COMPLEMENT SYSTEM & SECONDARY RESPONSE Flashcards by Jannine Mikaela

Responsible for the activation of Classical Pathway:

C1-C9

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Regulatory Proteins of Classical Pathway

1) C1 inhibitor (C1 INH),
2) C4 binding protein (C4bp)
3) Decay accelerating factor (DAF)
4) Complement receptor type 1 (CRI)
5) S protein
6) CD59
7) Homologous restriction factor (HRF)

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Activation of Alternative pathway is initiated when _____ is deposited on to the bacterial cell wall

C3b

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Causes rapid dissociation of C4b2a and C3b8b complexes

Decay accelerating factor (DAF)

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Alternative complement activation cascade

Factor B
Factor D
C3-C9

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Regulatory Proteins of Alternative Pathway

1) Properdin
2) Factor H
3) DAF
4) S-protein
5) CD59
6) HRF

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Regulatory protein, tightly controls the activity of C1 complex

C1 inhibitor (C1 INH)

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T/F:
Activation of C1 can occur spontaneously

FALSE. It cannot

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Inactivates C4b and C3b

Factor 1 + cofactor dierent proteins

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Regulation of complement is mediated by:

membrane bound and soluble proteins

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Dissociation of C3 convertase in the alternative pathway

Factor H

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Dissociation of C3 convertase in the classical pathway

C4bp

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Regulate the terminal pathway of complement and prevents the formation of MAC on the surface of autologous cells

CD59. HRF. S-protein (vitronectin)

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Inhibits the insertion of the C567 component of MAC

S- protein

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Chemoattractant for the chemotaxis of neutrophils

C5a

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May be deposited on the surface of immune complexes, serve as somrius for elimination

C3b or C3b fragment

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Serves as opsonin

C3b

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Hereditary angioneurotic edema (HANE) is caused by deficiency in:

C1 INH

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Pyogenic infections with encapsulated bacteria is caused by deficiency in:

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Bind to receptors on basophils causing degranulation and release ofinammatory mediators (histamine)

C3a, C4a, and C5a

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Immune complex disorders is caused by deficiency in:

C2 and C4

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Recurrent infections with Neisseria spp is caused by deficiency in:

C5,6,7,8,9

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Paroxysmal nocturnal hemoglobinuria is caused by deficiency in:

GPI Linkages (DAF CD59)

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Measurement of overall complement activity of the classical pathway

CH50

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Identify the Measurement of Complement Components: Light scatter as a result of contact with non-soluble particle is measure

Nephelometry

Measurement of overall complement activity of the alternative pathway

AH50

Expressed on the cell surface with heterodimers CD79a/CD79b

B cell receptors

Recognize and interact with antigens that will induce differerentiation to plasma cells. Recognize and interact through B cell receptor

B cells or B lymphocytes

Measurement of Complement Components

1) Radial Immunodiffusion 2) Nephelometry 3) Rate Nephelometry

Identify the Measurement of Complement Components: Precipitation of immune complexes in agar gels Serum proteins are added to wells cut into antibody containing agar gels

Radial Immunodiffusion

Identify the Measurement of Complement Components: Several measurements are made in succession

Rate Nephelometry

The sole purpose is to recognize and interact with antigens in a manner that will induce theirdierentiation to antibody secreting plasma cells

B cell receptors

Refers to the progressive expression of cell surface proteins on a cell until the cellmatures to the point that it can participate in host defense

B cell maturation

Some of the activated B cells will become _________ whose role will be **immunosurveillance**, but most of them will differentiate to plasma cells (live for only a few days and then die)

memory cells

One of the most significant steps in the maturation process is the expression of a?

B cell receptor (with unique variable regions in the light chain and heavy chain)

Both light chains of a receptor express the same variable region, as do both the heavy chains; however, the __________ in the light and heavy chains differ from one another

variable regions

Synonymous terms for B cell receptors and are used interchangeably

membrane bound antibody and membrane immunoglobulin

This is characterized by the de novo appearance of particular cell surface proteins and changes in the function of the developing cell.

B cell maturation

Expressed on pre-B and B cells, functions as an ion channel

CD20

During B cell maturation, there will be expression of unique B cell receptor which is the?

Monomeric IgM

ne of the molecules expressed during development CD19, continues to be expressed on the mature B cell and so is referred to as a

panmarker

Regulates B cell development, activation, and differentiation

CD19

Construction of unique regions as a result of random selection of gene segments for  rearrangement

Somatic recombination

Capable of autoimmune disorders

Autoreactive receptors

Occur in the bone marrow during the immature B cell stage of development.

The crucial step of deletion B cell clone

In heavy chain synthesis, Somatic recombination is activated by?

Allelic exclusion

Steps in heavy chain synthesis

1. Construction of variable region gene 2. rearrangement 3. formation of heavy chain encoding for IgM 4. expression on the B cell surface

Order of chain synthesis

Heavy chain is always **synthesized first** before the light chain

This is constructed by randomly selecting one “V” segment, one “D” segment, and one “J” segment

Variable region gene

The first antibody isotype to be expressed on a developing B cell surface is?

IgM, in its monomeric form

Similar to heavy chain synthesis, no D segment, V and J segment only randomly selected

Light chain recombination

Adjacent to the light chain constant region, transcription and translation of the protein

Light chain gene expression

Light and heavy chains associate to form intact ___________ transported to the surface

monomeric IgM molecule

Successful construction of a variable region gene generates signals to stop rearrangement on the other allele

Allelic exclusion

Random selection of V, (D), and J segments can create self-reactive BCRs that need deletion or inactivation

Tolerance induction

Occurs in the later part of B cell maturation, results in expression of IgM and IgD on the cell surface

Alternative splicing

Identify: mRNA will encode either μ constant region or δ constant region, but not both

Mechanism of IgM and IgD expression

Considered mature but naive, leaves the bone marrow and seeds peripheral tissues

B cell

Some mature B cells circulate in?

Immunosurveillance

Signals generated by interaction of cytokines lead to?

clonal expansion of naive B cells

_________ bind antigen to form a complex that is internalized by invagination of the plasma membrane such that the complex is enclosed within a special cytosolic vacuole (_______).

B cell receptors; endosome

Its initial encounter of a protein antigen and its subsequent activation occurs in a secondary lymphoid tissue

naive B cell

A different vacuole originating from the _____, and containing major histocompatibility complex (MHC) proteins (Class II), fuses with the endosome vacuole to form one large vacuole, where degraded antigen fragments bind MHC proteins.

golgi

Present in the cytoplasm, fuse with the endosome releasing enzymes that degrade the antigen into fragments/peptides.

Lysosomes

This large vacuole migrates to, and fuses with, the plasma membrane, resulting in the expression of the __________ on the B cell surface.

antigen fragment- MHC complex

Also known as somatic mutation

Affinity maturation

Differentiation to plasma cells that secrete IgM

Outcome of clonal expansion

The cell surface expression of antigenic fragment/MHC complex is Activated B cells that have received appropriate signals from ____ that undergo proliferation in the follicle of secondary lymphoid tissues, resulting in the formation of germinal centers

T cells

Proliferation leads to the generation of a B cell clone, a process referred to as?

Clonal expansion

Switching to a different isotype, a process referred to as isotype switching

Outcome of clonal expansion

One of the outcomes of Clonal expansion is differentiation to plasma cells that secrete the new isotype. If the switch was made to the y constant region, the B cell will differentiate to an?

IgG secreting plasma cell

Undergoing affnity maturation

Outcome of clonal expansion