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HUMORAL IMMUNE RESPONSE (IR)

PROPERTIES PRIMARY RESPONSE SECONDARY RESPONSE
[ Ig ] 3
2o Response
1 Response
o
4
1: Lag phase. 3
2
2: Exponential phase
GRAPHS 3: Steady state 4
4: Declining phase 2 1
1

0 Time, t
2/52 3.6/12

a) Inductive, latent or lag phase - In this phase the Ag is a) Lag phase - In a secondary response there is a lag phase by
recognized as foreign and the cells begin to proliferate and it is normally shorter than that observed in a primary response.
differentiate in response to the antigen. The duration of this b)Log phase - The log phase in a secondary response is more
phase will vary depending on the antigen but it is usually 5-7
rapid and higher Ab levels are achieved.
days.
c) Steady state phase.
PHASES b) Log or Exponential Phase - In this phase the Ab
d)Decline phase - The decline phase is not as rapid and Ab
concentration increases exponentially as the B cells that were
(KINETIC OF ANTIBODY may persist for months, years or even a lifetime.
stimulated by the Ag differentiate into plasma cells which
RESPONSE TO T- secrete antibody.
DEPENDENT ANTIGEN) c) Plateau or steady-state phase - In this phase Ab
synthesis is balanced by Ab decay so that there in no net
increase in Ab concentration.
d) Decline or decay phase - In this phase the rate of Ab
degradation exceeds that of Ab synthesis and e level of Ab falls.
Eventually e level of Ab may reach base line levels.
REPEATED EXPOSURE Same intensity > rapid & intense

SELF/NONSELF Absent Present

DISCRIMINATION
SPECIFICITY Absent Present

MEMORY Absent Present

EFFECTORS Leukocytes & NK cells T & B lymphocytes

IMMUNE RESPONSE Complement, lysosomal enzyme, acute phase protein, & interferons Cytokines & antibody

ANTIBODY Mainly IgM Mainly IgG

QUALITATIVE CHANGE a) Ig class variation - In the primary response the major class of Ab produced is IgM whereas in the secondary response it is IgG (or IgA
IN ANTIBODY or IgE). E Abs that persist in the secondary response are the IgG Abs.
b) Affinity - The affinity of the IgG Ab produced increases progressively during the response, particularly after low doses of Ag. This is
referred to as affinity maturation. Affinity maturation is most pronounced after secondary challenge with Ag. After a class switch has
occurred in the immune response, somatic mutations occur which fine tune e Abs to be of higher affinity.
c) Avidity - As a consequence of increased affinity, the avidity of the antibodies increases during the response.

Aliahs Y1B2
d) Cross-reactivity - As a result of the higher affinity later in the response there is also an increase in detectible cross reactivity.

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 ANTIGENS (Ags) = IMMUNOGENS
PROPERTIES DETAILS
Antigens: Immunogens:
a) Anti = antibody, gen = generator >>> antibody A substance that induces a specific
DEFINITION immune response.
generator.
b) A substance that reacts with the products of a
specific immune response.
a) Proteins: The vast majority of immunogens are proteins. These may be pure proteins or
they may be glycoproteins or lipoproteins. In general, proteins are usually very good
immunogens.
CHEMICAL b) Polysaccharides: Pure polysaccharides and lipopolysaccharides are good immunogens.
NATURE
c) Nucleic Acids: Nucleic acids are usually poorly immunogenic. However, they may become
immunogenic when single stranded or when complexed with proteins.
d) Lipids: In general lipids are non-immunogenic, although they may be haptens.
-Definition: A portion of an antigen that combines with the products of a specific immune response.
a) Epitopes recognized by B-cells. b) Epitopes that recognized by T-cells.
Compositio - Created by e primary sequence of - Created by e primary sequence of amino
n residues in e polymer (linear or acids in proteins. T cells do not recognize
sequence determinants) and/or by e polysaccharide or nucleic acid antigens. E
secondary, tertiary or quaternary determinants need not be located on the
structure of e molecule (conformational exposed surface of the antigen since
determinants). recognition of e determinant by T cells
ANTIGENIC requires that e antigen to be
DETERMINANTS, proteolytically degraded into smaller
EPITOPES peptides.
Size - Generally, antigenic determinants r - In general antigenic determinants are
small & r limited to 4-8 residues. (Amino small and are limited to approximately 8-
acids and or sugars). E combining site 15 amino acids.
of an antibody will accommodate an
epitope of 4-8 residues.
Number - Theoretically: 4-8 residues. - Theoretically: 8-15 residues.
- Practically: lower (limited to those - Practically: lower (limited to those
portions which r exposed to Ab). portions which can bind to MHC).
a) Contribution of Ag:
1. Foreignness
E immune system normally discriminates between self and non-self such that only foreign molecules
are immunogenic.
2. Size
There is not absolute size above which a substance will be immunogenic. However, in general, e
larger e molecule e more immunogenic it is likely to be.
3. Chemical Composition
In general, e more complex e substance is chemically e more immunogenic it will be. E antigenic
determinants are created by e primary sequence of residues in e polymer and/or by e secondary,
tertiary or quaternary structure of e molecule.
4. Physical form
In general particulate Ags r more immunogenic than soluble ones and denatured Ags more
immunogenic than e native form.
5. Degradability
Ags that are easily phagocytised r generally more immunogenic. This is because for most Ags (T-
dependant Ags) e development of an immune response requires that e Ags to be phagocytosed,
FACTOR processed and presented to helper T cells by an antigen presenting cell (APC).
INFLUENCING E
b) Contribution of e biological system:
IMMUNOGENICIT 1. Genetic Factors
Y Some substances r immunogenic in one species but not in another. Similarly, some substances r
immunogenic in one individual but not in others (i.e. responders and non-responders). The species
or individuals may lack or have altered genes that code for e receptors for Ag on B cells and T cells
or they may not have e appropriate genes needed for e APC to present Ag to e helper T cells.
2. Age
Age can also influence immunogenicity. Usually e very young and e very old have a diminished
ability to mount and immune response in response to an immunogen.
c) Method of administration:
1. Dose
E dose of administration of an immunogen can influence its immunogenicity. There is a dose of Ag
above or below which the immune response will not be optimal.
2. Route
Generally e subcutaneous (intradermal) route is better than e intravenous or intragastric routes. The
route of Ag administration can also alter e nature of e response.
3. Adjuvants
The use of adjuvants, however, is often hampered by undesirable side effects such as fever and
inflammation.
- Substances that can enhance e immune response to an immunogen.E use of adjuvants, however,
ADJUVANTS are often hampered by undesirable side effects such as fever and inflammation. Eg: Al(OH)2: Vaccin
will be better exposed to APC when combines when adjuvants.

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 - On its own, hapten cant induce e production of Ab, but becomes possible when attached
HAPTENS covalently to a carrier protein. E Ab sproduced will react with free hapten. In such conjugates, the
type of carrier determines whether e response will be T-independent or not.

T-INDEPENDENT Ag PROPERTIES T-DEPENDENT Ag SUPERANTIGENS

No REQUIRE T-CELLS Yes When e immune system
Absent MEMORY RESPONSE Present encounters a conventional T-
dependent antigen, only a
High EFFECTIVE DOSE Low
small fraction (1 in 104 -105)
Simple & Repetitive STRUCTURE > complex of e T cell population is able
IgM & IgG3 Ab CLASS FORMED All to recognize e antigen &
Slow METABOLISM IN VIVO Fast become activated
(monoclonal/ oligoclonal
Easy INDUCTION OF > difficult response). However, there r
TOLERANCE some antigens which
May or May not Ag PROCESSING Required polyclonally activate a large
fraction of e T cells (up to
25%). These antigens r called
superantigens. Eg:
Staphylococcal enterotoxins
(food poisoning).
ANTIBODIES (Abs): IMMUNOGLOBULINS (Igs)
PORTIONS DETAILS
- Immunoglobulin (Ig) or gamma globulins: Glycoprotein that carry Ab activity, i.e. property of specific
DEFINITION combination with e substrates which elicited their formation (Ags).
a) Ag binding: Igs bind specifically to one or a few closely related Ags. Each Ig actually binds to a
specific epitope. Ag binding by Abs is the primary function of Abs and can result in protection of the
host. The valency of Ab refers to the number of epitopes that an individual Ab molecule can bind. The
GENERAL valency of all Abs is at least two and in some instances more.
FUNCTIONS b) Effector function: Fixation of complement - This results in lysis of cells and release of biologically
active molecules & binding to various cell types - Phagocytic cells, lymphocytes, platelets, mast cells,
and basophils have receptors that bind immunoglobulins. This binding can activate the cells to perform
some function.
a) Heterogenous group of proteins.
b) Approximally 20% of total plasma proteins.

