(Q3-1997)

The biological functions of the complement system

 Cytolysis(membrane attack complex)

o C5b, 6,7,8,9 complexes disrupt the structure of the cell membrane of
target cell, causing entry of water and electrolytes which caused the lysis
of the cell.
o Even there is no C9, MAC can make hole but lysis more effective with C9.
 Anaphylatoxins
o C3a, C4a, and C5a cause degranulation of mast cells which release
mediators, such as histamine, leading to increased vascular permeability
and smooth muscle contraction
o They can bind directly to smooth muscle cells of the bronchioles and cause
bronchospasm.
o C5a, by far, is the most potent
o Anaphylaxis caused is less common compared to type I hypersensitivity.
 Chemotaxis
o Movement of a cell @ organism(neutrophils) in response to the stimulus
of a chemical gradient concentration(low 5ahigh 5a).
o C5a, and the C5, 6, 7 complex attract neutrophils.
o They migrate especially well toward C5a.
o C5a also enhances the adhesiveness of neutrophils to the endothelium.
 Opsonization
o Microbes such as bacteria and viruses are phagocytized much better in the
presence of C3b, since many phagocytes have C3b receptor on their
surface.
o The role of C3b is for helping phagocytosis and binds to surface Ag.
 Enhancement of antibody production
o The binding of C3b at its receptors on the surface of activated B cells
greatly enhances antibody production compared with that by B cells that
are activated by B cells alone.
  Antigen antibody complex solubilization
o Break up big molecules into smaller sizes to enchance phagocytosis
o Not too smallnot get recognizedless phagocytosis.

Reference:

 Levinson (2008), Review of Medical Microbiology and Immunology, 10 th Edition,

Lange

(Q1- 1998)
1. The Functional Features that Distinguishes B Cell from T Cell.

N Features B cell T cell

o
1 Antigen receptor recognize only processed peptides in association with MHC No Yes
protein
2 Antigen receptor recognizes whole, unprocessed proteins and has no Yes No
requirement for presentation by MHC protein
3 IgM on surface Yes No
4 CD3 proteins on surface No Yes
5 Immunoglobulin synthesis Yes No
6 Regulator of antibody synthesis No Yes
7 IL-2, IL-4, IL-5, and gamma interferon synthesis No Yes
8 Effector of cell-mediated immunity No Yes
9 Maturation in thymus No Yes
10 Maturation in bursa or its equivalent Yes No

Reference : Review of Medical Microbiology and Immunology, pg 408, Table 58.1

(Q3-1999)
Alternative pathways

C3
C3a+C3b

Factor B Factor D

C3bB

C3
convertase
Circulating plasma undergoes spontaneous hydrolysis to become C3(h2O) which acts like C3b

With mg ions,the c3(h2o) will bind to c2-like protein factor(factor B) and C1 like protein(factor D0 to
form altenative pathways c3 convertase.

C3 convertase is stabilize by properdin

C3 convertase also bind and cleave an additional c3 tp form c3bBbc3b which is c5 covertase

Common pathways

C5
convertase

C5 C5a + C5b

C5b+C6+C7

Complex + C8+C9 MAC Cytolysis

C5 convertase cleave c5 to c5a and c5b.C5b will bind to C6 and C7 to form a complex and this
complex will bind to C8 and C9 to form membrane attack complex will lead to cytolysis of the
antigen.without c9 MAC can lysis but more efficient with C9

(Q2-2000)
- characteristics of cytokines
Cytokines
-a group of low molecular weight proteins used for communication between cells
-has role similar to to hormones
-has role in cell growth, cell differentiation,and death
-acts in 3 manners which are
i. autocrine
ii. paracrine
iii.endocrine
-their actions could cause
-pleiotropy
-redundancy
-synergy
-antagonism

has 5 cytokine receptor families

-Ig superfamily
class I cytokine
class II cytokine
TNF receptor family
chemokine receptor

(Q1-2002)

The classical pathway of the complement system.

