21 1-5 Flashcards
Innate (nonspecific) defense system
Defenses we were born with.
2 lines of defense:
- external body membranes/surface barriers (skin/mucosae/chemicals)
- internal defenses (proteins/cells/inflammation)
Adaptive/specific/aquired immunity
3rd line of defense: specific, systemic, has memory
Functions of the immune system. 4
Defend against pathogens (virus/bacteria/fungi/parasite),
remove old/worn out cells and tissue,
immune surveillance (identify abnormal/mutant cells),
launching inappropriate responses (allergies/autoimmune)
PAMPS
Pathogen associated molecular patterns
TLRs
toll like receptors, special membrane receptors that allow recognition of invaders and follow with an alarm (i.e. histamine, cytokines).
Found on macrophages and some epithelial cells
Surface barriers, first line of defense
Skin, mucous, secretions.
Includes: acid mantle, enzymes (lysozyme), mucin, defensins, other chemicals, nasal hairs.
Internal defenses, second line of defense
Phagocytes, NK cells, Inflammation, antimicrobial proteins, fever
Adaptive defenses, third line of defense
Humoral immunity (B cells), Cellular immunity (T cells)
Surface barrier - Acid mantle
Lactic acid/sweat/oils form acid mantle which inhibits bacterial growth
Surface barrier - Enzymes
Lysozyme (in saliva/resp. mucus/lacrimal fluid) destroys bacteria. Enzymes in stomach also kill organisms.
Surface barrier - Mucin
Dissolved in water to form mucus which traps organisms.
Surface barrier - Defensins
Secreted by mucous membranes and skin. Broad-spectrum antimicrobial peptides. Output increases in response to inflammation.
Surface barrier - other chems
Sebum, dermicidin in sweat - toxic to bacteria.
Surface barrier - epidermis, mucosae
Physical barrier as long as they are intact. Also, keratin is resistant to most weak acids, bases, bacteria enzymes and toxins.
Internal innate defense - Phagocytes
Macrophages, Neutrophils, Eosinophils, Mast cells, Dendritic cells.
Confront microorganisms that breach external barriers.
Engulf and destroy pathogens that breach surface membrane barriers.
Also contribute to adaptive responses.
Internal innate defense - NK cells
Detect general abnormalities rather than specific antigens. Look for PAMP, but can’t tell one pathogen from another
Promote apoptosis by attacking directly.
Able to kill and lyse cancer cells and virally infected cells.
Secrete gamma interferon and perforins and granulzymes
Activated by interferons and cytokines released by macrophages. (large granular lymphocytes/null cells)
Internal innate defense - Inflammatory response
Occurs when tissues are injured by physical trauma, intense heat, irritating chems, infection by viruses/fungi/bacteria.
Internal innate defense - Antimicrobal proteins
Interferon, complement
Enhance the innate defenses by attacking microorganisms directly or hindering their ability to reproduce.
Internal innate defense - Fever
Systemic response to invading microorganisms initiated by pyrogens.
High body temp:
- Inhibits microbes from multiplying and enhances body repair process.
- Causes liver/spleen to sequester iron/zinc which are needed for bacterial growth.
- increases metabolic rate and speeds up repair.
Leukocytes and macrophages release pyrogens when they are exposed to foreign substances. Pyrogens act on hypothalamus to ↑ temp.
Macrophages
Most voracious of phagocytes, derived from monocytes, some are fixed in tissues - others wander.
Neutrophils
First responders, specialize in fighting bacteria, release cytokines to signal for inflammation.
Destroy themselves in the process.
Eosinophils
Weakly phagocytic, but defend against parasitic worms by releasing toxic substances
Mast cells
Have ability to bind with, ingest and kill a wide range of bacteria.
Release histamine to initiate inflammation.
non-motile, CT cells
Dendritic cells
Phagocytose pathogens, activate certain types of T cells.
Both innate and adaptive!!!
Benefits of the inflammatory response. 4
- prevents the spread of damaging agents
- disposes of cell debris and pathogens
- alerts the adaptive immune system
- sets the stage for repair
Four signs of inflammation
Chems cause dilation to increase blood flow and increase permeability which allows fluid containing clotting factors and antibodies to enter tissues.
Heat + redness (vasodilation/hyperemia)
Pain + swelling/increased exudate (Increased capillary permeability/)
(And 5th, loss of function)
Phagocytosis steps. 5
- Phagocyte adhers to pathogen/debris
- Phagocyte forms pseudopods that engulf the particles (phagosome)
- Lysosome fuses with the vesicle forming a phagolysosome
- Lysosomal enzymes digest the particles.