PROPERTIES
c) In electrophoresis of serum: majority reside in gamma zone of globulin protein.
d) Different populations of Igs also found in varying proportions in extravascular fluids, exocrine
excretions, n surf. of some lymphocytes.
e) An individual is capable of producing 10 8
different Ab molecules, each with distinct properties.
BASIC a) Heavy chain:
STRUCTURE Each Ig has 2 heavy chains.
(Y-SHAPED) Made up of 1 variable region (1V ) n at least 3 constant regions (3C : C 1, C 2, & C 3).
H H H H H

IgE & IgM have C 4. H

b) Light chain:
Each Ig has 2 light chains which r approximately half of e length & weight of e heavy region.
From amino end to half of e chain is made up of hypervariable region which consists of variable
amino acids.
Other half is made up of constant region which consists of almost same amino acids.
c) Variable & constant regions:
Light Chain - VL (110 amino acids) and CL (110 amino acids).
Heavy Chain - VH (110 amino acids) and CH (330-440 amino acids).
d) Hinge region: This is the region at which the arms of the Ab molecule form a Y. It is called the hinge
region because there is some flexibility in the molecule at this point due to e presence of proline to
make Ab-Ag binding easier.
e) Domains:
Ab is folded into globular regions each of which contains an intra-chain disulfide bond. These
regions r called domains.
1. Light Chain Domains - VL and CL
2. Heavy Chain Domains - VH, CH1 - CH3 (or CH4)
f) Disulphide bonds:
Inter-chain disulfide bonds - E heavy and light chains and e two heavy chains r held together by
inter-chain disulfide bonds and by non-covalent interactions. E no. of inter-chain disulfide bonds
varies among different Ig molecules.
Intra-chain disulfide binds - Within each of the polypeptide chains there r also intra-chain disulfide
bonds.
g) Oligosaccharides:
Carbohydrates are attached to the CH2 domain in most immunoglobulins. However, in some cases

Aliahs Y1B2
 carbohydrates may also be attached at other locations.
Fab Fragment Fc Fragment
Ag binding - These fragments were called e Fab - This fragment was called Fc because it was easily
fragments because they contained e Ag binding crystallized.
sites of the Ab. Each Fab fragment is monovalent - Effector functions - E effector functions of Igs r
whereas e original molecule was divalent. E mediated by this part of e molecule. Different
FRAGMENTS combining site of e antibody is created by both VH functions r mediated by e different domains in this
and VL. An Ab is able to bind a particular epitope fragment. Normally e ability of an Ab to carry out an
because it has a particular combination of VH and effector function requires the prior binding of an Ag;
VL. Different combinations of a VH and VL result in however, there are exceptions to this rule.
antibodies that can bind a different epitope.
- R based on differences in the amino acid sequences in the constant region of the heavy chains. All
immunoglobulins within a given class will have very similar heavy chain constant regions.
Ig CLASSES - IgG - Gamma heavy chains, IgM - Mu heavy chains, IgA - Alpha heavy chains, IgD - Delta heavy chains, &
IgE - Epsilon heavy chains.
- R based on small differences in the amino acid sequences in the constant region of the heavy chains. All
Ig immunoglobulins within a subclass will have very similar heavy chain constant region amino acid
sequences.
SUBCLASSE - IgG Subclasses: IgG1 - Gamma 1 heavy chains, IgG2 - Gamma 2 heavy chains, IgG3 - Gamma 3 heavy
S chains, & IgG4 - Gamma 4 heavy chains.
- IgA Subclasses: IgA1 - Alpha 1 heavy chains, & IgA2 - Alpha 2 heavy chains.
- Are based on differences in the amino acid sequence in the constant region of the light chain.
Ig TYPES - Kappa light chains & Lambda light chains.
Ig - R based on differences in the amino acid sequences in the constant region of the light chain.
SUBTYPES - Lambda subtypes: Lambda 1, Lambda 2, Lambda 3, & Lambda 4.
- Molecules that have structure similar to e structure of Igs. For example:
Ig GENE
a) T-cells receptors , , , & sigma chain.
SUPERFAMIL b) CD3 complex , , & chain.
Y c) MHC protein: class 1 & 2 microglobulin & class 11 & .

[Zakat (Charity)]

Spend (on charity), O son of Adam, and I shall spend

on you.

It was related by al-Bukhari (also by Muslim).

Igs CLASSES
Igs DETAILS & PROPERTIES
Heavy chain: gamma chain.
MW: 150,000 Daltons.
Account for about 75% total serum Igs.
Most abundant during 2 immune response.
o

4 subclasses: IgG1-IgG4.
E only Ig that can cross e placenta in human for neonate protection during 1 month of life: IgG2 does not
st

cross well. However, e maternal IgGs will decrease after 6 months old because e baby already has his own
IgGs.
IgG Can attract complement system through classical pathway: IgG3 > IgG1 > IgG2 > IgG4 (non-activating).
C1q binding site: CH2.
Diffuses > readily into extravascular spaces to neutralize toxins, microorganisms, & etc.
Acts in extravascular killing [ADCC (Ab dependent cell mediated cytoactivity) - K cells]: IgG complexes
interact with platelets to form aggregation & vasoactive amines release.
Synthesis largely depends on Ag stimulation.
Its catabolism is proportionately equal to IgG level.
Half life: IgG4- 7days & IgG1-3 -23 days.
Possesses agglutinating capacity &, anti-viral, toxin, & bacteria activity (strong).
IgA Heavy chain: alfa chain.
10-15% of total serum Igs.
Predominant Igs in sero-mucous secretions (saliva, tears, nasal fluids, sweat, colostrums, mothers milk, &
GIT, RT, UGT secretions).
Predominant Igs class produced by B-cells in Peyers Patches, tonsils, n other submucosal lymphoid tissues.
Important for defense against invasion at internal surface called milIieu interior.
Monomer: MW 160,000 Daltons with 2 subclasses in 5:1 ratio (IgA1 & IgA2). IgA2 divides into d2 L21 & (d2
L2) 2.

Aliahs Y1B2
 Dimers: joined by J chain. (Mucosal cells secrete sIgA endocytised by epithelial cells excreted into
lumen.
Secretory IgA (sIgA) has secretory component & it inhibits adherence of microorganisms to mucosal cell
surfaces.
Aggregated IgA activates complement system via alternative pathway.
Possesses a strong agglutinating capacity & anti-viral, antibacterial, & antitoxin activity.
Half life: 5.5 days.
Heavy chain: mu chain.
MW: 900,000 Daltons (pentameric form).
6-10% (1.0 mg/mL) of total serum Igs.
Valency: 2-10 (monomeric - pentameric, but normally 5 Ags).
E best Ab to activate complement system due to its big size (binds to C1q binding site - CH ). 3
IgM
Agglutinating agent: cytolytic agent.
In blood: isohaemaglutinins - indicates e type of blood one is having (T-independent Ab with no memory, eg:
Anti A).
Possesses anti-viral & antibacterial (strong) activity but not antitoxin activity.
Half life: 5 days.
Heavy chain: epsilon chain.
MW: 200,000 Daltons.
0.002% (< 0.00002 mg/mL) of total serum Igs.
Fixes on most cells/basophils which when linked with allergies causes degranulation of MC/B Type 1
Hypersensitivity reaction.
IgE Has an extra C H domain.

