Innate immunity nonspecific defenses of the host-final

THE CONCEPT OF IMMUNITY Immunity

• Ability to ward off disease caused by microbes

Susceptibility• Vulnerability or lack of immunity

Innate• Defenses present at birth

Specific resistance• Immunity/resistance to a specific

pathogen Nonspecific resistance

• Defenses against any pathogen

SkinMucous membranesCiliary escalatorLacrimal apparatusSalivaUrineVaginal secretions

MECHANICAL FACTORS

Skin

Skin

• Intact skin prevents microbes from entering the skin

• Broken skin – port of entry for microbes

• How?– Bacteriocidal secretion by the sebaceous

glands– Keratin - Desquamation– Dryness - Perspiration

Mucous Membranes

• Barrier protection

• Lining of the respiratory tract, GI tract and genitourinary tract

• Mucus – a glycoprotein produced by goblet cells that keeps surfaces moist

• Mucosal cells are rapidly dividing flush out of the body along with attached bacteria

Epithelial lining of the trachea

• Digestive tract – Mouth and lower digestive tract – How?

• Mucus• Saliva (contains lysozyme)• Bile (alkaline) in small intestine• Stomach acids• Defecation• Mucus contain antibacterial agents,

antibodies and immune cells called phagocytes

Mucous Membranes

• Genitourinary tract– Urinary tract is sterile in a health person

except the distal urethra – How?

• Urination• Secretion (vaginal and seminal fluid)• Low pH of vagina (presence of

several Lactobacillus sp.)

Mucous Membranes

• Respiratory tract– Nose - nasal hair, mucus

secretions (phagocytes and antibacterial enzymes), irregular chambers

– ciliated epithelium (nasal cavity, sinuses, bronchi and trachea)

– Cough reflexes– Alveolar macrophages

Mucous Membranes

Lacrimal apparatus

• Protection for the eye

• Tears are produced by the lacrimal gland

• Tears and their washing action helps keep the surface of the eye free from bacterial accumulation

• LYSOZYME is also found in tears and this enzyme has anti-bacterial action as well

Lacrimal apparatus

CHEMICAL FACTORS

Sebum Perspiration – lysozyme Gastric juice Vaginal secretions – glycogen Urine – lysozyme, pH (average of

6), urea and other metabolic products

NORMAL MICROBIOTA

Microbial antagosism• Normal microbiota compete

with pathogens

SECOND LINE of DEFENSE

• Once beyond the protective outer barrier of the body, the invading microbes will encounter a series of nonspecific cellular and chemical defense mechanisms

Mechanisms:Inflammation – a series of events that removes or contain the offending agent and repair the damageChemotaxis – movement of cells toward a chemical influence (chemokines or chemotatic agents)Phagocytosis – process in which cell ingest foreign matter

Many are carried out by the white blood cells in blood

Blood Components

• Fluid portion

– Serum: liquid portion of clotted blood

– Plasma: liquid portion with clotting factors

– “Plasma can clot; Serum cannot”

– Contains antibodies & other proteins

• Clotting factors (proteins)

– Fibrinogen

– Prothrombin

I. Erythrocytes – red blood cells (RBC) – carry oxygen and carbon dioxide; no nucleusII. Leukocytes – white blood cells (WBC) - defenseIII. Platelets – thrombocyte particles – clotting; no nucleus

Formed Elements in Blood

White Blood Cells

• Granulocytes

–Neutrophils

–Eosinophils

–Basophils

• Agranulocytes

–Monocytes

–Dendritic cells

–Lymphocytes

Monocytes(marcophage)

Lymphocytes

Neutrophils

Eosinophils

Basophils

Erthrocytes(RBC)

Platelets

Wright’s stain of the peripheral blood cells can identify granulocytes based on properties of the granules. It contain two dyes:

• Eosin dye stains basic cell components reddish• Methylene blue dye stain acidic cell components blue-ish

White Blood Cells

WBC differentials

• Never – neutrophils 60-70%

• Let – lymphocytes 20-25%

• Monkeys – monocytes 3-8%

• Eat – eosinophils 2-4%

• Bananas - basophils 0.5-1%

Formed Elements In Blood

Formed Elements In Blood

Wandering or Fixed

Can you identify these leukocytes?

erythrocyte

platelet

A

B

C

D

E

F

G

H

I

Granulocytes Neutrophils (aka polymorphonuclear cells or

PMN)• Most common leukocytes in the blood.

Granules unstained.• mobile cells and can pass through

capillaries and engulf bacteria by phagocytosis

• secrete a fever inducing agent called pyrogen which also helps the body fight infection.

Eosinophils • the granules of cytoplasm are stainable

with eosin (red) • The exact function of eosinophils has

been a mystery for many years, but research has pointed to its role in allergy, asthma and parasitic (helminth) infection; some phagocytosis.

