Non Specific Immune Reactions - Norazli@CUCST · INTRO. CELL&ORGAN HOW DISEASE TEST 1. Definisi 2. Kepentin gan 3. Jenis2 keimunan (Type 4. Ciri-ciri Imun (General characteristi c)

Non Specific Immune

Reactions

INTRODUCTION

FIRST BARRIER

• Mechanical defense

SECOND BARRIER

•Phagocytosis

•Inflammation

•Complement activation

Learning Objectives:-

1. Explain the concept of non-specific immune response

2. Describes the first defense and examples

3. Describes the scope of the second line and the examples

a) Explain the stages in phagocytosis and cells

involved

b) Explain the concept and components of

inflammation and the process involved

c) Describes how the activation of complement

system and its importance

INTRO. CELL&ORGAN HOW DISEASE TEST

1. Definisi

2. Kepentin

gan

3. Jenis2

keimunan(Type

4. Ciri-ciri

Imun (General

characteristi

c)

Cell

1. Agranulosit

• Limfosit

• Monosit

2, Granulosit

• Neutrofil

• Basofil

• Eosinofil

3. Dendritic cell

4. Mast cell

5. Others

Organ

1. Limfoid

primer

• Bone marrow

• Thymus

2.Limfoid

sekunder

• Lymphatic

Vessel

• Lymph Nodes

1. Antigen

2. Antibodi

3. Agglutinasi

4. Reaksi

imun

tidak

spesifik • First barrier

• Scnd barrier 5. Reaksi Imun

spesifik

• Third barrier

6. Sitokin

1. Hipersen

sitiviti

2. HLA

3. Immunol

ogical

disorder

1. Immun

oesei

2. Immun

openda

flour

Introduction

Mechanisms to fight / protect the body

banked dangerous pathogens through

existing mechanisms naturally from birth

Factors influencing the immune system:

The influence of age

Dietary factors

Hormone

Genetic

IMMUNITY

TAK SPESIFIK SPESIFIK

First barrier:

•Skin

•Membrane

mucosa

Second barrier:

•Phagocytosis

•Inflammation

•Antimicrobial protein

(complement system)

Third barrier:

Lymphocyte

Antibodies

Non-specific immunity Vs Specific

immunity

Body Defense against pathogen

1. First barrier

◦ Non-specific defense that stops all pathogens from invading the body.

Examples: Skin and mucous membranes.

2. Second barrier

◦ Non-specific defense that provides rapid response to entry of pathogens into the body.

◦ Respond after the pathogen enters the body

◦ Examples: Fever, phagocytes (macrophages and neutrophils), inflammation.

3. Third barrier

◦ Immune response against a specific antigen

◦ Attack specific target antigens after antigen

beyond the second line

◦ Examples: Antibodies and lymphocytes.

FIRST BARRIER

1. Skins

The largest organ in the human

Normal skin flora inhibit the presence of

other pathogens by producing antibacterial

fatty acids

Epidermis - protect the body from injury and

infection

Sweat - sebum secretion, lactic acid & fatty

acids which lower the pH of the skin

Lysozyme sweat - kill bacteria

2. Mucosal Membrane

Goblet cells from epithelial secrete mucus

Protect epidermal cells and prevent

membrane dehydration

Trap pathogens before the infection occur

Example:

◦ Lysozyme in saliva kill bacteria

◦ Lysozyme in tears break the bacterial cell wall

◦ Cilium in airways and coughing sweep foreign

particles out of the body

1. Respiration System

◦ This entire system is lined with moist

epithelium.

◦ In the upper respiratory tract the

epithelium contains mucus-secreting cells

and is covered with cilia that sweep mucus

up to be coughed up.

MECHANICAL DEFENSE

2. Conjunctiva:

◦ A mucous membrane covering the

inner surface of the

◦ eyelid and the anterior region of the eye

keeps bacteria from penetrating the

eye.

◦ Tears contain Lysozyme, and enzyme

that breaks down bacterial cell walls.

3. Lacrimal apparatus:

Continual washing and blinking prevents

microbes from settling on the eye surface.

4. Saliva:

Washes microbes from teeth and mouth

mucous membranes.

5. Mucus:

Thick secretion that traps many microbes.

