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What is innate Immunity?
- Routine, non specific, protection
- involves patter recognition of specific molecules
What is the first line of defense in the innate immunity?
Skin and mucous membranes
What does innate immunity involve?
- Anatomical and physical barriers
- cells of the immune system
- sensor systems
What are the levels of skin?
What are the movements of the mucous membrane?
- peristalsis of intestines
- mucociliary escalator of he respiratory tract
What is keratin?
protein that repels water and maintains dry environement found on the epidermis
What are the antimicrobial substances?
- peroxidase enzyme
- lactoferrin and transferrin
Where is the antimicrobial substance salt found?
Where is the antimicrobial substance lysozyme found?
- Tears, saliva, mucous
- breaks down peptidoglycan
Where is the antimicrobial substance Peroxidase Enzyme found?
- breaks down H2O2 to form ROS to kill bacteria
Where is the antimicrobial substance lactoferrin and transferrin found?
- lactoferrin: saliva, mucous
- transferrin: blood and tissue fluids
- binds to iron so pathogens cannot
Where is the antimicrobial substance defensins
- produce by epithelial cells
- insert into bacterial membranes to form pores
How does normal microbiota help the immune system?
- compete with pathogens
- consume available nutrients
- production of toxic compounds
What are examples of normal microbiota producing toxic compounds?
- E.coli may synthesize colicins in intestinal tract
- lactobacillus in vagina produce low pH
What are the cells of the immune system?
What is the origin of all blood cells?
hematopoietic stem cells
What are the 3 categories of blood cells?
What are the 4 types of leukocytes?
- mononuclear phagocytes
- dendritic cells
Why are granulocytes name as such?
They contain cytoplasmic granules
What are the three granulocytes?
What are neutrophils involved in?
engulf and destroy bacteria and other material via phagocytosis
What are basophils involved in?
filled with mediators that produce allergic reactions
What are eosinophils involved with?
What do mononuclear phagocytes comprise?
mononuclear phagocyte system (MPS)
What are the 2 cells that come from mononuclear phagocytes?
- Dendritic cells
How are macrophages named?
- For their location
- ex. kupffer cells-liver
- microglial cells- brain
- alveolar- lungs
What is the function of dendritic cells?
- sentinel cells
- They engulf cells and bring them to the adaptive immune system for inspection
What are the cells that comprise lymphocytes?
What is the difference between B, T cells and NK cells?
- B, T cells are highly specific in recognition of an antigen
- NK cells lack specificity
What are surface receptors?
"eyes" and "ears" of the cell
What is a ligand?
molecule that bind to a surface receptor in order to communicate what is going on in the environment to the interior of the white blood cell
What are cytokines
- Serves as "voice"
- produced a chemical that diffuses to other cells to induce changes
- changes include growth, differentiation, movement, apoptosis
What are the 5 different types of cytokines?
- colony stimulation factors
- tumor necrosis factor
What are chemokines?
- chemotaxis of immune cells
- movement of cells
What are colony stimulating factors (CSFs)
proliferation (multiplication) and differentiation of leukocytes
What do interferons (IFNs) do?
control viral infections and regulate inflammatory response
What do Interleukins (ILs) do?
made by leukocytes, ex. activation of B and T cells
What do Tumor necrosis factor (TNF) do?
induces inflammatory response and also apoptosis
What do adhesion molecules do?
- allow cells to adhere to other cells
- ex. endothelial cells (blood vessel wall) adhere to phagocytic cells in blood to allow them to exit the blood stream
What are the 3 types of Pattern Recognition Receptors (PRRs)
- Toll-Like Receptors (TLRs)
- NOD-like receptors (NLRs)
- RIG-like receptors (RLRs)
What are the three things identified by Pattern Recognition Receptors (PRRs)
- Pathogen associated molecular pattern (PAMPs)
- Microbe-associated molecular patterns (MAMPs)
- Danger-associated molecular patterns (DAMPs)
What are PAMPs?
- pathogen associate molecular patterns
- ie. peptidoglycan, lipopolysaccharides, viral RNA molecules
What are MAMPS?
- Microbe-associated Molecule patterns
- Things associated with all microbes, not just pathogens, ie flagella
What are DAMPs
- Danger-associated molecular patterns
- molecules that indicate host cell damage
What do TLRs detect?
