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Immunology COM > Antibodies and Complement > Flashcards

Antibodies and Complement Flashcards

1
Q

Define the following: Isotype, Idiotype, Allotype

A

Isotype: Abs that differ by constant regions (ie, IgG, IgM, IgE, IgD)
Idiotype: Antibodies that differ by hypervariable region
Allotype: Abs that differ among individuals due to polymorphisms (more than two allels) in heavy and light chains

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2
Q

A simple “Y” shaped antibody is composed of two heavy chains and two light chains (named according to molecular weight) connected by disulfide bonds. Each chain is composed of variable and constant regions. What are the functions of these regions?

A

Variable regions of both heavy and light chains mediate antigen binding. The constant regions of the heavy chains serve effector functions binding to receptors on immune cells (eg, IgE can attach to mast cll receptors; IgG can attach to natural killer cells) and activating complement

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3
Q

What are hypervariable regions?

A

Three sequences of amino acids with profound variability located within the variable regions of both heavy and light chains. They are responsible for the specificity of abs

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4
Q

How many heavy chain constant domains (constituents of constant regions) are present on IgG, IgA, IgM and IgE?

A

IgG and IgA have three while IgM and IgE have four (all light chains have one constant domain)

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5
Q

What are the Fab and Fc fragments? Which one is at the amino terminus and which one is at the carboxyl terminus? What separates Fab and Fc fragments?

A

Fab fragment is part of an Ab that contains the Ag-binding sites located at the amino terminus. The Fc fragment, located at the carboxyl terminus, is composed of heavy-chain constant domains and serves effector functions. Fab and Fc are separated by the hinge region

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6
Q

What is the function of the hinge region of the immunoglobulin?

A

Allows flexibility within an antibody, resulting in a broader array of binding conformations

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7
Q

What does the identification of the presence of both the kappa and gamma light chains suggest about a sample of antibody?

A

The antibodies are not monoclonal. Abs have either kappa or gamma light chains, but never both. Thus, the presence of both implies that there must be at least two different types of Abs in the sample

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8
Q

What is the function of the J chain on IgA and IgM isotypes?

A

The J chain plays a critical role in the stabilization of the multimeric forms of IgA and IgM. In its absence, all isotypes would be monomeric.

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9
Q

Define the following:
Affinity
Valency
Avidity

A

Affinity: Binding strength at a single ab variable region and ag epitope
Valency: Number of sites at which an ab binds an ag
Avidity: Overall strength of an interaction between ab and ag, determined by both affinity and valency

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10
Q

What isotype has the highest avidity and why?

A

IgM because it has 10 binding sites (ie, valence of 10)

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11
Q

What isotypes of abs allow for B cells to achieve ag presentation?

A

The membrane-bound form of IgM and IgD (which only exists as a membrane bound form) functions to recognize and allow endocytosis of ags within the naive B cell, allowing them to subsequently be presented to T cells. This constitutes the recognition phase of humoral immune responses

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12
Q

How does the structure of IgM in its secreted form differ from its membrane bound form? What is the function of secreted IgM?

A

Membrane bound IgM is a monomer, but secreted IgM a pentamer. IgM is the main antibody in the primary response of humoral immunity

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13
Q

IgG is the main ab in the secondary response of humoral immunity though both IgG and and IgM can opsonize. How do they differ in this regard?

A

IgG can directly opsonize, while IgM acts indirectly through complement activation

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14
Q

Microbial pathogens entering the nasopharynx will most likely encounter which immunoglobulin isotype?

A

Dimeric IgA is concentrated in secretions (mucosa, tears, saliva, respiratory/intestinal/genital secretions) to neutralize microbial pathogens

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15
Q

What protects IgA from being digested by intestinal enzymes?

A

The secretory component synthesized by epithelial cells protects IgA from proteolysis

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16
Q

What two immune processes does IgE mediate?

A
  1. Type I hypersensitivity (allergy, anaphylaxis)

2. Helminth immunity

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17
Q

Antibodies are found associated with the surfaces of which types of cells?

A

B cells (IgM and IgD, recognition phase, are membrane-bound receptors). Antibodies bind to other receptors on the following cells: mononuclear phagocytes (IgG, opsonization), NK cells (IgG, antibody-depnedent cellular cytotoxicity), mast cells and basophils (IgE, anaphylaxis), and eosinophils (IgE, helminth immunity)

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18
Q

What Ab isotype is most abundant in serum?

A

IgG

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19
Q

What isotype is produced in the largest amount?

A

IgA. About two-thirds of all ab production is IgA, found in secretions over extensive surface area of the body

20
Q

Which Ig istotypes can initiate the classical complement cascade?

A

IgG and IgM both have Fc regions which are recognized by C1q–the first molecule in the complement cascade

21
Q

What is the most common immunoglobulin isotype found in fetal serum

A

Maternal IgG

22
Q

Why is IgG the only maternal isotype found in the fetus?

A

The Fc portion of the IgG molecule is recognized by a special type of Fc receptor in the placenta, thus facilitating its transfer

23
Q

Why is IgA the predominant isotype found in milk?

A

Due to specific Fc receptor-Fc region mediated transfer of IgA, facilitating secretion of IgA into breast milk

24
Q

What is the immunoglobulin isotype primarily produced by the fetus?

A

IgM but the fetus also produces very small amounts of IgG and IgA

25
Q

Define antibody-mediated cell cytotoxicity (ADCC). What two cells utilize ADCC? What isotypes are involved in each case?