- exocytosis removes indigestible and residual material
Inflammation - basic 3 step process
- Inflammatory chemical release ( Flood of inflammatory chems are released by injured or stressed tissue into extracellular fluid, also from mast cells/macrophages)
- Vasodilation +↑ permeability (Chems cause dilation of surrounding vessels to ↑BF and ↑permeability allowing clotting factors and antibodies to enter)
- Phagocyte mobilization (damaged site is invaded by neutrophils and macrophages)
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Inflammatory process, Release of inflammatory chemicals
- Arterioles dilate –> Local hyperemia –> Heat/Redness –> Locally increased temp ↑ metabolic rate of cells
- ↑ cap permeability –> Caps leak fluid/exudate –> Leaked protein-rich fluid in tissue spaces –> Pain/swelling –> possible impapairment of function AND Caps leak fluid/exudate –> Leaked clotting proteins form interstitial clots that wall off area to prevent injury to surrounding tissue –> Temp fibrin patch forms scaffolding for repair
- Attract Neutrophils –> Leukocytes migrate in –> Margination –> Diapedesis –> Phagocytosis –> area cleared of debris
- directly to margination
- directly to Pain/swelling. ALL END in HEALING
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Inflammatory process, Release of Leukocytosis inducing factor
Release of Leukocytosis inducing factor –> Leukocytosis (↑ WBC in bloodstream) –> Leukocytes migrate in –> Margination –> Diapedesis –> Phagocytosis of pathogens (neutrophils short term/macrophages long term) –> area cleared of debris
Key chemicals released in inflammatory response
Histamine - activates inflammation
kinins lead to bradykinin,
prostaglandins and complement also release
All inflammatory chems dilate local arterioles and make local caps leakier.
Some also attract leukocytes to injured area.
Histamine
Key molecule that activates inflammation.
Granules of mast cells and basophils.
Released in response to mechanical injury/presence of certain microorganisms/chem from neutrophils.
↑ vasodilation, ↑ permeability, promote exudate formation.
Kinins
Group of inactive proteins that participate in a chain reaction resulting in bradykinin formation.
↑ vasodilation, ↑ permeability, promote exudate formation, induce chemotaxis of leukocytes, prompt neutrophils to release lysosomal enzymes, induce pain
Bradykinin
Universal pain signal, promoter of vasodilation
Prostaglandins
Fatty acid molecules from arachodonic acid, generated by enzymes of neutrophils, basophils, mast cells, etc.
↑ vasodilation, ↑ permeability, promote exudate formation, induce neutrophil chemotaxis, induce pain.
Exudate
Fluid containing clotting factors and antibodies (seeps from the blood into tissue spaces)
Leukocytosis
4-5 fold increase in # of circulating neutrophils. Neutrophils enter from red bone marrow in response to leukocytosis inducing factors. (in the span of a couple hours)
Phagocyte mobilization steps
- leukocytosis - recruiting more cells (neutrophils enter blood from bone arrow and migrate to injury site.)
- margination (neutrophils encounter CAMs (produced in inflamed endothelium) in the capillary wall and stick/tumble getting ready for exit)
- diapedesis (neutrophils flatten and sqeeze thru caps into tissue space)
- chemotaxis (neutrophils follow chem trail). (Interleukin/other Chema released by bacteria/injured tissue)
CAMs
Cell adhesion molecules. Endothelial cells put up selectins, leukocytes put up another type of CAM - integrin.
Interferons
Proteins released by virus infected cells and certain lyphocytes; act as chemical messengers to protect close by uninfected cells from viral takeover; mobilize immune system.
Interfere with viral reproduction with RNA degrading enzymes and protein synth inhibitors.
Interferon steps
- Virus enters cell
- Interferon genes switch on
- Cell produces interferon molecules
- Interferon binding stimulates cell to turn on genes for antiviral proteins
- Antiviral proteins block viral reproduction
What 3 ways can the complement system be activated?
- CLASSICAL PATHWAY Binding to antibodies that are already attached to bacterial cells
- LECTIN PATHWAY Binding to a serum protein, mannose binding lectin, mannose containing carbs on bacteria or viruses
- ALTERNATIVE PATHWAY Binding directly to carbs present on the surface of a broad range of bacterial cells
3 ways complement protects against infection
- Recruiting more phagocytes by Functioning as opsonins - make it easier for phagocytes to adhere
- Enhance inflammatory response by triggering the release of histamines by mast cells/basophils and attracting neutrophils
- develops a membrane attack complex (MAC) passageway/hole in membrane that results in lysis of the cell
Gamma interferon
Gamma interferon is not secreted by virus infected cells, but rather by active T and NK cells
(enhances phagocytosis in macrophages/boosts antibody production/supress growth of tumors.)
How does fever help protect the body?
High temp is systemic response to microorganisms.
Pyrogens are released by leukocytes and macrophages that act on the hypothalamus.
Fever causes the liver and spleen to sequester iron and zinc which are needed for bacterial growth.
Fever increases metabolic rate and speeds up repairs process.
Interleukin 1 is a pyrogen.
Endogenous comes from within, exogenous are proteins from pathogens
Antimicrobial proteins
Enhance the innate defenses by attacking microorganisms directly or by hindering their ability to reproduce.
Interferons, complement system.
Explain the importance of phagocytosis and NK cells in innate body defense.
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