08 - Adaptive Immunity Flashcards
What are the differences between innate and adaptive immune system
Innate:
- PRR recognize PAMPS
- PAMPs essential for pathogen survival
- limited specificity
- broad cross reactivity across many pathogens
- perfect self vs non-self discrimination
- common to many lifeforms
- immediate response
- no memory
Adaptive:
- B cells and T cells have receptors that can recognize specific antigens
- antigens binded to can be any kind of molecule (protein/lipid/card) –> must be educated, can harm wrong stuff
- receptors are generated by recombining a few genes (near unlimited repetoire of specificities
- extremely narrow cross-reactivity (very specific)
- good, but imperfect self vs non-self discrimination (mistakes)
- restricted to jawed verterbrates
- initial responses are slow (3-5 days to initiate)
- memory
Describe B cells and T cells (lymphocytes
- both derived from the common lymphoid progenitor in the bone marrow (B cells develop in bone marrow, t cells develop in the thymus) –> develop immunocompetence and learn self-tolerance
- naive b &t cells (never seen antigen before) travel to lymph nodes to await antigen exposure
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What is special with b and t cells
long lifespan
divide rapidly (can clone) and attack the pathogen
each cell has a unique receptor that recognize antigen
Describe the b cell receptor
2 antigen recognitiion site
can be membrane bound or released as an antibody
variable regions make up the antigen binding sites
allows b cell to “see’ antigen
Describe t cell recpetor
1 antigen recognition site
membrane bound
variable regions make up the binding sites
allow t cells to ‘see’ processed antigens and to communicate with other immune and host cells
- t cells can only bind to small fragment of viruses
What is somatic recombination, why do we need it
rearrange and recombine a few gene segments, we can generate an almost unlimited number of combinations to make brand new receptors in b and t cells
10^12 different possible antigens, but we only have ~30,000 genes in our entire genome (cant make a unique b cell or t cell receptor for each antigen)
What are antigens (Ag)
any molecule that can bind specifically to an antiboy (generates and antibody response)
may be a pathogen, toxin, non-toxic foreign mol or self-mol
may be proteins, polysaccharides or sometimes lipids
What are epitope
small segment of an antigen that can induce an immune response
most antigens have severla epitopes
also called antigenic determinants
What is the major histocompatibility complex (MHC)
glycoproteins found in plasma membrane in all nucleated cells
your “self-antigens” –> mark your cells as yours – strongly antigenic to other individuals
everyone has unique MHC on all nucleated cells
function to help T cells recognize self from non-self (tissue typing based on this)
aka human leukocyte antigen (HLA) –> on humans
What are the types of MHC
MHC Class 1 –> on all nucleated cells (one tail)
MHC Class 2 –> on professional antigen-presenting cells (two tails) –> takes stuff from outside cell and signals it came from outside
What are professional antigen presenting cells (APCs)
process and display antigenic peptides on MHC class 2 molecules
- engulf extracellular molecules and put it on MHC
activate t cells
dendritic cells (DCs) are the best at being APCs although macrophages and b cells can be APCs too
Why is antigen processing and presentation necessary
b cells can bind native (unprocessed antigens), but T cells cannot
T cells can only ‘see’ fragments of antigens presented in the context of MHC mol
there are two types of MHC molecules because there are two different pathways for antigen processing
What the MHC class 1pathway
MHC class 1
- binds to and presents cytosolic peptides (anything made inside host cells is on MHC class 1)
- endogenous antigens –> antigens present inside the cell
- presents antigen CD8+ T cells (“cytotoxic” or “killer”) –> if T cell recognizes antigen docked is because it’s a virus or pathogen and cell has to die (cytotoxic t cell gives it the signal to die)
kills one cell
What is the MHC class 2 pathway
binds peptides from inracellular vesicles (comes from outsdie)
exogenous antigens: antigens that have been brought into the cell from outside (through phagocytosis or specific binding)
presents antigen to CD4+ T cells
- provides help to b cells to allow them to mature into plasma cells and make antibodies and do the killing
- can also help CD8+ cell
*useful for attacking things outsdie the cells (virus, bacteria…)
What are the types of adpative immunity
How are t cells involved
antibody-mediated (humoral) immunity
cell-mediated immunity
t cells aid both types of immunity
- the two types of immunity are inter-related and can work together
What is humoral immunity
antibody-meidated
antibodies are produced by plasma cells (differentiated/mature B cells) and circulate freely in blood and lymph
bind to bacteria, toxins, free virus, etc…
help immune system to fight off invadors
What is cell-mediated immunity
mediated by living cells and has cellular targets (direct cell-to-cell killing)
largely mediated by “cytotoxic” T cells
infected cells, cancer cells, foreign cells are killed
(can be either direct or indirect)
what is costimulation
naive “helper” T cell needs 2 signals (costimulation to becoem activated
