Innate immunity nonspecific defenses of the host-final
Transcript of 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