ICL 1.2: Function of Immune System Flashcards
which cells are the most important in the immune system?
phagocytes
what is phagocytosis?
intracellular killing, inflammation and tissue damage
is carried out by several cell types, including the neutrophils, monocytes/ macrophages
what is the CD marker for neutrophils?
CD66
what are neutrophils?
neutrophils contain the enzyme-rich lysosomes, which can facilitate destruction of infectious microorganisms
they’re the most abundant WBC
short-lived phagocytic cells, they die within a few hours after entry, and form the pus at infected tissue
is phagocytosis extra or intracellular?
it can be both!!
macrophages can kill bacteria inside and outside of them
what are the three functions of monocytes/macrophages?
- engulf: removal of bacteria and parasites, lysosomal granules break down materials into simple amino acids, and sugars
- cytokine producing cells: TNFα, IL-1, IL-8
- antigen-presenting cells: take up antigens, process them by denaturation or partial digestion and present them to T cells
what are SOS signals?
how does our body know that bacteria has entered the body?
SOS signals are induced by N-formal methionine-containing peptides that are released by bacteria (stupid bacteria lol)
this peptide induces neutrophil and macrophage migration to the site of infection; it’s a chemoattractant factor
which chemicals induce SOS signals?
N-formyl methionine-containing peptides
clotting system peptides
complement products
cytokines released by tissue macrophages
which receptors do phagocytes have?
phagocytes bear different receptors that recognize microbial components and induce phagocytosis
these include:
- TLR4 (LPS Receptor)
- TLR2 (LTA receptor)
- FPR (fMLP receptor)
- Mannose Receptor
what do the receptors on phagocytes do?
phagocytes bear different receptors that recognize microbial components and induce phagocytosis
binding of bacteria to these innate receptors causes activation of the phagocyte
this results in the synthesis and release of cytokines and the induction of lipid mediators of inflammation
the binding to the receptors also enhances phagocytosis and promotes killing of the bacteria
what happens during phagocytosis?
Microbes are ingested into phagosomes, which fuse with lysosomes, and the microbes are killed by enzymes and ROI and NO = intracellular killing of microbes
the same substances may be released from the phagocytes and kill extracellular microbes
what are the steps to phagocytosis?
- microbes bind to phagocyte receptors
- phagocyte membrane zips up around microbe
- microbe ingested in phagosome
- lysosome fuses with phagosome, killing microbe
how do phagocytes kill bacteria?
phagocyte first forms pseudopods that engulf the bacterium, and this vesicle called the phagosome
fusion of a lysosome granule with the phagosome to form the phagolysosome releases the lysosomal proteins into the phagolysosome
what are the lysosomal proteins?
- proteases and lysozyme
- defensins
- production of reactive forms of oxygen
what are defensins?
small cysteine-rich cationic proteins (18-45 amino acids).
They insert into membranes, creating pores that cause
components of bacteria to leak out
what do ROS do to bacteria?
production of reactive forms of oxygen that are toxic to many bacteria, such as superoxide oxidizes disulfide linkages and inactivates essential bacterial surface
proteins
what do lysozymes do?
hydrolyses mucopeptides in the cell wall
what does lactoferrin do?
deprives pathogens of iron
which molecules are involved in phagocyte oxygen-independent killing of bacteria?
- lysozyme
- lactoferrin
- hydrolytic enzymes (proteases)
how does oxygen-dependent killing of bacteria in phagocytes work?
NAPHD oxidase
intracellular bacteria in phagolysosomes are susceptible to reactive oxygen species, which damage cell wall components and fragment genomic DNA
Reactive Oxygen Intermediate (ROI) production is initiated by membrane-bound NADPH oxidase, which is activated by IFN-γ
O2 + NADPH –> NADP + superoxide radical via NADPH oxidase
O2- is further metabolized by superoxide dismutase (SOD) into peroxide
O2- + H+ –> O2 + H2O2
when do granulomas form?
they may form when the macrophage cannot kill intracellular bacteria
a granuloma consists of a central core of infected macrophages, which can include multinucleated giant cells formed by macrophage fusions, surrounded by large single macrophages often called epithelioid cells
mycobacteria can persist in the cells of the granuloma
the central core is surrounded by T cells
which cells kill foreign and altered self targets?
