L3: Antigens and Antibodies Flashcards
List and describe the features on the adaptive immune system in our bodies
- ) Specificity: specificity of each lymphocyte against one epitope
- ) Immunologic memory: faster and more vigorous response upon re-exposure to antigen as a result of memory cells, which has more sensitivity to antigen
- ) Diversity: numerous pre-existing antigen-specific lymphocytes
- ) Self-regulation: removal of antigen should mean no further immunologic stimulation, activated lymphocytes die, regulation
- ) Discrimination of self v non-self: adaptive responses only against foreign antigens, not self as self-specific immune cells are destroyed or regulated
What is immunogenicity?
- properties that promote immune responses
- adjuvants cause increased immunogenicity
What is antigenicity?
- properties that allow a substance to react with an antibody
What are haptens?
- small molecules that cannot induce antibody formation by themselves, they require carrier molecule to induce antibodies
- eg. Penicillin:albumin = antibody response
Important features of immunogen
- Size: >10000 MW
- Internal complexity: more complex, more immunogenic
- Degradability
- Foreigness
- Accessibility
Different types of antigen conformations seen by antibody
- ) Conformational determinants: only native conformation recognized, not denatured
- ) Linear determinants: recognized in both native and linear form (from denaturation or processing)
- ) Neoantigenic determinants: determinant not present in native form, requires proteolysis
What types of determinants/antigen conformations will T cells only recognize?
- Only linear determinants, resulting from processing
Of all the types of antigens (protein, lipoprotein, etc.) available, what is the most immunogenic?
- Protein
What immunoglobulins are expressed on naïve B cells?
- IgM and IgD
What immunoglobulins to mast cells and basophils have Fc receptors for?
- They have Fc-epsilon receptors for IgE
Difference between monoclonal and polyclonal antiserum?
- Polyclonal = abs that bind to more than one particular antigen
- Monoclonal = abs that bind to one specific antigen
What does antibody titer refer to?
- 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
In what fraction of serum proteins are most antibodies found?
- Gamma fraction
Describe structure of antibody
- 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
What is a J-chain?
- J-chains are found in secretory forms if IgM and IgA and allow formation of pentamers of IgM or dimers/trimers of IgA
What does papain and pepsin digestion of antibody result in?
- Pepsin: single fragment of arms bound together (Fab2) + no surviving Fc fragment
- Papain: two arm fragments (Fab’s) + one Fc fragment
Classification of antibodies isotypes. Describe, list function
- ) 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
- ) IgM: exists in pentamer with J-chain, best activator of complement, predominates in primary immune response
- ) 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)
- ) 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
- ) 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
Which antibody isotype is the best activator of complement?
- IgM
What is the main antibody isotype in a primary immune response? Secondary?
- Primary: IgM
- Secondary: IgG
Avidity vs affinity
- 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)
Which antibody isotype has greater affinity? Avidity?
- IgG has greater affinity
- IgM has greater avidity due to pentameric form it primarily exists in
What is allotype? Idiotype?
- 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