6. Nose Hair:

Coated with mucus filter dust, pollen, and

microbes.

7. Coughing and sneezing:

Expel foreign objects.

9. Urination:

Cleanses urethra.

10. Vaginal Secretions:

Remove microbes from genital

tract.

SECOND BARRIER

•PHAGOCYTOSIS

•INFLAMATION

•COMPLEMENT SYSTEM

Definition

Ingestion by individual cell of invading

foreign particles

Characteristic of phagocytes cells

◦ Actively phagocytic

◦ Contains digestive enzymes to digest particles

◦ Important link between innate immunity and

acquired immunity

PHAGOCYTOSIS

Phagocytosis Process

1) Chemotaxis

Cells phagocytes move toward chemical stimulation

release by infectious agents and damaged tissue.

Phagocytes will release cytokine resulting in

activation of the complement

Cytokine stimulates other cell responses to

infectious agents

Phagocytes are Attracted to Site of

Infection by Chemotaxis

2) Attachment

Phagocytes bind to the surface of

microorganisms

Receptors on the surface of phagocytes that

detect microorganisms (C3b receptor, Fc

receptors)

Opsonization - (process of opsonin binding

to the target)

3) Ingestion

◦ Swallow and form a layer of wall (capsule)

around pathogen.

◦ The capsule is called phagosome

4) Digestion

Enzim Lysozyme in the phagocyte will merge with

phagosome and formed phagolysosome

To destroy and breakdown pathogen into smaller

molecules.

5) Exocytosis

- Undigested and unused particles will be remove

from cells.

Process of Phagocytosis

Phagocyte Cell

1. Neutrophil

2. Macrophage

3. Eosinophil

4. Basophil

5. Dendritic cell

6. Mast cell

Professional

Macrophage Attacking E.coli (SEM x8,800)

28

Alveolar (Lung) Macrophage Attacking E. coli (SEM x10,000)

29

SECOND BARRIER

•PHAGOCYTOSIS

•INFLAMATION

•COMPLEMENT SYSTEM

WHAT YOU SHOULD KNOW?

Definition

Causes

Characteristics

Proceses

Chemical

Mediator

DEFINITION

The reaction of the body against cell

injury e.g. infection or trauma.

the Body's immune response not only to

infection, but also for chemicals

microorganisms, ultraviolet light, etc..

CAUSES

Burns

Chemical irritants

Frostbite

Toxins

Infection by pathogens

Physical injury, blunt or penetrating

Immune reactions due to hypersensitivity

Radiation

CHARACTERISTICS

Redness (RUBOR):

◦ When the cells damaged, histamine is released from basophils and mast cells.

◦ Histamine causes dilation of blood vessels and increased it permeability.

◦ Dilation of blood vessels cause an increase in blood flow to the injured area and the area becomes red.

Heat (CALOR):

◦ Increased blood flow to the injury area will cause the skin to feel warm when the touch.

• Swelling (TUMOUR):

- Increase permeability of the blood vessel causes the fluid to gather in the injury causes edema or swelling.

• Pain/(DALOR):

- Pain associated with tissue damage & also due to the secretion of bradykinin a peptides at the site of injury.

- Substances called prostaglandin seem to intensify bradykinin’s effect.

• Loss of Function (FUNCTIO LAESA)

INFLAMATION PROCESES

1. TISSUE DAMAGE

- Injury to the tisue and blood capilaries :

cuts

- Injured cells will secrete chemical

mediator e.g. bradykinin

- Blood clotting mechanisms activated.

2) VASODILATION AND INCREASE

PERMEABILITY OF BLOOD VESSEL.

- This will cause extra volume of blood flow to

injury area.

- Increase permeability will make more

immunity cells (macrophage, neutrophil)

transferred to injury area.

3) ARRIVAL OF PHAGOCYTES &

PHAGOCYTOSIS

- Cells membrane secrete prostaglandin which

will attract phagocytes to injury area.

4) HEALING OF TISSUE

- Healing process activated and continued until

the tissue healed.

(CHEMICAL MEDIATOR)

1) Histamine

Mast cells and basophile released histamine

Histamine

◦ a vasoactive amine which cause blood vessel dilation, increase permeability and increase muscle contractions.

◦ Fluid from blood vessel move into suraunding tissue - hyperemia.

