IMMUNO LEC 6 ADAPTIVE

B cells attack invaders found where?

extracellular

T cells attack invaders found where?

intracellular

B and T cells are considered _______ before they are trained (interact with pathogen/ are presented with pathogen)

naive

how long does it take for adaptive immunity to kick in after you have been infected with a pathogen?

1 week

a single lymphocyte progenitor cell gives rise to a bunch of naive lymphocytes each with a different specificity. these lymphocytes undergo ______ to remove any that are potentially self reactive.

colonal deletion

mature lymphocytes are then tested against a foreign antigen in a process called _______

colonal selection

each T and B cell is colonal meaning what?

only has one specific type of receptor for specific pathogen

(cells undergo colonal expansion to make more of themselves)

what is the difference between receptors of innate and adaptive immune system?

innate has many types of PRR on one cell

adaptive has only 1 specific type of receptor on one cell

what are the 4 basic prinicples of colonal selection?

1. each lymphocyte has a single specific receptor type

2. interaction between lymphocyte receptor and foreign molecule binds with high affinity and activates lymphocyte

3. differentiated effector cells are from an active lymphocyte have identical receptors to the parental cell

4. lymphoctes with receptors for self are deleted at early stage and do not make the cut for mature lymphocyte cells

T lymphocytes develop in bone marrow and mature in the _________

thymus

B lymphocytes develop in bone marrow and mature in the _________

bone marrow

what makes a nieve lymphocyte become an effector cell?

+ag (antigen contact)

two types of T cells:

CD4 helper cells- help cytotoxic T cells and B cells

CD8 cytotoxic cells- kill virally infected and damaged cells

primary/central lymph organs:

sites of lymphocyte development and maturation: thymus and bone marrow

secondary/ peripheral lymph organs

sites where mature lymphocytes encounter antigen and become activated: spleen and lymph nodes

mature lymphocytes circulate between what fluids/organs?

blood, primary lymph and secondary lymph organs

more specific examples of secondary lymph organs include

spleen, peyers patch, appendix, tonsil,

popliteal (under knee lymph node randomly mentioned in class)

where are adaptive immune responses activated?

secondary lymph

what cells are responsible for activating T cells in the periphreal (secondary) lymph organs?

dendritic cells (as well as any innate immune cells but primarily dendriitic)

why is it important that lymph nodes concentrate immune cells?

they provide a space for antigen on dendritic cell to come into contact with rare- antigen specific lymphocytes that would be diffucult to find if they were spread through entire body

what is an antigen vs epitope

an antigen is a molecule recognized by body as forigen

an epitope is a specific part of the antigen that is recognized by antibody/antigen receptor

(a single antigen can have many epitopes and each epitope can have specifiic immune cells targeted for it)

many different specific BCR/TCR can detect the same antigen (T/F)

T- each one may be endoded to a specific epitope on that antigen

BCR vs antibody/Ig

BCR- B cell receptor embedded in B cell membrane

antibody/Ig- B cell receptor secreted by plasma cell

Ig/antibodies bind to pathogen/ toxic product in extracellualr spaces (main B cell effector function)

what does this do?

recruits other molecues and cells to destroy the bound pathogen (ie. complement and other leukocytes)

what pathway of compliment can be connected with Ig/antibodies?

classical- can be triggered by binding an antibody

what antibodies can C1 of classical compliment pathway bind? what region?

IgM and IgG

Fc (fragment crystallizable) region- heavy chains near carboxyl end of antibody

(OPPISITE OF WHERE AN ANTIGEN BINDS)

an antibody unit is made out of _______ light chains and ______ heavy chains

2 heavy (H), 2 light (L)

what is weight of heavy and light chains?

heavy 50kDa

light 25kDa

each antibody unit has how many antigen binding sites? at which terminal?

2

amino terminal

each antigen binding site is made of what chain(s)?

1 heavy, 1 light

each heavy chain is linked to a light chain and each heavy chain is attached to eachother by

disulfide bonds

what links upper and lower portion of each heavy chains?

what links the heavy chains together?

hinge joint

disulfide bond

H and L chains on each half of antibody are identical (T/F)

T

the carboxy terminal of an antibody is made of what chain types?

2 heavy

what is the diff between avidity and affinity

avidity- total strength of antibody andtigen interaction (both antigen sites on antibody)

affinity- strength of antibody antigen interaction (one antigen site on antibody)

what chains have constant and variable regions?

heavy and light

what terminal are variable (V) regions found at?

amino (where antigen binds)

each H and L chain consists of multiple Ig domains

each domain is ______AA in length

L chain has ___ Ig domains

H chain has ______ Ig domains

110 AA

L chain 2 Ig domains

H chain 4-5 Ig domains

what determines antigen binding specificity to an antibody?

variable region (Vh and Vl)

what determies the class/effector function of antibody?

the constant region of the carboxyl terminal (Ch and Cl)

how many constant and variable regions does each (heavy vs light) chains have?

light- 1 variable, 1 constant

heavy- 1 variable, 3-4 constant (depend on class)

what are the types of heavy chain and what are the corresponding types of antibody class?

mu- IgM

gamma-IgG

alpha- IgA

delta- IgD

epsilon-IgE

does constant or variable region determine type/class of antibody?

constant

antibody molecule can be readily proteolytically cleaved by _______ found in papayas

papain

papain cleaves antibody to 3 peices _______, _______ and _________ at the ______

Fab, Fab and Fc at the hinge joint

when an antibody is assembled it has ___ equal sized globular portions

3

what is Fab vs Fc?

