Lecture8 Non-Specific Defense

8/3/2019 Lecture8 Non-Specific Defense

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Lecture 8

Non-specific Host Defense

Mechanisms

NORBEL A. TABO, RM, SM


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Learning Objectives

1. Briefly describe the three lines of defenses

2. Differentiate non-specific from specific host defensemechanism

3. Identify three ways by which the digestive system isprotected from pathogens

4. Name three cellular and chemical responses to microbialinvasion

5. Describe the benefits of complement activation

6. List the cardinal signs and symptoms associated withinflammation

7. Outline the four steps in phagocytosis.

8. Cite ways in which pathogens escape destruction byphagocytes

9. Categorize the disorders and conditions that affect the

bodys non-specific host mechanisms


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Overview of the Immune SystemImmune System

Innate

(Nonspecific)

Adaptive

(Specific)

Anatomical

Barriers

Humoral

Components

Cellular

Components

Mechanical

Chemical

Biological

Complement

Coagulation

Cytokines

Neutrophils

Eosinophils

Monocytes and

Macrophages


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Anatomical Barriers - Mechanical Factors

System or Organ Cell type Mechanism

Skin Squamous epithelium Physical barrier

Desquamation

Mucous

Membranes

Non-ciliated epithelium

(e.g. GI tract)

Peristalsis

Ciliated epithelium (e.g.

respiratory tract)

Mucociliary

elevator

Epithelium (e.g.

nasopharynx)

Flushing action of

tears, saliva,

mucus, urine


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Anatomical Barriers - Chemical Factors

System or Organ Component Mechanism

Skin Sweat Anti-microbial

fatty acids

Mucous

Membranes

HCl (parietal cells)

Tears and saliva

Low pH

Lysozyme and

phospholipase A

Defensins (respiratory &GI tract)

Antimicrobial

Sufactants (lung) Opsonin


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Anatomical Barriers - Biological Factors

System or Organ Component Mechanism

Skin and mucousmembranes

Normal flora Microbialantagonism


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Microbial antagonism

Inhibitory capability of normal flora

Competition for colonization sites

Competition for nutrients

Production of substance that kill other bacteria

The effectiveness of this antagonism is

frequently decreased after prolonged

administration of broad spectrum antibiotics


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Humoral Components

1. Complement system

2. Coagulation system

3. Lactoferrin and transferrin

4. Interferons

5. Lysozymes

6. Cytokines


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Complement System

The major humoral non-specific defense

mechanism.

Once activated, complement can lead to

increased vascular permeability, recruitmentof phagocytic cells, and lysis of bacteria


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Coagulation system

Some products of coagulation system are

directly antimicrobial

Example:

Beta lysin

Protein produced by platelets can lyse G+

bacteria by acting as a cationic detergent


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Lactoferrin and Transferrin

Proteins that can limit bacterial growth.


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Interferons

protect cells from viral attack (among other

functions).

alpha, beta, and gamma interferon

produced by virus-infected cells and also bymacrophages and some lymphocytes, which are

stimulated to produce interferon via activation by

antigens.

the effect of interferon on healthy cells is to stimulate

them to produce antiviral proteins (AVP) which

protects them from viral infection.


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Lysozymes

Breaks down the cell wall of bacteria


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Interleukin I

Induces fever and production of acute phase

proteins (C-reactive proteins which is a

laboratory marker for inflammation)


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Cytokines

Chemical mediators that are released from

different types of cells.

They enable cells to communicate with each

other.


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Cellular Components

Cell Functions

Neutrophils Phagocytosis and intracellular killing

Inflammation and tissue damage

Macrophages Phagocytosis and intracellular killing

Extracellular killing of infected or altered self

targets

Tissue repair

Antigen presentation for specific immune

response

NK and LAK cells Killing of virus-infected and altered self

targets

Eosinophils Killing of certain parasites


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Leukocytes

There are typically 5,000 to 10,000 of these

per cubic millimeter of human blood ( 5-10

billion per liter ).

The white cell count typically increases inresponse to infection.

Leucocytes play a role in both specific

(antibody-based) and non-specific host

defense mechanisms.


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Polymorphonuclear neutrophils (PMNs)

about 55-70% of circulating wbc's are PMNs.

