c39 lec 6.5 and 7 Flashcards
what is the main function of B cells
to produce antibodies
where are antibodies present
in the blood, lymph, and extracellular fluids
where they bind to extracellular bacteria and viral particles
also found at mucosal surfaces
how are B cells activated?
multiple surface B cell receptors bind to the same antigen and this causes B cell receptors (BCRs) to cluster together … this clustering and CROSS linking sending activation signals into the B cell
antigen interactions with IgM-BCRs on a B cell surface bring multiple BCRs close together
cross linking
this allows for signalling cascades to proceed and induce activation
describe the structure of a T cell receptor (TCR)
made up of 2 polypeptides, alpha chain and beta chain
have a variable and constant region
(V alpha and B beta, C alpha and C beta)
what type of pathogens are presented on MHC class I to mediate cell killing
intracellular pathogens
what type of pathogens are what professional antigen presenting cells uptake, process and present on MHC class II
extracellular pathogens
why are CD4 helper T cells called help cells? what help do they provide?
they produce cytokines, this helps macrophages degrade the pathogens that they uptake and furthermore they help B cells with the production of antibodies
proteins are degraded into peptides that can be loaded onto MHC molecules
antigen processing
pathogens proteins are broken down into peptides (in the cytosol) moved to the ER and then to plasma membrane to be present on MHC class ____
MHC class I
protein transports proteasome peptides to the ER for loading of MHC class I proteins
TAP: transporter associated with antigen processing
MHC class I is assembled where and then transported to where
ER to plasma membrane/cell membrane
where does peptide loading happen for MHC class I
in the ER
trims peptides to the right size for MHC class I antigen presentation
endoplasmic reticulum aminopeptidase (ERAP)
because peptides must be within a specific size range for MHC class I
- happens in the ER but it happens after the peptide is loaded
where does MHC class II get made
in the ER
how do we ensure that peptides that are supposed to bind to MHC class I don’t bind to MHC class II in the ER
CLIP: class II associated invariant chain peptide: MHC class II presentation is carefully regulated by multiple proteins including CLIP
- CLIP basically takes up MHC II binding pocket in the ER so peptides don’t bind
antigens are brought in through MHC II pathway in professional antigen presenting cells (pAPCs) but presented on MHC class I to activate CD8 T cells
cross-presentation : only applies to pAPCS
its when extracellular antigens are presented on MHC class I
white blood cells move from blood into tissues
diapedesis/extravasation
if T cells recognize class I in the thymus then is it
CD8 cytotoxic T cells
if T cells recognize class II in the thymus then it is
CD4 helper T cells
_______proteins are co-receptors to the TCR that also ensure that CD4 helper T cells bind to MHC class II and CD8 cytotoxic T cells bind to MHC class I
CD4 and CD8
what are the three signals that T cells require to be activated?
- TCR and CD4 and CD8 co-receptor recognize a specific peptide presented on MHC class II/I
- costimulatory receptor, CD28, binding to B7 on antigen presenting cell (APC) that is presenting antigen
- cytokines
- need all signals for the T cell to be activated
what is the T cell inhibitory co-receptor and what is the T cell activation co- receptor
activation: CD28
inhibitory/no activation: CTLA-4
once T cell gets first and second activating signal what happens
it starts to produce IL2
the IL2 goes into external environment and acts on the T cell that made it
activated T cells make IL2 for it to act back on those same cells
autocrine action
after IL2 binds to T cell what happens
this makes T cell replicate/proliferate many times and produce many clones with same peptide
what is IL2
an autocrine cytokine that acts as the third and final signal for T cell activation
IL2 acts as a
autocrine cytokine
before any of the three signals in T cell activation, what do we need to happen?
dendritic cells break down pathogen into peptides/antigens and then are loaded onto MHC I and II
unresponsive to antigen
anergy
what is the main role of CD4 t cells
help other immune cells when they are trying to deal with pathogens
- can help macrophages, can help activate antibodies etc
CD8 T cells cannot do their function unless the first time they interact with MHC
they interact with pAPC
forces T cells to interact with things that they are not specific for
superantigens
ADAPTIVE IMMUNE cells learn from
first infection…this is called memory
what kind of immunity generates memory
adaptive immunity
majority of activated B cells that survive the germinal center reaction become
plasma cells
some of these become memory cells
one _____ helps determine if the B cell is a plasma cell or memory cell
cytokine
when our body creates an immune response itself
active immunity
when we are given things that help us be immune to things
passive immunity
activated CD4 and CD8 T cells both generate
effector (TE) and memory T cells (TM)
what are the three types of memory T cells?
