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Immunity

Body is protected against


invading micro-organism by
various physical barriers like
skin &epithelial lining of lungs,
eye, ear & GIT called as first line
of defense.
If the first line of defense fail to
control the invading pathogen
then the second line of defense
immune system is activated.

Immune system
Immune system

Natural
(Non-specific)

Acquired
(specific)

umoral ResponsesCellular ResponsesHumoral Responses


Cellular Response

luble factor in serum


Neutrophil, mono,
B-Lymphocyte &
nd body fluid.
Macrophages
Antibodies
g comp. system
-Interferon
-CRP
- NK
- It is acquired after

T- Lymphocyte

birth, exposu

is available since birth


.
Micro-organism.
ot specific to a particular
- Specific for each species of
croorganism.
micro organism

Natural immune system


Humoral responses: Due to
soluble factor in the serum &
body fluid via1. complement system
2.C-reactive protein
3.Interferon's
4.Natural killer cells

Complement
system
The complement system includes 11
enzymatic proteins which are identified by
the number C1 to C9 ,B & D.
All these are present in blood.
Activation of this system then start a
sequence of CASCADE REACTIONS that
activates other components of the system.
Its act two way
1.Classical pathway- initiated by antibody
binding to antigen.
2.Alternative or properdin pathwayinitiated by polysaccharides on bacterial
cell wall &yeast cell (zymosan).

Complement system
Classical pathway-this is activated
by antigen-antibody reaction. When
antibody bind with antigen then a
specific reactive site on the constant
portion of the antibody become
uncovered where the protein C 1 bind
&thus gets activated .
The activates the other
complement in a series of cascade
reaction.

Classical pathway
Ag-Ig-C1

Ag-Ig-C1 C4b

Ag-Ig-C1 C4bC2 a

Ag-Ig-C1 C4b-C2a-C3b

Ag-Ig-C1 C4b-C2a-C3b
C5b-C6 C7 C8 C9

auses Lysis of the cell


Membrane of Bacteria

C4
C4 a
+
C4 b
C2
C 2a
+
C2 b
C3
C3 a
+
C3 b
C5
C5 a
+
C 5b

Causes-activation & Degranulation


Of mast cell & Basophiles
Is a kinin & causes
Vasodilatation
Act as Opsonin
Alternative Pathway
Polysacch. + factor- 1
C3bBb
Factor-Bb
+
Factor-Ba

Factor -D
Factor-B
Causes- Chemo taxis &
Degranulation

Alternative Pathway
Alternative or Properdin
Pathway is initiated by binding
of the factor I(properdin)with
polysaccharide present in the
cell wall of invading
microorganism (bacterial
endotoxin) & yeast cell
wall(zymogen).
This binding start chain of
reaction that activate C3 &C5

Effect of activation of
complement system
Opsonization activated C3a product act as
opsonin.
Lysis destruction of Bacteria by rupturing
the cell membrane due to membrane
attack complex is formed by C5b-C6-C7-C8-C9.
Chemo taxis attraction of WBC to the site
of Antigen-Antibody Reaction.it enhanced
by C5b-C6-C7 complex.
Activation & Degranulation Of mast cell &
Basophils by C4b

Complement system

Complement system

C- Reactive Proteins
Entry of foreign invaders then
activate C-RP which coats the
invading antigen.
C-RP coated organisms
activate the complement
system which in turn
phagocytosis.

Interferon's
Virally infected cells release
interferon's which help in
1. Forms a protective ring on
uninfectable cells thus decrease
spread of infection.
2. Inhibits proteins synthesis by
degradation of mRNA so inhibits
replication of viruses.

Natural killer cells


1.They kill cell without
sensitization & involvement of
major Histo compatibility
Antigen.
2.They Destroy malignant cells
3.They kill antibody coated viruses.
4.Help in first line of defence
against viruses.

Cellular Responses
By help of Circulating
Phagocytes1.Neutrophil act as 1st line of
defence .
2.Monocyte - act as 2nd line of
defence .
. RES of Liver ,spleen, lymph
nodes kill invading organism.

