Lecture 3 - Antigens

Question 1

What is the fn of the immune system?

Answer 1

to protect the body against invading organisms

Question 2

What is an antigen?

Answer 2

any substance that can induce antibody generation (induce specific immune responses - can be bound by B or T cell receptors)
-also called immunogens

Question 3

What do B cell receptors (Ab) recognize?

Answer 3

peptides sugars, lipids, nucleic acids and hormones

Question 4

What do T cell receptors recognize?

Answer 4

only peptides that have been processed or degraded

-gamma/delta T cells recognize lipids directly on pathogen surface

Question 5

what is an allergen?

Answer 5

antigen that induces an allergic reaction/immune response

Question 6

What are epitopes?

Answer 6

smaller portions of large molecules that have the structure bound by the Ab or T cell receptor
-also called an antigenic determinant

Question 7

Can an Ag contain more than one epitope?

Answer 7

each Ag contains many epitopes individually able to bound by Ab or T cell receptors

Question 8

What is multivalency?

Answer 8

when epitopes are repeated several times on a macromolecule

Question 9

How do antigenic-specific cells (B and T cells) recognize epitopes?

Answer 9

B cells have receptors (Ab) that can bind directly to the native Ag

• T cells require presentation of the epitope by an MHC molecule
• different lymphocytes/receptors can recognize different epitopes on the same Ag

Question 10

What influence does spatial arrangement of epitopes on a single Ag have?

Answer 10

it affects how Abs can bind to the macromolecule

-ususally Ab epitopes are limited to those accessible to the Ab, and crowding can exclude access of Ab to all epitopes

Question 11

How are antigenic determinants (epitopes) limited?

Answer 11

limited to those portions of the Ag that can bind to MHC molecules –> differences in the responses of different individuals

Question 12

What if there is no MHC mol to present a particular epitope?

Answer 12

can’t generate Abs for that epitope

Question 13

What are haptens?

Answer 13

small molecules that are not normally immunogenic but become antigens when linked to another structure (carrier) –> linkage forms a new epitope which is now big enough to be bound by Ab or T cell receptors

Question 14

What are common results of haptens?

Answer 14

drug allergies –> common due to the tendency for them to bind larger proteins

Question 15

Give examples of haptens?

Answer 15

• penicillin –> binds to albumin

- urushiol –> toxic agent of poison ivy (converted to a reactive cmpd which reacts with skin proteins)

Question 16

What are blood group Ags?

Answer 16

• A-type blood contains an A-type enzyme
• B-type blood contains a B-type enzyme
• AB-type blood contain both enzymes
• O-type blood lack both types of enzymes

Question 17

What types of Ab do haptens generate?

Answer 17

1) against the carrier
2) against the hapten
3) against the new epitope generated by the hapten-carrier linkage
- normally don’t generate Abs against carrier (own RBCs)

Question 18

What are T independent Ag?

Answer 18

Ags that are immunogenic enough that T cells are not required to activate B cells for Ab production

• usually very complex molecules
• have repeating epitopes (multivalent)
• cross-link B cell receptors (Abs) on the surface of a B cell
• stable in vivo

Question 19

When can these T ind. Ags occur?

Answer 19

early in an immune response and assist in host clearance of certain pathogens
-B cells bind enough epitopes to Abs to activate

Question 20

What makes a good Ag (generate a strong Ab response)?

Answer 20

• size (large)
• Complex (last long enough so immune response can be generated)
• intermediate stability (not too stable so T cells can’t break down)
• Foreign enough
• more different immunogen is from recipient –> stronger the immune response

Question 21

Rate macromolecules on how good antigens they would be (proteins, simple polysacch, complex carb,, nucleic acids, lipids)

Answer 21

• Proteins - excellent Ags if greater than 1000Da
• Simple Polysaccharides - poor Ags (readily degraded in cells)
• Complex carb - usually good Ags (esp if bound to proteins)
• Nucleic acids - usually poor Ags (unless bound to proteins)
• Lipids - usually poor Ags (unless linked to proteins)

Question 22

What influences immunogenicity?

Answer 22

Host factors and environmental factors

Question 23

What host factors affect immunogenicity?