PAMPs, pathogen associated molecular patterns
What happens when a TLR( toll like receptor) detects a PAMP?
a signal is transmitted to the cell's nucleus to express certain genes
Where are TLRs?
Where are NOD-like receptors?
cytoplasm of sentinel cell
What do NOD-like receptors do?
detect PAMPs within the cell and initiate a series of events to protect the host
Where are rig-like receptors?
What do RIG-like receptors detect?
Viral RNA within the cell
How do RIG-like receptors respond to Viral RNA
Produces interferons as a response to the viral infection, these then diffuse into neighboring cells to produce iAVPs
What is iAVP?
inactive Antiviral Proetins
What do iAVP do?
activated by viral dsRNA and degrade host mRNA to undergo apoptosis
The complement system is called that because
the proteins assist the immune system
What are the numbers of the complement system proteins?
When are complement proteins activated?
When they are split into fragments which also causes a cascading activation
What are the 3 outcomes of the complement system?
- inflammatory response
- Lysis of foreign cells
What occurs during opsonization?
C3b binds to bacterial cells and allows phagocytes to engulf them more easily
What occurs during the inflamatory response from the complement system?
C5a attracts phagocytes to area; C3a and C5a increase permeability of blood vessels, induce mast cells to release cytokines
What occurs during lysis of foreign cells from the complement system?
membrane attack complexes (MACs) formed by proteins C5b, C6, C7, C8, C9 molecules cause cell lysis after inserting themselves into gram negative membranes
What are the steps in phagocytosis?
- recognition and attachment
- phagosome maturation and phagolysozome formation
- destruction and digestion
What occurs during the chemotaxis step in phagocytosis?
Phagocytes are recruited to the site of damage by chemoattractants
What occurs during the recognition and attachement phase of phagocytosis?
- phagocytes use various receptors to bind invading microbes.
- ex. C3b or antibodies
What occurs during the engulfment phase of phagocytosis?
pseudopods surround the microbe and engulf it; forming a phagosome
What occurs during the phagosome maturation and phagolsozome formation step of phagocytosis?
- Phagosome fuses with lysozome
- pH is lowered in lysozome delivers enzymes
What occurs during the destruction and digestion phase of phagocytosis?
- toxic ROS is produce
- pH decreases
- enzymes degrade invader
- defensins damage membrane
- lactoferrin binds iron
What occurs during exocytosis phase of phagocytosis?
the phagolysozome fuses with the plasma membrane and expels undigested remains or invader
What are the two types of phagocytes?
macrophages nad neutrophils
What do macrophages act as?
scavengers and sentries
What are activated macrophages?
increased macrophages via T cells
What consitutates a giant cell?
macrophage, giant cells and T cells
What is a granuloma
- a giant cell, macrophage and T cell
- found in tuberculosis
What to neutrophils act as?
rapid response team: move into area and elimante invaders
What is the difference between a neutrophil and a macrophage?
- Neutrophils are more powerful, but have a shorter lifespan
- MAcrophages are not as powerful, but have a lifespan of weeks to months
How do neutrophils eliminate invaders?
- releasing granules that kill invaders
What is the cause of inflammation?
What are the symptoms of inflammation?
swelling, redness, heat, pain and sometimes loss of function
What is the purpose of inflammation?
- contain site of damage
- localize response
- eliminate invader
- resotre tissue function
What is inflammation triggered by?
TLRs and NLRs that detect PAMPs and DAMPs
What are examples of inflammatory mediators?
What occurs when blood vessels are damaged?
coagulation of blood and increased blood vessel permeability
What is diapedesis?
when leukocytes phase out of the vessel into tissue
What is acute inflammation?
- short term;
- macrophages clean up damage by ingesting dead cells and debris
What is chronic inflammation?
- when acute inflammation fails
- macrophages and giant cells accumulate and granulomas form
programmed cell death
What is pyroptosis?
programmed cell death, causes inflammation
What regulates host temperature?
What causes a raise in body temperature?
What are endogenous pyrogens?
made by macrophages, fever inducing
What are exogenous pyrogens?
microbial products that induce fever
What occurs from increased temperature?
increases enzyme activity and decreases microbial growth