PHS 3342 Lecture Notes - Lecture 5: Natural Killer Cell, Innate Immune System, Adaptive Immune System
28 Apr 2018
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January 19, 2018
The Immune System and Resistance to Disease
The Immune System
Innate defences: protect against foreign substances/abnormal cells without having to specifically identify them
-React to generalized carbohydrate/lipid cell surface markers that bind to toll-like receptors (TLRs) on phagocytic
cells
Adaptive defences (acquired immunity): subpopulations of lymphocytes recognize and attack the specific target
-As your immune system matures throughout childhood, you become exposed to microorganisms and build up
small populations of cells that recognize that specific microorganism (memory cells)
-Uses subpopulations of B-cells and T-cells that are specialized to recognize that specific pathogen
Innate Defenses (Nonspecific)
Many components:
-External defences
-Inflammation
-Interferons
-Complement system
-Fever
-Natural killer cells
External Defences
External defences: skin and mucous membranes
-Effective, but can be breached
-Composed of the physical barrier of skin and mucosal membranes
Skin:
-SALT = skin-associated lymphoid tissue
•Within the deeper layers of the skin to look out for invaders
-Skin acidity
-Sebum produced by hair follicles of the skin contains bactericidal chemicals
Uroreproductive tract: flow of urine, vaginal secretions - washes out anything that gets in
GI system: gastric HCL
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January 19, 2018
Saliva and lacrimal fluid contain lysozyme (destroys bacterial cell wall)
Mucus in respiratory tract (mucus elevator) and digestive pathways: trap invaders and slow down their movement
Inflammation
A response to any type of injury
4 key signs: redness, heat, swelling, pain
Functions:
-Isolates area and prevents spread of damaging agents to nearby tissues - swells and compresses nearby vessels
to prevent the spread of the infection
-Disposes of cell debris and pathogens - vessels become more leaky allowing the macrophages, etc. to leave the
blood system and come clean up
-Sets the stage for repair processes
Inflammation occurs as part of nonspecific defences and can be amplified by specific immune system responses
Inflammatory chemicals released by injured cells, macrophages, lymphocytes
Steps producing inflammation:
-Bacteria are engulfed by macrophages, which secrete cytokines and chemotaxis
-Activated mast cells release histamine
-Histamine dilates local blood vessels and widens the capillary pores
-The cytokines cause neutrophils and monocytes to stick to the blood vessel wall
-Chemotaxins released by macrophages attracts neutrophils and monocytes, which squeeze out of the vessel
(diapedesis) and migrate to the infection
-Monocytes enlarge into macrophages and newly arriving macrophages/neutrophils engulf the pathogens and
destroy them
Two important steps:
-Local arteriolar vasodilation: produced redness and heat
•Leads to increase in crucial plasma proteins, such as complement-system proteins
-Increased local capillary permeability: produces swelling and pain
•Leads to local accumulation of fluid and increases phagocytes in the tissue
Interferons
Secreted by virus-infected cells - diffuse to nearby non-infected cells and block proteins synthesis at the level of
ribosomes
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-Causes the infected cell to die, but also prevents the spread of the virus since viruses rely on protein synthetic
machinery of host cell for their reproduction
-Eventually the virus will run out of cells that it can use to support its replication
Also activate macrophages and mobilize natural killer cells, allowing for some anti-cancer effects
Complement System
Complement system: group of ~30 plasma proteins circulating in an inactive state
Once activated, various components amplify all aspects of inflammation
On its own, can also kill bacteria and certain other cell types
Extracellular killing
-Will form the MAC, that pokes a hole into the cell wall of the bacteria in order to kill it
2 pathways to C3 - common terminal pathway causing cell lysis
-C3 splits into C3a and C3b
•C3a activates mast cells to amplify the inflammatory response
•Some C3b will activate the complement system (MAC formation), some C3b will function as opsonins
-Opsonization = coating the bacteria to make it more identifiable by phagocytic cells
-C3b binds to bacteria and marks them for destruction and phagocytosis - makes it harder for the bacteria to
hide
-Pathway 1: innate system
•Carbohydrate complexes on microbes (not normally present on our cells) will activate the compliment system
-Pathway 2: adaptive system (aka classical system)
•Antibodies produced against that invader
•Antibodies bind to the bacteria and activate the complement system
Functions of complement proteins:
-Direct destruction of invading microbes by membrane attack complex
-Vasodilation and increased permeability of capillaries and venules to proteins
-Chemotaxis
-Enhancement of phagocytosis (opsonization)
Fever
Body’s thermostat normally set at 37 °C
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Document Summary
Innate defences: protect against foreign substances/abnormal cells without having to speci cally identify them. React to generalized carbohydrate/lipid cell surface markers that bind to toll-like receptors (tlrs) on phagocytic cells. Adaptive defences (acquired immunity): subpopulations of lymphocytes recognize and attack the speci c target. As your immune system matures throughout childhood, you become exposed to microorganisms and build up small populations of cells that recognize that speci c microorganism (memory cells) Uses subpopulations of b-cells and t-cells that are specialized to recognize that speci c pathogen. Composed of the physical barrier of skin and mucosal membranes. Salt = skin-associated lymphoid tissue: within the deeper layers of the skin to look out for invaders. Sebum produced by hair follicles of the skin contains bactericidal chemicals. Uroreproductive tract: ow of urine, vaginal secretions - washes out anything that gets in. Saliva and lacrimal uid contain lysozyme (destroys bacterial cell wall)
