Ch2: Innate Immunity Flashcards
What are the components of innate immunity? 8
- Anatomical barriers
- Antimicrobial substances
- Normal flora that competes with pathogens
- Immune cells
- Sensor systems
- Phagocytosis
- Inflammation
- Fever
What is the specificity of innate immunity?
Structures shared by classes of microbes or damaged cells
What is specificity of adaptive immunity?
Structural detail of microbial molecules (antigens)
Receptors for innate immunity are encoded where?
Germline
Which has more diverse receptors, innate or adaptive?
Adaptive
What encodes adaptive immunity receptors?
Genes produced by somatic recombination of gene segments
How is the distribution of receptors described in innate immunity?
Nonclonal: Identical receptors on all cells of same lineage
How is the distribution of receptors described in adaptive immunity?
Clonal: Clones of lymphocytes with distinct specificities express different receptors
Can both adaptive and innate immunity discriminate against self?
Yes
How long does innate immune response last?
From 0-4 hours
When does the early induced response occur?
4-96 hours
When does the adaptive immune response occur?
After 96 hours
What is the skin’s mechanical, chemical and microbiological barrier to infection?
Mechanical: Perspiration and sloughing
Chemical: Sebum and Defensins
Microbiological: Normal flora
What is the GI tract’s mechanical, chemical, and microbiological barrier to infection?
Mechanical: Flow of fluid/food
Chemical: Acidity, enzymes, defensins
Microbiological: Normal flora
What is the respiratory tract’s mechanical, chemical and microbiological barrier to infection?
Mechanical: Flow of fluid, mucus, air
Chemical: Lysozyme in nasal secretions & Defensins
Microbiological: Normal flora
What is the urogenital tract’s mechanical, chemical and microbiological barrier to infection?
Mechanical: Flow of fluid
Chemical: Acidity in vaginal secretions, spermine and zinc in semen, defensins
Microbiological: Normal flora of urogenital tract
What are the eyes’ mechanical, chemical and microbiological barrier to infection?
Mechanical: Flow of tears
Chemical: Lysozyme in tears, Defensins
Microbiological: Normal flora
What is mucin?
Host cell derived glycoproteins that coat pathogens and inhibit adherence
Acids and bile salts have what effect in stomach?
Make is difficult for organisms to move past stomach
What do lysozymes degrade?
Peptidoglycans
Function of lactoferrin?
Sequester iron so bacteria don’t have access
What are alpha and Beta defensins?
Cationic peptides that damage negatively-charged membranes
Defensins are comprised of what?
35-40 amino acids containin 3 intra-chain disulfide bonds
Charge of defensins?
Why is this important?
Positively
Can interact with negative charged membranes
Are defensins hydrophobic or hydrophilic?
Both: amphipathic
Function of defensins?
Disrupt membrane integrity of bacteria, viruses, and fungi
Defensins are formed as what first?
Inactive precursors
What is the main source of defensins in the intestine?
Paneth cells
When a bacteria enters a surface wound, what happens? 3
- Resident effector cells secrete cytokines
- Vasodilation and increased vascular permeability
- Tissue is inflamed
3 types of cells created from lymphoid progenitor cell?
B Cell
T Cell
NK Cell
B Cells do what?
Produce antibodies
What do B cells transform into?
Plasma cell
What do plasma cells do?
Secrete antibodies
What do natural killer cells do?
Kill cells infected with certain viruses
What does a neutrophil do?
Phagocytose microorganisms
What does an eosinophil do?
Kills antibody-coated parasites through release of granules
What does a basophil do?
Control immune response to parasites
What does a dendritic cell do? 2
- Activates T Cells
2. Initiates adaptive immune response
What does a mast cell do?
Expulsion of parasites from body through release of granules containing histamine
What is a monocyte?
Circulating precursor cell to macrophage
What does a macrophage do? 2
- Phagocytose microorganisms
2. Activates T cells –> Initiates immune response
What does a megakaryocyte do? 2
- Platelet formation and 2. wound repair
What does an erythrocyte do?
Oxygen transport
4 types of white blood cells?
- Granulocytes
- Mononuclear phagocytes
- Dendritic cells
- Lymphocytes
4 types of granulocytes
- Neutrophils
- Basophils
- Eosinophils
- Mast cells
What is the most abundant cell in innate response?
Neutrophil
How long relatively is a neutrophils life?
Short
What 3 granulocytes are involved in allergic reaction?
- Basophils
- Eosinophils
- Mast Cells
What common cell is a member of the mononuclear phagocyte system?
Monocytes
What differentiate from monocytes?
Macrophages
What are four common macrophages differentiated from blood monocyte?
- Microglia (CNS)
- Kupffer cell (Liver)
- Alveolar macrophage (Lung)
- Osteoclasts (bone)
Dendritic cells are involved in which immune response?
Adaptive
Dendritic cells do what?
Finds material in tissue and brings it to adaptive immunity cells
Lymphocytes are involved in which immune response?