NK and LAK cells
ADCC cells
activated macrophages
eosinophils
CD8 T cells
what are NK cells?
large granular lymphocytes (10%)
develop in bone marrow
circulate in blood, part of the innate immune system
no specific antigen recognition
what’s the function of NK cells?
cell killing
the secretion of IFN-γ
when are NK cells activated?
NK cells are an early component of host defense against infections
they control the initial infection until adaptive immune system can eliminate the virus
NK cells are activated by TNF, IFNα and IFNβ made by infected cells and macrophages
how does positive feedback work with NK cells?
NK cells release IFN-γ
IFN-γ activates macrophages
macrophages release TNFα and IL 12 which activate NK cells
what type of cells do NK cells recognize and target?
- antibody-covered target cells
FcγIII receptor (CD16)
- “altered self” cells
altered MHC I molecules
how does antibody dependent cytotoxicity of NK cells work?
NK cells have FcγRlll receptors (CD16) on their surface. when these cells encounter cells coated with antibody, they rapidly kill the target cell
- antibody binds to antigens on the surface of target cells
- FcγRIII (CD16) receptors on NK cells recognize bound antibody on the target cell
- cross-linking of Fc receptors signals the NK cell to kill the target cell
- target cell dies by apoptosis
why are normal cells not killed by NK cells?
NK cells express non-TCR-related receptors, called killer-cell inhibitory receptors (KIR), which bind to MHC class I molecules
when ligated, KIRs protect the cell from being
killed by NK cells
MHC class I on normal cells is recognized by KIRs so the NK cell doesn’t kill the normal cell
how are cancer cells killed by NK cells?
infected or tumor cells have reduced MHC class I on their surfaces
so when such cells encounter NK cells, they fail to engage these killer-cell inhibitory receptors (cannot stimulate a negative signal) and therefore activated NK cell releases granule contents to kill the target cells
altered or absent MHC class I cannot stimulate a negative signal so the NK cell is triggered by signals from activating and release granule contents inducing apoptosis in target cell
how do inhibitory receptors of NK cells work?
the inhibitory receptors of NK cells recognize self class l MHC molecules, thus ensuring that NK cells do not attack normal host cells
what does ADCC stand for?
Antibody-dependent Cellular Cytotoxicity
what is ADCC?
a mechanism by which antibodies enhance innate immunity
neutrophils, eosinophils, macrophages, and especially natural killer (NK) cells show enhanced killing of target cells that are precoated with specific IgG antibody
the lytic process is called antibody dependent cellular cytotoxicity (ADCC)
recognition of bound antibody occurs through a low affinity receptor on the leukocyte called FcγRIII or CD16
what are the over-arching steps in ADCC?
ADCC = antibody dependent cellular cytotoxicity
the way it works is that there are antigens on the surface of the target cell
there are specific IgG antibodies that recognize the surface antigen, bind to it and coat the target cell
the antibody-coated target cell is then recognized by effector cells like NK cells and the target cell is destroyed
what are LAK cells?
LAK - lymphokine activated killer cell
if IFN and IL2 cytokines both bind to LAK cells, they will induce the cell to release granules and kill transformed and malignant cells
LAK cells are great for treating cancer!
what percent of lymphocytes are B vs. T cells?
B cells = 10-15%
T-cells = 75-80%
what do T cells do?
they help activate B lymphocytes
they’re part of cell-mediated immunity
what are null cells?
include specialized lymphocytes lack T or B cell surface (NK cells) that kill certain tumors markers and virus-infected cells
what are cytotoxic T cells?
Cytotoxic CD8 T cells release granules that contain perforin and granulysin
these enzymes make pores in the target-cell membrane through which the granzymes can enter and cleave certain cell proteins that initiate apoptosis
how do cytotoxic T cells work?
activated cytotoxic T cells express the cell-surface cytokine Fas ligand, which binds to Fas molecules on the target-cell surface
T cell releases granules at site of cell contact
this interaction sends signals to the target cell to undergo apoptosis through capsase family
what does CTL stand for?
Tk-Ly T-lymphocyte
cytotoxic T lymphocyte
what are the characteristics of NK cells?
Large granular lymphocytes
no specific antigen recognition
do not express T-cell receptor
do not express Ig genes
circulate in blood, part of the innate immune system
what are the three ways phagocytes can kill microbes?
- Oxygen-independent killing (proteases, lysozyme and defensins)
- O2-dependent killing
Reactive Oxygen Intermediate (ROI) - Nitric Oxide mediated killing
which cells are cytotoxic cells?
NK
LAK
ADCC
CD8T