Function: protection against certain parasites like helminths (worm).

Very high concentration in allergy (Type 1) n helminthic infections (can be detected by examine e stool
whether helminth is present or not in e stool).
Half life: 2.0 days.
Exists only in monomeric form.

Heavy chain: delta chain.

MW: 180,000 Daltons.
0.2% (0.05 mg/mL) of total serum Igs.
IgD Present on surfaces of lymphocytes especially B-cells.
Functions: Acts as Ag receptor for B lymphocytes activation.
Half life: 2.8 days.
Exists on;y in monomeric form with extra CH domain.

FORMATION OF ANTIBODIES
STAGE OF
B-CELLS Immature B- Mature B- Activated B- Ab-secreting
Stem cells Pre B-cells
MATURATI cells cells cells cells
ON
Low rate Ig
PATTERN secretion, High rate Ig
Cytoplasmic
heavy chain secretion,
OF Igs heavy Membrane Membrane
None isotype reduced
FORMATIO chain & pre- IgM IgM & IgD
switching membrane
NN B receptor
affinity Ig
maturation.

CS CS CS CS
IgA IgE IgG IgD IgM

PROPERTIES OF ANTIBODY
PROPERTIES DETAILS
ISOTYPE Definition: Isotypes r antigenic determinants that characterize classes & subclasses of heavy chains
& types & subtypes of light chains.
Location:
1. Heavy chain isotypes r found on e Fc portion of e constant region of e molecule.
2. Light chain isotypes r found in e constant region.

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 Occurrence:
1. Isotypes r found in all normal individuals in e species.
2. E prefix Iso means same in all members of e species.
3. Some individuals with immunodeficiencies may lack one or more isotypes but normal individuals
have all isotypes.
Example:
1. Heavy chain:
a. Isotypic variant: IgG, IgA, IgM, IgE, & IgD.
b. Subclasses: IgG1 & IgG2 as well as IgA1 & IgA2.
2. Light chain:
a. Subtype: O2+ & O2- (on cq).
b. Subgroup: VH, VHII, & VHIII (on Va/VL).
Importance - Antibodies to isotypes r used for:
1. E quantitation of Ig classes & subclasses in various diseases.
2. In e characterization of B cell leukemia.
3. In e diagnosis of various immunodeficiency diseases.
ALLOTYPE
Definition: Allotypes r antigenic determinants specified by allelic forms of e Ig genes.
Represents slight differences in e amino acid sequences of heavy or light chains of different
individuals.
Even a single amino acid difference can give rise to an allotypic determinant, although in many cases
there r several amino acid substitutions that have occurred.
Allotypic variant r detected by using antibodies directed against allotypic determinants.
- These antibodies can be prepared by injecting the Ig from one person into another.
- In practice however we obtain anti-allotype antisera from women who have had multiple
pregnancies or from people who have received blood transfusions or from some patients with
rheumatoid arthritis.
- Allotypic variant is important especially in case of IgA deficiency.
- Allotypic variant has no effect on Igs functions. It is just because e variant constant region
sequences can be immunogenic.
Location: In man e allotypic differences r localized to e constant region of the heavy and light chains.
Occurrence:
1. Individual allotypes r found in individual members of a species.
2. All allotypes r not found in all members of e species.
3.E prefix Allo means different in individuals of a species.
Human Ig Allotypes
1. Nomenclature - Human Ig allotypes r named on e basis of e heavy or light chain on which it is
located.
2. An allotype on a Gamma 1 heavy chain is given e name: G1m(3).
3. An allotype on a Kappa light chain is given e name: Km(1)
Genetics:
1. Codominant autosomal genes:
- Allotypes that represent amino acid substitutions at e same position in a heavy or light
chain.
- E.g.: G1m(3) and G1m(17) or Km(1) and Km(3) r inherited as codominant autosomal genes.
2. Allelic Exclusion:
- Although in a heterozygote both alleles r expressed, any individual Ig molecule will only
have one allotype. This is because an individual B cell can only expresses one allele.
- This is called allelic exclusion: Allotypes that represent amino acid substitutions at different
locations in a molecule.
- E.g.: G1m(1) and G1m(17) can be found on e same molecule.
Example:
1. Gm groups on IgG: Gm 1-25.
2. IgA:
a. IgA2: (2L2)1 Different allotypes
b. IgA2: (2L2)2
c. Kappa: Km 1-3
Importances:
1. Monitoring bone marrow grafts - Bone marrow grafts that produce a different allotype from e
recipient can be used to monitor e graft.
2. Forensic medicine - Km and Gm allotypes r detectable in blood stains & semen & r useful in

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 forensic medicine.
3. Paternity testing - E Ig allotypes r one of e characteristics used in legal cases involving paternity.

Definition:
1. Idiotype: Unique antigenic determinants present on individual Ab molecules or on molecules of
identical specificity or antigenic determinants created by e combining site of an Ab.
2. Identical specificity: All Ab molecules have e exact same hypervariable regions.
3. Anti-Id antibodies: E Abs elicited to e idiotypes.
Idiotypes r e antigenic determinants created by e hypervariable regions of an Ab & e anti-idiotypic
Abs r those directed against e hypervariable regions of an Ab.
Location: Idiotypes r localized on e Fab fragment of e Ig molecules.
- Specifically, they r localized at or near e hypervariable regions of e heavy & light chains.
- In many instances e actual epitope (i.e. idiotype) may include some of e framework residues near
e hypervariable region.
IDIOTYPE
- Idiotypes r usually determinants created by both heavy & light chain HVR's although sometimes
isolated heavy and light chains will express e idiotype.
Importances:
1. V region marke: Idiotypes r a useful marker for a particular variable region.
2. Regulation of immune responses: There is evidence that immune responses may be regulated by
anti-Id Abs directed against self-Id.
3. Vaccines: In some cases anti-idiotypic Abs actually stimulate B cells to make antibody & thus
they can be used as a vaccine. This approach is being tried to immunize against highly
dangerous pathogens that cannot be safely used as a vaccine.
4. Treatment of B cell tumors: Anti-idiotypic Abs directed against an idiotype on malignant B cells
can be used to kill e cells. Killing occurs because of complement fixation or because toxic
molecules r attached to e Abs.
CLASS
SWITCHING
AFFINITY
MATURATION
ANTIBODY
DIVERSITY
Igs GENES

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 INNATE IMMUNE RESPONSE (IIR)
SUBTOPIC DETAILS
Definition: any inborn resistance that is already present e 1
st
time a pathogen is encountered.
Properties: Functions:
1. Present from birth. 1. Protect host throughout life.
OVERVIEW
2. Not depend upon prior exposure to any particular
2. Ags.
Kill invading microbes.
3. Effective against a wide range of potential Ags.
3. Activate adaptive immune response.
4. Ready to be mobilized upon infection.
5 types:
ANTIGENS 1. 4.
Intracellular Ags: viruses, some bacteria, & small parasites. Autoantigens: in
2. Extracellular Ags: most bacteria & large parasites. autoimmune disease.
3. Allergens: aeroallergen, food, & chemical. 5. Neoantigens: in
1.Species & strain: malignancies.
C. diphtheria: causes disease in guiea pig & human.
M. tuberculosis: causes effect in mice & rabbits but not in lower, intermediate, & higher organisms.
Vaccine/disease in human: high responder is very susceptible while low responder is resistant &
asynpthomatic.
2.Race:
Leprosy & Nasopharyngeal carcinoma (NPC) happen a lot in Chinese especially lepromatous
leprosy.
Malaria: Gambians (West Africa).
HLA-BW 53 a/w P. falciparum.
HLA-B15* 13 in orang asli, Malaysia.
3. Individual difference:
Hereditary: tuberculosis 3x in homozygous twin if 1 st
present.
FACTORS HLA: HLA-B27 with ankylosing spondylitis.
DETERMINE IIR Sickle cell anemia & palcifarum.
4.Age:
1 st
6-12 months: seldom ill.
Early childhood: > frequent & > severe.
Adults: polio & chicken pox: > severe & > active immune response.
Elderly: increase susceptibility; reduce immune response, longer exposure to hazardous substances
such as smoke & toxin.
5. Hormonal/sex.
6.Nutrition:
Eat healthy food in correct amounts.
Avoid food that can cause allergy.
7.Exercise:
Strengthen e body & give a fresh & healthy body.
MECHANISMS ANATOMICAL BARRIERS
Common portals of entry of microbes:
1. Milieu exterior: Skin.
2.
Milieu interior: respiratory tract (RT), gastrointestinal tract (GIT), & urogenital tract (UGT).
3. Others: eyes & ears.
Methods of entry: physical contact (cuts, abrasions, burns, skin loss, etc), ingestion, & breathing.

