Innate resistance protects against
Most infectious disease
Innate resistance
- Exists at birth and always present
- Natural host resistance
- Can be specific for tissues
Parts of innate resistance
Chemical + physical barriers, special immune system cells, physiological processes and molecular defenses
Natural host resistance
Susceptability to pathogens varies from species to species
Example of natural host resistance
Anthrax: fatal blood infection in cattle vs. cutaneous in humans
Infection site and tissue specificity
Pathogens prefer a specific body site to initiate infection
Skin prevents
Invasion by microbes
Protective protein of skin
Keratin
pH of skin
Slightly acidic pH 5
High [NaCl} in skin means
Periodic drying
Mucous traps
Microbes
Mucous contains
Antimicrobial secretions
Example of mucous membrane secretions
Lysozyme and defensins
Lysozyme does what?
Cuts beta-1,4 glycosidic bonds in peptidoglycan
Defensin mechanism
Antimicrobial peptides that poke holes in bacterial cell membranes
The mucocilliary escalator
Cilliated cells line the mucous membranes of the airways
Sweeping action moves mucous and microbes away from the lungs
Stomach acidity
pH ~2
Proteolytic enzymes
Destroys most microbes
Small intestine
Rapid change in pH
Pancreatic enzymes
Bile
Destroy microbes
Large intestine: normal microbiota
Microbes that already reside and on the human body
Large intestine: normal microbiota action
Take up attachment sites, limit available nutrients, make antimicrobial compounds
Genitourinary tract protection
Urine, flushing action, normal microbiota
Vaginal epithelial cells produce
Glycogen
Lactobacillus acidophilus ferments
Glucose to lactose acid
Lymphatic system
Collection of tissues that bring specialized cells (lymphocytes) into contact with foreign material (antigens)
Lymphatic system is made of
Lymph vessels and lymphoid organs
Lymph
Similar to blood containing white blood cells (leukocytes) but without red blood cells
Primary lymphoid organs
Bone marrow and thymus
What happens in bone marrow and thymus?
Leukocytes are produced and mature
Secondary lymphoid organs
Lymph nodes, spleen, MALT
Secondary lymphoid organs contain
Leukocytes arranged to filter out microbes and antigens
Mucosa associated lymphoid tissue action
Leukocytes constantly sample their surroundings by phagocytosis looking for foreign material
Leukocytes
Cells that circulate in the blood and lymph, and reside in lymphoid organs
Leukocytes are involved in
Both branches of the immune response (innate and adaptive)
Granulocytes
Cytoplasm contains granules filled with reactive chemicals that can kill microbes and signal other components of immunity
Types of granulocytes
Basophils and mast cells
Eosinophils
Neutrophils
Basophils and mast cells granules stain with
Basic dyes
Basophils and mast cells are
Non-phagocytic
Basophil and mast cell location
Circulate in blood (basophils) or reside in mucosal tissue (mast cells)
Basophils and mast cells can be triggered to
Degranulate
Basophils and mast cells release
Vasoactive mediators
Vasoactive mediators
Trigger inflamation
Type of vasoactive mediator
Histamine - involved in the allergic response
Eosinophils granules stain with
Acidic dyes
Eosinophils are
Non-phagocytic
Eosinophil location
Can leave the blood and enter tissues in areas of inflammation
Eosinophils attack
Large parasites - protozoa and parasitic worms
Eosinophils release
Reactive oxygen intermediates that destroy parasite from the outside
Oxygen intermediates
O2-, H2O2, OH
Neutrophils
Granules are filled with digestive enzymes
Digestive enzymes
Lysozyme and defensins
Neutrophil locations
Circulate in blood and migrate to infection sites
Neutrophils action
Highly phagocytic - “eat” invading bacteria
Central component of innate immunity
Neutrophils
Monocytes location
Circulate in the blood, and then migrate to tissues, and differentiate into macrophages and dendritic cells
Monocyte mechanism
Strongly phagocytic cells involved in antigen presentation
Macrophages location
Reside in tissues - lungs, liver, spleen, connective tissues
Macrophages have
Specific surface molecules that recognize pathogens - toll-like receptors
Toll-like receptors are found on
LPS, peptidoglycan, fungal cell walls that induces phagocytosis
Dendritic cell location
Reside in tissues that serve as common entry points for pathogens: skin (langerhan’s cells) and mucous membranes of the nose, lungs, and intestines
Dendritic cells sample their surroundings using
Phagocytosis
Dendritic cell action
Migrate to lymphoid organs then present foreign antigens on their surface to B and T lymphocytes - trigger the specific (adaptive) immune response
Lymphocytes are
Specialized leukocytes involved primarily in the adaptive immune response
Lymphocyte location
Circulate through the blood and reside in lymphoid organs
B lymphocytes
Antibody producing cells
B lymphocytes are involved in
Humoral immune response
T lymphocytes are involved in
Cell mediated immune response
Natural killer cells destroy
Abnormal cells: cancer cells, cells infected by bacteria or viruses
Innate immunity has the ability
To destroy a pathogen that has never been encountered before
Innate immunity involves
Phagocytic leukocytes (neutrophils and macrophages)
Phagocytic leukocytes can recognize
Pathogen-associated molecular patterns (PAMPs)
Pathogen-associated molecular patterns are found on
Lipopolysaccharide
Lipoteichoic acid
Flagellin
What do we find on phagocytes?
Toll-like receptors
Toll-like receptors on phagocytes do what
Interact with a PAMP
Triggers phagocytosis
Phagocytes engulf by
Cell membrane invaginates around a foreign particle and engulfs it into a phagosome
Phagolysosome
A phagosome fused with a lysosome
Phagolysosome is filled with
Lysozyme and defensins
Proteases
Lipases
Nuclease
Proteases
Degrade proteins
Lipases
Degrade phospholipids
Nuclease
Degrade nucleic acids
Oxygen dependent killing
Activated phagocytes produce reactive oxygen compounds that kill ingested microbes by oxidizing cell components
Oxygen compounds
H2O2, O2-, OH-, HOCl, NO
Once invaders have been killed in oxygen dependent killing…
Neutrophils perform exocytosis - fragments are expelled from the cell
Macrophages and dendritic cells become antigen presenting cells
Antigen presenting cells
Fragments of the intruder are presented on the cell surface to trigger an adaptive immune response
Inflammation
General, non-specific reaction to pathogens, toxins, or tissue damage
Five cardinal signs of inflammation
Redness, warmth, pain, swelling, and loss of function
In response to infection, injured tissue and leukocytes release
Proinflammatory cytokines
Proinflammatory cytokines cause
Blood vessels to dilate - brings more leukocytes to the area
Extravasation
Allows leukocytes to squeeze into tissues and attack invading pathogens
Blood leaking into tissue spaces prevents
Movement of pathogens by clotting