- presents immune response from happening accidentally (autimmunity, allergy)
- in the absence of costimulation the T cell becomes inactived (anergic)
What do activated antigen presenting cells do
What does it evoke
present antigen to T cells in the lymph nodes
- dentritic cell encountered pathogen, cytokines tell to express a molecule to alert danger –> meets with naive helper t cell (binds at MHC)
signal 1 –> MHC-TCR binding
signal 2 –> b7 provided by dentritic cell (inflammation) –> fully activated, T cells will make copies of itself
signal 3 –> cytokines from DC tell T cell what to do
some reside in for memory
elicits the primary cell mediated response
- helper t cell will provide cytokines to a cytotoxic t cell
What are the types of T cells
T cells differentiate and proliferate to become effectors
TH1 cells: provide cytokines that cytotoxins need
TH2 cells: provide cytokins that B cells need to turn into plasma cells
What happens with activated killer T cells in the lymph nodes
undergo clonal selection (expansion) and leave lymph nodes to travel to the site of infection
- DC talks to APC –> makes copies of itself –> send copies out into circulation and rides bv into tissues (get to inflammation)
- looks at every individual host cell and see which has that antigen in its MHC
(recognizes pathogenic epitopes in the context of MHC-I on infected cells, cancer cells, and transplanted cells
Direct cell to cell killing –> via perforin/granzyme
also produces IFN-y which can activate tissue macrophages (mop up crew to eliminate all debris)
What is T-cell dependent activation (humoral immunity)
the most common way B cells are activated
B cell interalizes bound antigen
processes and presents antigenic fragments on MHC II
(chops it up and puts it out)
a “matching T helper cell” (specific for the same antigen) binds to MHC II + antigen via its TCR and provides a second signal (costimulation) in the form of cytokines
- signals: MHC docking with T helper cells & cytokine (costimulation)
B cell undergoes clonal expansion and matures into plasma cells (secreting antibodies) or memory B cells (long lived)
turn into effector cells/plasmocytes (plasma cells) and memory B cells
What is T-Cell independent activation
Because b cells can “see” native (unprocessed) antigen on their own through their BCR
- but antigen alone is not enough to stimulate an adaptive response –> another signal is required
T cell independent activation of B cells is less common
other microbial constituents provide the “secondary” signal
type of antibody created is lower grade –> can’t get out to tissues
does not result in a robust humoral response
- lower quality antibodies are made (these antibodies are restricted to circulation)
no memory cells are produced
How do antibodies protext us from pathogens
neutralize antigens/toxins because binds with surface pf native pathogens to prevent them from adhering/entry
- enhance phagocytosis: tail of antibody because flag to alert phagocyte to gobble it up (opsonization: tagging something for destruction)
- phagocytes have cell surface receptors that recognize tail of antibodies look for Fc component
prevent attachment of viruses to cells
immobolize bacteria (block cilia/flagella)
activate complement will kill the bacteria by forming MAC (membrane attack complement) –> pokes holes and deflates it
Helps natural killer cells: antibody binds to abnormal/foregin proteins on cell surface for targeting killing by NK cell
What are the 5 classes/isotypes of antibodies
Differ from localization, structure and function
- IgG
- most abundant, secondary responses (created second time u encounter an antigen), neutralize, opsonize, activate complement, placental transfer (maternal circulation) - IgA
- secreted dimer (two antibodies attached tail to tail), secreted by mucosal surfaces of respiratory, gi, urogential - IgM
- pentamer (ten binding sites), precipitate (brings all antigens together), only in cirulatory because too big to get out, primary responses, fixes compliment - IgE
- binds mast cells (encounteres pollen/dander and binds to antigen –> gives signal to release histmaine –> inflammation, dilation, swelling…), responsible for allergies, protection against worm
What is primary immune response
steady and slow
begins 3-6 following exposure (lag phase)
first exposure
memory T cells and B cells may remain for decades
antibody titres usually fall within 28 dyas
What are the two features of the adaptive immune response
1) specificty: each B cell or T cell only recognizes one antigen
- when vaccine B
2) memory: responsible for the secondary response (basis for vaccination)
primary response dominated by IgM production, while secondary responses involve class switching to IgG
What is negative selection
both T and B cells
in the bone marrow cells express any antigen we generate ot the new B cells –> tell B cell to die (dont want if recognize itself)
to prevent autoimmunity
What is secondary immune response
occurs following re-exposure to same antigen (no lag phase)
faster, stronger and more prolonged than 1st exposure
onset within hours; antibody titre remains elevated for weeks to months
pathogen can be destroyed before they can even multiply – may be no symptoms
memory cells can result in lifetime immunity
What is positive selection
T cell
T cell can interact with MHC
(MHC restriction
then goest to negative selection
to prevent autoimmunity