Formed by skin: acts as a physical & mechanical barrier that is very impermeable to
most infectious agents.
Mechanisms of defense:
MILIEU
EXTERIOR 1. Desquamation of skin epithelium: helps remove bacteria and other infectious
agents that have adhered to the epithelial surfaces. Give out skin low pH
2. Sweat gland: secretes sweat that contains lactic acid. (acidic): directly inhibits
bacterial growth except
3. Sebaceous gland: secretes sebum than contains fatty acid.

MILIEU
INTERIOR
Formed by RT, GIT, & UGT.
E mechanisms:
i. All these tract are lined by continuous epithelial cells that physically interfere with e
entry of microbes:
1. Produce peptide antibiotics that kill bacteria.
2. Contain intraepithelial lymphocytes:
a. Belong to e T-cell lineage but express Ag receptors of limited diversity.
b. Often recognize microbial lipids & other structures that r shared by
microbes of different types.
c.Serve as sentinels against infectious agents that attempt to breach e epithelia.
d. Outward movement due to cilia or peristalsis: helps to keep air passages
and e GIT free from microorganisms.
e. Trapping effect of mucus that lines e RT & GIT: helps protect the lungs and

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 digestive systems from infection by blocking e Ag adhesion due to its stickiness.
ii. Watch-dog:
1. Cough: to expel out e dust, Ags, or any foreign bodies out of respiratory tract into
e air.
2. Sneezing (sternutation): to remove e irritant from nose.
Mechanism: irritant (allergen) get inside e nose message is sent to e sneeze
centre in e brain impulses r sent to e involved muscle sneezing.
iii. Washing actions:
1. Tears, saliva, & nasal secretion: Lysozyme and phospholipase contained can
facilitate e breakdown of e cell wall (peptidoglycan) of bacteria and destabilize
bacterial membranes.
2. Urine: very sterile to bacteria when firstly produced.
iv. Body fluids & secretions with anti-bacterial component:
1. Gastric juice: very low pH (<1) for any bacterial growth, except for E. coli.
2. Semen: contains spermine & zinc that can kill organisms & Ags.
3. Milk: contains lactoperoxidase that can lyse e bacteria.
4. Defensins (low MW proteins) found in the lung and GIT: have antimicrobial activity.
5. Surfactants in the lung: act as opsonins (substances that promote phagocytosis of
particles by phagocytic cells).
Consists mainly of normal flora.
Mainly found in e skin, GIT, & vagina.
Live symbiotically with human body: produces certain beneficial products to human
body such as vitamin K in colon & glycogen metabolism by vaginal flora.
BIOLOGICA Mechanisms of defense:
L FACTOR 1. Exhibits competitive inhibition of nutrients & cell surface attachment towards
pathogenic bacteria or fungi.
2. Produces colicins & lactic acids which function as antimicrobial & bactericidal
activity.
3. Occupy receptors which prevent e colonization of other pathogens.
HUMORAL BARRIER

Humoral factors r found in serum & formed at the site of infection.

Components of humoral factors:
1. Complement system:
E major humoral non-specific defense mechanism.
In IIR, C system can be activated through mannan - lectin pathway.
Once activated complement can lead to increased vascular permeability, recruitment of
phagocytic cells, as well as lysis and opsonization of bacteria.
Serves three functions in host defense:
a. C3b coats microbes & promotes e binding of these microbes to phagocytes.
b. Some breakdown products of C proteins r chemoattractants for neutrophils & monocytes
& promote inflammation at e site of C activation.
c. C activation culminates in e formation of a polymeric protein complex that disturbs e
permeability of microbial membrane cells & causes either osmotic lysis or apoptotic death
of e microbe.
2. Coagulation cascade:
May or may not be activated.
Some products of the coagulation system:
a. Have an ability to increase vascular permeability and act as chemotactic agents for
phagocytic cells.
b. Are directly antimicrobial for example beta-lysin, a protein produced by platelets during
coagulation can lyse many Gram positive bacteria by acting as a cationic detergent.
3. Cytokines:
In IIR, large amount of cytokines r produced by macrophages & they maybe distant from e
site of secretion.
Examples:
a. Interferons: Proteins that can limit virus replication in cells.
b. Interleukins: IL-1 induces fever and the production of acute phase proteins, some of which
are antimicrobial because they can opsonize bacteria.
4. Lactoferrin & transferrin: By binding iron, an essential nutrient for bacteria, these proteins limit
bacterial growth.
5. B-1 cells: a population of B lymphocytes which have a limited diversity of Ag receptors. They can
be found in peritoneal cavity & secrete circulating natural IgM found in e blood of normal person.
They respond to microbial toxins that pass through e walls of e GIT.
CELLULAR BARRIER
E CELLS 1. Neutrophiles or polymorphonuclear cells (PMN): Motile phagocytic cells with lobed
nuclei & can be identified by their nucleus & granules or by an antigen present on
e cell surface called CD66.
2. Monocytes or macrophages: Phagocytic cells with a kidney-shaped nucleus which

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 can be identified morphologically or by the presence of the CD14 cell surface
marker.
3. Natural killer (NK) cells:
Characteristics:
a. Do not have TCR 0r BCR but being activated by IL-12 secreted by
macrophages.
b. Have receptors that detect MHC class 1 - many virus infected cells display a
significantly reduced amount of MHC class 1.
c. Comprise 10% of peripheral lymphocytes.
Functions:
a. Specialized in killing virus infected cells & tumor cells (by cytotoxins:
perforins& granzymes).
b. Participate in fas-ligand mediated apoptosis.
c. Kill w/o prior exposure to virus, neither enhanced by exposure nor specific
to any virus.
d. Can kill w/o Ab, but IgG enhances their effectiveness.
Attachment to a bacterium e phagocyte extends pseudopods around the bacterium
PHAGOCYTOS & engulf it bacterium is enclosed in a phagosome e granules or lysosomes of the
IS phagocyte fuse with the phagosome & empty their contents into it bacteria is killed
by intracellular killing.
ACUTE PHASE RESPONSE
In acute phase response:
1. E [ ] of e mediators increases as much as 1000-folds.
2. E liver temporarily increases its synthesis of > than 30 different serum proteins called acute
phase proteins.
Acute phase proteins: Protein mediators that r found in relatively small amounts in e serum under
normal condition.
E properties of acute phase response:
1. Primitive, nonspecific defense reaction, mediated by e liver.
2. Can be triggered by infections, burns, trauma, loss, tissue necrosis, advanced cancer, & etc.
3. Can be measured by erythrocytes sedimentation rate.
E components of acute phase response:
1. C-reactive protein
AFPs trigger platelets
2. 1-antitrypsin vasoactive amines attack
3. 2-macroglobulins Ags.
4. Factor B
Prolonged response can lead to anemia & generalized loss of body mass called wasting or cachexia.
CLINICAL 1. Antibiotics:
CORRELATION Made up by harmless microorganism such as penicillin.
Act by counteracting an Ag with other bacteria or microorganism.
If e course is not completed, normal flora will be affected & reduced in number.
This will increase opportunity for any infection of other bacteria or fungi such as candida &
Clostridium difficile (pseudomembranous colitis iatrogenic).
CELLULAR IMMUNE RESPONSE
SUBTOP DETAILS
IC
HISTORI Jenner in 1796: exposure to cowpox protect against small pox.
Louis Pasteur in 1890s: vaccination can protect against rabies.
CAL Von Behring & Kitasato in 1890: serum can transfer immunity to diphtheria from immunized animals to non-
BACKGR immunized animals.
OUND Metchnikoff in 1883: phagocytes r effectors of immunity.

