C2 - LESSON 1: NATURAL IMMUNITY Flashcards
Ability of the individual to resist infection by means of normally present body functions
NATURAL IMMUNITY
Factors involved in natural immunity:
- Physical barriers, such as skin and mucous membranes
- Genetically controlled susceptibility and non-susceptibility to certain diseases
- Inflammation- involves a vascular response and a cellular response by phagocytic cells
- Acute-phase plasma proteins, such as C-reactive protein, haptoglobin, and fibrinogen, which are produced in response to injury and aid in wound healing
Factors Influencing Innate Immunity:
a. Age
b. Nutritional Status
c. Hormonal Levels
Mechanisms of Innate Immunity
a. Anatomic Barriers
b. Physiologic Barriers
c. Phagocytosis
d. Inflammatory Responses
- first barrier to infection.
• Unbroken Skin and mucosal membrane surfaces
Keratinization
- microorganisms normally inhabiting the skin and membranes
• Normal flora
provides additional protection to the respiratory tract.
• Constant motion of the cilia of the tubules
• Secretions - mucus adhering to the membranes of the nose and nasopharynx traps microorganisms, which can be expelled by
coughing or sneezing.
- produced by the sebaceous glands of the skin and lactic acid in sweat both possess antimicrobial properties.
Sebum (oil)
- protects the auditory canals from infectious disease
Earwax (cerumen)
Secretions produced in the elimination of
liquid and solid waste
Acidity and alkalinity of the
stomach and intestinal tract
Acidity of the
vagina
- characterized as a nonspecific mechanism.
Natural immunity (inborn or innate resistance)
If a microorganism penetrates the skin or mucosal membranes, a (?) becomes operational.
second line of cellular and humoral defense mechanisms
The elements of natural resistance include:
▪ phagocytic cells
▪ complement
▪ acute inflammatory reaction
Cellular Factors
- Phagocytes
- Basophils and Mast Cells
- Natural Killer Cells
- Antigen Presenting Cells
Humoral Factors
- Complement System
- Cytokines
- Interferons
- Inflammatory Substances
Phagocytic Cells
polymorphonuclear neutrophilic (PMN) leukocyte
Neutrophils
50-70% of total population
Neutrophils
10-15 um in diameter
Neutrophils
Contain neutral staining granules
Neutrophils
Neutrophil granules
➢ Primary (Azurophilic granules)
➢ Secondary (Collagenase and lysozymes
12-15 um in diameter
Eosinophil
1-3% of circulating WBC (Non-allergic individual)
Eosinophil
In staining-takes up the acid eosin dye
Eosinophil
Found in very small numbers
Basophils
10-15 um in diameter
Basophils
Contains course densely staining deep-bluish granules
Basophils
Basophil Granules:
histamine, small amount of heparin and Chemotactic factor –A
Resembles basophils
Mast Cells
Widely distributed through-out the body
Mast Cells
Mast Cell Granules:
acid phosphatase, alkaline phosphatase and protease
Important in hypersensitivity reaction
Mast Cells
12-22 umm in diameter
Monocytes/Mononuclear cells
Horse shoe shape nucleus
Monocytes/Mononuclear cells
Dust like granules
Monocytes/Mononuclear cells
4-10% of total circulating WBC
Monocytes/Mononuclear cells
Stay in the peripheral blood for up to 70 hours then migrate to tissues to become macrophages
Monocytes/Mononuclear cells
Contains peroxidase enzyme
Monocytes/Mononuclear cells
All arise from monocytes
Tissue Macrophages
25-80 um
Tissue Macrophages
No peroxidase enzyme
Tissue Macrophages
Names are specific for tissue location
Tissue Macrophages
Tissue Macrophages Functions:
Microbial killing, tumoricidal activity, intracellular parasite eradication, phagocytosis and antigen presentation
Covered with long membranous extensions
Dendritic Cells
Dendritic Cells Main function:
Phagocytosis and presentation of antigens to helper T lymphocytes
Classified according to tissue location
Dendritic Cells
TOLL-LIKE RECEPTORS
Originally discovered in the fruit fly Drosophila
TOLL-LIKE RECEPTORS
Set of transmembrane receptors that recognize different types of PAMPs.
TOLL-LIKE RECEPTORS
TLRs are found on
macrophages, dendritic cells and epithelial cells
The highest concentration of these TLRs occurs on monocytes, macrophages, and neutrophils
TOLL-LIKE RECEPTORS
The process of 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, and
(4) digestion and release of debris to the outside
- Physical Contact Between the WBC and the foreign particle
• Neutrophils
• Selectins
• Diapedesis
• Chemotaxis
• Receptors
• Opsonins
• Chemo-attractants:
• Clean up injured or dead host cells
- Serum proteins which attach to the foreign substance and prepare it for phagocytosis
Opsonins
Chemo-attractants
cell membrane invaginates and pseudopodia (outflowing of cytoplasm) surround the pathogen
Formation of Phagosome
Increase in Oxygen consumption
Formation of Phagosome
Contact with cytoplasmic granules
Fusion between granules and phagosome occurs
Digestion: Granules-
results from the generation of bactericidal metabolites.
Oxygen-dependent Pathway
- Hexose monophosphate shunt: NADP (nicotinamide adenine dinucleotide phosphate) → NADPH
Oxidative metabolism
- Radical O2(superoxide) is formed- highly toxic
Oxidative metabolism
- By adding hydrogen ions, the enzyme superoxide dismutase (SOD) converts superoxide to hydrogen peroxide or the hydroxyl radical OH
Oxidative metabolism
- enhanced by the formation of hypochlorite ions through the action of the enzyme myeloperoxidase in the presence of chloride ions.
