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108 Cards in this Set

  • Front
  • Back
Which type of immunity can one survive without?
Adaptive
-Cannot survive without innate immunity however!
Is innate immunity ever not on?
no
What is the timeframe for an innate immune reaction?
Within 0-12 hours of infection
What is the purpose of the innate immune system?
To prevent infection or eliminate a particle/infectious agent
Is innate immunity completely separate from adaptive immunity?
No - some effector mechanisms of innate immunity help to eliminate organisms/pathogens in adaptive responses
How does innate immunity mesh with adaptive immunity?
It stimulates and influences the adaptive immune response to optimize its effect
What are the 3 functions of epithelia in innate immunity?
1. Physical barrier to infection
2. Kill microbes by locally produced antibiotics
3. Kill microbes/infected cells by intraepithelial lymphocytes
4 epithelial barriers in the body:
1. skin
2. gut
3. lungs
4. eyes/nose
What is the mechanical mechanism that allows epithelium to resist infection in all barriers?
Tight junctions that join the epithelial cells
Which epithelial barriers have longitudinal flow of air/fluid?
Skin and Gut
Which epithelial barrier has movement of mucus by cilia?
lungs
What epithelial barriers have chemical mechanisms consisting of antibacterial peptides?
-Skin
-Gut
-Lungs
Where are fatty acids an effective chemical mediator of immunity?
On the skin
Where are low pH and enzymes an effective chemical mediator of immunity?
In the gut
Where are salivary enzymes like lysozyme chemical agents of immunity?
In the eyes/nose
Where are normal flora found as a microbiological mechanism of immunity?
In the skin and gut
How does normal flora on the skin act as an immune barrier?
Microbiota compete with pathogens for nutrients and colonization sites
What is the environment of the skin like chemically?
Dry and acidic
What are 3 chemical factors found on the skin that act immunologically?
-Fatty acids
-Lysozyme
-Immunoglobulins
What special cells act to prevent infection at the skin?
Intrinsic immune sentinels
SALT
Skin associated lymphatic tissue
What are 2 types of intrinsic immune sentinels?
-Resident langerhans cells (dendritic cells)
-Intraepidermal lymphocytes
How many bacteria make up the normal commensal microbiota of the GI tract?
10^14
List the 5 mechanisms of innate immunity at Mucosal surfaces (resp, GI, and UG):
1. Anatomic barriers
2. Physiologic barriers
3. Commensal microbiota
4. Secretory antibodies
5. Intrinsic immune sentinels
What is the mucosal antibody?
IgA
What is the function of secreted IgA?
To prevent bacterial adherence to mucosal epithelial surfaces.
Where is IgA transported into the gut lumen?
Through epithelial cells at the base of crypts
What is the cellular response of innate immunity called?
Inflammation
What are the 3 main components of an inflammatory reaction?
1. Recruitment of wbcs
2. Activation of WBCs
3. Elimination of the pathogen
What are 4 means of pathogen elimination by innate immunity?
1. Macrophage eating
2. Complement activation
3. Neutrophil eating/respiratory burst
4. Solule mediators - eicosanoids, NO, and ROS
List the 4 main players in inflammatory reactions:
1. Cytokines
2. Complement
3. Neutrophils
4. Soluble Mediators
What causes rubor and calor during inflammation?
Vasodilation
What causes tumor?
Increased vascular permeability - exudate
What causes dolor (pain)?
Damage to tissue and phagocyte influx
What are the phagocytes that act during inflammatory response?
-Neutrophils
-Macrophages
(resident to the skin or mucosal surface)
What are the 3 steps in the functional response of phagocytes during inflammation?
1. Recruitment to site
2. Recognition of microbes
3. Phagocytosis
What is Phagocyte Recruitment?
Protein:protein interactions between traveling WBCs and the blood vessels
What proteins are on WBC surfaces that allow it to bind to ECs on blood vessels?
-Integrin (low affinity)
-Selectin ligands
What is responsible for rolling of WBCs on ECs?
Sialyl glycoproteins binding to e-Selectin and p-selectins on ECs
What has to happen to EC's in order for rolling of WBCs??
Cytokine release from macrophages that ate microbes; it activates ECs to increase their E-selectin expression
What are the macrophage produced cytokines that increase selectins on ECs?
-TNF
-IL-1
What molecules are responsible for pavementing and stable adhesion of WBCs to ECs?
Integrin binding
What increases the integrin to high affinity state on WBCs?
Chemokines
What is the final step in recruitment after pavementing?
Diapedesis
Once WBCs get into the interstitial space, what is their job next?
To recognize the microbial targets
What feature of WBCs allows them to recognize the microbial targets?
PRRs
PRR:
Pattern recognition receptor
Are there PRRs on host cells?
no
Can PRRs undergo somatic hypermutation?
No; they are encoded in germline DNA.
What is the source of dsRNA as a pattern for WBC microbial recognition?
Replicating viruses
What is the principal receptor for dsRNA? Response?
-TLR3
-Causes Type I IFN production
What is the source of LPS as a pattern for WBC microbial recognition?
Gram negative bacteria
What is the principal receptor for LPS? Response?
Receptor: LBP and TLR4
Response: Macrophage activation
What is the source of Flagella as a pattern for WBC microbial recognition?
Bacteria and protozoa
What is the principal receptor for Flagella? Response?