Cellular Responses
By help of Circulating
Phagocytes1.Neutrophil act as 1st line of
defence .
2.Monocyte - act as 2nd line of
defence .
. RES of Liver ,spleen, lymph
nodes kill invading organism.

The Acquired immune


System

If natural immune system fail


against invading pathogen then
the acquired immune system
activated.
Acquired immunity is mainly two
types.
1.Humoral immunity due to
circulating antibodies
- it major defence against
bacterial infection.

2.

The Acquired immune


System

Cellular immunity Via T Lymphocytes


- it major defence against
- viruses,
- fungi
- intracellular bacteria.
It also responsible for
- Delayed allergic reaction.
- rejection of transplant of foreign
tissue.
- Lysis of tumor cells.
- Autoimmune disease.

Stages of cellular immune


Response
1. Antigen Processing & Presentation .
Whenever antigen (bact. & virus)
enter host body then first
phagocytosis by the Macrophages
K/a Antigen presenting cell(APCs).

Degradation
Antigen
Antigen Polypeptide Fragme
APCs

APF + MHC-I
(Bact)

Move on the surface of AP

APF +MHC-II
Viruse

Move on the surface of AP

igen Polypeptide Fragments


(APF)

2. Recognition of antigen by T-Lymphocyte


Antigen recognition
receptors present on TLymphocyte k/a T- cellReceptors (TCRs).
Now APF bind with TCRs
on T-Lymphocytes And TLymphocyte can be
differentiated in to CD4
/T4 & CD8 Lymphocyte.
CD8 cell Recognized &
combine with MHC-I
Antigen.
CD4 cells Recognized &
combine with MHC-II
Antigen.

3. T- Lymphocyte
Activation

The CD8 type of T- lymphocyte after


combine with MHC-I Antigen, are
activated & differentiate into
- Cytotoxic T-cell
- Suppressor T- cell
- Memory T-cell
The CD4 type of T- lymphocyte after
combine with MHC-II Antigen, are
activated & differentiate into- Helper T-Cell

4. Attack Phase of cell mediated


Immunity
1. Role of cytotoxic T-cell (Tc Cell)
Tc & NK Cells are responsible for the attack
phase of cellular response .
Cytotoxic T- cell have some receptors on their
surface & bind with Antigen Bearing cells (Target
cell/macro) & destroy them by following
mechanism.
1.Perforin killing Tc release hole forming protein
called Perforin
2.Lysis through cytotoxic substance.
3.Induction of Apoptosis Tc secrete TUMOUR
NECROSIS FACTOR-B (TNF-B) which increase the
ca+2 permeability of antigen bearing cell.

Role of cytotoxic T-cell (Tc Cell)

Attack Phase of cell mediated Immunity


2. Role of Helper T-cells- Helper T cell are Two types
TH1 & TH2
1. Helper TH1 cells- released 3 -cytokines
a). Interleukin-2(IL-2)-activate CD8 cell to diff
in to Cytotoxic & suppressor T- cells.
b). - interferon(IFN-)- kill antigen bearing
cells.
c).Tumor necrosis factor-B(TNF-B)-induce
apoptosis in antigen bearing cells.
2. Helper TH2 cells- secrete IL-4,5,6,10 &13
act on B-lymphocyte to produce antibodies.

Figure 32.7 T-CELL RESPONSES

Figure 32.11 T-DEPENDENT


ANTIGEN
TRIGGERING OF A B CELL

Attack Phase of cell mediated


Immunity
3. Role of suppressor (Ts) cells1.Ts cells regulate the activity of
cytotoxic T-cells.
2.Ts cells prevent cytotoxic T-cells
destroy own body tissue .
3.Ts cell also suppress the
activities of Helper T- cells.

Humoral immunity
Humoral immunity is mediated by
antibody.
It defense against most of
Extracellular bacterial pathogen
&viruses.
It participates in immediate
Hypersensitivity reaction type-I ,II ,&
III
It is also associated with certain
autoimmune disease's

Stage of Humoral immune


Response

Antigen processing & presentation.