Adaptive
What is main difference of Natural killer cells and T & B cells?
NK Cells don’t have specificity
What is first thing to happen when first line barriers are breanched?
Tissue-resident macrophages and complement recognize the material
Recognition by macrophage and complement leads to what? 4
- Macrophage cytokine production
- Cell migration
- Inflammation
- Initiation/activation of adaptive response
Macrophage cytokine production causes what? 2
- Host cells to produce cytokines
2. Induce expression of cell surface molecules by epithelial cells
E and P selectin are examples of what?
What do they do?
Cell surface molecules
Bind sialyl-Lewis
ICAM’s are examples of what?
What do they do?
Cell surface molecules
Bind integrins
5 main ways a pathogen is recognized?
- Mannose-binding lectin
- Macrophage mannose receptor
- Scavenger receptor
- Toll-like receptor
- Nucleotide-binding oligomerization domain protein
Mannose-binding lectin is found where?
Part of what family?
What does it bind?
Free plasma
Collagenous lectin (collectin) protein family
Carbohydrates expressed by pathogens
Define a lectin
Any protein that is not an antibody nor from the immune system but binds to carbohydrate-receptors on cell surfaces
Macrophage mannose receptor is what type of molecule?
What is it dependent on?
What does it bind to?
Lectin
Calcium
Sugars on pathogens
Scavenger receptors recognize what? (2)
- Anionic polymers
2. Acetylated low-density lipoproteins
Toll-like receptors recognize what?
PAMP’s
Nucleotide-binding oligomerization domain (NOD) proteins are similar to what?
TLR’s
Main effects of triggering receptors on macrophages? 2
- Increase phagocytosis
2. Increase proinflammatory cytokine production
Define phagocytes
Cells that engulf and digest microbes and cellular debris
Which phagocytes are found even in healthy tissues? (2)
- Macrophages
2. Dendritic cells
Which phagocyte only appears when needed?
Neutrophils
What bacteriocidal agents does a phagocyte have? 6
- Acidification
- Toxic oxygen-derived products
- Toxic NO
- Antimicrobial peptides: Defensins & Cationic
- Enzymes: Lysozyme and Hydrolases
- Competitors: Lactoferrin & VB12-BP
What is respiratory burst?
Rapid, transient release of ROS
What are the steps for producing ROS? 3
- In endocytic vacuole, NADPH oxidase produces superoxide.
- Superoxide dismutase converts this to peroxide
3A. Peroxidase and iron convert this to hypochlorite and hydroxyl radicals
3B. Catalase converts this to H2O and O2 to increase pH for activation of defensins and lysozymes
Nitric oxide production also occurs which is produced by what?
What induces this?
NO Synthase
IFN-Gamma
What type of receptor is a Toll-like receptor?
Pathogen recognition receptor
What do Toll-like receptors recognize?
PAMP’s
Toll-like receptors are expressed intracellularly or extracellularly?
Both
What do intracellular TLR’s usually recognize?
Nucleic acids
What TLR’s recognize bacterial lipopeptides?
TLR-1:TLR-2
TLR-2:TLR-6
What TLR’s recognize bacterial peptidoglycan
TLR-2
What TLR’s recognize LPS?
TLR-4
What TLR’s recognize bacterial flagellin?
TLR-4
What TLR recognizes dsRNA?
TLR-3
What TLR’s recognize ssRNA?
TLR-7 and TLR-8
What TLR’s recognize CpG DNA?
TLR-9
What bacteria will be noticed by TLR4?
Why?
Gram-negative bacteria
Have LPS
What is required for LPS recognition by TLR4? (3)
LPS-binding protein (LBP)
MD2
CD14
Steps of TLR activation and the result? 5
- TLR is engaged by bacteria or virus
- TIR signaling domain recruits adaptor proteins
- Activation of transcription factors occurs (NF-KB and IRF’s)
4A. NF-KB causes an increase in expression of cytokines, adhesion molecules, costimulators
4B. IRF’s cause a production of type 1 interferon (IFN alph/Beta)
5A. Increased expression causes acute inflammation and stimulation of adaptive immunity
5B. Production of IFN causes an antiviral state
What do cytokines do?
Bind to surface receptors and regulate cell function
What is cytokine redundancy?
Multiple cytokines perform similar functions
What does it mean if a cytokine is pleiotropic?
Single cytokine can stimulate multiple functions
What is a chemokine?
Cytokine important in chemotaxis
What is a colony stimulating factor?
Cytokine important in multiplication and differentiation of leukocytes
What is an interferon?
Important cytokine that controls viral infections and inflammatory response
What is a interleukin?
Important cytokine that is produced by leukocytes for both innate and adaptive immunity
What is tumor necrosis factor?
Cytokine that kills tumor cells and initiates inflammation
What are five common pro-inflammatory cytokines?
IL-6 TNF-Alpha IL-1Beta CXCL8 IL-12