Innate immunity Flashcards
hygiene hypothesis
proposes a decrease in diversity and levels of microbes in our normal microbiota may negatively affect immune responses
results of germ-free animals
- microbe free environments lead to underdeveloped immune systems
- normal microbiota have a direct role in immune system development
self non-self model
- burnet in 1949
- on a T cell you have receptors for self and non-self
- if you have a self antigen binding to a self receptor the T cell will not respons
- if you have a non-self antigen it will bind to the non-self receptor and the T cell will trigger a response
stranger theory
could not explain why such strong immune responses are elicited in sterile conditions such as ischemic injuries, trauma, tumors, tissue transplants, and autoimmune diseases
danger theory
injured tissues were postulated to release intracellular molecules DAMPs that activate the immune system
DAMPs
- damage-associated molecular patterns
- molecules that have a physiological role inside the cell, but acquire additional functions when they are exposed to the extracellular environment; they alert the body about danger, stimulate an inflammatory response, and finally promote the regeneration process
innate immunity characterisitcs
- immediate reaction
- non-specific
- limited potency
- no memory
- composed of physical and chemical barriers, phagocytic leukocytes, dendritic cells, natural killer cells, and plasma proteins
adaptive immunity characteristics
- longer to respond
- specific
- high potency
- creates memory
- adaptive immune system is composed of B and T cells
first line defenses
- mechanical: tears, mucus membranes
- chemical: lysosomes in tears, mucus, salvia, and breast milk, stomach acid
- physical: skin
defensive components of blood
- plasma (made of water + nutrients, proteins, iron binding compounds, complement proteins and antibodies)
- defensive blood cells: leukocytes (erythrocytes, platelets, and leukocytes)
eosinophils
- account for <5% of the total WBC population
- contain large cytoplasmic granules that stain red-orange
- nucleus is bilobed connected by a thin band
- possess granules containing diverse enzymes and antimicrobial toxins
- exhibit moderate phagocytic activity
- parasites and allergies
eosinophilia
elevated eosinophil count
basophils
- <1% of WBC population
- contain a double-lobed nucleus and cytoplasmic granules
- possess granules packed with defense molecules
- combat parasitic infections and have role in allergic responses
mast cells
- reside in tissues
- release histamine
- play a role in allergies and fighting parasites
- able to conduct phagocytosis
- common in tissues near body openings
neutrophils
- most numerous white blood cells in circulation
- contain multi-lobed segmented nucleus
- first leukocyte recruited to injured tissues
- release potent antimicrobial peptides (AMPs)
- phagocytose foreign cells and viruses
- elevated neutrophil count may indicate an acute bacterial infection
neutropenia
low neutrophil count
what can monocytes mature into
macrophages or dendritic cells
**professional phagocytes
monocytes
**key phagocyte
- largest agranular WBC
- contain horse-shoe shaped nuclei
- account for ~10% of circulating leukocytes
- levels can increase due to chronic infections and inflammation, autoimmune disorders, and certain cancers
- migrate out of the circulatory system into tissues and mature into macrophages
macrophages
- white blood cells that act as professional phagocytes
- develop from hematopoietic stem cells
- ingest microorganisms, senescent cells, dead apoptotic cells, and 10^11 senescent RBCs everyday
dendritic cells
- highly phagocytic found in most body tissues
- abundant in tissues next to body openings
- patrol tissues and phagocytize a broad range of antigens
- prevent immune system from attacking self and overreacting to nonthreatening substances
natural killer cells
- abundant in the liver
- innate protection against viruses, bacteria, parasites, and tumor cells
- direct killing of infected cells
- IL-12 stimulates NK cell to produce IFN-gamma which stimulates macrophages to kill microbes
chemokines examples
- 40+ types
- monocyte chemoattractant protein-1
monocyte chemoattractant protein-1
- recruit WBCs to areas of injury or infection
- have roles in wound healing, blood vessel formation/repair, lymphoid tissue development and activation of innate and adaptive immune responses
interleukins examples
IL-1 family and IL-2 family
IL-1 family
regulate inflammation, stimulate innate and adaptive immune responses, and generate fever
IL-2 family
influences T cell development; roles in generating immune system self-tolerance
interferons examples
- Interferon-alpha
- interferon- beta
- interferon-gamma