a. The classical pathway required the presence of antibody to bind to the

antigen to form the antigen-antibody complex to be activated.
b. Non-immunologic activators (activation in the absence of Ab) are bacteria,
viruses, urate crystal surface, myelin basic protein, denatured protein and
bacterial endotoxin 7 polyanions.
c. Antigen–antibody complexes (1 molecule IgM @ 2 IgG) activate C1(each C1
complex composed of c1q,2c1r,2c1sheld by Ca ions) to form a protease,
which cleaves C2 and C4 to form a C4b,2b complex.
d. The C4b,2b complex is C3 convertase, which cleaves C3 molecules into two
fragments, C3a and C3b. C3a is an anaphylatoxin, which is involved in the
degranulation of mast cells to produce histamine.
e. C3b forms a complex with C4b,2b, producing a new enzyme, C5 convertase
(C4b,2b,3b), which cleaves C5 to form C5a and C5b. C5a is an anaphylatoxin
and a chemotactic factor.
f. C5b binds to C6 and C7 to form a complex that interacts with C8 and C9 to
produce the membrane attack complex (C5b, 6,7,8,9), which causes cytolysis.
(Q1-2003)

Humoral Immunity

 Humoral immunity is the production of antibody molecules in response to an antigen

mediated by B- lymphocytes, named after the bursa of Fabricius in birds.
 B-lymphocytes undergo multiplication and processing in lymphoid tissue elsewhere than in
the thymus but there is some evidence to suggest that such processing occurs in the bone
marrow itself or in the fetal liver.
 Among the functions of B-lymphocytes are to interact with antigenic epitopes by using their
imunoglobulin receptors, subsequently develop into plasma cells, secreting large amounts of
specific antibody, circulate as memory cells and to present antigenic peptides to T-cells,
consequent upon internalization and processing of the original antigen.
 Antibodies are Y-shaped molecules, there are five classes of antibodies (IgM, IgD, IgG, IgE,
IgA)
 IgM
1. The predominant early antibody, the one first activates in an initial attack of antigen
2. Has 5 binding sites, an effective agglutinator of antigen
 IgD
1. Activating and suppressing lymphocytes activities.
2. Found in large quantities in cell walls of many B-lymphocytes, has a single binding
site
 IgG
1. Stimulates phagocytic cells, activates the complement system, binds neutrophils, and
can neutralize toxins, opsonisation
2. The only antibody that can cross placenta and confer immunity on the fetus
3. Has a single binding site
 IgE
1. Mediator in allergic response
2. Activates histamine secreting cell
3. Also appears to play a role in parasitic infection
4. IgE has a single binding site
 IgA
1. Found in secretions and also in colostrums ( a golden liquidy substance that a nursing
mother expels from her breasts 24-48 hours after delivery ) to transfer antibodies to
a newborn infant for about six months

( Q1-2001)

1. Antigen processing and presentation to Th and Tc cells

Native antigen is presented to B cells while others such as:

i) Exogenous= T helper cells
 ii) Endogenous= T cytotoxic cells

Antigen is presented by APC (antigen presenting cells) to lymphocytes. Antigen is presented via 2
pathways which are cytosolic (class 1) pathway and endocytic (class 2) pathway. For cytosolic
pathway, it is specialized for endogenous antigen such as virus and some bacteria such as Chlamydia,
rickettsia and plasmodium. These antigens are processed at all nucleated cells by proteosome. The
presentation of this antigen in association with class 1 MHC protein to CD8 T cytotoxic cells. The site
of Ag-HLA binding for this antigen is RER and TAP-1 and TAP 2 as the transporters.

In endocytic pathway (class 2) pathway, the exogenous antigen (bacteria) is processed by

lysosomal enzyme and presented by APC in association with MHC class 2 protein to CD4-positive
helper T cells. Also displayed is B7 protein, which acts as a costimulator of Thelper cell.

Generally, before presentation, foreign material is ingested and degraded into smaller
fragments. The degradation steps when fragment associates with MHC proteins. The complex is
transported by specialized transporter proteins.

