L3: Antigens and Antibodies

Question 1

List and describe the features on the adaptive immune system in our bodies

Answer 1

1. ) Specificity: specificity of each lymphocyte against one epitope
2. ) Immunologic memory: faster and more vigorous response upon re-exposure to antigen as a result of memory cells, which has more sensitivity to antigen
3. ) Diversity: numerous pre-existing antigen-specific lymphocytes
4. ) Self-regulation: removal of antigen should mean no further immunologic stimulation, activated lymphocytes die, regulation
5. ) Discrimination of self v non-self: adaptive responses only against foreign antigens, not self as self-specific immune cells are destroyed or regulated

Question 2

What is immunogenicity?

Answer 2

• properties that promote immune responses

- adjuvants cause increased immunogenicity

Question 3

What is antigenicity?

Answer 3

• properties that allow a substance to react with an antibody

Question 4

What are haptens?

Answer 4

• small molecules that cannot induce antibody formation by themselves, they require carrier molecule to induce antibodies
• eg. Penicillin:albumin = antibody response

Question 5

Important features of immunogen

Answer 5

• Size: >10000 MW
• Internal complexity: more complex, more immunogenic
• Degradability
• Foreigness
• Accessibility

Question 6

Different types of antigen conformations seen by antibody

Answer 6

1. ) Conformational determinants: only native conformation recognized, not denatured
2. ) Linear determinants: recognized in both native and linear form (from denaturation or processing)
3. ) Neoantigenic determinants: determinant not present in native form, requires proteolysis

Question 7

What types of determinants/antigen conformations will T cells only recognize?

Answer 7

• Only linear determinants, resulting from processing

Question 8

Of all the types of antigens (protein, lipoprotein, etc.) available, what is the most immunogenic?

Answer 8

• Protein

Question 9

What immunoglobulins are expressed on naïve B cells?

Answer 9

• IgM and IgD

Question 10

What immunoglobulins to mast cells and basophils have Fc receptors for?

Answer 10

• They have Fc-epsilon receptors for IgE

Question 11

Difference between monoclonal and polyclonal antiserum?

Answer 11

• Polyclonal = abs that bind to more than one particular antigen
• Monoclonal = abs that bind to one specific antigen

Question 12

What does antibody titer refer to?

Answer 12

• Reciprocal of last dilution of antiserum that still yields a demonstrable antibody binding reaction.
• Example: if reactions seen in 1:8, 1:16, 1:32 and 1:64, but not in 1:128, then titer is 64. The higher this number, the larger the concentration of antibody to a specific antigen is present

Question 13

In what fraction of serum proteins are most antibodies found?

Answer 13

• Gamma fraction

Question 14

Describe structure of antibody

Answer 14

• 2 identical heavy and 2 identical light chains
• Heavy chains connected by disulfide bonds
• Light chains connected to heavy chains by disulide bonds
• Each of the chains consists of constant (C) and variable (V) regions. Variable regions subdivided into hypervariable (fingertips) and framework (fingers) regions
• Antigen binding site = VL and VH seen on both arms
• G, A and D Igs have hinge regions, which provide flexibility to antibody arms
• Except for D Igs, have secretory and membrane form

Question 15

What is a J-chain?

Answer 15

• J-chains are found in secretory forms if IgM and IgA and allow formation of pentamers of IgM or dimers/trimers of IgA

Question 16

What does papain and pepsin digestion of antibody result in?

Answer 16

• Pepsin: single fragment of arms bound together (Fab2) + no surviving Fc fragment
• Papain: two arm fragments (Fab’s) + one Fc fragment

Question 17

Classification of antibodies isotypes. Describe, list function

Answer 17

1. ) IgG: has sub-classes 1-4, most abundant, activates complement, 1 and 3 can opsonize using Fc-gamma receptor on phagocytes, coats tumor or virally-infected cells for ADCC facilitation with NK cells, crosses placenta, in mother’s milk, predominates in secondary immune response
2. ) IgM: exists in pentamer with J-chain, best activator of complement, predominates in primary immune response
3. ) IgA: has sub-classes 1-2, exists in dimer/trimer with J-chain in secretions but monomeric in secretions (when secreted, coupled to secretory piece to protect from proteolytic enzymes), mediator of mucosal immunity, present in tears/saliva/colostrum and milk, participates in eosinophil-mediated ADCC of certain parasitic infections (worms)
4. ) IgD: always membrane bound, primarily on naïve B cells, important in transduction of signals across plasma membrane to result in antigen-driven B cell activation
5. ) IgE: participates in eosinophil-mediated ADCC of certain parasitic infections (worms), binds to Fc-epsilon receptors on basophils and mast cells to mediate allergies and anaphylaxis

Question 18

Which antibody isotype is the best activator of complement?

Answer 18

• IgM

Question 19

What is the main antibody isotype in a primary immune response? Secondary?

Answer 19

• Primary: IgM

- Secondary: IgG

Question 20

Avidity vs affinity

Answer 20

• Avidity: overall strength of antibody attachment taking into account how many antigen combining sites antibody has bound
• Affinity: strength of binding for antigen of one antigen combining site (on arm)

Question 21

Which antibody isotype has greater affinity? Avidity?

Answer 21

• IgG has greater affinity

- IgM has greater avidity due to pentameric form it primarily exists in

Question 22

What is allotype? Idiotype?

Answer 22

• Allotype: differences in constant region of antibodies of the same isotype
• Idiotype: collection of hypervariable regions contributed by H and L chains that form the antigen-binding site