Introduction to Immune System Part I Flashcards
3 Circulating effector cells of innate immunity
Neutrophils, macrophages and NK cells
3 Circulating effector proteins of innate immunity
Complement
Mannose-binding lectin
C-reactive protein
TNF, IL-1, chemokines
Inflammation
IFN-a, IFN-B
Resistance to viral infection
IFN-y
Macrophage activation
IL-12
IFN-y production by NK cells and T cells
IL-15
Proliferation of NK cells
IL-10, TGF-B
Control of inflammation
Opsonization
Process by which a pathogen is marked for elimination
PMN
Polymorphonuclear
Neutrophils
Majority of WBCs (60-70%) PMN granulocytes phagocytosis and digestion of microbes Short lived (2-3 days) Produce inflammatory mediators
Eosinophils
PMN granulocytes
Allergic rxns, defense against helminths
2-5% of WBC
granules for extracellular digestion
Basophils
Circulate in the blood
PMN granulocytes
Allergic rxns, contribute to elimination of parasites
Key role in anaphylactic reactions
Mast cells
Tissue fixed
PMN granulocytes
Allergic rxns
Monocytes
Mononuclear
Circulating macrophage precursor
3-8% of the blood
Important phagocytes
Macrophages
Tissue fixed
Mononuclear
Phagocytosis and digestion of microbes, antigen presentation
What comprises majority of WBCs?
Neutrophils
Main function of neutrophil?
Phagocytosis
Neutrophils and basophils produce these inflammatory mediators
Cytokines, prostaglandins and leukotrienes
Neutrophils have cytoplasmic granules that contain
Peroxidase
Lysozyme
Degradative enzymes
Defensins
Eosinophilic granules contain
Basic proteins
peroxidases
antimicrobial substances
Eosinophils secrete granules for
extracellular digestion of infectious pathogens
Which cell plays key pathogenic role in anaphylactic reactions
Basophils
Basophil granules contain
Histamine
Serotonin
Heparin
Cytokines and chemokines
Monocytes are
Blood precursor cells of tissue macrophages
Dr. Shnyra thinks this cell type is the beast to end all beasts
Macrophage
Macrophages in connective tissue called
Histocytes
Macrophages in liver called
Kupffer cells
Macrophages in lungs called
Alveolar macrophages
Macrophages in the CNS called
Microglial
Functions of macrophages in innate immunity
Phagocytosis and degradation
Produce and release enzymes
Produce and release inflammatory mediators
Macrophages produce and release these enzymes
Lipases, galactosidase
Macrophages produce and release these inflammatory mediators
Cytokines and chemokines Reactive oxygen intermediated (ROI) Nitric oxide (NO)
NK Cells
Recognize and destroy a variety of target cell types without prior stimulation or immunization
NK cells targets
Virus cells
Cancer cells
Transplant cells
NK cells cytotoxic mechanism
secretion of perforin
Which part of the immune system do NK cells belong?