OVERVI Definition: E specialized immune mechanism that function to eradicate intracellular microbes (microbes that
survive & replicate within host cells) constitute cell-mediated immunity.
EW Mainly involved T lymphocytes.
To enhance e microbicidal actions of phagocytes & eliminate e microbes.
FUNCTI To be responsible for specific recognition of microbes which later be destroyed by phagocytes.
ONS To activate B cells, to stimulate e production of Abs, & to activate eosinophils & mast cells in parasitic
infection.
MECHA EFFECTOR FUNCTION OF CD4+ T CELLS
NISMS TH
TH1 differentiation occurs in response to microbes which infect & activate macrophages & NK cells such
1
as Listeria, some parasites, & microbacteria.
These microbes elicit IIR which is associated with e secretion of IL-2, IL-18, & type 1 IFN which induce
CD4+ T cells to differentiate into TH1.
Activated TH1 then secretes IL-2 & IFN-.
- IL-2: An autoactivator of of TH1.

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 - IFN-: A macrophage activator (called classical macrophage activation) & stimulator of e production
of opsonizing & complement-fixing IgG (promotes e phagocytosis of microbes).

MACROPHAGE ACTIONS
Macrophage is activated by T 1 cells through contact-mediated signals delivered by CD40L-CD40R
H
interaction & by IFN-.
- CD40L-CD40R interaction: Ensures that macrophages (APC) that r in direct contact with T cells r e
one that r activated best.
- IFN-: Enhances macrophage activation & amplifies e response.
Mechanism:
- Macrophage acts as APC & ingest Ags MHC class II presents antigenic peptide to TH1 cell TH1
cell express CD40L on its cell surface CD40L binds to CD40R on macrophage TH1 cell secretes
IFN- which then binds to its receptor on macrophage activation of intracellular signal
transduction pathway in e macrophages production of several transcription factors activation of
e transcription of genes synthesis of microbicidal ROS & NO.
E effector functions of activated macrophages:
1. Kill phagocytosed microbes mainly by producing microbicidal ROS, NO, & lysosomal enzymes.
- All e potent microbicidal agents r produced within e lysosomes of macrophages & e killing start
after phagosomes fuse with lysosomes.
- These toxic substances may also be released into adjacent tissues to kill extracellular microbes
& may cause damage to normal tissues.
2. Stimulate acute inflammation through e secretion of cytokines mainly TNF, IL-1, & chemokines as
well as short-lived lipid mediators such as PAF, PG, & leukotrienes.
- E mediators stimulate e recruitment of PMNs, MNCs, & T cells to e site of infection & causes
inflammation.
3. Remove dead tissues & facilitate repair after e infection is controlled.
- Activated macrophages secreted platelet-derived growth factor that stimulates e growth &
activities of fibroblasts & endothelial cells which help in tissue repair after infection.
Tissue injury & inflammation caused by T 1 cells & activated macrophages r e hallmark of Delayed Type
H
Hypersensitivity reactions.

TH2 differentiation occurs in response to helmints & allergens which cause persistent & repeated t cells
stimulation with little inflammation & macrophages activation.
These Ags also cause chronic T cell stimulation w/o strong IIR that r required for TH1 differentiation.
Ag-stimulated CD4+ T cells secrete small amount of IL-4 from their initial activation whose
concentration increases gradually due to e persistence of e Ags. Mast cells also secrete IL-4 which
induces e formation of TH2 cells.
TH2 cells mediated IR r e underlying cause of allergic reactions.
Activated TH2 cells secrete IL-4, IL-13, & IL-5.
- IL-4:
1. Stimulates e production of helminth-specific IgE which opsonize e helminth. E IgE-coated helminths
TH activates mast cells & causes its degranulation.
2 2. Stimulates peristalsis in GI tract.
3. Stimulates e production of neutralizing IgG which does not promote phagocytosis or activate complement
system efficiently but r capable of neutralizing microbes & toxin.
- IL-5:
1. Directly activates eosinophils in e vicinity of e helminths. Activated eosinophils release their
granules contents (major basic & cationic protein) which r capable of destroying e integumens of
helminths.
- IL-13:
1. Capable of activating macrophages to express mannose receptors & to express enzymes
that promotes collagen synthesis & fibrosis >>> called alternative macrophage activation.
2. Stimulates mucus production in GI tract.
- All cytokines secreted by TH2 cells:
1. Can lead to granuloma formation & tissue remodelling due to macrophage activation.
2. Involved in blocking entry & promoting expulsion of microbes in mucosal tissues.
EFFECTOR FUNCTION OF CD8+ T CELLS (CTLs)
CTLs recognize class I MHC-associated peptides on infected cells & kill these cells as well as eliminate e
reservoir of infection.
Source of peptides:
1. Protein Ags synthesized in e cytoplasm.
2. Protein Ags of phagocytosed microbes that escape from phagocytic vesicles into e cytoplasm.
Mechanisms:
- Ag receptors of e differentiated CTL recognize MHC-associated peptides on e target cell e recognition
induces clustering of T cell plasma membrane proteins & their ligand on e target cell an immunological
synapse forms b/w e two cells biochemical signal r generated activation of signal transduction
pathway activation of CTL exocytosis of e contents of CTLs granules into e immunological synapse

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 delivery of granule proteins into e target cells apoptosis occurs.
Effector functions of CTLs:
1. Through e exocytosis of e content of e CTLs granules:
a. Granzymes:
-
Include granzymes A, B, & C which r serine proteases (caspases) that cleave protein after
aspartate residues in e cytoplasm of e target cells in order to induce apoptosis.
b. Perforin:
- A membrane-pertubing molecule homologous to C9 complement protein.
- Main function is to facilitate delivery of e granzymes into e cytosol of e target cells.
- Has e property of polymerizing & forming pores in membranes which may facilitate granzymes
delivery into e target cells.
c. Serglycin:
- A sulfated proteoglycan which serves to assemble a complex containing granzymes & perforins.
2. Through e formation of Fas-FasL:
- Mediated by e interactions of membrane molecules on e CTLs & target cells.
- On activation, CTL expresses FasL that bind to death receptor of Fas expressed on target cells.
- E interaction results in e activation of caspases & apoptosis of e target cells.
CTLs dont kill adjacent cells that do not display e Ag because e killing is highly specific due to e presence of
immunological synapse.
- Immunological synapse is a space at e site of contact b/w CTLs & target cells where e molecules that
perform e killing r secreted into.
NATURAL KILLER CELLS
Many viruses avoid killing by CTLs by block e expression of class I MHC on e surface of e cells theyve
infected.
In this case, NK cells inhibitory receptors r not engaged, & they become activated to eliminate e infected
cells.
E mechanisms of action of NK cells:
1. Degranulation of NK cells consists of killing proteins:
- E granule proteins include molecules that alter e permeability of e infected cells & e molecules which
activate enzymes that induce apoptotic death in e infected cells.
- E net result: killing of e infected cells & eliminating e reservoirs of infection.
2. Synthesis & secretion of IFN-:
-
NK cells secrete IFN- IFN- activates macrophages macrophages ingest microbes & kill them as
well as secrete IL-12 more NK cells r activated efficient intracellular killing.
E whole killing mechanism:
- APC presents viral Ags to CTLs virus shuts off MHC expression NK cells r activated infected cells r
killed.

