2 Hour Surprise Complement Lecture Flashcards
Immunization
Ag stimulus that stimulus specific adaptive immune response that can be recalled during subsequent infections
Passive - Ab/antiserum only
Active - intro Ag that induces adaptive immune response
Herd immunity
Immunity acquired when a critical number of individuals in a population are vaccinated
Considerations for immunization schedule
Timing of exposure
Immunological maturity of child
Passively transferred Ab that may interfere with immune response of vaccine
Interference
Passively transferred maternal IgG is completely degraded
At 9 months of age
Criteria for effective vaccine (only indicated item)
Must induce protective T cells
Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses
Also need T cells to activate B cells for Ab production
Inactivated vaccines contain
Killed/ inactivated viruses
Subunits or components
Toxoid
Conjugated Ag
Adjuvants
Increase vaccine efficacy
Bacterial components or media that prolongs exposure or induces mild inflammation to attract phagocytes (increases chance that Ag will be picked up and presented)
Conjugate vaccines
Capsular polysaccharides from pathogenic bacteria elicit a t independent response
Must conjugate the vaccines by linking to a polysaccharide to Ag or toxoid to form an immunogen (t-dependent Ag)
HiB vaccine
Immunological tolerance
Unresponsiveness of adaptive immune system to Ag as a result of inactivation or death of Ag-specific lymphocytes, induced by exposure to the Ag
Factors that promote immune tolerance
Soluble, aggregate free, simple small molecules Improper processing Oral/IV presentation Age (too young or too old) Dose (too large or small)
Characteristics that promote adaptive immune response
Large, aggregated complex molecules Proper processing Subcutaneous or IM exposure Intermediate dose not young af or old af
Functions of complement
Triggering, amplification of inflammation Attraction of phagocytes by chemotaxis Clearance of immune complexes Cellular activation Direct microbial killing Development of humoral response
Classical pathway is activated by
Ab-Ag complex stimulates C1 binding
Either IgG or IgM (must bind multiple globular domains of C1q in order to activate)
Alternative pathway activated by
Spontaneous lysis of C3
Lectin pathway initiated by
MBL binding lectin and recruiting MASP1 + MASP2
C1qrs can be inhibited by
C1 inhibitor
Binds C1r and C1s to prevent cleave of C4 and C2
C3 convertase classical pathway consists of
C4b2a
C5 convertase classical pathway consists of
C4b2a3b
Inserts into membrane and forms small pore
C4b67
Recruits 10-16 copies of C9
C8
Host cells protect themselves from spontaneous lysis of C3 by expressing high levels of what on their cell surface
Sialic acid
Factor D
Cleaves factor B –> Bb and Ba
Binds C3bBb and C3bBb3b and prevents increases half-life
Properdin
Alternative C3 convertase
C3bBb
Alternative C5 convertase
C3bBb3b
Binds N-acetylglucosamine on bacterial cell wall to induce autocleavage of MASP1 and MASP2
Ficolin
Deficiency resulting in: High degree of SLE from failure to clear circulatory immune complexes - deposits on endothelial cells and activates alternative complement, local inflammation
C2 deficiency
Deficiencies in Factor H and Factor I mimic
C3 deficiencies - unregulated C3b generation exhausts C3 from serum
Deficiency results in increased susceptibility to Neisseria gonorrhoeae and N. meningitidis
MAC deficiencies (C5-C9)
Factor I
Cleaves C3b and C4b
Cofactors: Factor H, MCP, C4BP, CR1
SERINE PROTEASE
Factor H
Binds C3b and displaces Bb
Also serves as a cofactor for Factor I cleavage of C3b
C4BP
C4 binding protein - binds C3b and displaces C2
Cofactor for Factor I cleavage of C4b
DAF functions in a similar capacity as what two RCAs?
Factor H (alternative pathway) C4BP (classical pathway)
MCP
Also known as CD46
Cofactor for Factor I cleavage of C3b and C4b
DAF
Displaces C2b from C4b (classical)
Displaces Bb from C3b (alternative)
Aka inactivates the C3 convertases
CD59
Blocks C9 binding and prevents formation of MAC
Vibronectin
S protein - prevents C5b67 from penetrating (heh) membrane
Hereditary Angioneurotic Edema
C1 inhibitor deficiency
Swelling attacks from physical trauma/emotional stress
Affects extremities, face, GI tract
Treat with androgens (increase transcription of C1 inhibitors)
Paroxysmal nocturnal hemoglobinuria
Deficient DAF
Hemolytic disorder with spontaneous episodes of RBC lysis, leukocytes, platelets sensitive to complement
Treat with EPO
Type III Hypersensitivity
Little Ab and excess Ag will lead to small immune complexes that are not cleared from circulation because they do not fix complement –> local inflammation –> basophils degranulation, platelet aggregation –> increase vascular permeability –> complex deposition –> attract neutrophils who further mess it up
==> increased Bp and vascular turbulence
Biological functions of complement
Opsonization (C3b, and a little C4b) Waste management (C3b binds CR1 of RBCs to transport Immune complexes to spleen/liver) Cell lysis (mac) Inflammatory mediators (anaphylatoxins C3a, C5a, C5b67)
Prokinin
Also known as C2b - cleaved by plasmin to yield kinin –> edema
Epstein Barr virus abuses complement to gain entry into cells by
Using CR2 as a receptor for attachment
Measles utilizes the complement system to infect cells by
Using MCP (CD46) as a receptor
West Nile hijacks complement machinery by
Coating viral particles in C3b to gain entry into cells by CR3
Neisseria meningitidis escapes complement degradation by
Expressing protein on its cell surface that block the formation of convertases
CH50 assay tests for
Test ability of patients blood to perform Complement mediated hemolysis
Classical deficiency
Increases risk of developing immune complex diseases like SLE
MBL deficiency
Increases risk of infection by yeast sacchromyces cerevisiae and encapsulated bacteria
Alternative pathway deficiency
Decreases opsonization activity and increases risk of infection by encapsulated bacteria
C3 deficiency
Leads to Defective opsonization Defective leukocyte chemotaxis Decreased bactericidal killing activity (no MAC) Also indicated in immune complex disease
MAC deficiency
Increased risk of infection to N. meningitidis