Lecture 7: Molecular Basis Of Antigen Recognition

Question 1

There are 2 membrane bound lymphocyte receptors: ______ and ______. There is one type of soluble receptor, which are ___________

Answer 1

BCRs; TCRs

Antibodies

Question 2

Antigen presenting molecules are MHC types I and II, also known as ______ types I and II

Answer 2

HLA

Question 3

On what cells would you find class I HLAs?

Answer 3

All nucleated cells

Question 4

On what cells would you find class II HLAs?

Answer 4

Professional APCs (dendritic cells, macrophages, B cells)

Question 5

What are 6 major members of the immunoglobulin superfamily?

Answer 5

IgG
TCR
Class I MHC
CD4
CD28
ICAM-1

[members of the same family due to similarities in domain structure, function, and evolution]

Question 6

__________ = the part of a molecule that is recognized by the immune system and is loosely associated with adaptive responses

Answer 6

Antigen

Question 7

________ = an antigen that evokes a specific immune response

Answer 7

Immunogen

Question 8

True or false: all immunogens are antigens

Answer 8

True; note that not all antigens are immunogens

Question 9

________= an antigen that induces immunologic tolerance

Answer 9

Tolerogen

Question 10

__________ antigens are the body’s own cellular components or intracellular pathogens

Answer 10

Endogenous

Question 11

Endogenous antigens can be further classified into:

_______= self-antigens

_______= tissue-specific antigen, which is present in one individual of a species but not in others (ex: ABO, HLA, etc.)

_______ = viruses, IC bacteria, and parasites

Answer 11

Autoantigens

Alloantigens

Intracellular pathogens

Question 12

__________ antigens = antigens that enter the body or system and freely circulate in fluids and are trapped by APCs. The uptake of these antigens by APCs are mainly mediated by phagocytosis

Answer 12

Exogenous

Question 13

A ________ is a small molecule which cannot induce an immune response on its own

Answer 13

Hapten

Question 14

Under what condition can a hapten induce an immune response?

Answer 14

When coupled with a carrier protein

Question 15

What are matters of clinical importance concerning haptens?

Answer 15

Drug allergies (penicillin itself is a hapten - not enough to elicit a response, must first bind to host proteins. IgG antibody may bind drug on RBC surface and cause hemolysis)

Vaccine design

Question 16

The BCR is composed of a surface __________ and two invariant chains (______ and ______)

Answer 16

Immunoglobulin

Ig-Alpha; Ig-beta

Question 17

What is the role of the Ig-alpha and Ig-beta complexing with the BCR?

Answer 17

They ensure surface expression of the immunoglobulin and function in signal transduction

[the BCR alone cannot participate in cell signaling–does not have ITAMs on cytoplasmic tails]

Question 18

Circulating Abs are soluble ________ that recognize and bind Ags.

They promote killing and/or removal of the immune complex formed through the activation of effector mechanisms.

They also function as membrane-bound surface Ag-receptors on B cells and play a key role in B cell ____________.

Answer 18

Glycoproteins

Differentiation

Question 19

Antibodies consist of _____ polypeptide chains

Answer 19

4

Question 20

What is the basic structure of an antibody?

Answer 20

2 Heavy chains (each with variable and constant regions)

2 light chains (each with variable and constant regions)

Question 21

The variable regions of the Ab are also called the ____ region

Answer 21

Fab

Question 22

The constant regions of Abs are also called ____

Answer 22

Fc

Question 23

Which structural chain of the Ab determines its class? (Like IgA, IgM, etc.)

Answer 23

The constant region of the heavy chains

Question 24

All antigen binding occurs in what region of the Ab?

Answer 24

Fab region (the variable regions of both chains)

Question 25

What is the effect of papain digestion of an Ab?

Answer 25

Cleaves the Ab in two places, separating the two Ag binding regions (now have 2 Fabs that can each bind in monovalent manner), leaving the Fc portion complete

Question 26

What is the effect of Pepsin digestion of an Ab?

Answer 26

Cleavage and degradation of Fc portion of Ab, leaving behind the Fab portion (now called F(ab')2) which maintains its bivalent binding capability Basically chops off the tail of the Y, leaving behind the V

Question 27

Each variable domain of an Ab has ____ hypervariable regions flanked by ____ framework (FR) regions

Answer 27

3; 4

Question 28

True or false: The hypervariable regions of Abs are located on 3 of the loops located farthest from the constant region

Answer 28

True

Question 29

The framework regions of antibodies correspond to the _____ sheets and the remaining loops

Answer 29

Beta

Question 30

What is the primary purpose of the hypervariable region of an Ab?

Answer 30

Intimately involved in Ag binding by creating an interaction site that is: Complimentary in shape, charge, and hydrophobicity to the epitope that it binds

Question 31

What region of the antibody increases flexibility so that an Ab can bind to Ag epitopes that are close together or far apart?

