immune responses

Primary Immune Response to initial antigenic stimulus
is slow, sluggish, short live with low antibody titer
that do not persist for along time ,antibody formed are
1gM.
Primary Immune Response:

• The antibody classes start with 1gM followed by
IgG and described as Antigen specific response.



First exposure to antigen X
Antibodies to X
Secondary immune response to antigen X
Primary immune response to antigen Y
Antibodies to Y
Time (days)
Second exposure to antigen X, first exposure to antigen Y
Primary immune response to antigen X

• Secondary Immune Response to subsequent
stimuli is prompt, powerful prolonged and with
much higher level of antibody it vast for long
time
• Antibody predominatly formed are IgG,
prescence of memory cell which are specific for
antigen, so always if we give multiple dose of the
mechanisum , The antigen type is in these
same Antigen to the same host will lead good
responses is B- dependent- Antigen .
immune response because of the regulatory

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—Ill Cross section post-capillary venule
Postcapillary venule
Primary lymphoid
follicle
B lymphocytes I



Cell cooperation in the antibody response
AFC ;
AFC
IL-4r IL-7
resting
decay of receptors
T cell proliferation
division
antigen
AFC

3
1 2
After a macrophage engulfs and degrades a bacterium, it displays a peptide antigen complexed with a class II MHC molecule.
A helper T cell that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophage, forming a clone of activated helper T cells (not shown).
A B cell that has taken up and degraded the same bacterium displays class II MHC–peptide antigen complexes. An activated helper T cell bearing receptors specific for the displayed antigen binds to the B cell. This interaction, with the aid of cytokines from the T cell, activates the B cell.
2
Endoplasmic reticulum of plasma cell
T
1
3
Class II MHC molecule
Macrophage
Bacterium
The activated B cell proliferates and differentiates into memory B cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same bacterial antigen that initiated the response.

factors affecting antibody
production
Nutritional status
Route of administration
Size and Number of doses
Adjuvant
Immunosuppressive agent
Age
Multiple antigens

Lymphokine have several biological function
Cellular Immune Response: -
The term cell rnediated immunity refers to the
specific immune responses that do not involve
antibodies, induction of cell mediated immune
response (CMI) consists of specifically sensitizing
T-lymphocytes comes against the antigen. When
lymphokines : material required as secreted
Presenting Cell (APC) ,so T- cell under goes blast
transformation and clonal proliferations
selectively in paracortical areas of lymph nodes.
sensitized T- cell comes in contact with antigen
determinant (epitopes)by the function of Antigen
proteins from the activated T- cell , These

Epliapes (aniFgenIc determloants0 on Drillge n

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V
Antigen: ag
APC
CU, T-cell
A
<›
yoor
p .4
Clearance,
Neutralization
Lys is
rorayrne etc.
bizath signals: Perforin
A
B-cell
Cytokines And Interferon
Cb4+ T-cell

T- cell recognition of antigen
infected cell
MHC molecule presents
peptide
antigen peptide bound
to MHC molecule
T-cell receptor recognizes
MHC and peptide

Differentiation into
specialized T cells
Antigen
challenge
mmature
T cell
Memory
T cell
;•
Cytotoxic
T cell (Tc)
Helper
T cell (TH)
ralren aitlilLE UM MIR WM IL Sim

1
After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Cell-mediated immunity (attack on infected cells)
Dendritic cell
Figure 43.15
2 3
Humoral immunity (secretion of antibodies by plasma cells)
1
2 3
R
Pe tide anti en

1-Effect on Lymphocytes:This role is done by:
a-- Blastogenic factor (BF)
b Potentiation factor (PF)
lympholdnes: material required as secreted
proteins from the activated T-- cell , These
c- Cell co-operation factor (CE).
Lymphokine have several biological function

2-- Effect on macrophage : This Lymphokine is
function is covered out
by the following:
a-- Macrophage inhibition Factor (MIF)
c- Macrophage chemotactic Factor (MCF)
b Macrophage aggregation Factor (MAF)

• 3-Effect on granulocytes:
a- Inhibition factor
b Ch em otactic factor

• 4-Effect on tissue culture:
a-L ymphotoxine
b Interferon
C Proliferati on inhibition

M .
• Antibody or
lmmunoglobulin
Are glyeoproteins present in the gama- globuline
fraction of serum. Immunoglobulin generally
natural present in blood without previous
Immunoglobulin that
are antibody
Immunoglobulin while no all Immunoglobulin
stimulation . Thus all antibodies are
Produce specifically by B-cell afterantigenic
antigenic stimulation However antibody are the



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glycoprotein in nature.
specific to antigine induce them.
React specifically with their own antigen
The charateriste of antibody are :
fluid, Urine ,Saliva , Ear wax and tears.
Antibody are distributed in serum, body