central memory t cells
and
effector memory t cells
and
tissue resident memory T cells
activated T cells that circulate the body and scan our secondary lymphoid tissues for infection
Central memory T cells (T CM)
activated T cells that cannot enter our secondary lymphoid organs, only non lymphoid tissues, to scan for infection
Effector memory T cells (T EM)
activated T cells that enter the tissues during repair of tissue damage can remain there and become
tissue resident memory T cells (T RM)
antigen interactions with IgM-BCRs on a B cell surface bring multiple BCRs close together
cross linking
this allows for signalling cascades to proceed and induce activation
what gives the first signal for B cell activation
cross-linking
what can lower threshold of activation of B cells
co-receptors
- can also bind to antigens along with BCRs
antigen binding both ______ and ______ increase the signalling of activation of B cells by 1000-10 000 fold
BCRs and co-receptors
= increased sensitivity to the antigen
what can B cells walk along in lymphoid organs (lymph nodes)
follicular dendritic cells (FDCs)
FDC network guides B cells and presents antigens
- not actually dendritic cells!
B cells that interact with and bind antigen (pathogen) on FDCs receive _____
1st activation signal (recognizing and binding antigen)
how many activating signals do B cells have?
2
- walks along FDC and binds to antigen
- from T cell
when does B cell receive its 2nd activation signal
after the B cell binds to the antigen, the B cell migrates to the T cell zone ( a special part of the lymph node)
At the boundary of the B cell follicle and T cell zone it will meet a CD4 helper T cell that recognizes the same antigen
The B cell will then present the antigen to the T cell and there it will receive the 2nd activation signal
cell-cell interactions
immunological synpase
Pairing of T cells and B cells forms an
immunological synpase
T dependent B cells require
T cells
what kind of T cells help B cells to get that second activation
CD4 helper T cells
what forms the germinal centers
when cognate pairs (helper T cells and B cells) move back to the medullary cords and B cells produce short-lived plasma cells
then other B cells move back and proliferate in the B cell area creating the germinal centers
evolution on a really fast scale
germinal centers
what are the two stages that activated B cells go through within germinal centers?
- B cells proliferate and mutate their BCR (centroblasts in dark zone)
- undergo testing and selection to see if those mutations were harmful or beneficial (centrocytes in light zone)
a process that introduces random point mutations into the variable (V) region of immunoglobulin (Ig) genes- specifically in activated B cells
somatic hypermutation
the more cells stay in germinal centers the more _____ they accumulate
mutations
affinity of surviving B cells to antigen increases over time (multiple rounds of somatic hypermutation)
affinity maturation
the result of somatic hypermutation
affinity maturation
changing the class of immunoglobulin protein without changing the antigen specificity
isotype switching
________ mediates somatic hypermutation and isotype switching (class switch recombination)
AID: activation-induced cytidine deaminase
- involved in both somatic hypermutation and isotype switching
immunoglobulins(Ig)/antibodies differ in their
constant region (Fc region)
what are the five different classes of immunoglobulins
- IgG
- IgM
- IgD
- IgA
- IgE
the first BCR and secreted antibody that is made
IgM
the second BCR that is made
IgD
- dominant BCR on the surface of anergic B cells
- no class/isotype switching for IgD
- mostly made as a BCR not an antibody
the main antibody produced in our associated lymphoid tissues, keep commensal bacteria in check
most abundant class of antibody
forms dimers
IgA (think most abundant antibody, starts with A, a for abundant: IgA)
- typically can only make IgA after the B cell has been activated
- helps with gasteroinestinal or mucosal stuff
- not free floating, sits on epithelial surfaces etc
receptor mediated transport from one side of a cell to the other
transcytosis
recruits granuloctes and induces effector functions (degranulation)
involved in allergy!!!!
IgE
- we cannot phagocytose parasitic pathogens, so IgE helps us evolve methods to eject/eliminate them from our bodies
- theres also IgE mediated pathogen killing by granules
most abundant immunoglobulin in our body fluids (lymph and blood)
most flexible of the immunoglobulin family due to hinge region
IgG
IgG is transported from
blood to tissues (transcytosis)
NK cells can recognize human cells that are coated with specific IgGs and kill them
ADCC: antibody dependent cell-mediated cytotoxicity
which immunoglobulin do we typically not make as an antibody
IgD
if we lack AID what kind of antibody will the body primarily produce?
igM antibodies
another name for the CLIP chain is
the invariant chain: blocks peptide loading on to MHC Class II in the ER
blocks loading of self-peptides instead of foreign peptides