Answer 31

Hinge

Question 32

In what 4 ways do the different classes of Ig differ?

Answer 32

Size Charge AA sequence Carbohydrate content [there are both structural and functional differences]

Question 33

Each Ig isotype has its own _____. There are ____ isotypes in humans.

Answer 33

Gene; nine

Question 34

___________ refers to allelic differences in the heavy chains of Abs

Answer 34

Allotype [we all have IgG isotypes, but these may have subtle differences from person to person]

Question 35

________ refers to antigenic determinants on the V regions of antibodies

Answer 35

Idiotype [we may all see an antigen, but we respond with slightly different V region determinants]

Question 36

Which Ig isotypes exist as monomers?

Answer 36

IgG IgD IgE

Question 37

Which Ig isotype exists as a dimer?

Answer 37

IgA

Question 38

Which Ig isotype exists as a pentamer?

Answer 38

IgM

Question 39

Which Ig isotype is produced in the primary response to antigens, as well as the first Ab produced in neonates?

Answer 39

IgM

Question 40

IgM makes up ______% of total serum Abs. It is a pentamer, so it has ______ Ag binding sites. This makes it highly efficient for binding Ags with multiple repeating epitopes like ______ and _______, in addition to efficient binding of ____________ It can be expressed on B lymphocytes as a ___________

Answer 40

5-10%; 10 Viruses; RBCs; classical complement Monomer

Question 41

The ______ chain consists of an Fc linked polypeptide disulfide-bonded to 2 of the 10 mu chains.

Answer 41

J

Question 42

Which Ig isotypes have J chains?

Answer 42

IgA IgM [mnemonic = JAM]

Question 43

What is the purpose of the J chain found on IgM and IgA?

Answer 43

Binds to secretory cells to cross mucosa

Question 44

What is the predominant Ab of secondary immune responses?

Answer 44

IgG

Question 45

Which Ig isotype is a constituent of secondary immune responses and its secretory form functions in mucosal immunity?

Answer 45

IgA

Question 46

Which Ig isotype is the most abundant class in the serum?

Answer 46

IgG

Question 47

How many subclasses of IgG are there? How are they different?

Answer 47

4: IgG1-4 IgG1 is in highest concentration, IgG4 is least Differences are on the H chain, and there are other subtle structural differences as well as important functional differences

Question 48

Which Ig isotype is able to activate the classical complement pathway?

Answer 48

IgG or IgM

Question 49

Which Ig isotype crosses the placenta?

Answer 49

IgG

Question 50

IgA makes up _____% of total Ab in serum, and is usually in ___________ form but can be a dimer via J chain link

Answer 50

10-15 | Monomer

Question 51

Secretory IgA functions in mucosal immunity. Where is it typically found?

Answer 51

Colostrum Saliva Tears Mucus

Question 52

The __________ component of IgA is a polypeptide produced by epithelial cells of mucous membranes that binds to Fc domains of IgA dimer

Answer 52

Secretory

Question 53

What is the significance of secretory IgA?

Answer 53

Present at entry point for antigens Efficiency as a polymeric Ig isotype (dimer) Newborn immunity (breastfeeding)

Question 54

What Ig isotype is a constituent in secondary immune responses and is in lowest concentration in the serum?

Answer 54

IgE

Question 55

IgE binds to blood _______ and tissue ______ cells by Fc receptor with very high affinity.

Answer 55

Basophils; mast [via CD23a and CD23b]

Question 56

IgE plays a role in what powerful pharmacologic reactions?

Answer 56

Asthma, allergies, helminth infections

Question 57

Which Ig isotype makes up less than 1% of serum Ab concentration and has no known function in the serum?

Answer 57

IgD

Question 58

A ________ form of IgD is present as an Ag-specific receptor on mature B cells. A B cell may express monomeric IgD and monomeric _____ as their receptor, though both of these will have the same Ag specificity.

Answer 58

Monomeric IgM (mIgM)

Question 59

True or false: ligation of mIgD leads to activation of B lymphocytes

Answer 59

False! Because they do not have an Ig-alpha + Ig-beta complex with them

Question 60

Abs bind Ags via _________bonds

Answer 60

Non-covalent [like hydrogen bonds, electrostatic bonds, Van der Waals forces, hydrophobic forces]

Question 61

The binding between Abs and Ags is _______ compared to covalent bonding, but together generate a _______affinity interaction

Answer 61

Weak; high

Question 62

True or false: Ab/Ag binding is reversible

Answer 62

True

Question 63

The strength of the interaction between a univalent Ag (epitope) and univalent Ab (idiotope) is loosely referred to as ________

Answer 63

Affinity

Question 64

The strength of the interaction between a multivalent Ag and a multivalent Ab is referred to as its ________

