Innate Immunity Flashcards
Immunity
•Defends body against pathogens: anything that can cause cell injury/infection, compromises human health, cause disease/illness
•Ability to resist infection and disease is immunity
Innate (“nonspecific”) defenses
- Present at birth, immediate response
innate - Responds to all pathogens in same way
Goals: Deny entry, limit spread
• 1st line of defense: physical barriers (intact skin, mucosa)
• 2nd line of defense: phagocytes, NK-cells, other cells, anti-microbial
proteins- INFLAMMATION
- Interact and cooperate with specific
Adaptive (specific) defenses
- 3rd line of defense: cells and proteins protect against specific pathogens
- Develop after birth due to exposure, takes more time
- Depends on activities of B and T cells
• Recognition of antigens
• Basis of vaccines
1st line: Physical barriers (innate)
•physical barrier prevents entry!….epithelium
- Skin: Cells tightly attached, keratinized (sloughs off)
• Accessory structures: hair
• Sebaceous and sweat glands: flush, have enzymes, low pH, antibodies
- Mucous membranes: line all body cavities that open to outside
• Sticky mucus traps microbes, anti-microbial agents
• Acid in stomach
• Saliva contains anti-bacterial agents
• Normal flora (nonpathogenic microorgs) prevent growth of pathogens
2nd line: Cells, proteins
- Remove cellular debris and microorganisms when 1st line breached
•Phagocytic cells: Macrophages and neutrophils - Macrophages: Monocytes that enter tissues- 2 types
1. Fixed: permanent residents of organ
(Kupffer cells in liver, microglia in brain)
2. Free: wander in connective tissue
• Macrophages are antigen presenting cells:
(stay tuned) - Display parts of pathogen phagocytosed on their plasma membrane - activate T cells
•Neutrophils (microphages)
-In blood but enter tissues in response to chemical signals: 1st to arrive
-Phagocytose cell debris and bacteria
Phagocytosis
• Identify and bind to pathogen (adhesion), phagocytose
- Easier with opsonization: pathogen coated with a protein
• Phagolysosome: lysosome enzymes digest pathogen
• Neutrophils kill themselves too, macrophages will live to kill again
• Other possibilities:
- Neutrophils can release defensins:
make holes in pathogen’s membrane
- Destroy large pathogens by releasing
toxic chemicals into interstitial fluid
- Antigen presentation: processes pathogens and “present” so other cells can destrov
NK cells: the police
• Immunological surveillance: in blood, lymph
• Not phagocytic
• Non-specific: destroy unhealthy cells (virus infected cell & cancer cells)
- b/c non-self/abnormal surface markers
•Release cytotoxic chemicals
- Perforins: proteins “perforate” unhealthy cell’s plasma membrane by forming pores
Granzymes enter cell through pores
• Cell dies by self-contained apoptosis: cell shrivels up and dies
Basophils and mast cells
Basophils (blood) and Mast cells (tissues, mucous membranes)
• Proinflammatory, chemical secreting cells
- Increase fluid movement from blood to injured tissue
- Chemotactic chemicals attract other immune cells
- Release granules during inflammatory response:
• Histamine: ^ vasodilation and capillary permeability
• Heparin: anticoagulant
• Eicosanoids: increase inflammation
2nd line: Anti-microbial proteins
•Innate immunity also mediated by proteins
• Leads to pathogen destruction or interferes with pathogen reproduction:
interferons and complements
•Interferons (FN): “interferes” with spread of viral infection
- Class of cytokines: chemical messengers for cell-cell communication.
Virus-infected cell releases IN to protect healthy neighbor
• Healthy neighbor makes anti-viral proteins, prevents viral replication
- IFNs stimulates macrophages and NK cells to destroy virus-infected cells
Anti-microbial proteins: complement system
•Complement (C): 20-30 liver made plasma proteins
•Activation following entry of pathogen into body by 2 pathways:
- Classical: inactive C binds to antibodies bound to foreign antigen
- Alternative: less efficient, C directly binds pathogen membrane
• Result: “complements innate and adaptive immunity”
- Opsonization: Enhanced phagocytosis
- Increased inflammation, attracts immune cells
- Pore formation (membrane attack complex (MAC) formed) -lyses target cell
- Elimination of antibody-antigen
Inflammation: Hallmark of 2nd
line of defense
• Body’s immediate, local, non-specific response to tissue damage
• Hallmark of 2nd line of defense
• Advantages:
- Walls off wound (prevents spread of damaging agents to nearby tissues)
- Disposes cell debris and pathogens, temporary repair
- Gets the area ready for repair
• (4) cardinal signs of acute inflammation:
- Redness
- Heat
- Swelling/edema
- Pain
- 5th? - loss of movement function
Inflammatory response
Chemical alarm
- Damaged cells, mast cells and infectious organisms release numerous chemicals!
Chemical alarm!
• Mast cells (and basophils) - key to
inflammation, release:
- Histamine: vasodilator, increase capillary perm.
- Heparin: anticoagulant
- Prostaglandins: stimulates pain nerves, attracts neutrophils
- Other chemicals to attract WBCs
• Macrophages:
- Release cytokines in response to
foreign pathogens
- Attract WBCS
• Injured cells release leukocytosis-inducing factors
- WBCs leave bone marrow and enter bloodstream
Vascular changes due to chemicals released during inflammatory response
-Vasodilation and ^ capillary permeability (histamine), endothelial cells provide cell adhesion molecules (CAMs)
-More blood flow with immune cells, proteins to area, flushes out toxins
Recruitment of leukocytes during inflammatory response
- Margination: leukocytes stick to CAMs
- Diapedesis: squeeze out of blood vessel
- Chemotaxis: migrate to injury site following chemical “trail”
