Complement System Flashcards
innate immune system
The component of the immune system in animals that is genetically determined and is nonspecific, as distinguished from the adaptive immune system
Elements of the innate system include (6)
mucous secretions, complement proteins, and certain white blood cells, especially neutrophils, macrophages, and dendritic cells
adaptive immune system
The component of the vertebrate immune system involving lymphocytes (B cells and T cells) containing a small number of genetically encoded proteins that combine to produce an enormous variety of proteins capable of recognizing and deactivating specific antigens
two major functions of the complement system
alters the membrane of pathogens and cellular debris
enhance the inflammatory response via release of anaphylatoxins that promote cell activation (e.g. mast cell degranulation) or migration to an inflammatory site (chemotaxis)
opsonization promotes removal of particles via
complement receptors on host cells
Opsonization also leads to assembly of the
membrane attack complex on pathogens and subsequent lysis
The complement system becomes activated on a target, such as (3)
apoptotic cells, tissue debris, or pathogens
This occurs by at least three mechanisms that are independent of a prior adaptive immune response :
(i) natural, spontaneous turnover (i.e. ‘tick over’) of C3 engages the alternative pathway (AP)
(ii) binding to the target of naturally occurring antibodies (Abs) engages the classical pathway (CP)
(iii) binding of lectins to carbohydrates on the target engages the lectin pathway (LP)
In adaptive immunity, natural Abs are replaced by
specific Abs
complement triggers (3)
phagocytosis
inflammation
membrane attack
phagocytosis by
opsonizing agents
what has the most important ozonizing activity?
C3b
inflammation by
chemotactically attracting macrophages and neutrophils (anaphylatoxins C3a and C5a)
membrane attack by
rupturing the cell wall of bacteria
Inflammation is a local response to cellular injury that is marked by (5)
capillary dilatation, leukocytic infiltration, redness, heat, and pain
inflammation serves as a mechanism initiating the elimination of
noxious agents and of damaged tissue
Swelling is produced by the release of serum into the tissues (wheal), and redness of the skin, resulting from the dilation of
blood vessels (flare)
The Classic Pathway is triggered by activation of the
C1-complex
The Mannose-Binding Lectin pathway is homologous to the — —, but uses the —; mannose-binding lectin (MBL), and ficolin, instead of C1q
classical pathway
opsonins
The Alternative pathway is continuously activated at a low level, as a result of spontaneous
C3 hydrolysis
spontaneous C3 hydrolysis due to the breakdown of the
internal thioester bond
C3 is mildly unstable in
aqueous environment
The alternative pathway does not rely on — — — like the other pathways
pathogen-binding antibodies
in the classical pathway of complement, there is cleavage of (3)
C2
C4
C3
C1, is a complex of (3)
C1q, C1r, and C1s
C1q is composed of
six identical subunits with globular heads and long collagen-like tails. The tails combine to bind to two molecules each of C1r and C1s, forming the C1 complex C1q:C1r2:C1s2. The heads can bind to the constant regions of immunoglobulin molecules or directly to the pathogen surface, causing a conformational change in C1r, which then cleaves and activates the C1s zymogen.
diseases which involve complement in their mechanism (7)
- Paroxysmal nocturnal hemoglobinurina
- Atypical Hemolytic uremic syndrome (aHUS)
- Hereditary angioedema
- Autoimmune diseases (Systemic lupus erthrymetosis, dermatomyositis, rheumatoid arthritis)
- Age-related macular degeneration
- Primary immune deficiency syndrome
- Mannose-binding lectin deficiency
Paroxysmal nocturnal hemoglobinurina
Acquired disorder that results in premature death and impaired production of blood cells
Paroxysmal nocturnal hemoglobinurina effects (3)
RBCs, leukocytes and platelets
how does Paroxysmal nocturnal hemoglobinurina effect by gender
affects both sexes equally,
when is Paroxysmal nocturnal hemoglobinurina usually diagnosed
usually diagnosed in young adulthood
Paroxysmal nocturnal hemoglobinurina is a deficiency of the
DAF protein
Atypical hemolytic uremic syndrome results from
chronic uncontrolled activation of the complement system
in Atypical hemolytic uremic syndrome, multiple blood clots form throughout body in small blood vessels which can lead to (4)
stroke
heart attack
kidney failure
death
Atypical hemolytic uremic syndrome is due to mutations in (3)
factor H
factor I
membrane cofactor protein
the most common functional defect in atypical hemolytic uraemic syndrome and age-related macular degeneration is
reduced cofactor activity (MCP or factor H) for C3b
Hereditary Angioedema is recurrent attacks of
severe swelling
types 1 and 2 Hereditary Angioedema
mutations in the gene that makes the C1 inhibitor
type 1 is a deficiency of
C1
type 2 is an atypical
C1 protein that is less capable of suppressing activation of the complement system
type 3 Hereditary Angioedema is often due to mutations in
factor XII gene