Recognition of Antigen by Lymphocyte.
Activation of B- Lymphocyte
Production of Plasma & Memory cell by BLymphocyte.
Production of Antibodies by Plasma cell.
Inactivation of Antigen by Antibodies by Two ways1. Direct attack on the invading agents
2.Attack on the Antigen Through Complement system.

B Cells and Humoral


immunity
The humoral response is carried out
by antibodies which are produced by
Plasma cells.
Plasma cells are derived from
activated B-cells that are produced in
the bone marrow

The natural immune system


activates Acquired immunity
Cells of the innate immune system
activate the specific immune response.
A group of cells called Antigen presenting
cells (APC) activate the acquired immune
system.
Macrophages, Dendritic cells and B-cells
are examples of types of APCs.
APCs turn on the acquired immune system
by activating T-Helper cells (TH-cells).
TH-cells in turn activate either the cell
mediated or the humoral immune system.

APC

The Microbial antigen


is ingested by an APC
and partially digested.
Fragments from
microbe bind with the
MHC II to form a MHC
II /Ag complex on the
surface of the APC

APC

APC

TH

A Helper T cell,
specific for the
presented antigen,
binds to the MHC
II/Ag complex

APC

APC

APC

TH

TH
B

The helper T
cell then
activates an
appropriate B
cell by

APC

TH

The interaction
between the TH-cell
and the B-cell
causes the B- cell
to differentiate into
Plasma cells and
memory cells.

Humoral
immunity
APC

APC

AP
C

TH

TH
B

Memory cells
Memory cells do not react right away but
are held in reserve for later infections.
The secondary response that is carried out
by memory cells is different in 3 ways.
Memory cells produce antibodies that bind
with greater affinity to their antigens than
the antibodies produced in the initial
response.
The response time is much vaster than the
primary response
A greater number of antibodies are
produced.

Function of Antibodies
Antibodies function in 6
ways to protect the body
Aggltination: Enhances
phagocytosis and reduces
number of infectious units
to be dealt with
Opsonization: Coating
antigen with antibody
enhances phagocytosis
Neutralization: blocks
adhesion of bacteria and
viruses to mucosa. Also
blocks active site of toxin

Function of Antibodies

Activation of complement

Increases inflammation
through the by products of the
complement system (C5a and
C3a)

Antibody dependant cell


mediated cytotoxicity:
Antibodies attached to target
cell cause destruction by non
specific immune system cells.

Cont..

Antibodies
Antibodies or immunoglobulin's are
globulins, produce by plasma
cells to Antigenic stimulation.
All Antibodies are immunoglobulin's
but all immunoglobulin's are not
antibodies.
Antibodies are five types
IgG, IgA,
IgM, IgD & IgE

structure

IgG type of
antibody Basic
unit of all Igs.
Igs is Y shaped
molecular it
consist of four
Polypeptide
chain.
-2
Heavy (H) & 2Light(L) chain.

structure
Heavy chain- Heavy chain have Molecular weight of 50,000 D.
- H- chain are antigenically different for each class
of Ig and are named as- in IgA
- in IgD
- in IgG
- in IgM
- in IgE
Each H chain consist of Variable region (N
Terminal) & constant region (C Terminal) Becoz
variable sequence of amino acid & constant
sequence of amino acid present.
Each heavy chain consist of 440amino acid.

structure
Light chain
- Molecular weight of light chain is
25,000 D.
- L- chain are of two type K (kappa) &
(Lambda).
- L- chain consist of variable region
towards (NH2) Terminal & Constant
region towards (COOH- Terminal)
- Each Light Chain Contain 220 Amino
Acid .
- In the Light chain there are two

Difference in Antibodies
Feature
IgD
Structure

IgG
IgE
monomer

monomer
monomer
- H chain class
y1,y2,y3,y4

- L chain class
&
M W inKD
150
&
&
180
190
Carbohydrate content % 3
13
12
Serum concn ng/dl
12
0.03
0.00004
Half life (days)
21
3
2
Placental transfer
yes
No
No
Complement fixation classical
classical
None
None
Role in the body
the
Role not

Protects the
type I
body fluid

IgA
monomer

IgM
panatamer

1,2
&
160-385

&
900

12

1.2

6
No

5
No

Alternative
Protect the
body surface

Protect
blood

Acquired immune deficiency syndrome

The red ribbon


is a symbol for
solidarity with
HIV-positive
people and
those living
with AIDS.

