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Clinical Immunology & SerologyA Laboratory Perspective, Third Edition

Copyright © 2010 F.A. Davis CompanyCopyright © 2010 F.A. Davis Company

Introduction and Natural Immunity

Chapter One


Copyright © 2010 F.A. Davis Company

Introduction and Natural Immunity Immunology can be defined as the study of

the reactions of a host when foreign

substances are introduced into the body.

An antigen is a foreign substance that

induces such an immune response in a host.

Immunity In a host is the condition of being

resistant to infection.



Introduction and Natural ImmunityHumoral Immunity vs. Cellular Immunity

Humoral immunity involves antibodies.

Cellular immunity involves direct cell-to-cell

interaction.

Both are essential for a healthy host.



Introduction and Natural Immunity Natural or innate immunity is the ability of

the host to resist infection by means of

normally present body functions.

No prior exposure is required; nonadaptive

or nonspecific and are the same for all

pathogens or foreign substances to which one

is exposed.

The response does not change with

subsequent exposures.



Introduction and Natural Immunity Acquired immunity is characterized by

specificity for each individual pathogen, or

microbial agent, and the ability to remember

a prior exposure, which results in an

increased immune response.

Both natural and acquired immune

responses are required for a healthy host.



Introduction and Natural Immunity The natural defense system can be

considered as being composed of two parts:

the external defense system and the internal

defense system.

External system: Attempts to prevent entry of

pathogens.

Internal system: Deals with pathogens that

gain entry.

Both systems promote phagocytosis.



Introduction and Natural ImmunityThe external defense system includes

Unbroken skin and mucous membranes

Acidity in sweat, urine, vaginal fluid and

stomach

Respiratory tract’s mucous secretions and cilia

Flushing action (saliva, feces, urine)

Exclusion by normal flora



Introduction and Natural ImmunityThe internal defense system

Recognizes molecules unique to infectious

organisms

Enhances phagocytosis

Is enhanced by soluble factors called acute

phase reactants



Introduction and Natural Immunity Acute phase reactants include

• Complement

• Fibrinogen

• C-reactive protein

Acute phase reactants are stimulated by cytokines.

Cytokines are chemical messengers produced by monocytes and macrophages during the inflammatory response.



Introduction and Natural ImmunityCytokines include

Interleukin-1b (IL-1b)

Interleukin-6 (IL-6)

Tumor necrosis factor alpha (TNF-a)




Cellular defense mechanisms include

Actions of myeloid cells, including

• Neutrophils (See Figure 1-1)

• Basophils (See Figure 1-3)

• Eosinophils (See Figure 1-2)

• Monocytes & Macrophages (See Figure 1-5)

• Mast Cells (See Figure 1-4)

• Dendritic Cells



Introduction and Natural Immunity Certain surface molecules are found on

human leukocytes and some nonleukocyte cell

types, and these are called Toll-like

receptors (TLRs).

The highest concentration of these receptors

occurs on monocytes, macrophages, and

neutrophils.

Each of these receptors recognizes a different

microbial product.



Introduction and Natural Immunity See Figure 1-6

Once a receptor binds to its particular

substance, or ligand, phagocytosis may be

stimulated, or the cell produces cytokines that

enhance inflammation and eventual

destruction of the microorganism.




Figure 1-1




Figure 1-6




Figure 1-2




Figure 1-3




Figure 1-4




Figure 1-5




Phagocytosis consists of four main steps

1. Physical contact between the white cell and

the foreign particle

2. Formation of a phagosome

3. Fusion with cytoplasmic granules to form a

phagolysosome

4. Digestion and release of debris to the outside



Introduction and Natural Immunity; 1-7

Figure 1-7



Introduction and Natural Immunity Resting cells that engage in phagocytosis

normally derive their energy from anaerobic

glycolysis.

However, when phagocytosis is triggered, the

respiratory burst produces greater energy

via oxidative metabolism.

A radical known as O2– (superoxide) is

formed. Superoxide is highly toxic but can be

rapidly converted to more lethal products



Introduction and Natural Immunity By adding hydrogen ions, the enzyme

superoxide dismutase (SOD) converts

superoxide to hydrogen peroxide or the

hydroxyl radical OH.

Its effect is potentiated by the formation of

hypochlorite ions.

This is accomplished through the action of the

enzyme myeloperoxidase in the presence of

chloride ions.



Introduction and Natural Immunity Hypochlorite ions are powerful oxidizing

agents.

All of these substances contribute to killing

within the phagocyte.

See Figure 1-8




Figure 1-8



Introduction and Natural Immunity Opsonization enhances phagocytosis.

Opsonins are serum proteins that attach to a

foreign substance and facilitate phagocytosis

by neutralizing repulsive forces on neighboring

cell membranes.

Examples of opsonins include C-reactive

protein, complement components, and

antibodies.



Introduction and Natural ImmunityCellular defense mechanisms include the

action of

Lymphocytes

Macrophages

Mast cells

Dendritic cells



Introduction and Natural Immunity Inflammation: Both cellular and humoral

mechanisms are involved.

The four cardinal signs / clinical symptoms of

inflammation are

• Redness

• Swelling

• Heat

• Pain



Introduction and Natural ImmunityMajor events associated with the process of

inflammation are

Increased blood supply to the infected area

(due to vasodilation)

Increased capillary permeability

Migration of white blood cells, mainly

neutrophils to the injured area (diapedesis)

Migration of macrophages to the injured area

(chemotaxis)

See Figure 1-9




Figure 1-9



Introduction and Natural Immunity Neutrophils are the primary cell involved in

the acute inflammatory response.

Neutrophil emigration may last 24 to 48 hours

and is proportional to the level of chemotactic

factors present in the area.

Migration of macrophages from surrounding

tissue and from blood monocytes occurs

several hours later and peaks at 16 to 48

hours.



Introduction and Natural Immunity Macrophages attempt to clear the involved

area through phagocytosis, and in most cases

the healing process is completed with a return

of normal tissue structure.

Tissue damage and loss of function may result

from chronic inflammation.

C-Reactive Protein (CRP) is the most widely

monitored of the acute phase reactants and is

the best indicator of acute inflammation.

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