Complement

System
Characteristics of Complement
Plays a role in cytolytic action
Inactivated in the sera
IgG and IgM only react with complement
Bound to all antigen-antibody complexes
Found in all mammalian sera and lower
animals
Complement is non-specific
portions of the system contribute to
chemotaxis, opsonization, immune
adherence, anaphylatoxin formation and
virus neutralization


Characteristics of Complement
*chemotaxins - C5a, C5b, C6, C7
*for immune adherence - C3b
*kinin activator - C2b
*anaphylatoxins - C3a, C4a, C5a
*opsonins - C3b, C4b, C5b
*for virus neutralization - C4b, C1
THREE Pathways of Activation

CLASSICAL PATHWAY

a. C1 - RECOGNITION UNIT
- trimolecular complex
- C1q attaches to at least two Fc
- C1s activates C4


C1q
C1r
C1s
Antigen-IgG-complement
complex
Antigen-IgM-complement
complex

C1q
C1r
C1s
b. C4 - FIRST ACTIVATION UNIT
- cleaved into C4a and C4b


c. C2 SECOND ACTIVATION UNIT
- cleaved into C2a and C2b
- C2a combines with C4 to form
C4b2a complex
d. C3 - THIRD ACTIVATION
UNIT/AMPLIFICATION
PHASE UNIT
- C3b combines with C4b2a to form C4b2a3b
e. C5, C6, C7, C8, C9 MEMBRANE ATTACK
PHASE UNITS



ALTERNATIVE PATHWAY OF
COMPLEMENT ACTIVATION

a.Factor B activated into its active form Bb with
the participation of C3
-Bb will cleave C3 into C3a and C3b and will
combine with C3b to form C3bBb

b. Factor D - cleaves Factor B into Bb in the presence
of C3 and Mg++ ions

Therefore,
Factor B + Factor D + C3 + Mg++ C3bBb

c. Properdin (Factor P) - binds to C3bBb to prevent
spontaneous decay of the complex




ACTIVATING FACTOR: MANNOSE GROUPS OF
CHO IN MICROBIAL CELL
EFFECTORS:
MBP/MBL- MANNAN-BINDING PROTEIN/LECTIN
MASP MBP-ASSOCIATED SERINE PROTEASE
CLASSICAL ALTERNATIVE LECTIN
ACTIVATING
SUBS.
IMMUNE
COMPLEXES
(IgG OR IgM)
LPS (bacterial
capsule)
IgA
Mannose
groups on
microbial cell
RECOGNITION
UNIT
C1q, C1r, C1s C3, Factor B,
Factor D
MBP, MASP-1,
MASP-2
C3
CONVERTASE
C4b2a C3bBb C4b2a
C5
CONVERTASE
C4b2a3b C3bBb3b C4b2a3b
MAC
C5b6789
END RESULT
CELL LYSIS

CLINICAL SIGNIFICANCE:
Elevated complement components - have little clinical
importance
Decreased complement components
Causes : - complement has been consumed
(e.g. in disease states)
- complement may be decreased or absent due to
genetic defect

MEASUREMENT OF COMPLEMENT COMPONENTS
DEFICIENT COMPONENT ASSOCIATED DISEASE
C1q Sex-linked agammaglobunemia
Hypocomplementemic urticarial
vasculitis
Severe combined immune
deficiency
SLE-like syndrome
Increased susceptibility to
bacterial infection

C1r URT diseases
Chronic kidney disease
SLE-Like syndrome
C1s SLE-like syndrome
Increased susceptibility to
bacterial infection
DEFICIENT COMPONENT ASSOCIATED DISEASE
C1sINH Hereditary angioneurotic
edema
C4 SLE
Glomerulonephritis
Pyogenic Infections
C2 SLE
Dermatomyositis
Repeated Infectious
disease
Chronic renal disease
Autoimmune disease
Increased susceptibility to
bacterial infection
DEFICIENT
COMPONENT
ASSOCIATED
DISEASE
C3 Recurrent pyogenic
infections
SLE-like syndrome
Post-streptococcal
glomerulonephritis
Pyogenic infections
C3b inactivator Recurrent pyogenic
infections
Urticaria

C5 SLE
Neisseria infections
DEFICIENT COMPONENT ASSOCIATED DISEASE
C5 dysfunction Leiners disease
Gram Negative skin and bowel
infections

C6 Neisseria infection
SLE
Raynauds phenomenon
Scleroderma like syndrome
Vasculitis
C7 Neisseria infection
SLE
Raynauds phenomenon
Sclerodactyly
Telangiectasia
DEFICIENT
COMPONENT
ASSOCIATED
DISEASE
C8
Neisseria infection
Xeroderma pigmentosa
SLE-like syndrome
C9 Neisseria infection
Properdin

Factor D
Pyogenic infections

Pyogenic infections


C-REACTIVE PROTEIN
CRP - most sensitive indicator of acute inflammation
- fastest responding acute phase protein and will
disappear when condition becomes chronic
INFLAMMATION

- a nonspecific exaggerated physiologic response
which involves a vascular response and a cellular
response by phagocytic cells to infection/injury

Rapid Latex Agglutination Test
- most popular of CRP tests and is claimed to be the
most sensitive.
Principle: Reverse Passive Agglutination Test




Latex coated + Pxs serum Aggln
With Anti-CRP with CRP
+
CLINICAL SIGNIFICANCE:


ELEVATED LEVELS (ABOVE THE NORMAL 0.6 mg/dL) indicates:

- inflammation
- tissue damage

AS SEEN IN

- bacterial and viral infections
- rheumatic diseases such as RA
- myocardial infarction
- burn injuries
- tuberculosis
- renal transplantation
- malignancies