Innate
-broad, non-specific cytotoxic activity
Basic mechanism of self non-self discrimination
PAMPs - pathogen associated molecular patterns
PAMPs
Basic mechanism of recognizing self/non-self
No structural similarity with self Ags
Cell receptors recognizing PAMPs are termed
Pattern recognition receptors (PRRs)
Mannose-tailed glycans are
Essential surface molecules of bacteria and viruses
PRRs Receptors
Encoded in germline (in gamete producing cells)
Limited diversity
PRR distribution of receptors
nonclonal; identical receptors on all cells of the same lineage
PRR discrimination of self and nonself
Yes; host cells are not recognized or they may express molecules that prevent innate immune reactions
Toll-like Receptors (TLRs)
Some are present on cell surface where they recognize products of extracellular microbes
Others are located in endosomes into which microbes are ingested
TLRs present on cell surface
TLR1 TLR2 TLR4 TLR5 TLR6
TLRs located in endosome
ONLY respond to nucleic acids TLR3 TLR7 TLR8 TLR9
TLR1
Bacterial lipopeptides
TLR2
Bacterial lipopeptides
Bacterial peptidoglycan
TLR4
LPS
TLR5
Flagellin
TLR6
Bacterial lipopeptides
TLR3
dsRNA
TLR7
ssRNA
TLR8
ssRNA
TLR9
CpG rich DNA
TLR that recognizes Gram + bacteria PGN
TLR2
TLR that recognizes Gram - bacteria LPS
TLR4
TLRs Trigger
Activation of immune cells
NF-kB
Role of PRRs in Phagocytosis
Microbes bind to phagocyte receptors
Phagocyte membrane zips up around microbe
Microbe ingested in phagosome
Fusion of phagosome with lysosome
Killin of microbes by lysosomal enzymes in phagolysosomes or killing of phagocytksed microbes by ROS and NO
Complement System
Set of serum proteins which normally exist as soluble inactive precursors
Upon activation, cleaved into two fragments
Complement large fragments
have enzymatic properties and activate the downstream components resulting in formation of Membrane Attack Complexes (MAC)
Complement small fragments serve as
Opsonins
Chemotactic factors
Anaphylatoxins
Opsonins
Deposited on microbes and enhance their uptake by phagocytes bearing complement receptors
Chemotactic factors
attract immune cells
Anaphylatoxins
cause degranulation of mast cells/basophiles and release vasoactive substances
Activation of complement can be triggered 3 ways
Classical pathway
Alternative pathway
Lectin pathway
Classical pathway
activated by Ag-Ab complexes
Alternative pathway
activated by microbial-cell walls
Lectin pathway
activated by interaction of microbial carbohydrates with mannose-binding protein in the plasma
2 Phases of Complement activation
Activation of C3 component
Activation of C5 component
Acute Phase Proteins
Blood circulating proteins involved in defense against infections
These plasma proteins are induced rapidly by cytokines after infection
Ex. Mannose-binding lectin
C-reactive protein
Mannose-binding lectin
acute-phase protein
protein that recognizes microbial carbohydrates and activates the complement cascade through the lectin pathway
C-reactive protein
Binds to phosphorylcholine on membranes and coats the membranes for phagocytosis by macrophages
Cytokines
Small proteins secreted by many cell types
Mediate inflammation, immunity and hematopoiesis
Can be endocrine, paracrine or autocrine
Pro or anti-inflammatory
Chemokines
Small protein chemoattractants important for trafficking of immune cells
Cell source TNF
M, T cells
Cell source IL-1
M, endothelial cells, some epithelial cells
Cell source Chemokines
M, endothelial, T lymphocytes, fibroblasts, platelets
Cell source IL-12
M, DCs
Cell source IFN-y
NK cells, T lymphocytes
ONLY cytokine that doesn’t come from M
IFN-y
Cell source IL-12
M, T cells - mainly Th2
Cell source IL-6
M, endothelial cells, T cells
Cell source IL-15
M, others
Cell source IL-18
M
TNF
Endothelial cells - activation Neutrophils - activation Hypothalamus - fever Liver - synthesis of acute phase proteins Muscle, fat - catabolism Many cell types - apoptosis
IL-1
Endothelial cells - activation (inflammation, coagulation)
Hypothalamus - fever
Liver - synthesis of acute phase proteins
Chemokines
Leukocytes - chemotaxis, activation
IL-12
NK cells and T cells - IFN-y synthesis, increased cytolytic activity
T cells - Th1 differentiation
IFN-y
Activation of macrophages
Stimulation of some antibody responses
Type I IFNs (IFN-a, IFN-B)
All cells - antiviral state, increased class I MHC expression NK cells - activation
IL-10
Macrophages - inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules
IL-6
Liver - synthesis of acute phase proteins
B cells - proliferation of antibody-producing cells
IL-15
NK cells - proliferation
T cells - proliferation
IL-18
NK cells and T cells - INF-y synthesis