Answer 23

Genetics - genes that encode the specific antigen receptors can vary btw individuals
-MHC, T cell receptors, Abs
Age - specific immunity in particular is deficient in neonates and in senescent individuals

Question 24

What environmental factors affect immunogenicity?

Answer 24

dose, route of exposure, adjuvants (recognition factors)

• increased: large, intermediate dose, complex, particular, denatured, multiple diffs, slow release, bacteria, effective interaction with host MHC
• decreased: small, high or low dose, simple, soluble, native, few diffs, rapid release, no bacteria, ineffective interaction with host MHC

Question 25

What is cross-reactivity?

Answer 25

process by which one epitope is similar enough to trigger a response against another epitope, even on very different molecules --> specific immunity against apparently unrelated Ags

Question 26

Give an example of cross-reactivity

Answer 26

blood antigens - bacteria contain glycoproteins with carb sidechains similar to those found on RBCs

Question 27

Describe different situations of Ag exposure

Answer 27

- Ags encountered in tissues are taken up by dendritic cells (and macrophages) tehn moved to draining lymph nodes --> elicit IgG isotype Abs - Ag encountered on mucosal surfaces are generally taken up through specialized M cells or via dendritic cells that extend through the epithelial lining --> elicit IgA and IgE isotype Abs - diff Abs elicit diff immune responses

Question 28

What is Ag processing?

Answer 28

degradation of proteins into peptides that can bind MHC molecules for presentation to T cells

Question 29

What is Ag presentation?

Answer 29

display of Ags as peptide fragments bound to MHC molecules on surface of a cell

Question 30

How are diff cell origins presented?

Answer 30

- exogenous Ags (outside cell) --> MHC class II mols | - endogenous Ags (inside cell) --> MHC class I mols

Question 31

What are Antigen-presenting Cells?

Answer 31

highly specialized cells that can display processed Ag as peptide fragments on cell surface

Question 32

What does Ag processing involve?

Answer 32

uses surface mols encoded by Major Histocompatibility Complex

Question 33

What determines the pathway for Ag break down?

Answer 33

which class of MHC mols used which depends on origin of Ag - Ags in cytosol --> MHC class I (contact cytoplasm) - Ags from outside cell --> MHC class II (separate from cytoplasm)

Question 34

What are autoantigens?

Answer 34

self antigens -normally ability for immune system to recognize self proteins is blocked. If errors occur, Abs and reactive T cells canb e generated against them

Question 35

Give examples of autoantigens

Answer 35

mitochondria, sperm, nucleic acids | -usually requires a host genetic predisposition for disease

Question 36

How can pathogens induce autoimmunity?

Answer 36

molecular mimicry | -infection with particular pathogens is associated with immune response against self epitopes

Question 37

What is molecular mimicry?

Answer 37

when some pathogens express proteins or carb residues that resemble host mols

Question 38

What does mol mimicry result in?

Answer 38

``` activation of T cells that also recognize host cell proteins presented by normal, homeostatic MHC class I mols -sequestered self Ags may be released following damage by pathogens --> exposes them to adaptive immune cells ```

Question 39

Name some types of Ag associated with pathogens or infections

Answer 39

H antigens - flagellum F antigens - pili K antigens - capsule O antigens - cell wall

Question 40

What are tumor antigens

Answer 40

self antigens used to identify tumors (not expressed often) - presented on surface of tumor cells by MHC class I and II mols - not found on normal cells

Question 41

What are superantigens?

Answer 41

- usually secreted exotoxins that are highly mitogenic and stimulatory for T cells - don't require prior processing in order to bind to T cell receptor - most work by cross-linking MHC and TCR to overstimulate T cells and drive hyperinflammation - T cell thinks there's an epitope and creates an immune response

Question 42

What's the difference btw innate and adaptive?

Answer 42

innate system recognizes many chemical structures or signatures without first processing a larger mol - determinants recognized by innate immmune system differ from those recognized by adaptive immune system - Abs, B/T cell receptors recognize discrete determinants and demonstrate high degree of specificity - innate immune system recognize broad molecular patterns found in pathogens but NOT in host --> lack a high degree of specificity --> sometimes called Pathogen Associated Molecular Patterns (NOT antigens)