HUMORAL IMMUNE RESPONSE (HIR)

PORTIONS DETAILS
Definition: A type of host defense that is mediated by secreted Abs to protect against extracellular
OVERVIEW microbes & their toxins.
A specific immune response mediated mainly by B lymphocytes & Abs.
IgG 1. Neutralization of microbes & toxins.
2. Opsonization of Ags for phagocytosis by macrophages & neutrophils.
3. Activation of e classical pathway of complement system.
4. ADCC mediated by NK cells.
5. Neonatal immunity: transfer of maternal Abs across e placenta & gut.
6. Feedback inhibition of B cell activation.
IgM 1. Activation of e complement system via e classical pathway.
EFFECTOR 2. Ag receptor of nave B lymphocytes.
FUNCTIONS 3. Activation of B lymphocytes & phagocytes.
OF 4. Effective antigenic agglutinator due to high no. of antigenic binding sites (5 sites).
ANTIBODY 5. Predominant early Abs.
IgA 1. Mucosal & neonatal immunity.
2. Activation of complement system by e lectin pathway or by e classical pathway.
IgE 1. Mast cells degranulation in hypersensivity type 1 reaction.
2. Main cells in parasitic infection.
IgD 1. Help in activating & suppressing lynphocytes activity.
2. Ag receptor of nave B lymphocytes.
FUNCTIONS Neutralizati
Why: Many microbes mediate their pathological effects by binding to membrane protein
OF on
or lipids (cellular receptors) on e surface of e host cells. Infected cells may be damaged &
ANTIBODY e microbes will be released & infect e neighboring cells.
Requires e Aim: To prevent microbes from invading, infecting, & colonizing e host cells.
formation of
Requirement: E Ag-binding region (Fab) of e Abs, thus it may be mediated by Abs of any

Aliahs Y1B2
 AgAb isotype in e secretion & circulation.
complex. Mechanisms:
1. Abs block binding of microbes & infection of host cells.
2. Abs block injection of adjacent cells from infected neighboring cells.
3. Abs block binding of toxin produced by microbes to cellular receptors.
Results:
1. Allosteric effect: Ab binds to a microbe & induces conformational changes in surface
molecules that prevent e microbe from interacting with cellular receptors.
2. Steric hindrance: Ab binds to microbial structures & interferes (hinders) with e ability
of e microbe to interact with e cellular receptors.
Examples: Tetanus toxin is neutralized when specific IgG binds to it thus preventing e
toxin binding to motor end plates & causing persistent stimulation & sustained muscular
contraction.

Opsonization: coating of bacteria for which e Abs Fab region has specificity & promoting
their phagocytosis by binding to Fc receptor on e phagocytes.
Phagocytosis: A process that involves the engulfment and destruction of pathogens,
cellular and particulate matter by phagocytes.
- Mononuclear phagocytes & neutrophils express receptors for e Fc region of IgG that
specifically bind opsonized particles.
- Microbes may also be opsonized by C3b & phagocytosed by binding to a leukocyte
receptor for C3b.
- Phagocytes Fc receptors:
1. FcRI (CD64):
High affinity receptors which binds to IgG1 & IgG3 strongly.
Composed of an Fc region-binding chain associated with a disulphide-linked
Opsonizatio homodimer of a signaling protein called FcR chain (homologous to signal-
n& transducing chain of TCR).
Phagocytosi Binds Abs attached to Ags better than binds to free Abs.
s
2. FcRIIB:
An inhibitory Fc receptor which has an ITIM motif in its cytoplasmic tail.
In phagocytes, engagement of FcRIIB may attenuate signaling from other
activating receptors including FcRI & thus prevents phagocytosis &
inflammation.
Mechanism:
Opsonization of microbe by IgG Binding of opsonized microbes to phagocytes Fc
receptors (FcRI) Fc receptors signals activate phagocyte phagocytosis of microbe
killing of ingested microbe.
Opsonization-phagocytosis mediated by Ab is e major mechanism of defense against
encapsulated bacteria.
Spleen is important site of phagocytic clearance of opsonized bacteria because it contains
lots of phagocytes.

Mainly involved NK cells which use their FcRIII to bind to Ab-coated cells.
Occurs only when e target cell is coated with Ab molecules.
Free IgG in e plasma neither activates NK cell nor competes effectively with cell-bound
ADCC IgG.
Mechanism:
Opsonization of microbe by IgG binding to FcRII receptor on NK cells NK cells
activated synthesis & secretion of cytokines such as IFN- discharge of NK cells
contents extracellular killing of microbes.
IgG & IgM can activate complement system via classical pathway.
E activation is accomplished by e binding b/w Fc region of AgAb complex with C1q of e
Complemen complement system.
t Activation
E activation of complement system leads to e formation of MAC which lyses e bacterial
wall (osmotic death).
Agglutination of particulate matter including bacteria & viruses.
Agglutinatio
n IgM is particularly suitable for this as it is able to change its shape from a star into crab-
like form.
Abs against bacterial ciliae or flagellae will hinder their movement & ability to attach to
Immobilizati
receptors on host cell
on
Only Fab region involved.
Others 1. Expulsion as a consequence of mast cell degranulation:
Ags (e.g.: parasitic worms) bind to e Fab region of IgE AgAb complex bind to IgE
receptor on e mast cells via Fc region activation of mast cells degranulation
release of mediators smooth muscle contraction diarrhea & expulsion of
paracites.
2. Precipitation of soluble Ags by immune complex formation:

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 Soluble Ags bind to Abs complex becomes precipitated (size depends on e ratio of
Ag: Ab) complex fixes at one site removed by phagocytes.

Sites: Respiratory tract & GI tract.

Components of immune system:
1. Mainly IgA: Produced in e mucosal lymphoid tissues & secreted through e mucosal epithelium into e
lumens of e organs (isotype switching to IgA occurs > efficiently in mucosal lymphoid tissue).
MUCOSAL 2. To a lesser degree IgG.
IMMUNITY 3. Lymphocytes.
- All r organized into lymphoid follicles that r located underneath e epithelia of RT & GIT.
Mechanisms:
- IgA binds to microbes & toxins present in e lumen IgA blocks their entry into host cells by
mechanism of sneezing or e movement of cilia microbes r expelled out.
1. Ab alone:
Blocks entry of toxin & virus: IgG, IgM, & IgA.
Immobilizes bacteria: (IgM > IgG).
Agglutinates bacteria: (IgM > IgG).
ANTI- 2. Ab & complement system:
BACTERIAL Lysis of bacteria: IgM & IgG.
IMMUNITY 3. Ab & immune cells:
Opsonization of bacteria & fungi for phagocytosis: IgG.
Activation of extracellular killing: IgG.
Activation of complement system & formation of MAC.
Free virus 1. Ab alone: neutralization of virus to cells.
2. Ab & complement: MAC.
ANTI-VIRAL
Virus- 1. Ab & complement: MAC & phagocytosis.
IMMUNITY
infected 2. Ab bound to infected cells: ADCC by NK cells & macrophages.
cells
Abs across e placenta:
- Mainly involved by IgG.
- Mediated by neonatal Fc receptor called FcRn (resembles a class 1 MHC).
- In post-neonatal period, e receptor (on e surface of epithelium) functions to protect plasma IgG from
catabolism & enhances its half-life.
NEONATAL
IMMUNITY FcRn binds to circulating IgG promotes endocytosis of e IgG complexes with e receptor protects
e internalized IgG from intracellular degradation recycles e bound IgG to e cell surface
releases IgG back to e circulation.
Abs in e milk & colostrums:
- Breast milk & colostrums r full with maternal IgA & IgG which r ingested by infants. Thus, during e 1st-
6th month of life, infants r less prone to deseases.
T LYMPHOCYTES
PORTIONS DETAILS
ORIGIN
MATURATION
ACTIVATION
OF CLONES
EXPRESSION
OF UNIQUE B
CELL
RECEPTORS
RECIRCULATIO
N
HOMING
TOLERANCE
INDUCTION
TYPES OF
ANTIGENS
TYPES OF
THELPER CELLS
TYPES OF IR
% OF TOTAL
LYMPHOCYTES