These are phagocytic cells that play an important role in

the defense against bacterial pathogens.

Eosinophils

represent about 5 % of circulating wbc's.

These are capable of phagocytosis under some

conditions, but are more directly concerned with the

extracellular destruction of invading organisms, particularlyparasites such as helminths.

High eosinophil numbers are typically associated with

helminth infections.

Types ofLeukocytes


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Basophils

constitute 1% or less of circulating wbc's.

Basophils produce a variety of biologically active chemicals

including histamine (involved in allergic response) and

heparin (an anticoagulant). Monocytes

Constitute about 5-8 % of circulating wbc's.

Like, PMNs, these cells are capable of phagocytosis.

In the tissues, these cells can be transformed into

macrophages which phagocytize invading cells and processand "present" antigens to B-lymphocytes, stimulating them to

produce antibodies.

Types ofLeukocytes..


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Lymphocytes

about 20% of circulating wbc's are lymphocytes.

These cells are largely responsible for both humoral and

cellular immunity.

There are two general types of lymphocytes,

B cells (plasma cells) that produce soluble (humoral)

antibodies, and

T cells which are responsible for cellular immunity. There

are 5 different types of T-cells, each with its own set of

functions (discussed later): Helper cells (Th)

Suppressor cells (Ts)

Delayed hypersensitivity cells (Td)

Cytoxic [killer] cells (Tc)

Types ofLeukocytes..


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Natural killer cells (Nk) - destroy tumor cells,

transplanted tissue, and cells infected with intracellular

bacteria such as the Rickettsia and Chlamydias.

Both Tc and Nk cells produce a protein called perforin

which bores a hole in the membrane of the attackedcell, much like the membrane attack complex( MAC) of

complement.

While lymphocytes are generally considered to be part

of the "specific" immunity system (involving antigens

and antibodies), the Nk cells do not require an antigen

to activate them, and so are perhaps best considered

to be part of the body's non-specific defense system.

Lymphocytes


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Phagocytosis and

Inflammatory Response


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Phagocytosis

able to engulf and destroy bacteria and some

other invading organisms

polymorphonuclear neutrophils and

monocytes and other cells calledmacrophages (tissue cells derived from

monocytes)


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Phagocytosis

1. Chemotaxis

2. Attachment

3. Ingestion

4. Digestion


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Inflammation

a complex interwoven series of processesthat increase the blood supply to an infectedsite.

The symptoms of inflammation: swelling,warming, reddening, and pain are all theresult of the increased blood supply broughtabout by capillary dilation.

A series of chemical mediators includinghistamine and the prostaglandins are alsoinvolved in inflammatory processes.


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Inflammatory Response

Large number of

phagocytes are

attracted to the wound

area

Blood vessels dilate

Phagocytes move out

from the blood

Phagocytes engulf the

pathogen


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Classical signs and symptoms

1. Calor - heat

2. Dolor - pain

3. Rubor - redness

4. Tumor swelling

5. Fluor - secretions


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Importance ofInflammation

1. To localize infection

2. To prevent spread of pathogens

3. To destroy and detoxify pathogens

4. To aid in repair and healing


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fever

Creates an unfavorable thermal environment

for bacteria whose thermal optimum is 37o C.

Speeds-up chemical reactions that are part of

the chemical defense mechanism


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Mechanisms by which pathogens

escape destruction by phagocytes

1. Production of capsules

2. Secretion of leukocidins

3. Presence of waxes in the cell wall (M.

tuberculosis)

4. Growth within the phagocytes (Rickettsia,

Legionella, Brucella, Coxiella, Listeria)

5. Growth within the leukocytes (Ehrlichia,Anaplasma)


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Disorders and conditions that adversely affect

phagocytic and inflammatory processes

Leukopenia

Low number of circulating leukocytes

Chediak-Higashi Syndrome

Inability of leukocytes to migrate in response

to chemotactic agents

Chronic Granulomatous Disease

Incapability of phagocytes to kill the pathogens


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Factors that can impair host defense

mechanisms

1. Nutritional status

2. Increased iron levels

3. Stress

4. Age

5. Cancer and Cancer chemotherapy

6. AIDS

7. Drugs

8. B-cell and T-cell deficiency


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Lecture8 Non-Specific Defense