Acquired immune
deficiency syndrome
Acquired immune deficiency
syndrome(AIDS) in which decrease the
number of Helper-T cell due to infection
of human immunodeficiency virus (HIV)
AIDS was first detected in USA in 1981.
HIV is Two types HIV-I AND HIV-II.

SPREAD OF DISEASE
Causes- Sex workers.
- drugs addicts.
- homosexual male.
- extramarital relations.
- Recipients of unscreened blood
transfusion.

Transmission
There are mainly three routes of
Transmission.
1. Parenteral route- is through blood
contact
- Unscreened blood Transfusion,
- Tattooing
- Use of infected razors , syringes
and needles etc.
- organ transplants.

Transmission
2. Sexual route accounts for about
85% of HIV infection due to- multiple sex partners,
- sex workers
- homosexual
-artificial insemination

Transmission
3. Trans-

placental
routeinfection
can be
transmitted
from
infected
mother to
her fetus.

Structure - HIV
HIV is a retrovirus
having rounded
outline and consist
of CORE the core has
two single strands of
genomic RNA ,
enzyme-reverse
transcriptase ,
protein P15
associated with
genomic RNA.

Genomic RNA is surrounded by


two covering.
- Inner covering is cone
shaped consisting of p-24
antigen.
- Outer covering of P-17.
Genomic has two types of
genes- 1).overlapping &
2).split genes.
Virus is surrounded by host
derived envelop with spikes
containing protein components
to CD4 or T4 receptors present
on the surface of Helper T- cell,

Virus multiplication
Virus multiplication when virus

comes in contact with the cell


having receptors of T4 antigen
(Helper-T cells , Monocyte ,
macrophages and some nerve
cells) its sticks to the receptors
site and then passes into the
cell. Then free Genomic RNA
synthesis a copy DNA with
Help of enzyme reverse

Incubation Period
Varies from 2 to 10 years.
The first 2 to 6 month are called
window period because in this
period test are negative. Then
onwards HIV positivity is
indicated by
1.Presence of P-24,
2.Antiviral antibodies
3.Reduction in number of T cell.

Signs and symptoms

Signs and symptoms are


mostly of secondary infection
due to decrease immunity.
- Repeated episodes of
diarrhoea.
- Unexplained weight
loss.
- Prolonged cough.
- night sweating
- continuous fever
- Tuberculosis
- Brain damage
- Ulcers
- Kaposi sarcoma (Cancer
of skin).

- Unexplained
weight loss

HIV
Tests
Lab test employed for diagnosis of
HIV infection may be classified into
three groups.
1. Screening tests are used to
screen Antibodies against HIV.
- BY ELISA
2. Supplement tests.- These test also
detect antibodies against HIV.
- BY Western blot assay.
3. Confirmatory tests- these test
confirm HIV infection in individual
who is sero positive.
- virus isolation
- Detection of P24 antigen
- Detection of Viral nucleic acid by
Polymerase Chain Reaction.

Treatment
Triple drugs
treatment is
employed1. Protease inhibitor,
2. Reverse
transcriptase
inhibitor
3. AZT
(azidothymidine)
4. Interleukins.

Prevention
Prevention measures against HIV
infection include.
- Education.
- Screening is carried out in case of
blood donors, organ donors , semen
donors, Foreigners and Sex worker.
- Ban on Prostitution.
- Safer sex with single Partner , use
of Condoms and Barrier creams.
- Use of disposable syringes, needle,
blood bags And I/V sets.

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