◦ Constriction of bronchia and mucus secretion during allergy.

2) Bradykinin

Bradykinin ia a plasma protein produce during clotting factors production.

Bradykinin also a vasoactive mediator which increase vascular permeability, vasodilation, and muscle contraction.

It also stimulate pain sensation.

3) Prostaglandins

More than one types

Released from cells membrane

Prostaglandins

◦ Causes redness by increasing vasodilatation and permeability

◦ Pains (increase sensitivity of nerve endings)

◦ Increase platelets count for blood clotting.

◦ Act as chemotactic factor to attract neutrophils to injury area.

BLOOD VESSEL CHANGES

DURING INFALAMTION

1) Dilation of blood vessel

Chemical mediators release will cause the muscle of vessel to relax which allow a lot blood to flow in.

Vasodilation occurs first at the arteriole level, progressing to the capillary level.

Brings about a net increase in the amount of blood

This result more protein plasma, glucose and oxygen and cells to be transferred to injury area.

2) Blood Vessel Permeability

Increase blood clotting efficiency.

Because increase permeability a lot of fluid gather to tissue surrounding the injury resulting to edema, swelling and pains.

CELULAR CHANGES

1) Neutrophils

Neutrophils are pulled from the blood stream to

the site of inflammation.

more neutrophils are released from the bone

marrow.

2) Monocytes

Arrive latter

Monocytes are large immature forms of a

macrophage, which normally circulate in the blood

stream for about 3 days before maturing and

becoming a fixed macrophage

3) Neutrophils and the monocytes

They destroy the antigens that they have

ingested.

These cells have granulated enzymes

(lysosomes - contain lytic enzymes),

which help digest what they has engulfed.

MOLECULAR CHANGES

INTERFERON:

Interferons are a group of protein / chemical

mediators releases pd naturally by cells of

injured tissues during inflammatory process

because of viral infection or cancer.

Also play a role as immune stimulants, immune

regulators and in intercommunication of cells.

Interferons are part of non-specific defense

mechanisms

The Most common are alpha, beta and gamma

inteferons.

1. TYPE I: Fights viruses and cancer.

Alpha Interferon:

About 20 types of known. Dihasilkan oleh T sel (T-lymphocytes) and macrophages.

Stimulate Natural Killer Cells to kill virus infected cells.

Beta Interferon:

One type. Released by fibroblasts and epithelial cells infected by virus.

Stimulate production of antiviral proteins (AVP) which will disrupt virus replication process.

2. TYPE II:

Gamma Interferon:

◦ Produce by lymphocytes and NK cells

which is sensitive to foreign antigens

such as spt tumor cells, viruses and

bacteria.

◦ Increase activity - lymphocytes, NK cells

and macrophages.

FEVER

Increasing of basal body temperature because of Pyrogens (substance/agent producing fever),

Indirectly increase the setting of the temperature-regulating center in the brain, the hypothalamus.

Exogenous pyrogens cause by pathogens toxin.

Pathogens Toxin Cause Fever by

◦ Stimulate production of endogenous pyrogen from

macrophages.

◦ This endogenous pyrogen called interleukin-1 (IL-

1) is spread into blood flow & stimulate

prostaglandin production.

◦ prostaglandins reset the hypothalamus thermostat

at a higher temperature.

Importance :

◦ (1) Increase body temperature to optimum

temperature which will inhibit microorganism

Growth.

◦ (2) increasing the rate of chemical reactions

in the body

◦ (3) fever makes a patient feel ill, condition which

makes the patient more likely to rest.

Cells injured

PATHOGENS INVADE TISSUES

Capillaries become more permeable

Release histamine and other substances

Blood vessels dilate

Antibodies pass from blood into inflamed area

Phagocytes migrate to region

Brings needed phagocytes,

nutrients, and antibodies

Increased blood flow to area

Systemic response

Phagocytosis

Fever

Redness Increased temperature

Release endogenous pyrogens

Pain Edema

CONCLUSIONS

http://en.wikipedia.org/wiki/Inflammation#Proc

ess_of_acute_inflammation

SECOND BARRIER

•PHAGOCYTOSIS

•INFLAMATION

•COMPLEMENT SYSTEM

Refers to a group of 30 yg protein plays a role in the

body's defense.

