class I molecule and interaction of CD8 co-receptor with the MHC
TCR of CD4+ helper T cells binds to symetrical MHC class II molecule and interaction of CD4 co-receptor with the MHC
Cytokines in T cells
what are cytokines?
what are a major source of cytokines?
Cytokines – chemical messengers in immune system; cells have receptors to ‘read’ chemical messages
T cells are a major source of cytokines, especially CD4+ Th cells (co-ordinated immune respone)
Th cells can produce cytokines to respond to different types of infection
Th cells for different types of infection
what are the different types?
describe their lineage?
what they are used for?
Naive CD4-T -> IL-12 -> Th1 -> IFN-y + TNF-a cell-mediated immunity (intraceullar immunity, bacteria)
Naive CD4-T -> IL-4 -> Th2 -> IL-4. IL-5, IL-13 humoral immunity (extracellular parasites)
Naive CD4-T -> IL-6 -> Th17 -> IL-17A, IL-17F, IL-22 cell-mediated inflammation, autoimmune diseases (extracellular phogens, fungi)
Naive CD4-T -> TGF-B -> Treg -> TGF-B, IL-10 immunoregulation (peripheral tolerance)
Balancing CD4+ T cell responses
what will secreted cytokines do for the different sub classes?
how do they know which one to differentiate into? (2)
Cytokines secreted by different T cells will promote proliferation of that sub-class but inhibit the pro-liferation of other subclasses
So many different instrcutions hence very complex process
Cytokines released in different concentrations
Cytokines bound to MOST receptors will win
Th1-mediated immune response
function, diseases and main cytokine
3 main functions?
main cytokines? (2)
effector?
3 Th1 mediated diseases?
Function
Protecting against intracellular infections by viruses and bacteria; eliminating cancerous cells
Proinflammatory responses (via cytokines)
Production of IgG for opsonisation
Main cytokine
Polarizing: IL-12
Effector: IFNγ (promote + inhibit)
Th1-mediated disease
Granulomas
MS
Some autoimmune disease (type 1 diabetes)
