Exam 1: Innate Immunity & Phagocytes Flashcards
Innate Immune System
Definition
Set of host defense mechanisms that are always in place to provide early protection against microbial infections.
Innate Immunity
Functions
- Controlling infection and in some cases eliminating microbial pathogens prior to any symptom onset
- Facilitating the initiation and development of pathogen-specific adaptive immune responses
- Cooperating with adaptive immune defenses to effectively eliminate microbial pathogens
- Removes damaged tissues and promote repair
External Defenses
Physical and Mechanical Barriers:
- Stratified squamous epithelium
- Mucus layer
- Mucocilliary escalator
- Peristalsis
- Normal Flora
Chemical and Biochemical Barriers:
- Sweat and sebaceous secretions
- Lactic acid
- Fatty acids
- Waxes
- Alcohols
- Gastric acid
- Digestive enzymes
- Bile salts
- Lysozyme
- Lactoferrin
- Transferrin
Internal Defenses
Cellular Components:
- Neutrophils
- Monocytes/macrophages
- Natural killer cells
Soluble Components:
- Complement system
- Cytokines
- Chemokines
- Acute phase proteins
Innate Immunity
Recognition
- Recognize repeating patterns of molecular structure that are common to certain classes of pathogens ⇒ PAMPs
- Recognize tissue damage associated molecules ⇒ DAMPs
- Structures are not expressed by host cells and signal the presence of non-self or foreign antigens or injury
- Shows coarse specificity
Pathogen Associated Molecular Patterns
(PAMPs)
- Conserved molecular structures common to classes of pathogens
- Often part of essential structures with limited variability
- Recognized by cells of the innate immune system
Damage Associated Molecular Pattern Molecules
(DAMPs)
-
Molecules generated or released following tissue damage
- Induced by microbial infection
- Induced during a non-infectious inflammatory response where cells are damaged or stressed
- Trauma
- Burns
- Chemical toxic exposure
- Ischemia/reperfusion injury
- Released during necrotic death but not apoptotic death
- Recognized by the innate immune system
Pattern Recognition Receptors
(PRR)
Innate immune system receptors for PAMPs and DAMPs
- Germ-line encoded (no somatic recombination)
- Limited repertoire compared to T/B cell receptors
- Are not clonally distributed
- Present on all cells of the same lineage
- I.E. all macrophages have a certain type regardless of location
- Families of PRR’s exist to respond to specific treats i.e. extracellular, cytosolic, and endosomal classes
-
Cell-associated PRR:
- Toll-like receptors
- Scavenger receptors
-
Soluble recognition molecules:
- Collectins
- Collagen-containing carbohydrate binding proteins
- Complement
- Collectins
-
Cell-associated PRR:
Toll-Like Receptors
- Prototypical PRR
- On cytoplasmic and endosomal membranes
- After binding ligand will dimerize to transduce a signal
- Have relatively conserved cytoplasmic tails
- Activate common adaptor proteins
Toll-like Receptor
Activation
Functions through two common adaptor proteins:
-
MyD88
- Activates NF-𝛋B transcription factors
- Turns on genes associated with:
- Proinflammatory response
- Cytokine response
- Stimulation of adaptive immunity
-
TRIF
- Activates IRF transcription factors
- Turns on Type 1 Interferon genes
- Important in viral infections
Activated PRR
Functions
- Phagocytosis and killing of the organism
- Recruitement of immune cells to the site of infection
- Production of effector molecules that:
- Limit pathogen growth
- Recruit and activate additional immune cells to the site of infection (T/B cells)
- Influence the development of the adaptive immune response
- Tissue repair and remodeling
Innate Immunity
Defense Against Extracellular Bacteria
- Phagocytes
- IFN-γ
- Complement
- Inflammation
Neutrophils
(PMNs)
- Short-lived cell
- Predominant WBC of peripheral blood
- Contains numerous granules which fall into two categories:
- Primary (Azurophilic) granules: contain myeloperoxidase and cationic proteins
- Secondary (specific) granules: contain lysozyme and lactoferrin
- First cells to arrive at an inflammatory focus (~6-12 hrs)
- Major phagocytic cell
-
Major defense against pyogenic bacteria:
- Staphylococcus
- Streptococcus
- Neisseria
Mononuclear Phagocytes
Monocytes/Macrophages
- Large, long-lived cells
- Monocytes in blood ⇒ macrophages in tissue
- Assume different names depending on which tissue they reside in
- Resident macrophages found at sites of filtration where microorganisms can be removed
- Circulating monocytes move from blood into tissue in response to infection and inflammation
- Arrives after neutrophils (~12-24 h)
- Can become “activated” ⇒ potent effector cells
Resident Macrophages
- Clean up and maintain homeostasis of tissues
- Filter fluids to remove microorganisms
- Functions as gaurds in tissues