Question 1
In the heterophil antibody test, when serum is
absorbed with beef cells
A. there is a decrease in the titer of IM antibodies
B. there is an increase in the titer of GPKC
antibodies
C. Serum sickness are not absorbed
D. Forssman antibodies are absorbed

ANSWER : A
Question 2
The Fluorescein-antihuman gamma globulin
used in the FTA-ABS test
A. makes the antigen-antibody reaction visible
B. Is added to the serum before the antigen is
added
C. is added to the antigen before the serum is
added
D. makes the antibody visible
ANSWER : A

QUESTION 3
Forssman antibodies are absorbed by :
A. boiled beef cells
B. Guinea pig kidney antigen
C. neither beef cells nor guinea pig kidney antigen
D. both beef cells and GPKC

ANSWER : B
QUESTION 4
Which of the following represents the
reported titer in quantitative VDRL test ?
A. Lowest dilution giving a weakly reactive result
B. Lowest dilution giving a reactive result
C. Highest dilution giving a weakly reactive result
D. Highest dilution giving a reactive result

ANSWER : D

QUESTION 5
A hemolysin is an antibody that
A. causes lysis of red blood cells
B. causes agglutination of red blood cells
C. lyses T-cells
D. Sensitizes white blood cells

ANSWER : A
QUESTION 7
How can cell-mediated immunity be
transferred to a normal individual ?
A. with lymphoid cells from a hypersensitive
individual
B. with transfer of specific liver cells from an
infected individual
C. with transfer of monocytes from a normal
person
D. with polymorphonuclear cells from a normal
person
ANSWER : A
QUESTION 8
The random movement of antigen or antibody
to form antigen-antibody complexes in semi-
solid medium occurs in :
A. agglutination
B. immunofluorescence
C. complement fixation
D. gel diffusion

ANSWER : D
QUESTION 9
Interferon can be produced by which of the
following ?
A. macrophages
B. T-lymphocytes
C. virus-infected cells
D. All of the above

ANSWER : D
QUESTION 10
The binding strength of an multivalent
antibody to its multivalent antigen is referred
to as its :
A. specificity
B. affinity
C. avidity
D. titer

ANSWER : C
QUESTION 11
When a precipitation reaction is converted to
agglutination by increasing the size of antigen
particles, the test is then referred to as :
A. direct agglutination
B. capillary precipitation
C. passive agglutination
D. hemagglutination inhibition

ANSWER : C
QUESTION 13
A post-zonal reaction is caused by
A. too little antigen
B. too much antigen
C. too much antibody
D. not by differing amounts of antigen and
antibody.

ANSWER : B
QUESTION 14
The basic immunoglobulin structure consist
of:
A. 1 light and 2 heavy chain
B.2 light and 2 heavy chain
C. 2 light and 1 heavy chain
D. 1 light and 1 heavy chain

ANSWER : B

QUESTION 15
After an antibody has been fragmented, which
term denotes the antigen binding fragment ?
A. Fc
B. disulfide bond
C. Fab
D. Carboxyl terminal

ANSWER : C
QUESTION 16
A positive reaction in a complement fixation
test is expressed as ?
A. agglutination
B. hemolysis
C. inhibition of hemolysis
D. neutralization

ANSWER : C
QUESTION 18
What does the ASO test measure in the
patient serum ?
A. Oxygen labile streptolysin
B. antibody to streptolysin O
C. Sheep red blood cells
D. Streptococcal antibodies

ANSWER : B
QUESTION 20
The Widal and Weil-Felix reactions are
examples of techniques used to detect :
A. heterophil antibodies
B. reagin
C. febrile agglutinins
D. Forssman antigen

ANSWER : C
QUESTION 21
What is the incubation temperature for the
cold agglutinin test ?
A. body temperature
B. room temperature
C. refrigerator temperature
D. freezer temperature

ANSWER : C
QUESTION 22
The RPR test is rotated at what speed for what
length of time?
A. 200 rpm for 10 mins.
B. 100 rpm for 8 mins.
C. 180 rpm for 4 mins.
D. 125 rpm for 2 mins.

ANSWER : B
QUESTION 23
What role does cardiolipin play in the VDRL test ?
A. it is the center for absorption of tissue lipids
B. it is related to the sensitivity of the test
C. it is related to the reactivity of the test
D. all of the above

ANSWER : C
QUESTION 24
Which of the following cold reacting
antibodies is present infections of
Mycoplasma pneumoniae ?
A. anti-I
B. anti i
C. anti- Lewis
D. anti K

ANSWER : A
QUESTION 26
A hapten is :
A. A carrier molecule for an antigen that is not
antigenic alone
B. A determinant capable of stimulating an IR only
when bound to a carrier
C. An immunoglobulin functional only in the
presence of complement
D. Half of an immunoglobulin molecule
ANSWER : B
QUESTION 27
Which of the ff. characteristics is not true for B
cells ?
A. become memory cells
B. Contain surface immunoglobulins
C. Differentiate into plasma cells
D. secrete the C5 components of complement

ANSWER : D
QUESTION 28
THE HLA complex is located primarily on :
A. Chromosome 3
B. Chromosome 6
C. Chromosome 9
D. Chromosome 17

ANSWER : B
QUESTION 29
What is the predominant type of antibody
found in the serum of neonates born after
full-term gestation?
A. Infant IgA
B. Infant IgD
C. Infant IgG
D. Maternal IgG

ANSWER : D
QUESTION 30
Which class of immunoglobulin possesses 10
antigenic binding sites ?
A. IgA
B. IgD
C. IgG
D. IgM

ANSWER : D