interferon alpha and beta roles
- made by virus-infected cells to signal neighboring cells to mount antiviral defenses
- stimulate innate and adaptive immune responses to viruses, bacteria, and parasite
- INF-alpha can also trigger fever
interferon gamma
mainly made by NK cells and certain T cells to activate macrophages and stimulate innate and adaptive immune responses to viruses, bacteria, and parasites
tumor necrosis factors examples
tumor necrosis-factor alpha (TNF-alpha)
tumor necrosis-factor alpha (TNF-alpha)
mainly made by macrophages; induces inflammation and kills tumor cells; can induce fever
6 stages of phagocytosis
- chemotaxis
- adherence
- ingestion
- maturation
- killing
- elimination
function of cytokines
- stimulate inflammation
- generate fever
- recruit leukocytes to fight infection
- stimulate tissue and blood vessel repair
- promote leukocyte and lymphatic tissue development
- interferons create antiviral effects
- role in immune system regulation/activation
functions of iron-binding proteins
limit ability of free iron to reduce bacterial growth
complement proteins functions
- stimulate inflammation
- tag targets for elimination (opsonization)
- directly kill targeted cells (cytolysis)
classically activated macrophage M1
- active state –> kills
- release ROS, NO, lysosomal enzymes for microbicidal actions (phagocytosis, killing bacteria and fungi)
- release IL-1, IL-12, IL-23, and chemokines to cause inflammation
alternatively activated macrophage M2
- anti-inflammatory state
- pushed to cause repair
- roles in anti-inflammatory effects, wound repair, and fibrosis
ways of nonphagocytic killing
- killing by eosinophils
- killing by natural killer lymphocytes (NK cells)
- killing by neutrophils
killing by eosinophils
attack parasitic helminths by attaching to their surface then secrete toxins that weaken or kill the microbe
what is eosinophilia indicative of
a helminth infestation or allergies
killing by natural killer lymphocytes (NK cells)
- secrete toxins onto surface of virally infected cells and tumor cells
- once adhered the NK cell and golgi physically align and NK secretes a protein that causes lysis of abnormal cells
killing by neutrophils
- destroy microbes without phagocytosis
- produce chemicals that kill nearby invaders
- generate extracellular fibers called neutrophil extracellular traps (NETs) that bind to and kill bacteria
NET formation
- damage triggers net formation
- Neutrophil elastase is released into cytoplasm
- NE migrates to the nucleus and assists the decondensation of chromatin
- chromatin expands
- NET is released, and the pathogen is trapped
roles of NETs
- trapping
- barriers
- immune signaling
- countering inflammation
immunogenicity
ability of a substance to induce an adaptive immune response
antigen immunogenicity
the degree to which the antigen provokes an immune response varies and depends on the antigens biochemical features
antigenicity
ability to be specifically recognized by T cell receptors or antibodies as a result of an immune response
immunogenicity trend
proteins>polysaccharides>lipids>small molecules
C-type lectin receptor (CLR)
- transmembrane protein localized at the plasma membrane
- recognize glycans from the wall of fungi and some bacteria
NOD-like receptor (NLR)
- cytoplasmic sensors
- recognize bacterial, viral, parasitic, and fungal PAMPs
Toll-like receptor (TLR)
- transmembrane proteins localized either at the plasma membrane or in endosomes
- recognize proteins, nucleic acids, glycans, etc.
RIG-I like receptor (RLR)
- cytoplasmic sensors of viral RNA
- signal via the mitochondrial adaptor proteins (MAVS)
interferons
**chemical defense against pathogens
- protein molecules released by host cells to nonspecifically inhibit the spread of viral infections
- cause many symptoms associated with viral infections
- 2 types: Type I (alpha and beta) and Type II (gamma)
actions of alpha and beta interferons
- virus infects the cell
- viral replication in cell triggers transcription and translation of IFN
- interferon is released, diffuses into neighboring uninfected cells, and binds to receptors
- binding triggers transcription and translation of inactive antiviral proteins (AVPs)
- meanwhile the infected cell dies, releasing viruses
- when the second cell becomes infected with viruses, double-stranded RNA of the virus activates AVP
- active AVPs degrade mRNA and bind to ribosomes, which stops protein synthesis and viral replication
complement cascade
complement proteins react with one another in an amplifying sequence of chemical reactions in which the product of each reaction becomes an enzyme that catalyzes the next reaction many times over
what does complement activation result in
- inflammation
- opsonization
- cell lysis