(Q2-2004)
Natural killer cell

 One of lymphocytes
 Kill infected host cells
1) Secrete macrophage activating cytokines IFN-y
2) Kill the antigen directly by producing cytoplasmic granules which enter the target cell. The
granule activated the enzyme that induce apoptosis

 Do not express kinds of distributed antigen receptors that B and T cell do

 Component of innate immunity
 Rapid attack the infected cell
 Activation of NK cell depend on activating receptor and inhibitory receptor
 Activating receptor recognize the cell surface that commonly present by stress cell like
infected cell
 Inhibitory receptor of NK cell specific for class 1 MHC molecule that present on all healthy
cells and function to block signaling by activating receptors

(Q2-2006)
2. The differentiation of naïve T helper cells to TH1 and TH2 cells
Group 9

1. TH1 and TH2 cells derive from common precursors cells that have the capacity to differentiate
into either TH cells.
2. Cytokines are the most important determinants of TH differentiation.
3. IL-12, produced by activated macrophages, causes antigen-primed naïve T cells to differentiate
into TH1 cells.
4. TH1 in turn produce IL-2 and IFNɣ, particularly effective in enhancing immune response involving
macrophages and other phagocytes.
5. IL-4 promotes differentiation of naïve T cells into TH2 cells.
6. TH2 cells in turn produce IL-4 and other cytokines that promote mast cells and eosinophil-
mediated responses.
7. Differentiatiion of naïve T cells to either TH1 or TH2 cells may involve an intermediary cell,
designated TH0.
8. TH0 responsible in producing IL-2, IFNɣ and IL-4.
9. TH1-derived IFNɣ inhibit the development of TH2 cells.
TH2-derived IL-4 prevents the development of TH1 cells

(Q3-2008)
Interferons:

There are 2 groups of interferons: Type I and Type II

Type I consists of IFN-α, IFN-β, IFN-ε, IFN-κ, IFN-ω

Type II consists of IFN-γ

Interferon Mechanisms of antiviral activity Other biological actions

Type I - IFN type I causes the - Stimulates the

cell to synthesize development of TH1
enzymes that can cells in humans
interfere with virus
- Promotes sequestration
replication. This effect
of IFN could be of lymphocytes in lymph
nodes
paracrine, i.e. the
infected cell produces - Inhibits the proliferation
IFN type I to bring its of cells to block viral
surrounding cells into replication
an antiviral state, or
autocrine, i.e. the
infected cell will inhibit
viral replication within
itself after self-
producing and receiving
IFN type I

Type II - Not really potent - Promotes

antiviral cytokine
- It activates the
macrophages to kill
phagocytosed viruses
by activating synthesis
of enzymes in the
differenciation of naïve
CD4+ T cells into TH1
subset and inhibits the
differentiation of TH2
cells.
- Promotes antibody
 synthesis of respiratory class-switch in B cells
oxygen species and
- Stimulates expression of
nitrogen oxide
class I and class II MHC
molecules and
costimulators on APCs

(Q1,2-2009)
1. Uses of human leucocytes antigen (HLA) typing.
- Transplantation (tissue typing or histocompatibility testing)
- Disease association
 Ankylosing spondylosis (disease of spine)
- Exclusion of paternity.
 The baby will inherit both maternal and paternal HLA.
 If HLA not present on baby, they are not the parent.
- Anthropological study.
 Only among certain group of people which means certain tribe has distinct HLA.

2. The main characteristic of cytokines. Give examples for each.

- Pleiotropy – act on more than one cell type (INF α/β)
- Redundancy – more than one cytokine can do the same thing (INFα/β and INFγ),( IL-1
and TNF)
- Synergy – two or more cytokines cooperate to produce an effect that is different or
greater than the combined effect of two cytokines functioning separately (IL-12 and IL-
18)
- Antagonism – two or more cytokines work against each other (IL-4 and IL-12)

Q2 2002

Transplantation rejection reaction

1) Hyperacute (0-24 hours)

- mediated by type ii hypersensitivity reaction

- example is end-stage kidney failure that lead to hemodialysis and graft to transplant

-and azotemia or uremia that is destruction of RBC

2) Accelerated type (1-4 days)

-second set reaction

-cell-mediated

3) Acute (5 days to 3 month)

-first set reaction

-cell mediated immune involve

-new classification - early (10 days)

- late

4)chronic (>3month)

-due to failure of immunosuppression treatment

-as a result recurrent of the same disease of the graft