Microbial effect
is a powerful oxidizing agent and is highly toxic for microorganisms.
Hypochlorite
depolarizes the membrane when fusion with the phagosome occurs, allowing hydrogen and potassium ions to enter the vacuole
NADPH oxidase
alters the pH
NADPH oxidase
released from lysosomal granules
Defensins
are able to cleave segments of bacterial cell walls without the benefit of oxygen
Defensins
kill a wide spectrum of organisms, including both gram-positive and gram-negative bacteria, many fungi, and some viruses
Defensins
- damage bacterial cell membrane
Cathepsin G
Digestion and Release of Debris to the outside of the cell
Exocytosis
Overall reaction of the body to injury or invasion by an infectious agent
INFLAMMATION
Cardinal Signs
i. Rubor
ii. Calor
iii. Tumor
iv. Dolor
v. Functio Laesa
Major Events
1. (?) to the infected area
2. (?) caused by retraction of endothelial cells lining the vessels;
3. (?), mainly neutrophils, from the capillaries to the surrounding tissue;
4. (?) to the injured area
5. (?) stimulate phagocytosis of microorganisms
Increased blood supply
Increased capillary permeability
Migration of white blood cells
Migration of macrophages
Acute-phase reactants
- chemical mediator released from injured mast cells- cause dilation → redness and heat (rubor and calor)
Histamine
→ allows fluids in the plasma to leak to the tissues→ swelling and pain
• Increased permeability of the vessels
• Soluble mediators- (?)→ initiate and control the response
APR
→ occurs through formation of clots; triggering the fibrinolytic system Neutrophils- mobilized within 30-60 minutes o major type of cell present in acute inflammation
• Amplification
- mobilized within 30-60 minutes ; major type of cell present in acute inflammation
Neutrophils
- last 24-48 hours
• Neutrophil emigration
- peaks at 16-48 hours, attempt to clear the area through phagocytosis
• Macrophage migration
is prolonged→ tissue damage→ loss of function
• Chronic- inflammatory process
Mediators of Inflammation
- binds to receptors on nearby capillaries and venules, causing vasodilatation and increased permeability.
- Histamine
- Tissue injury activates these small peptides, which then cause vasodilatation and increased permeability of capillaries.
- Kinins
- produced at an increased concentration in plasma during acute-phase reaction, as a nonspecific response to microorganisms and other forms of tissue injury.
- Acute Phase Proteins
- cationic peptides that produce pores in membrane of the bacteria and thereby kill them.
- Defensins
sensitive indicators of the presence of inflammatory disease and are especially useful in monitoring such conditions.
Acute-phase reactants
These are normal serum constituents that increase rapidly by at least 25 percent due to infection, injury, or trauma to the tissues
Acute-phase reactants
are normal serum constituents that increase rapidly because of infection, injury, or trauma to the tissues.
Acute-phase reactants
Many acts by binding to microorganisms and promoting adherence, the first step in phagocytosis.
Acute-phase reactants
Synthesized in the liver in response to cytokines called proinflammatory cytokines
Acute-phase reactants
proinflammatory cytokines:
interleukin-1 (IL-1), interleukin-6 (IL-6)
Trace constituent of serum
C-Reactive Protein
C-Reactive Protein Elevated levels:
Bacterial infection, Rheumatic fever, Viral infection, malignant diseases, Tuberculosis, After heart attack
• C-Reactive Protein Function:
Capable of opsonization, Agglutination, Precipitation, Complement activation
In plasma, it has a high affinity for HDL cholesterol and is transported by HDL to the site of infection.
Serum Amyloid A
Acts as a chemical messenger, similar to a cytokine, and it activates monocytes and macrophages to then produce products that increase inflammation.
Serum Amyloid A
The overall function is the mediation of inflammation
Complement
Complement Major function:
Chemotaxis, Opsonization, Lysis of cells
Able to recognize foreign carbohydrates such as mannose and several other sugar
Mannose Binding Protein
Lack of (?): Associated with recurrent yeast infection
Mannose Binding Protein
Major component of the alpha band in serum electrophoresis
Alpha-1 Antitrypsin
Produced from Leukocytes
Alpha-1 Antitrypsin
Counteract the effects of elastase
Alpha-1 Antitrypsin
Regulates expression of proinflammatory cytokines such as TNF-α, interleukin-1β, and interleukin-6
Alpha-1 Antitrypsin
Primary function
o (?) to free hemoglobin
o Acts as an (?)
o (?) of free hemoglobin
o Plays important role in protecting the (?) from damage
o Prevents loss of (?) by urinary excretion
Bind irreversibly
antioxidant
Prevents loss
kidney
iron
Most abundant of the coagulation factors in plasma
Fibrinogen
Forms fibrils that make up a fibrin clot
Fibrinogen
Fibrinogen Function
Increases strength of wound and stimulates endothelial cell adhesion
Principal copper-transporting protein in human plasma, binding more than 70% of the copper found in plasma
Ceruloplasmin
Acts as an enzyme, converting the toxic ferrous ion (Fe2+) to the non-toxic ferric form (Fe3+).
Ceruloplasmin
Opsonization, complement activation
C-reactive protein
Removal of cholesterol
Serum Amyloid A
Protease inhibitor
Alpha1-antitrypsin
Clot formation
Fibrinogen
Fibrinogen
Haptoglobin
Binds copper and oxidizes iron
Ceruloplasmin
Opsonization, lysis
Complement C3
- major humoral (fluid) component of natural immunity.
Complement proteins
Other substances of the humoral component include (?), sometimes described as natural antibiotics.
lysozymes and interferon
is a family of proteins produced rapidly by many cells in response to viral infection
Interferon
it blocks the replication of virus in other cells.
Interferon