-TLR5
Response: macrophage activation and cytokine production
What is the source of Unmethylated CpG DNA as a pattern for WBC microbial recognition?
Bacterial DNA
What is the principal receptor for Unmethylated CpG DNA? Response?
TLR9
Response: macrophage activation
What is the source of N-formyl peptides as a pattern for WBC microbial recognition?
Bacterial protein
What is the principal receptor for N-formyl peptides? Response?
fMLP
Response: neutrophil and macrophage activation
What is the source of mannose as a pattern for WBC microbial recognition?
Surface glycans on bacteria
What is the principal receptor on WBCs for mannose? Response?
-Mannose receptor
-Mannose Binding lectin
Response: phagocytosis and opsonization
What is the source of phosphorylcholine as a pattern for WBC microbial recognition?
Microbial cell membranes
What is the principal receptor for Phosphorylcholine? Response?
C-reactive protein
Response: opsonization and complement activation!
Once the wbc's recognize microbes via their PRRs, what needs to happen?
Phagocytosis
3 types of microbicidal molecules used during phagocytosis:
1. Lysosomal enzymes
2. ROIs
3. NO
What is the enzyme that phagocytes use to make Nitric oxide?
Inducible nitric oxide synthase
What is the precursor of nitric oxide?
Arginine
What is the enzyme used to make ROIs?
NADPH oxidase
In what organelle does killing by lysosomal enzymes occur?
Phagolysosomes
Why is overproduction of ROIs and NO harmful?
Because they can cross the cell membrane and kill extracellular microbes and host tissues.
When Macrophages eat bacteria, what 2 processes result?
1. Loading of antigen onto Class II MHC and presentation to Th cells
2. Production of chemical mediators
List 4 mediators released by activated macrophages:
1. Cytokines
2. Chemokines
3. Nitric oxide
4. Lipid mediators
What is the first WBC to emigrate during inflammation?
Neutrophils
3 special chemical mediators made by neutrophils:
-Defensins
-Lysozyme
-Lactoferrin
What is the principal event that allows neutrophils to kill ingested bacteria?
Respiratory burst
Which enzyme is essential for the respiratory burst?
Phox - phagocyte oxidase
In what disease is phox activity deficient?
Chronic granulomatous disease
What inheritance pattern is seen in the majority of CGD cases?
X-linked
What is the prominent clinical feature of CGD?
Recurrent pyogenic bacterial infections
2 diagnostic features of CGD:
-Neutrophilia
-NBT dye reduction - no change
What do eosinophil granules contain?
-Heparin
-Hydrolytic enzymes
-Major basic protein
What do basophil granules contain?
Histamine
What do mast cell granules contain?
Heparin and histamine
Which cells are important in allergic responses?
Basophils and mast cells
Which granulocytes are capable of phagocytosis?
-Neutrophils
-Eosinophils
Are basophils phagocytic?
no
What cells are the progenitor of dendritic cells?
The same cell that makes monocytes and macrophages
What type of receptors are on dendritic cells?
The same PRRs as on macrophages and neutrophils
What is TLR
a PRR
What is the maturation of dendritic cells like?
-Born in bone marrow
-Migrate to reside in tissues
-Ingest microbes/particles via macropinocytosis (immature)
-Migrate to present ingested Ag to T lymphs in periph lymphoid tissues (mature)
So what is the main difference between dendritic cells and macrophages?
-Dendritic cells leave tissues to present Ag to lymphocytes
-Macrophages stay in tissue at infection site to eliminate the pathogen there.
What type of cell are Natural Killer cells?
Lymphocytes - large and granular
How are NK cells different from T and B lymphocytes?
They lack TCR or BCR
What CD is TCR?
CD3
What activates NK cells?
Nothing; they're active without prior Ag exposure or presentation
What 2 types of cells are NK cells specialized to kill?
-Virus infected cells
-Tumor cells
What 2 cytotoxins do NK cells secrete?
-Perforin
-Granzyme
What is the ultimate result of NK cytokine secretion?
Apoptosis of virus/tumor cells via Fas-FasL interactions.
2 Ways by which NK cells kill:
1. Direct
2. Indirect
What is the direct method of NK killing infected cells?
ADCC - antibody dependent cellular cytotoxicity
What happens in ADCC?
A virus-infected cell is bound by IgG, which triggers the NK cell to kill the infected cell.
What is the indirect method of NK cytotoxicity?
A macrophage with ingested microbe secretes Il-12 which activates the NK cell to produce IFN-y, which activates the macrophage so it can kill the microbes it ate.
3 mediators that are capable of activating NK cells:
-IL-12
-IFN-a
-IFN-B
What does IFN-y secreted by NK cells do?
-Activates TH1 type T cells
-Activates macrophages
What are the receptors that normal NK cells express?
-Activating receptor
-Inhibitory recepto
What is the ligand for NK cell's
-Activating receptor
-Inhibitory receptor
Activtng: a ligand on normal autologous cells
Inhibiting: Self class I MHC with self peptide on it
What happens when NK cells engage with the ligands on normal self cells?
Nothing; the NK cell is not activated.
What happens when NK cells engage with the ligands on virus infected cells?
Virus infected cells lack Class I MHC and so the NK cell missing the inhibitory signal is activated and kills the infected cell.