lecture 1: Innate And Adaptive Immunity Flashcards
Cells with adapted immunity increase ________ and _______ of response to antigen second exposure.
Rate and size
4 concepts of adaptive immunity
- Inducible
- Specificity
- Memory
- Self-tolerance (non-responsive to self)
What cells secrete antibodies?
B cell lymphocytes
Under what morphological conditions to antigens activate B cells?
When they have more than 1 identical epitope because the B cells are only activated when their antigen specific receptors are cross-linked by more than one epitope
True or false: antibody-antigen interactions are permanent
-False: they are reversible and follow the law of mass action
2 ways to increase the binding/effectiveness of an antibody for an antigen are…
- increase the affinity
2. Increase the valency of antibody
Does valency of an antibody have pertain more to avidity or affinity?
- Avidity: which is the sum total of antigen binding at all Ag binding sites
- Whereas affinity measures the strength of binding at single binding site
What flanks CDRs in the variable region of an antibody?
Framework regions: regions important for Ig fold structure that are less variable in sequence
Framework regions contain hypervariable regions called ______. How many are there and what do they do?
CDR: complementarity determining regions
- 3 of them
- make the contact with antigen
- loops
How do antibodies achieve their specificity?
-Occurs through unique combinations of heavy and light chain variable regions
What determines what isotype an antibody is?
-Heavy chain constant region
Which molecules (large or small) are eluted first in column chromatography?
-Larger molecules
Experiments have shown that antibody size changes with time of response. What is this relationship and why does this occur?
- Larger antibodies on day 7 and then smaller antibodies on day 21
- First Ab made is IgM and then switches to IgG
In what morphological state can IgA cross the epithelial barrier?
-As dimers (polymers)
Antibodies Fc region is important in initiating effector activities. What are the 4 chief effector activities?
- Opsonization
- Antibody-dependent cell-mediated cytotoxicity
- Complement
- Neutralization
Opsonization mechanism
- IgG subclasses bind to microbes
- Then recognized by FcR on phagocytes
- Signals from FcR promote phagocytosis of opsonized microbes and activate phagocytes to destroy microbe
Ab-dependent cell-mediated cytotoxicity mechanism
- Ab of certain IgG subclasses bind to cells
- Fc regions of bound Ab recognized by Fc(gamma)R on Natural Killer cells
- NK cells activated to kill antibody-coated cell
Mast cell degranulation
- Mast cells express FcER that binds IgE molecules
- Activated when allergen cross links the IgR bound to FcER
- Rapid release of chemical mediators
Chemical mediators released from mast cells upon allergen interactions cause what 3 responses?
- Increase vascular permeability
- Vasodilation
- Bronchial and visceral smooth muscle contractin
Classical pathway of complement activation:
- cascade of serum proteins which can be activated by Ab-Ag complexes
- Complement disposition marks them for destruction
- Accomplished by enzymatic activity that results in nonselective ion channels being drilled in cell surface
- Initiated by IgM or >2IgG
3 mechanisms of neutralization by antibodies
- prevent binding of microbes to cells and thus blocks the ability of microbes to infect host cell
- inhibit spread of microbes from an infected cell to an adjacent uninfected cells (viral infections)
- block binding of toxins to cells and thus inhibit the pathological effects of the toxins
Pepsin vs. Papain digestion of antibodies
Pepsin: end with 2 pieces; 1 bivalent Fab2’ and 1 Fc fragment
Papain: end with 3 pieces; 2 monovalent Ag-binding lacking avidity and 1 Fc’ fragment
IgM
primary response low affinity high avidity best at fixing complement -naive B cell antigen receptor and complement activation
IgG
secondary response
high affinity
crosses placenta circulation
-opsonization, complement activation, ADCC, neonatal immunity, feedback inhibition of B cells
IgA
mucosal immunity
dimer crosses epithelia
-neutralization
IgE
Defense against parasites
elevated in allergic reactions
mast cell degranulation
-defense against helminthis parasites, immediate hypersensitivity
IgD
co-expressed with IgM on naive B cell surface
unknown function
Plasma vs. Serum definitions.
- plasma is the soluble fraction of blood including clotting factors
- serum is the soluble fraction of blood without the clotting factors
What is an antibody and what is another name for it?
- soluble (mainly serum) proteins secreted by cells of the B cell lineage that bind to offending agents such as pathogens or toxins
- aka immunoglobulins (bc they are globular proteins
Antigen and antigenic-determinant definitions.
- Antigen: any foreign substance that induced a specific immune response
- antigenic determinant: the site(s) on an antigen that are physically bound by antibodies (aka epitope)
What do we call molecules with only 1 epitope?
-haptens
Begin with a cloudy test tube that is full of pre-existing Ab-Ag complexes. What would happen if you added excess antigenic determinants (haptens)? What does this tell us?
- causes the precipitates to dissolve
- shows that antibody-antigen interactions are reversible and therefore, follow the law of mass action
T/F: Both heavy and light chains have CDRs.
- true
- antibodies physically contact antigens via the CDR regions of the heavy and light chains
When referring the antibody isotypes, what is different?
- the heavy chain constant regions
- these different contant regions that make up these heavy chain isotypes elicit different types of effector activities
What is always the first antibody isotype produced in antibody responses?
-IgM
What antibody isotype is responsible for opsonization?
-IgG subclasses
What antibody isotype is responsible for antibody-dependent cell-mediated cytotoxicity? Why type of cell do they activate that carries out this function?
- IgG subclasses
- Natural killer cells
What 2 antibodies can trigger the classical pathway of complement activation?
- IgM or IgG on cell membrane of bacterium
- leads to formation of MAC complex