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 B LYMPHOCYTES
PORTIONS B LYMPHOCYTES
ORIGIN
MATURATION
ACTIVATION
OF CLONES
EXPRESSION
OF UNIQUE B
CELL
RECEPTORS
RECIRCULATIO
N
HOMING
TOLERANCE
INDUCTION
TYPES OF
ANTIGENS
TYPES OF
THELPER CELLS
TYPES OF IR
% OF TOTAL
LYMPHOCYTES

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 CYTOKINES
PORTIONS DETAILS
OVERVIEW
PROPERTIES
CYTOKINE
RECEPTOR FAMILY
TNF
ILs IL-1
IL-2
IL-3
IL-4
IL-5
IL-6
IL-7
IL-9
IL-10
IL-12
IL-15
IL-16
IL-17
IL-18
IFN ANTIVIRA
L IFN
IMMUNE
IFN
TRANSFORMING
GROWTH FACTOR
(TGFB)

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 NOMENCLATURE
Name Abbreviation Examples
Interleukins IL 1L-1, IL-2etc
Interferons IFN IFN, IFN, IFN
Tumour necrosis
TNF TNF, TNF
factors
Growth factors GF NGF, EGF
Colony stimulating
CSF M-CSF, G-CSF, GM-CSF
factors
chemokines - RANTES, MCP-1,MIP-1

DIFFERENCES BETWEEN CYTOKINES & POLYPEPTIDE HORMONES

CYTOKINES EXCEPTI FEATURES POLYPEPTIDE EXCEPTIO
ONS HORMONES NS
SOURCE
FUNCTION
TARGET CELL
MODE OF
ACTION

Dan apabila hamba-hambaKu bertanya kepadamu

(Muhammad) tentang Aku, maka sesungguhnya Aku
dekat. Aku kabulkan permohonan orang yang
berdoa apabila dia berdoa kepada-Ku. Hendaklah
mereka itu memenuhi (perintah)-Ku dan beriman
kepada-Ku, agar mereka memperolehi kebenaran.
(2:186).
Terima kasih ALLAH!

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 COMPLEMENT SYSTEM (CS)
PORTIONS DETAILS
E term complement (C) was used to refer to a heat-labile serum component that was able to lyse bacteria
(activity is destroyed (inactivated) by heating serum at 56 degrees C for 30 minutes).
A nonspecific system: same for any Abs.
Consists of at least 40 chemically & immunologically distinct plasma proteins & proteins on cell
membranes >>> capable of interacting with one another, Abs, & cell membranes.
OVERVIEW Plasma proteins mostly reside in beta globulins (15% of beta globulin) in serum electrophoresis
1 mediator of humoral IR & involved in e recognition of B lymphocytes.
o

Is a cascade system: step to step.

Mainly produced by hepatocytes & macrophages. The genes are located at chromosome 1 (C , C , C ) & 1 3 6
chromosome 6 (C4a, C4b, C2, B factor, & HLA).

Opsonize bacteria for enhanced phagocytosis.

It can recruit and activate various cells including polymorphonuclear cells (PMNs) and macrophages.
FUNCTIONS It can participate in regulation of antibody responses.
It can aid in the clearance of immune complexes and apoptotic cells by making them > soluble.
It can also have detrimental effects for the host: it contributes to inflammation and tissue damage & it
triggers anaphylaxis.
CLASSICAL PATHWAY, CP ALTERNATIVE PATHWAY, LECTIN PATHWAY, LP
PATHWAYS
AP
Response to Ag-Ab complex. Very similar to CP.
Provides a means of non-
Can only result when e person
is previously exposed to
specific resistance (1 line
st
Usually activated when binds to
defense) against infection w/o e e polysaccharides on Gram -ve
infection.
OVERVIEW participation of Abs. bacteria
Requires Factors B and D and Independent of Ag-Ab complex.
Mg2+ cations (all present in
normal serum).
Lipopolysaccharide on e
IgM: binding site - CH
3 (E best),
membrane of Gram -ve
Microbial polysaccharides.
only 1 Ag-Ab complex needed
bacteria.
in one time.
Teichoic acids at Gram +ve
ACTIVATORS IgG ,
3 1, 2: binding site- CH2, at bacteria.
least 2 Ag-Ab complexes Zymosan in fungi.
needed in one time.
Cobra venum factor (CVF)
s/thing that acts like C3 factor
via AP.

C,C,C,&C.
1 2 3 4 C , Factors B & D, Properdin (P),
3 Mannan-binding lectin, MBL
(C1q-like).
COMPONENT C -INH & C -BP.
1 4 Factors I & H, decay
*

S accelerating factor (DAF), MBL-associated serine protease:

Complement receptor 1(CR1), MASP1 (C1r-like) & MASP2 (C1s-
& etc. like).

INDICATORS Low level of both C 3 & C4.
DEFICIENCY C1INH: Hereditary angioedema
due to e overproduction of C2b
(prokinin).
C , C , C : Predisposition to SLE
1 2 4 bacteria.
by which e opsonization of
immune complexes help keep
them soluble, deficiency results
in increased precipitation in
tissues and inflammation.
Low level of C 3 & normal level Low level of both C 3 & C4.
of C4
Factors B or D: Susceptibility to MBL: Susceptibility to bacterial
pyogenic (pus-forming) infections in infants or
bacterial infections due to lack immunosuppressed due to
of sufficient opsonization of inability to initiate the lectin
pathway.
C : Susceptibility to bacterial
3
infections due to lack of
opsonization & inability to
utilize e MAC pathway.
C5, C6, C7 C8, & C9
Susceptibility to Gram-negative
infections due to inability to
attack e outer membrane of
Gram-negative bacteria.
Properdin (X-linked):
Susceptibility meningococcal
meningitis due to lack of
opsonization of bacteria.
Factors H or I: C 3 deficiency &
susceptibility to bacterial
infections due to uncontrolled

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 activation of C3 via AP resulting
in depletion of C3.
Hypocomplementaemia:
-2 types:
1. Primary: Hereditary angioedema (hae).
2. Secondary:
a) Post-steptococal granulomatitis: deficiency in C3.
b) Mesangial granulomatitis: C3 Necrotic Factor (C3 NeF).
c) SLE: Abs against nuclear Ag (ANA) which contains DNA. Target organs are skin, glomerulli, &
brain.

Activation of e three pathway leads to e activation of MAP which ranges from e lysis to e killing of
microbes or Ags.
MEMBRANE C 5 convertase: CP (C4b2a3b), LP (C4b2a3b), or AP (C3bBb3b) cleaves C5 into C5a and C5b C5a remains in e
ATTACK fluid phase & e C5b rapidly associates with C6 and C7 & inserts into e membrane C8 binds, followed by
PATHWAY several molecules of C9 C8 forms a pore in the membrane C9 amplifies it e cellular contents leak
(MAP) lysis occurs.
Lysis is not an enzymatic process; it is thought to be due to physical damage to e membrane.
E complex consisting of C bC C C C is referred to as e membrane attack complex (MAC).
5 6 7 8 9

1. Qualitative test: to test e function of CS - CH (50% complement hemolysis).

50
2. Quantitative test:
LAB TESTS Measurement of C & C plasma level by using single radial immune diffusion.
3 4

Normal value of C : 0.15-0.45 g/L & C : 0.85-1.75 g/L (neonates have value somewhere b/w these
4 3
ranges & e values will increase with increasing age).