Non-specific protein and is always present in the

body.

The complement system is activated by antigen-

antibody complex reaction.

Complement activation causes:

◦ 1. Cause a chain of reactions that can lyse the cell.

◦ 2. Increase phagocytosis.

◦ 3. Cause release of histamine by mast cells, which results in inflammation.

INTRO

Figure 21.13

COMPLEMENT

ACTIVATION

Complement activation can occur with 3

pathway

The pathway can occur simultaneously

Name of pathway

◦ Classical pathway

◦ Alternative pathway

◦ Lectin Pathway

All 3 pathway is difference in how the

process of forming C5 convertase.

Classical Pathway

Classical pathway required 9 complement

protein.

C1 to C9 respectively

C1

C1 exists in blood serum as a molecular complex containing:

◦ 6 molecules of C1q

◦ 2 molecules of C1r

◦ 2 molecules of C1s

C1q activated when it bind with Fc site on antibody.

C1q need at least 2 IgG or one IgM to bind.

C1 •After C1q

activated, C1r

conformation

changes and

become active.

•C1r will

activated C1s

•C1s

conformation

changes and

become active

Activation of C1s will cleave C2 & C4 complement

protein:

◦ C4 is cleaved into to C4a & C4b

C4a, released into blood stream (smaller,

inactive).

C4b bind to pathogen membrane

◦ C2 is cleaved into

C2a, which binds noncovalently to a site on

C4b.

Smaller, inactive, fragment of C2b which diffuses

away.

◦ The complex of C4b•2a is called "C3

convertase”

C3

◦ C3 is the most abundant protein of the complement

system. Because of its abundance and its ability to

activate itself

C4b•2a cuts C3 into two major fragments:

◦ C3b, which binds covalently to C4b•2a.

◦ Form C4b•2a•3b (C5 convertase)

◦ Macrophages and neutrophils have receptors for

C3b and can bind the C3b-coated cell or particle

preparatory to phagocytosis.

◦ C3b also an opsonin.

C3a is a small fragment that released into the

surrounding fluids. It can bind to receptors on

basophils and mast cells triggering them to

release their vasoactive contents (e.g.,

histamine).

Involve during severe allergic (anaphylactic

shock)

C5 (C4b•2a•3b)

◦ C5 convertase will cleave C5 complement

protein.

◦ C5 cleaved into C5a and C5b

C5a released into blood stream

C5b bind to the surface of phatogen

◦ This form the membrane attack complex

(MAC)

• Binding of C5b on pathogens surface will

be followed by successive binding of

complement protein C6, C7, C8 and C9 to

C5b.

• This event cause

– Holes drilled into pathogens cells membrane

poly C9.

– Holes permit movement of liquid into the cells

– This cause the pathogens cells to burst (lysis)

Complement Protein Source

◦ Intestinal epithelium

◦ Macrophage

◦ Liver

◦ Spleen

77

Alternative Pathway

In natural condition there always C3

complement protein floating in blood

flow.

This free C3 is slowly cleave into C3a

and C3b.

To form C5 convertase alternative

pathway need

C3 protein, factor B factor D and

properdin

Cleave C3b bound directly to foreign cells

surface.

Then factor B bind to C3b

Then factor D bind to C3bB complex

Binding of factor D causes factor B to

cleave and form C3bBb complex

C3bBb have same function as C3

convertase.

Properdin then bind to C3bBb to stabilize

it.

C3bBb complex can cleave free C3

protein to form C3a and C3b.

C3b then bind to C3bBb to form

C3bBb3b which have the same function as

C5 convertase.

From this onwards the formation of

membrane attack complex (MAC) is same

as classical pathways.

Lectin pathway

Another protein that can initiate

formation of C5 convertase is called

mannose-binding lectin (MBL)

MBL can bind to mannose residue on the

surface of microorganism cells.

MBL is a protein produce during

inflammatory reaction.

MBL function is similar to C1q

When MBL attach to cells surface two

protein that is MBL-associated serine

proteases,MASP-1 and MASP-2 bind to MBL.

The structure is similar to C1qrs complex.

This complex then cleave C4 and C2 protein

to form C3 convertase.

From this stage formation of MAC complex

on bacterial/ antigen is similar to classical

pathway.

END