Antigen-
Antigen-binding site
Variableregions
C C
ansmembranegion
A B cell receptor consists of two identical heavy
several disulfide bridges.
Figure 43.8a
(a)
chains and two identical light chains linked by
Cytoplasm of B cell
Heavy chains
Plasmamembrane
Constantregions

The basic structure of antibody Molecule
the antibody molecule is a four chains molecule which
are:
two light chain (I.C) consist of 214 amino acid, 106
amino acid respect the constant region of molecule
two heavy chain (HC) consist of440 amino acid,
•
residcus 322 amino acid occur in constant region
(CH). 118 amino acid in the variable region (VH)
while variable region consist of 108 amino acid
for Kappa & Lambda

BASIC STRUCTURE O IgG
1-NL...?lariable region
Heavy chain
Al i
...(fr.
mom/ Disulphide bonds V = Variable C = Constant
L-I
Hinge
region
— 40, Light chain
FC
region
Antigen
binding
sites
Fab
region
(Ieiiii

There are 5 Classes of (HC) Heavy chain content
for five Classes of lmmunoglobulines:
1-(Gamma) or lgG
2- (Mu) or lgM
3-(Alpha) or lgA
4-(Epsilon) or lgE
5- (Dalta) or IgD
Fab : it is amino acid terminal half of heavy chain &
determine biological properties of Immunoglobuline

chain (LC) are consist the antigen combination sit.
light, it act as Antigen binding fragment .
Fc : It is carboxyl terminal half of heavy chain &
The variable region in both heavy chain (HC) and light

lgG
Class
Principal functions
Basic s-tructure
Protects against intestinal pa.rasites_ Responsible for many of the symp?om-s of allergy
IgA
Secretory component
Dime rc: protects mucosa! surfaces
Pentameric: effective first line of defence against micro-organisms in the bloodstream. Produced in the primary response
CLASSES CIF itodviLJNOGLOBULINS
DR p!=-1 cic ordRe
n
) chain
Influences lymphocyte functions
igE
IgD
Protects extravascular compartment from micro-organisms and their toxins

PHYSICAL AND BIOLOGICAL PROPERTIES
OF HUMAN [MIVIUNOGLOBULIN CLASSES.
Cfass 1-leayy Number Mean
Chain of Serum
Desi g 31utP. Con.cen- Molecular Mean Biologic
natimi c1141Est s rntian Wright Survival ktivity
ingici.1 dawns days
IgG 1. I 1250 150..0I30 23 1. Opsonin
Fix complement
Crogses placenta
IgIvi rh 1 1213 11901,.13010 5 1. 1 ix complemcni
Aggluticaiion
Aniigein receptor
It a 2 281:1 1 70p1300 6 1. Secretory amlbcidy
2. gglutilnallicirr
Ion 6 2 a 1611.01113 3 1. Anti.geri receptor
IgE e 1 10.113 186,00111I 2 1. Anti.parasitc antibody
2. Allery antibody

• antigen -Antibody reactions
The following are the important tests based on
serological reactions.
. Antigen - antibody reactionsin vitro are called
Antigen and Antibody Reaction
Antigen-- Antibody reactions are useful in
Laboratory diagnosis of various diseases and in
the identification of infectious agents in
epidemiological survey

• • Agglutination
• Precipitation
• Redial —— immunoassay
• ELISA
• Immune fluorescence
• Neutralization
• Haemegglutination
• Complement fixation test. and other tests using
complement system
• Antiglobuline test ( comb’ s test )

• The antigen -Anti body complex is not. found
firmly together and may dissociate spontaneously
unless PH, salt concentration and temperature are
properly adjusted the major forces that hold
antigen
- antibody complex together are their ionic

when soluble antigen combines with its antibody
complex forms insoluble Precipitate.
temperature and PH the antigen — antibody
in presence of electrolytes (Nacl) at suitable
Precipitation:
multivalent. Antigens
movement antigen b- Bivalent Antigens, c-
attractions the antigen have three type which
affected theRaction Antigen — Antibody a -

Epitopes
(antigenic
determinants)
Antib
Antigen

one
antibody combine precipitation can, be produced in
solutions or in semisolid (agar gel) medium,
precipitation in solution can be shown by adding these
two on a slide and mixing well or in small narrow tubes
Cattic hypothesis:
It is multivalent antigens combine with bivalent
antibody in varying proportions , depending antigen
antibody ratio in reaction mixture Precipitation
results.
When large lattice is formed consisting of alternating
antigen and antibody molecules.
In general precipitation is maximum when optimal
proportions of
This possible only in the zone of equivalence. zone of
antigen and antibody excess lattic does not enlarge as
valiancy of antigen and antibody is fully satisfied .


