08 - Adaptive Immunity

Question 1

What are the differences between innate and adaptive immune system

Answer 1

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

Question 2

Describe B cells and T cells (lymphocytes

Answer 2

• 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

-

Question 3

What is special with b and t cells

Answer 3

long lifespan

divide rapidly (can clone) and attack the pathogen

each cell has a unique receptor that recognize antigen

Question 4

Describe the b cell receptor

Answer 4

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

Question 5

Describe t cell recpetor

Answer 5

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

Question 6

What is somatic recombination, why do we need it

Answer 6

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)

Question 7

What are antigens (Ag)

Answer 7

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

Question 8

What are epitope

Answer 8

small segment of an antigen that can induce an immune response

most antigens have severla epitopes

also called antigenic determinants

Question 9

What is the major histocompatibility complex (MHC)

Answer 9

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

Question 10

What are the types of MHC

Answer 10

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

Question 11

What are professional antigen presenting cells (APCs)

Answer 11

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

Question 12

Why is antigen processing and presentation necessary

Answer 12

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

Question 13

What the MHC class 1pathway

Answer 13

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

Question 14

What is the MHC class 2 pathway

Answer 14

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…)

Question 15

What are the types of adpative immunity

How are t cells involved

Answer 15

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

Question 16

What is humoral immunity

Answer 16

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

Question 17

What is cell-mediated immunity

Answer 17

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)

Question 18

what is costimulation

Answer 18

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)

Question 19

What do activated antigen presenting cells do

What does it evoke

Answer 19

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

Question 20

What are the types of T cells

Answer 20

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

Question 21

What happens with activated killer T cells in the lymph nodes

Answer 21

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)

Question 22

What is T-cell dependent activation (humoral immunity)

Answer 22

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

Question 23

What is T-Cell independent activation

Answer 23

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

Question 24

How do antibodies protext us from pathogens

Answer 24

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

Question 25

What are the 5 classes/isotypes of antibodies

Answer 25

Differ from localization, structure and function

1. IgG
   - most abundant, secondary responses (created second time u encounter an antigen), neutralize, opsonize, activate complement, placental transfer (maternal circulation)
2. IgA
   - secreted dimer (two antibodies attached tail to tail), secreted by mucosal surfaces of respiratory, gi, urogential
3. IgM
   - pentamer (ten binding sites), precipitate (brings all antigens together), only in cirulatory because too big to get out, primary responses, fixes compliment
4. 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

Question 26

What is primary immune response

Answer 26

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

Question 26

What are the two features of the adaptive immune response

Answer 26

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

Question 26

What is negative selection

Answer 26

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

Question 26

What is secondary immune response

Answer 26

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

Question 26

What is positive selection

Answer 26

T cell

T cell can interact with MHC
(MHC restriction

then goest to negative selection

to prevent autoimmunity