Basophils •rarest WBC in normal blood •Blue granules contain histamine•play a role in immediate hypersensitivity reactions and in some cell-mediated delayed reactions, such as contact hypersensitivity in humans, skin graft or tumor rejections

Granulocytes

Monocyte (Macrophage) Monocytes (the blood form) • the largest WBC's normally found in

blood • horseshoe or "U" shape nucleus, or it

may be folded• travel to different tissue to mature into

specific macrophage

Macrophage• As it developed from monocytes, its

size can increase 2-3 times• Wandering – motile and travel in

bloodstream; found throughout body• Fixed (histiocytes)– attached and

remain in the tissue• Removal and engulfment of foreign

particles and useless body cells/material

Lymphocytes

• The lymphocyte nucleus is usually round to slightly indented with a sharply defined edge, and deep, dense purple. Cytoplasm may be scant or form a narrow rim around the nucleus.

• Cornerstone of the

immune system: antibodies production & cell-mediated immunity

the ingestion of microorganisms or other matter by a cell. Many white blood cells engulf invasive microorganisms by the process of phagocytosis. – 1. Chemotaxis - phagocytes are attracted to

microorganisms.– 2. Attachment - phagocyte adheres to the

microbial cell. This adherence may be facilitated by opsonization – coating the microbe with plasma proteins.

– 3. Ingestion - Pseudopods of phagocytes engulf the microorganism and enclose it in a phagosome to complete ingestion.

– 4. Digestion - Lysosomes fuse with the phagosome to form a digestive vacuole. The microbe is killed and digested.

Phagocytosis

Stages of phagocytosis

Phagocytosis

Inflammation• Four cardinal signs

– Redness– Heat– Swelling – Pain

• Primary functions– Localize infection– Neutralize toxins at

injury site– Repair damage

tissue

• Major events– Vasodilation– Increase

permeability of capillaries

– Mobilization of leukocytes to site of injury (chemotaxis & emigration)

– Phagocytosis

Second Line of Defense

Inflammation

Inflammation – cont.

(Chemotaxis)

Fever

• Systemic response to injury

• Abnormally high body temperature

• Shivering - the result of a new higher set point for body temperature

• Death results if body temperature rises above 44 to 46 degrees Celsius

Antimicrobial Substances

• Complement

• Interferon

• Iron-binding proteins

• Anti-microbial peptides

Complement

• Defensive system of over 30 proteins that are made in the liver and circulate in the blood and tissues

• Activation of complement destroys microbes by lysis, inflammation, and phagocytosis

• Complement proteins act in a CASCADE, that is, one reaction triggers another

Complement

Interferon

• Classes of anti-viral proteins

• First discovered in the mid 1950’s

• Produced by cells such as lymphocytes, macrophages and fibroblasts AFTER viral stimulation - RNA viruses

• Interfere with viral multiplication

Interferon

• Three classes of interferons– Alpha - leukocytes– Beta - fibroblasts– Gamma - lymphocytes (T cells)

• Produced after viral infection• Induces near by cells to produce anti-viral to

protect against the virus• Currently produced by recombinant DNA

technology

Summary of Innate Immunity DefensesFIRST LINE OF DEFENSE: SKIN AND MUCOUS MEMBRANES

Component Function

PHYSICAL FACTORS

Epidermis of skin Forms a physical barrier to the entrance of microbes

Mucous membranes Inhibit the entrance of many microbes

Mucus Traps microbes in respiratory and GI tracts

Lacrimal apparatus Tears dilute and wash away irritating substances and microbes

Saliva Washes microbes from surfaces of teeth and mucous membranes of mouth

Hairs Filter out microbes and dust in nose

Cilia Together with mucus, trap and remove microbes and dust from upper respiratory tract

Epiglottis Prevents microbes from entering lower resp. tract

Urine Washes microbes from urethra

Vaginal secretions Move microbes out of female reproductive tract

Peristalsis, defecation, vomiting Expel microbes from the body

CHEMICAL FACTORS

Component Function

Sebum Forms a protective acidic film over the skin surface that inhibits growth of many microbes

Lysozyme Enzyme that digests peptidoglycan in perspiration, tears, saliva, nasal secretions, urine, and tissue fluids

Saliva Contains lysozyme, and uric acid, which inhibit microbes; and immunoglobulin A, which prevents attachment of microbes to mucous membranes. Slight acidity discourages microbial growth

Gastric juice Destroys bacteria and most toxins in stomach

Urine Contains lysozyme, urea, and uric acid, which inhibit microbes; slight acidity discourages microbial growth

Vaginal secretions Slight acidity discourages bacterial and fungal growth

SECOND LINE OF DEFENSE

Component Functions

Defensive Cells

• Phagocytes Phagocytosis by cells such as neutrophils, eosinophils, dendritic cells, and macrophages

• Natural killer (NK) cells

Kill infected target cells by releasing granules that contain perforin and granzymes. Phagocytes then kill the infected microbes

Inflammation Confines and destroys microbes and initiates tissue repair

Fever Intensifies the effects of interferons, inhibits growth of some microbes, and speeds up body reactions that aid repair

Antimicrobial Substances

• Complement system Causes cytolysis of microbes, promotes phagocytosis and contributes to inflammation

• Interferons Protect uninfected host cells from viral infection

• Iron-binding proteins Inhibit growth of certain bacteria by reducing the amount available iron

• Antimicrobial peptides

Inhibit cell wall synthesis, form pores in the plasma membrane that cause lysis; and destroy DNA and RNA