Antibodies & Complement (humoral) System Flashcards
What is the difference between humoral (antibody-mediated) and cell-mediated immune system?
Humoral immune system control of freely circulating EXTRACELLULAR pathogens, while cell-mediated immune system control of INTRACELLULAR pathogens.
Humoral: B cells
Cell-mediated: T cells
Antibodies and complement are part of the humoral immune system, which can be transferred by _______.
plasma
Which statements are true or false?
- Antibodies are present 7-10 days after infection.
- The humoral immune response is dominating compared to cell-mediate immune response.
Both are true!
1) What are antibodies?
2) What is an antigen?
3) What synthesizes antibodies? What are their two forms?
1) circulating proteins that are produced in response to exposure to foreign structures (antigens).
2) any substance that may be bound by a B cell or a T cell receptor
3) Antibodies are synthesized only by B cells and they exist in two forms: MEMBRANE-BOUND antibodies on the surface of B cells and SECRETED antibodies
T cells recognize _________, while antibodies recognize _______.
Both are very ________.
Antigen recognition is mediated by the _______ regions in both receptors.
peptides; anything!
diverse
variable
1) What are the same basic characteristics shared by all antibody molecules?
2) Where do they display remarkable variability?
1) An antibody molecule has a SYMMETRIC CORE structure composed of TWO identical LIGHT chains and TWO identical heavy chains.
2) They display remarkable variability in the regions that bind antigens.
Mark these statements as true or false:
1) Fab (fragment, antigen binding) is important for antigen recognition, while Fc (fragment, crystallizable) is important for effector function.
2) Membrane and secreted associated antibodies differ in the amino acid sequence of the amino terminal end of the heavy chain C region.
3) Antigens are also called gamma or immunoglobulin.
4) B-cell activation converts membrane IgM to secreted IgG.
1) True!
2) False. Membrane and secreted associated antibodies differ in the amino acid sequence of the CARBOXYL-terminal end of the heavy chain C region.
- False. ANTIBODIES are also called gamma or immunoglobulin.
- True!
An immunoglobin (Ig) domain contains two layers of __________, like two pieces of bread (B sandwich), with each layer composed of three to five strands of _________ polypeptide chain.
The two layers are covalently linked by a _______ ____ between cysteines and adjacent strands of each sheet are connected by ______ ______.
B-pleated sheet; anti-parallel
Disulfide bridge; short loops
(T/F) The amino acids in the disulfide bridge of an immunoglobin are the most variable and critical for antigen recognition.
False!
The amino acids in the short loops aka COMPLEMENTARITY DETERMINING REGION (CDR) loops that connect the adjacent strands of each b-sheet are the most variable and critical for antigen recognition.
(T/F) All proteins that contain domains with an Ig fold structure belong in the Ig superfamily.
True!
What is the difference between the variable and constant domains of an immunoglobin?
Variable domain is LARGER and contains EXTRA B-strands, called C’ and C’’.
The flexible loops formed between some of the B strands in the variable region contribute to the antigen-binding site.
1) Both heavy and light chains consist of amino-terminal _________ regions that participate in antigen recognition and carboxy- terminal ______ regions that mediate effector functions.
2) In the heavy chains, the V is composed of ____ Ig domain(s), while the C is composed of _____ Ig domain(s).
3) Each light chain is composed of _____ V region Ig domain and ____ C region Ig domain.
4) The V region of one heavy chain and the adjoining V region of one light chain form an _______________ ____.
1) Variable; Constant
2) One; Three/Four
3) One; One
4) Antigen-binding site
Why does an antibody molecule have at least TWO antigen-binding sites?
Because the core structural unit of each antibody molecule contains two heavy chains and two light chains.
*the variable region of one heavy and one light chain makes one antigen binding site
IgG cleaved by proteolytic enzymes generate fragments with distinct structural and functional properties.
What is the difference between the enzymes PAPAIN and PEPSIN?
Enzyme PAPAIN acts on the hinge region and cleaves the IgG into three separate pieces; 2 Fab and 1 Fc.
Enzyme PEPSIN acts on distal to the hinge region and generates a F(ab)’2 fragment of IgG with the hinge and the interchain disulfide bonds and two antigen-binding sites identical to the intact antibody, but without inducing the effector functions.
*antigen recognition functions and effector functions are spatially separated.
Where can we find the most of the sequence differences and variability among different antibodies?
In the hypervariable regions or complementarity-determining regions (CDR1, 2, & 3).
The three protruding loops connecting the adjacent strands of the b-sheets that make up the VARIABLE domains of Ig HEAVY and LIGHT chain proteins.
*2 variable light domains
*2 variable heavy domains
*each domain has its three CDRs; total of 12 CDRs
(T/F) In a complete antibody molecule, the pairing of a heavy chain and a light chain brings together the hypervariable loops from each chain to create a single hypervariable surface, which forms the antigen-binding site at the tip of each arm.
True!
*three fingers from the variable heavy chain and three fingers from the variable light chain in ONE antigen-binding site
What does confinement of the sequence variability to three short stretches allow?
Allows the basic structure of all antibodies to be maintained despite the variability of specificities among different antibodies.
Antibodies bind antigens via contacts in CDRS that are complementary to the ______ and _____ of the antigen.
What are the four different surfaces found on antibodies?
size; shape
1) pocket
2) groove
3) extended surface
4) protruding surface
Which kinds of forces hold together the antigen:antibody complex?
Noncovalent forces!
- electrostatic
- hydrogen bonds
- van der waals
- hydrophobic
- cation-pi
What is an epitope?
What are the two different types? Briefly describe each.
An epitope is any available shape or surface on a molecule that may be recognized by an antibody.
1) Discontinuous epitopes (conformational determinant): antibodies recognizes certain confirmations; if antigens denatures, no longer recognizable.
2) Linear epitopes (linear determinant): antibody can bind to determinant in both naive and denature protein OR antibody binds to denatured protein ONLY (neo-epitope).
Antibody molecules can be divided into distinct classes and subclasses on the basis of differences in the structure of … ?
HEAVY chain CONSTANT regions
- their constant regions are critical for antibody functions
- different isotypes and subtypes of antibodies perform different effector functions
Antibody molecules are flexible, permitting them to bind to different arrays of antigens.
What are the two angles found between the arms of antibodies?
60˚ (closely spaced cell surface determinants) and 90˚(widely spaced cell surface determinants)
What is the difference between the affinity and the avidity of an antibody?
Affinity: the strength of binding between a single combining site of an antibody and an epitope of an antigen
Avidity: the overall strength of attachment (low in monovalent, high in bivalent, and very high in polyvalent)
*avidity is much greater than the affinity of any one antigen-binding site
What are the three valency of interactions?
- Monovalent: one antibody binds to one antigen
- Bivalent: one antibody binds to two antigens
- Polyvalent: one antibody binds to more than 2 antigens