THE PATHWAYS OF THE

COMPLEMENT SYSTEM

Ca2+, Mg2+
AgAb
Ag + Ab
complex

Activated
C1qr2s2
(C1)
C1qr2s2 CLASSICAL PATHWAY

C4a + C4b
C4
C 2b
C 4a
LECTIN C 4b 2a
C2a + C2b (C3 convertase)
PATHWAY C2

C3a + C3b
Activated C3
MASPs
MASPs
C 3a

MBL/MASP-
1/MASP-2 tri- C 4b 2a 3b
molecular (C5
complex convertase)
MASP-1
& MASP- C5a + C5b
2 C5
MBL + Activated
pathogen C1q-like C6 + C7 + C8 + C9

C5b6789 Holes in
microbial
(MAC) membrane

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 C3bBbC3b
(C5
convertase) Microbial lysis
C 3a

C3a + C3b
C3 MEMBRANE
ATTACK
PATHWAY
C3bBb
(C3
convertase) C3b + B

C 3a Factor D

C3a + C3b
C3
ALTERNATIVE
PATHWAY
C3bBb C3i + Bb
(C3
convertase)
Factor
D
[Almighty Allah's Limitless Mercy]
C3i + B
O son of Adam, so long as you call upon Me and ask of Me, I shall forgive you for
what you have done, and I shall not mind. O son of Adam, were your sins to
reach the clouds of the sky and were you then to ask forgiveness of Me, I would Factor B
forgive you. O son of Adam, were you to come to Me with sins nearly as great C3i
as the earth and were you then to face Me, ascribing no partner to Me, I would C3
bring you forgiveness nearly as great at it.
Spontaneous
It was related by at-Tirmidhi (also by Ahmad ibn Hanbal). Its Isnad (chain of
authorities) is sound.
COMPONENTS OF COMPLEMENT SYSTEM
Fragment Activity Effect Control Factor (s)

C2a Prokinin, accumulation of fluids Edema C1-INH

Anaphylatoxin reaction, Basophil and mast cells

C3a degranulation; enhanced vascular permeability, Anaphylaxis C3a-INA
smooth muscle contraction

Opsonin, phagocyte activation: promotes

C3b Phagocytosis Factors H and I
phagocytosis by binding to complement receptors

Anaphylatoxin reaction, Basophil and mast cells Anaphylaxis (least

C4a degranulation; enhanced vascular permeability, potent, weaker C3a-INA
smooth muscle contraction than C3a)

Opsonin, phagocyte activation: promotes

C4b Phagocytosis C4-BP and Factor I
phagocytosis by binding to complement receptors

Anaphylatoxin reaction, Basophil and mast cells

Anaphylaxis
degranulation; enhanced vascular permeability,
(most potent)
smooth muscle contraction
C5a C3a-INA
Chemotaxis, stimulation of respiratory burst,
activation of phagocytes, stimulation of inflammatory
Inflammation
cytokines, & attraction of polymorphonuclear
leukocytes & macrophages (chemokinesis)

Opsonin, phagocyte activation: promotes

C5b Phagocytosis Factors H and I
phagocytosis by binding to complement receptors

Chemotaxis Inflammation
C5bC6C7 Protein S (vitronectin)
Attaches to other membranes Tissue damage

REGULATION OF COMPLEMENT SYSTEM

Component Regulation

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 All C1-INH; dissociates C1r and C1s from C1q

C3a C3a inactivator (C3a-INA;Carboxypeptidase B); inactivates C3a

Factors H and I; Factor H facilitates the degradation of C3b by

C3b
Factor I

C4a C3-INA

C4 binding protein(C4-BP) and Factor I; C4-BP facilitates

C4b degradation of C4b by Factor I; C4-BP also prevents association of
C2a with C4b thus blocking the formation of C3 convertase

RECEPTORS OF COMPLEMENT SYSTEM

Receptors Structures Ligands Cell distribution Function
Mononuclear
Phagocytosis,
phagocytes,
160-250 kD, multiple clearance of ICs,
Type 1 (CR1, CD35). C3b > C4b > iC3b. neutrophils, B & T
CCPRs. cofactor for cleavage
cells, RBC,
of C3b & C4b.
eosinophils, FDCs.
Coreceptors for B
B cells, FDCs, cells activation,
145 kD, multiple
Type 2 (CR2, CD21). C3d, C3dg > iC3b. nasopharyngeal trapping of Ags in
CCPRs.
epithelium. germinal centre,
receptors for EBV.
Phagocytosis,
Mononuclear
Type 3 (CR3, Mac-1, CD Integrin, with 165-kD iC3b, ICAM-1, also leukocyte adhesion
phagocytes,
11b/ CD 18). chain & 95-kD 2 chain. binds microbes. to endothelium (via
neutrophils, NK cells.
ICAM-1)
Mononuclear
Type 4 (CR4, p150/95, CD Integrin, with 150-kD Phagocytosis & cell
iC3b phagocytes,
11c/CD 18) chain & 95-kD 2 chain. adhesion.
neutrophils, NK cells.

Complement Fixation Test

1st exposure to an Ag: no Abs formed, no activation of CS via CP, thus, RBCs lysed by CS [-ve lysis & +ve reaction].
2nd & subsequent exposures: Abs present, CS is activated via CP, thus, no RBCs lysed by CS [+ve lysis & -ve reaction].

Aliahs Y1B2
 DIFFERENCES OF IMMUNE RESPONSE
CHARACTERISTICS INNATE IMMUNE RESPONSE ADAPTIVE IMMUNE RESPONSE
SPECIFICITY For structures shared by groups of related For Ag of microbes & nonmicrobial Ags.
microbes
DIVERSITY Limited, germline-encoded Very large, receptors r produced by somatic
recombination of gene segments
MEMORY None Yes
NONREACTIVITY TO Yes Yes
SELF
COMPONENTS
CELLULAR & Skin, mucosal epithelia, antimicrobial chemicals Lymphocytes in epithelia, Abs secreted at
CHEMICAL epithelia surfaces
BARRIERS
BLOOD PROTEINS Complement, others Abs
CELLS Phagocytes (macrophages, neutrophils), NK Lymphocytes
cells

DIFFERENCES OF LYMPHOCYTES
PORTIONS B LYMPHOCYTES T LYMPHOCYTES
ORIGIN Bursa dependent (equivalent to bone marrow) Thymus dependent
TYPE OF IR Humoral immunity Cell mediated immunity
RESPONSE TO Bacterial immunity Transplant, tumor, & viral
PRODUCTS Produce serum Ig Release soluble mediators: Lymphokines
LIFE SPAN Short life span Long life span
NO OF Ag 2 Ag recognition sites 1 Ag recognition site
RECOGNITION SITES
FUNCTIONS Monitor extracellular compartment of body Monitor intracellular compartment:
- Recognize small peptides derived from
microbes
- kill viruses
- help B cells produce Abs

DEVELOPMENT OF IMMUNE RESPONSIVENESS IN THE FETUS

GESTATION IMMUNE DEVELOPMENT
AL AGE IN
WEEK
4 Macrophages in yolk sac
6 Complement system detected
6 NK cell in liver
6-7 Thymic epithelium develops
7 Lymphocytes & macrophages in blood
7-9 Lymphocytes in thymus (training centre for lymphocytes): CD3+ (determines whether e cells can be a
lymphopcytes or not), 4+, 8+ (T helper cells), & TCR+ (T suppressor cells)
11 Serum IgM detectable in infection, eg: rubella & nitrogen responsiveness of thymocytes
12-14 Neutrophil leukocytes in blood
13 B cells in bone marrow
14 Nitrogen responsiveness of peripheral lymphocytes
17 Endegenous IgG in serum (during infection only)
20 Alloreactivity detected
TERM B cells: normal no. but immature CD5+
- Abs: IgM to protein, but not to carbohydrates Ags.
- Complements
- T cells
- Cytokines
Activity: TC and NK cells

albumin

Serum
(-) Electrophoresis
y (+)
2 1 2 1
- Most Igs reside in
x globulin protein
Aliahs Y1B2
portion.
- Most plasma