Fab-(fragment antigen binding) binds antigen (2 per cleavage of antibody)

Fc- (fragment crystalizable) doesnt interact with antigen, differs between H chain types (1 per cleavage of antibody)

4 distinct characteristics between antibodies in the C region of heavy chains (Hc)

1. number and location of sulfide bonds

2. number of attached carbs

3. number of C domains

4. length of hinge regions

Ig classes can occur as _______ or ______

BCR or antibody (Ig)

what is the most abundant antibody in serum?

IgG

most common subclass IgG1>IgG2>IgG3>IgG4 least common subclass

what antibody is made first by B cells?

IgM

what are the subclasses of IgA

IgA1 and IgA2

IgM is normally found in tissue not blood stream why?

IgM is a pentamer and is too heavy/ too big to enter blood stream

IgM pentamer formation increases avidity or afffinity?

avidity

IgM must become _____ to enter tissues

IgG

what two antibodies start compliment C1 classical pathway?

IgG, IgM

what Ig is transfered from mom→baby by placenta

IgG (1,2,3)

what antibody (Ig) binds mast cells and basophills in allergic rxn/ parasite?

IgE

what is the role of IgD

unknown, but present on mature B cells and can be used as a marker in experiments

what antibody is secreted at mucosal surfaces, gut, respiratory tract and breast milk?

IgA

what antibodies form polymers?

what holds together antibody polymers?

IgA- 2 Ig (in mucous and breast milk) -only 1 Ig in plasma

IgM- 5 Ig

J-chain

how many antigen binding sites in IgA and IgM?

IgA- 2-4 (depends on if monomer or dimer form)

IgM- 10

IgM antibodies binding sites have low _____ but the molecule has high ______

affinity (made early in immune response so weak affinity of binding sites)

avidity (5 monomers that combine to IgM make very high avidity)

in the variable region, what area has greatest specificity and makes direct antigen contact?

HVR (hypervariable region)

each antibody monomer has ___ HVRs

6

(3 in light chian, 3 in heavy chain)

what is another term for HVR?

complementarity determining regions (CDRs): CDR1, CDR2, CDR3

(aka HV1, HV2, HV3)

what is the most variable part of the HV/CD region?

what are the x and y axes on the graph used to determine this?

HV3 / CD3

x- heavy/light chain V region

y-variability

what is a FR region?

a framework region which exists between HV/CD regions in V domain providing structural framework

how many FR in each V doimain?

4 (FR1, FR2, FR3, FR4)

C term chains are constant between antibodies within a class (T/F)

T

N term chains are constant between antibodies within a class (T/F)

F

TCR are found in plasma and bound to cell (T/F)

F- TCR only in T cell membrane

TCRs consist of _____ chain and ______ chain

(and more rarely _____ and _____)

a-light and B-heavy

rarely- gamma delta T cell

on T cell receptor each chain (a and B) have how many C and V regions?

1C, 1V (on each a and B chain)

each T cell expresses only one type of TCR against one specific pathogen (T/F)

T

what is fuction of C (carboxyl) and N (amino) term of TCR?

C term anchors the TCR in T-cell and helps with signaling

N term variable antigen binding region of TCR

TCRs can only recognize _________ antigens, that are presented on ________

small peptides presented on MHC (/HLA)

what is another term for MHC when it relates to humans?

HLA (human leukocyte antigen)

peptide presented on MHC of an APC first is processed through _______________

proteolysis in cytosol or lysosomal degredation

what are the two classes of MHC moleucles

MHC1 and MHC2

MHC class 1 subunits

a1,a2,a3 and a soluble B2-microglobulin for structural support (with a3)

MHC class 2 subunits

a1, a2, B1, B2

MHC class 1 peptide binding cleft is made of what subunits?

a1+a2

MHC class 2 antigen binding region is made of what subunits

B1, a1

MHC class 1 binds small peptides of _______AA in length from _______ proteins

8-10AA, intracellular (viral)

MHC class 2 bind small peptides of ______ AA in length from ______ proteins

13-25AA, extracellular (bacterial)

in MHC ___ both a and B chains are transmembrane

2

MHCs bind to TCR and co-receptors: ____ or _____

CD8 or CD4

MHC1 binds what TCR coreceptor?

CD8

MH2 binds what TCR coreceptor?

CD4

on a T cell receptor complex can you label:

TCR

MHC

Co-receptor

CD3 complex (6 subunits)

yes? yayyy

why is TCR always expressed with CD3?

CD3 complex is required to bring TCR to surface of T cell

what does CD3 complex recruits ______ molecules taht activate when TCR engages driving T cell activation

signalling

what are 3 main CD3 components

CD3 epsilon, CD3 gamma, zeta chain

T cell receptors have dual specificity in that:

they interact with antigenic peptide and polymorphic features of MHC