Immunology� Introduction �By�Prof. Dr. Batool Hassan Al-Ghurabi

Immunology

• Immunology is a branch of biomedical science that covers the study of immune systems in all organisms. It deal with the response of an organism to antigenic challenge.
• Immunity (resistance)
• The word immunity was derived from the Lain word “immunis” meaning exempt.
• It is the sum of all naturally occurring defense mechanisms that protect humans from infectious disease.

Immune system

The immune system refers to a collection of organs, cells and proteins that function to protect all the body (skin, respiratory and intestinal tract and other areas) from foreign antigens, such as microbes ( bacteria, fungi, viruses and parasites). Two important types

I. Innate (natural) or non-specific immunity

II. Adaptive (acquired) or specific immunity

• Protection Against Invading Pathogens

1. First Line of Defense: Non-specific natural barriers which restrict entry of pathogen.

Examples: Skin and mucous membranes.

2. Second Line of Defense: Innate non-specific immune defenses provide rapid local response to pathogen after it has entered host.

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

3. Third line of defense: Antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense.

Examples: Antibodies and lymphocytes.

Natural or innate or non-specific immunity

-It is present at birth.

- Has the ability to resist infection by means of normally present body functions.

- Many of these mechanisms are subject to influence by factors as nutrition, age, fatigue, stress, and genetic determinants. �

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Innate defenses can be classified into three main groups:

1. Barriers to infection

2. Humoral factor (Soluble proteins).

3. Cells

1. Barriers to infection

- Physical and mechanical barriers

Skin and mucosal membranes act as physical barriers to the entry of pathogens. Tight junctions between cells prevent the majority of pathogens from entering the body.

• The flushing actions of tears, saliva and urine protect epithelial surfaces from colonization.

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• High oxygen tension in the lungs, and body temperature, can also inhibit microbial growth.
• In the respiratory tract, mucus is secreted to trap microorganisms. They are then mechanically expelled by:

• Beating cilia

• Coughing

• Sneezing.

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Chemical barriers

-The growth of microorganisms is inhibited at acidic pH (e.g. in the stomach and vagina).

-Lactic acid and fatty acids in sebum (produced by sebaceous glands) maintain the skin pH between 3 and 5.

-Enzymes such as lysozyme (found in saliva, sweat and tears) and pepsin (present in the gut) destroy microorganisms.

- Biological barriers (normal flora)

Normal flora is formed when non-pathogenic bacteria colonize epithelial surfaces. Normal flora protects the host by:

• Competing with pathogenic bacteria for nutrients and attachment sites

• Production of antibacterial substances.

2. Humoral factor (Soluble proteins).

When infectious agents have penetrated tissues another innate defense mechanism play role in protection. Humoral factors play an important role in inflammations, and these factors found in serum or they are formed at the site of infection.

• 1. Complement system: is a group of serum proteins which inactive functionally, but when activated they damage the membranes of the pathogenic organisms, either destroying the pathogens or facilitating their clearance.
• 2. Beta-lysin: is a protein produce by platelets during coagulation can lyses many bacteria by chemotactic agents for phagocytic cells.
• 3. Interferons (INF): which are group of proteins produced by virus infected cells. Among the many functions of INF is the ability to bind to nearby cells and induce a generalized antiviral state. There are three types of them (IFN α, γ, β).

• 4. Lactoferrin and transferrin: are iron-binding proteins that compete with microorganisms for iron, an essential metabolite.

5. Lysozyme: bactericidal enzyme in mucus, saliva, tears, sweat and breast milk, it cleaves peptidoglycan in the cell wall of microorganisms.

6. Cytokines: Tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-12.

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• 3. Cells of innate immunity The cells of the innate immune system consist of:

1. Phagocytes (Macrophage and Neutrophils )

• 2. Natural killer cells.
• Phagocytes

Phagocytes (macrophages and neutrophils) engulf and then destroy pathogens by process of phagocytosis.

Macrophages are long lived cells at sites of infection; they release cytokines that recruit the shorter-lived but more actively phagocytic neutrophils.

• Neutrophils comprise 50–70% of circulating white cells. Neutrophils arrive quickly at the site of inflammation and in the act of killing pathogens they die.

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Phagocytic cells

monocyte

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neutrophil

Stages of Phagocytosis

1.Chemotaxis: Phagocytes are chemically attracted to site of infection.

2.Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material.

3. Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome.

4. Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome. Lysosomal enzymes kill most bacteria within 30 minutes.

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Antigen presenting cells (APC)

• Antigen presenting cells- are cells that mediate cellular immune response by engulfment, processing and presenting antigens to the T-cell receptor.
• Traditional APC include: macrophages, dendritic cells, langerhans cells, and B- lymphocytes.

Natural killer (NK) cells

Large granular lymphocytes (not B-cell or T-cell)�Kills tumor cells & viral inf. cells (intracellular pathogens) NK cells do not require prior immunization or activation�They attach to ‘target’ cells, then cytotoxic granules are released onto surface of cell and effectors proteins penetrate cell membrane and induce death.

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• Inflammation: Triggered by tissue damage due to infection, heat, wound, etc.
• Major Symptoms of Inflammation

1. Redness 2. Pain

3. Heat 4. Swelling

May also observe: 5. Loss of function

• Functions of Inflammation

1. Destroy and remove pathogens

2. If destruction is not possible, to limit effects by confining the pathogen and its products.

3. Repair and replace tissue damaged by pathogen and its products.

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Adaptive or acquired or specific immunity

is a type of resistance that is characterized by specificity for each individual pathogen, or microbial agent, and the ability to remember a prior exposure, which results in an increased response upon repeated exposure.

• Adaptive immunity is often sub-divided into two major types depending on how the immunity was introduced:
• a. Naturally acquired immunity: is occurs through contact with a disease.
• b. Artificially acquired immunity: is develops only through deliberate actions such as vaccination.
• **Both naturally and artificially acquired immunity can be further subdivided depending on whether immunity is induced in the host or passively transferred from an immune host.

• Naturally acquired Placental transfer of antibody

(Passive)

• Recovery from disease (Active)
• Artificially acquired Administration of antitoxin

(Passive)

• Vaccination (Active)