An EibOdy-tICCee..!4 EqUiv AitifiCe
zone zone
Antige n
eXCeSS
SuperriatitrutS
excess Ag
Araihody a tied
Eigeri-tAXCetW want

Response)
Nine fraction of which are involve in complement
pathways which act as sequential manner and can
be activated or inhibited , properdin is important
on first exposure to Microorganism (first Immune
The Complement system
A plasma protein with 25 fraction these protein
heat sensitive at 56 C for 30 minutes , the
chemical structure of complement is polypeptide
chains interconverted by disulfide bound.
spleen as well as enterocytes with 25 fractions.
The complement system plays a major role in
host defense and the inflammatory process. The
complement component synthesized in liver ,

IRTHE CO.n.A.F -LEMENT CASCADE
The classical and alternative pathways join at the point of the conversion of C3 to C3b by the C3 convertasc 5_ either of the two C5 convertases, which are subsequently assembled. act on C5 to produce C5b (and C5a) to which C6 to C9 are added to form the membrane attack complex
Ic5b-9 1
ILASSICAL PATHWAY
[C5 convertasesi
Immune  complex
-4- Cl
Membrane attack complex

Occur inPlasma
Classical complement system pathway
On thesurface of cell
C 5,6,7 C 5,6,7 + C5a
Activates lternate pathwayOpsonin
Phospholipase activity
Anaphylotoxin & Chemotaxin
C4,2 C4,2
C3 C3b + C3a
C8 C9 C8,9 Membrance damage by
C1 C1

Occur in
Plasma
On the surface
of cell damage by
phospholipase activity
C8,9 C 8,9 Membrane
& chemotaxin
Anaphylotoxin
C5,6,7 C5,6,7 + C5a
C3 C3b + C3a
Properdin Aggr. IgA P+ C3 opsonin
Zymogen

Activators Di classical pathway
Complexes containing I gC, IgA or •gE (less efficient than classical pathway)
many Cram-positive and Crarn-negative bacteria
Some virus-infected cells, for example Eptein-Barr virus any fungi, eishmania 5pp.,. trypanOsomes
Dextran sulphate, erythrocytes from heterologous species Carbohydvates„ for example aga.rose
ImmurlOglobulin$ Bacteria
Viruses
Other
micro- o rgan is rin s
Macromolecules
Activators of alternative pathway
Complexes contain lug I gG IgG2 or I1G3 None but see below for lEpid A from LP Some, for example marine retrovirusel Mycoplasmas
Poly anions
DNA, Lipid A, cardiol.ipin (II contain P0,43-) Dextran sulphate, thondroitin sulphate and heparin (all contain SO4)2
Hannan proteins
JmrriuriOgl obul ins BacteW
Viruses
Other
icro-o rgan I m s
Macromolecules
COMPLEMENT ACTIVATIONI

Ftelease of inflammatory me-diators
.4r
imb 4D 4IP DP. m
• dr
A/fast cells/b-asophi Fs
?Cion-sp erri0.fl
Large granular lymphocyte-s. pha_gc)cy-tes
C3b
Fl
The major complcment components with biologicat activity are summarised here. C3 is a central component vvhFch is cleaved into C3a and C3b_ C5 is acted col, by conves-ta.se and C3 b to produce C5a. and C5 b. C3 b has severa.E different activities. the major one being as an lops-o-nin. C3a and C5a are anaphylotcixins which trigger mast cells to release inflamma.tory mediators. C5a Fs a chernotactic agent which recruits professional phagocytes to a site of iinflarrinnatiquri- C5E, to C9 interact to-form the membrane attack complex (f1 .AC) which inserts into membranes arid results in cell lysis
Tra.nsport. of Immune- Lysis ct-f cells
com,plexes
C5b to 9
41,
4110 11V:,)-•-ig*{
1C-b Erythrocytes
C)psonize-d bacteria
Cab, Cob, iC3b Phagocytic cells
Activation
1\leutrophils Pv‘acrcsphazes
C5a.
Cherriota_xis
C3a C5a.

Binding of antibodies to antigens inactivates antigens by
Agglutination of antigen-bearing particles, such as microbes
Activation of complement system and pore formation
Virus
MAC
Macrophage
Cell lysis
Phagocytosis
ads
Foreign cell
Soluble antigens
Bacterium
Pore
Complement proteins
Bacteria
Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis)
Precipitation of soluble antigens

bacterial LPS
6-Play a role in the non-specific resistance to
microbial infection
• 7-Associated with immune distraction - of
• The function of complement system:
The complement displays a wide range of
biologial activites when activated:
1-Mediated Antigen-Antibody Reaction
2-Mediated inflammatory response
5-Neutralize viruses effect & the effect of
4- Facilitate blood coagulation
3-Facilitate phagocytosis.
blood cellu lar component

• Complement fixation test:
This is very sensitive is very
sensitive test and is capable of detection Antigen &
Antibody it is used
for serological diagnosis with principle : The ability of
Antigen – Antibody
complex to fix complement used for diagnosis of disease
2. Rickettsial diseasee.g typhus fever.
4. Parasitic disease e.g kala-azar, hydatid cyst,
amoebiasis
3. Viral disease like lymphogranuloma venerum
1. Spirochaetal disease e.g Sphilis(wasserman reaction)