Answer 64

Avidity

Question 65

The avidity of an Ab for its Ag is dependent on the _________ of of the individual Ag combining sites

Answer 65

Affinities

Question 66

Epitopes generally contain __________ amino acids. The epitope may consist of either sequential or non-sequential amino acids. If non-sequential, the 3D conformation of the epitope is vital; it may consist of complex proteins containing multiple overlapping epitopes. Epitopes may be associated with _______ immunogens or ________ immunogens

Answer 66

Hydrophilic Soluble; particulate

Question 67

Define T-dependent Ags

Answer 67

Ags that require both T helper cells and B cells to stimulate and Ab response T-dependent Ags are PROTEINS

Question 68

Define T-independent Ags

Answer 68

NON-PROTEIN Ags, such as polysaccharides and lipids that can stimulate antibody responses WITHOUT T cell help. Usually multiple identical epitopes that can cross-link several BCRs.

Question 69

Like the B cell receptor, TCRs cannot participate in signaling by themselves. What other components of the TCR complex participate in signaling?

Answer 69

CD3 complexes (epsilon/gamma and epsilon/delta) = 4 total ITAMs Zeta chains = 6 total ITAMs [overall 10 ITAMs for T cell signal transduction]

Question 70

Most TCRs exist as a heterodimer - they consist of an alpha and a beta chain. Each chain has a ________ region and a _______ region

Answer 70

Variable; constant

Question 71

The ______ region of the TCR contains 3 hypervariable regions or CDRs. CDR ___ is the most hypervariable.

Answer 71

Variable 3 [CDR3 exists at the center of the molecule]

Question 72

The majority of T cells are alpha/beta, what is the other type of T cell and where are they found?

Answer 72

gamma/delta - found in epithelial and mucosal compartments, recognize lipid Ags, recognize DAMPs, do not seem to be MHC restricted [make up 5-10% of the T cell population]

Question 73

What co-receptor is found with helper T cell TCRs?

Answer 73

CD4 (one chain consisting of alternating V-H-V-H domains) [helps other cells of the immune system by activating macrophages for phagocytosis, secretion of cytokines, and stimulation of B lymphocytes to produce Abs]

Question 74

What co-receptor is found with CTL TCRs?

Answer 74

CD8 (alpha chain and beta chain) [functions to kill infected cells and transformed cells]

Question 75

TCRs recognize primary sequences of amino acids in ____________.

Answer 75

Proteins

Question 76

Are free peptides recognized by TCRs?

Answer 76

NO

Question 77

The antigenic determinants are limited to those portions of the Ag that can bind to _____ molecules. This is why there can be differences in the responses of different individuals.

Answer 77

MHC (HLA)

Question 78

Superantigens are not processed, but bind directly to MHC ____ molecules and ____ region of the TCR

Answer 78

Class II V-beta [each SAg activates a distinct set of V-beta expressing T cells, depending on which V-beta gene segment the T cell is expressing.

Question 79

The diseases associated with exposure to SAgs are, in part, due to hyperactivation of the immune system and subsequent release of biologically active cytokines by activated T cells. What are some diseases related to superantigen activity?

Answer 79

Food poisoning (staph enterotoxins) TSS (staph) Scaled skin syndrome (staph) Shock (strep pyrogenic exotoxin)

Question 80

True or false: bacterial SAgs are the best studied but there are SAgs associated with viruses and other microorganisms as well

Answer 80

True

Question 81

_________ antibodies are monospecific identical Abs that are produced by one immune cell. The immune cells are all clones of a single parent cell

Answer 81

Monoclonal

Question 82

What are some uses for monoclonal antibodies?

Answer 82

Prevention of transplantation rejection Metastatic cancer (colorectal and H&N) Diabetic retinopathy Hematologic cancer Rheumatoid arthritis Crohns disease

Question 83

Describe antigen recognition by B cells in terms of: Interaction with Ag: Binding of soluble Ag? Involvement of MHC molecules? Chemical nature of antigens: Epitope properties:

Answer 83

Interaction with Ag involves binary complex of membrane Ig and Ag Binding of soluble Ag = YES Involvement of MHC molecules = NONE required Chemical nature of Ags = protein, polysaccharide, lipid Epitope properties = accessible, hydrophilic, mobile peptides containing sequential or nonsequential amino acids

Question 84

Describe antigen recognition by T cells in terms of: Interaction with Ag: Binding of soluble Ag? Involvement of MHC molecules? Chemical nature of antigens: Epitope properties:

Answer 84

Interaction with Ag: involves ternary complex of TCR, Ag, and MHC Binding of soluble Ag = NO Involvement of MHC molecules = required! Chemical nature of antigens = mostly proteins Epitope properties: internal linear peptides produced by processing of Ag and bound to MHC molecules