A

Process by which Fc receptors on a cell bind Fc portion of Ag-bound Abs, resulting in activation of that cell

  1. NK cells via IgG lyse target cells
  2. Eiosinophils via IgE kill helminths
26
Q

An overwhelming proportion of a single clone of IgM antibodies in serum is suggestive of what disease?

A

Waldenstrom macroglobulinemia.
Because IgM is the largest immunoglobulin with the most binding sites, patients with advanced disease are likely to exhibit hyperviscosity syndrome, which can lead to irreversible blindness

27
Q

An overwhelming proportion of a single clone of IgG or IgA antibodies in serum is suggestive of what disease?

A

Multiple myeloma. Patients afflicted by this disease often exhibit puched-out lytic lesions within the bones, resulting in bone pain and hypercalcemia

28
Q

Name the three complement pathways and how they are activated:

A
  1. The classical complement pathways is activated when C1q binds to antigen-ab complexes consisting of IgG or IgM, or directly to the surface of certain pathogens or altered host cells
  2. The alternative pathway is activated when small amounts of C3b bind spontaneously to a microbial cell surface and then bind factor B.
  3. The lectin pathway is activated by mannose-binding lectin (MBL), which recognizes mannose residues on microbial cell surfaces. MBL then triggers other proteases.
29
Q

Why do free IgM or IgG not activate the complement cascade?

A

Binding of IgM/IgG to a microbial surface exposes the complement-binding regions

30
Q

How do IgM and IgG differ with respect to binding C1?

A

Only one IgM molecule is needed, whereas multiple IgG molecules are needed to bind C1q. Thus, IgM is more potent at activating complement

31
Q

C3 convertase cleases C3 to C3a (and C3b) in each complement pathway, but how does C3 convertase differ among pathways?

A

Classical and lectin pathways: C3 convertase is (C4b2a).

Alternative pathway: C3 convertase is (C3bBb)

32
Q

In the classical and lectin pathways what enzymes cleave C4 to C4b (and C4a) and C2 to C2a (and C2b)?

A

Classical: C1 (subunits C1q binds the Fc fragment, C1r and C1s are proteolytic)
Lectin: Proteases triggered by MBL

33
Q

In the alternative pathway a small amount of C3b is generated. Once C3b binds B (forming C3bB) on a microbial surface, what enzyme cleaves B?

A

Factor D cleaves B to Bb, converting C3bB to C3Bb (ie, C3 convertase)

34
Q

C5 convertase cleaves C5 to C5a (and C5b) in each complement pathway, but how does C5 convertase differ among pathways?

A

Classical and lectin: C5 convertase is C4b2a3b

Alternative: C5 convertase is C3BbC3b

35
Q

At which complement factor do all three complement pathways converge?

A

C5. Though C3 is present in all three complement cascades, it does not mark a convergence point

36
Q

What are the roles of the unbound protein fragments of the complement pathways, namely C3a, C4a, and C5a?

A

All three induce smooth muscle contraction and increase vascular permeability. C3a and C5a cause mast cell degranulation, leading to an anaphylaxis-like reaction. C5a also stimulates leukocyte chemotaxis and extravasation

37
Q

What is the role of late factors of the complement cascade, C5-C9

A

Responsible for generating the membrane attack complex (MAC), which forms pores into the microbe’s cell membrane. These pores disrupt the osmotic gradient maintained by the membrane, resulting in swelling and rupture of the microbe.

38
Q

What are the three effector mechanisms by which complement fights infection?

A
  1. C3b and its proteolytic derivates promote phagocytosis through opsonization
  2. MAC causes the osmotic lysis of the gram-negative microbes.
  3. C3a and C5a recruit leukocytes to areas of complement activation, thus secondarily stimulating various mechanisms of microbial immunity
39
Q

What is the most commonly identified complement deficiency?

A

C2 deficiency

40
Q

C1 inhibitor inhibits the classical pathway of complement activation, kallikrein of the kinin system, and some coagulation factors. What condition results from a deficiency of C1 inhibitor?

A

Heriditary angioedema is an autosomal dominant disease with edema in multiple organs, due to increased production of bradykinin. If the larynx is involved, the outcome can be fatal

41
Q

Severe pyogenic (Staphylococcus, streptococcus) respiratory and sinus tract infections result from a deficiency in what complement factor?

A

C3

42
Q

Deficiencies in the late factors of the complement cascade, C5-C9, result in susceptibility to what specific microbes?

A

The Neisseria species of bacteria (Neisseria meningitidis and Neisseria gonorrhoeae)

43
Q

What is the role of decay accelerating factor (DAF) in the complement cascade?

A

DAF inhibits formation of the alternative pathway C3 convertase by competing with factor B for binding to C3b and accelerates the decay of an existing C3 convertase by or displacing Bb from this enzyme

44
Q

What condition results from a deficiency of delay accelerating factor (DAF) due to increased complement mediated hemolysis?

A

Paroxymal nocturnal hemoglobinuria (PNH) is marked intermittent passing of dark hemoglobin-rich urine upon waking (reflects nightime pathology), which can lead to chronic anemia and venous thrombosis.

(lack of MAC regulation?)

45
Q

What is responsible for the specificity of the complement cascade to microbes and not host cells?

A

Regulatory proteins found on host cells but not microbes inhibit complement activation. Microbes lack the “off switch” for complement-mmediated lyss

46
Q

Name the two molecules that result in direct opsonization

A
  1. IgG

2. C3b

47
Q

Antibodies/immunoglobulins (Igs) are synthesized by B cells and perform what general functions?

A

Antibodies facilitate phagocytosis by opsonization and neutralize toxins and viruses

Immunology COM (11 decks)

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