look at this image a bit for review of what belongs where
1. What is the most abundant phagocyte in the blood?
1. role in what?
2. secrete what?
1. phagocytosis and killing of bacteria
2. pro-inflammatory cytokines
1. good for fighting what?
3. What happens when they crosslink?
1. parasitic infections
2. have Fc receptors for IgE
3. dump out a lot of toxic products to kill parasite
1. when surface IgE is cross-linked by binding to Ag - what will occur?
1. mast cells will degranulate, dumping out toxic and proinflammatory products
1. What is the process by which particles in extracellular fluid are taken up by phagocytes?
2. receptor-mediated or non-specific uptake?
3. What are the 3 major phagocytes?
3. macrophages, neutrophils, dendritic cells
1. Once a bacterium is engulfed in phagocytosis, for anything good to happen, one must happen following this?
2. What is responsible for this acidification?
3. What is the intracellular pocket created after phagocytosis called?
4. What is the purpose of the granules?
2. NADPH oxidase
3. phagosome (like the endosome)
4. They contain the enzymes that fuse with the phagosome and degrade it
1. What is this?
2. What are the five products?
3. What enzyme makes hydrogen peroxide?
4. What enzyme makes hypochlorite?
5. How do ROP damage stuff?
6. Doesn't start until what?
7. Which thing's macrophages make very little ROP?
1. When the cell uses oxygen to make reactive oxygen species
2. superoxide anion, hydrogen peroxide, singlet oxygen, hydroxyl radical, and hypochlorite
3. superoxide dismutase
5. bind to membranes
6. until NADPH oxidase is activated by acidification of the vesicle
(Reactive nitric oxide)
1. occurence in different species?
2. What is the equation to make it (including enyzme)
3. Does it react in the same way the ROP do?
1. humans and pigs a little, cattle some, rodents a lot!
2. O2 + L-arginine = NO + citrulline
enzyme is NO synthetase
(Natural Killer Cells)
1. What is ADCC?
2. How does this work?
3. Attacks what cells primarily?
1. Antibody dependent cellular cytotoxicity
2. receptors on NK cells that crosslink when they encounter antibodies on cell that triggers NK cell to dump out its contents and kill the target cell
3. tumor cells and virally infected cells (also some bacteria)
1. Why are NK cells needed when CD8 does the same thing?
2. So what serves as a signal for NK cell attack?
3. What will happen to animals deficient in NK cells?
4. What do NK cells secrete?
5. What happens when NK cells are stimulated by IFN-a and IFN-b (released by virally infected cells)?
6. What happens when they are stimulated by IL-12?
1. some cancers escape immunodetection by shutting down MHC I expression - NK cells can deal with these kinds of cells
2. lack of expression of MHC class I
3. get sick more cause recurrent viruses that inhibit MHC class I expression won't be dealt with
4. Pro-inflammatory cytokines (IFN-y and TNF-a)
5. cell killing
6. favors cytokine secretion (IFN-y and TNF-a)
1. When NK cell encounters MHC class 1 what happens?
2. What happens if there is no MHC class 1?
3. Do NK cells have a T cell receptor?
1. a negative signal is sent and NK cell doesn't do anything
2. positive signal; it's on
1. What are the things that send positive signal to NK cell?
2. When are they expressed?
3. So what if there are both MHC class I and the aforementioned signals?
1. MIC-A and MIC-B (carbohydrate ligands)
2. under times of stress
3. depends on the balance of signals it is receiving
(NK cells and ADCC)
1. What kinds of cells do NK cells kill?
2. What happens in ADCC?
3. Why is this important?
1. self cells
2. Fc receptors on the surface of the NK cell get crosslinked when they bind antibody on cell - release same things as Tc then (perforin, granzymes, etc.)
3. Tc takes awhile - NK cells can act faster
(Innate Lymphocytic Lineage Cells)
- several lymphocyte lineages behave as innate like cells
- have antigen-specific receptors (don't undergo clonal expansion)
1. most are derived when?
2. What one are we going to worry about?
3. are they part of immne response?
4. Do they release cytokines?
5. What do they recognize?
6. Does it have a T-cell receptor? how is it different?
1. early in life
2. gamma-delta T cells
4. yes (IL-23)
5. MHC class IB (an unusual one) - aka MIC-A and MIC-B
6. yes; doesn't see antigen directly (doesn't require antigen presentation)
(gamma delta T cells)
1. found mostly in what age?
2. do they have a t-cell receptor? what is different about it structurally?
3. Variation compared to normal T cell receptor? interact with CD4 or CD8? more or less V gene segments?
4. Do they undergo somatic hypermutation? are they clonally activated?
5. Where are they found mostly? why?
1. younger animals
2. yes; made of a gamma delta chain rather than alpha beta chain
3. less variation; no; fewer
4. no, no
5. along the surface of the gut mucosa; to recognize certain stress cells
(Gamma/Delta T cells)
1. Strong role in defense against what?
2. Do they have CD4 or CD8 molecule?
3. Situated where?
4. innate or adaptive?
5. some may recirculate where?
1. pathogens and in wound healing (yeah...)
3. at body's interface with environment
5. between tissues, blood, and lymph
(Antimicrobial peptides in innate immunity)
1-5. name the five antimicrobial peptides he wants us to know
for each - say where found - and function
2. histatins - alot of what responsible for what?
1. (Neutrophil and epithelial cells) bind iron - take it from bacteria which need it for replicating
2. (salivary glands) - cationic peptides (positively charged) disrput membranes (alot of histidine responsible for fungal fighting)
3. (neutrophils, mo)
4. (neutrophils) - cationic peptides (positively charged) disrput membranes
5. (neturophils, mo, epithelial cells) - cationic peptides (positively charged) disrput membranes
(Antimicrobial Peptides: Biochemical Characteristics)
1. How big? charged?
2. made by what?
3. what are the two main genetic categories?
1. small (12-50aa); (+2 to +11 charge) peptides
2. mammalian PMNs and epithelia l cells
3. defensins and cathelicidins
1. how many types?
2. how are they different?
1. alpha, beta, and theta
2. structurally (theta is circular peptide)
(Antimicrobial Peptides; role in host defense)
1. have acitivity against what?
2. Found where?
3. What types of expression?
4. what cells make them in gut?
1. bacteria, viruses, parasites, funguses
2. areas of interaction with the environment (gut lungs), also in many species in neutrophil granules
3. constitutive and induced expression
4. paneth cells
1. Defensins are electrostatically attracted to microbial membranes and do what to them?
2. Why does the positve charge help?
1. disrupt the structure and organization
2. Most bacterial membranes have a negative charge (our cells are neutral)
1. Rapidly diverged in mammals, with many genes in each class
2. Humans have how many b-defensins? mice? dogs?
3. How many clusters?
4. how are theta defensins formed?
5. what don't have theta defensins?
6. What wakes up theta defensins?
2. 30, 45, 60
3. 2 adjacent cluster on chromosomes 8 and 20 (will have variations in numbers of genes)
4. made by two peptides that are linked together covalentlely to make cirucular
5. primates (our genes developed stop codons)
6. retrocyclins (have anti-ciral activity)
1. are defensins inducible and highly divergent between tissues and species?
(Defensin gene expression)
1. alpha-defensins are expressed by what two things?
2. What do phagocytes use defensins for that they produce?
3. What in males has a high level of defensins? what is the source?
4. Why don't defensins kill good bacteria?
1. paneth cells in gut and leukocytes (macrophages)
2. released into phagolysosomes
3. reproductive tract; epithelial cells
4. because bacteria have defense against them
(Defensins as Immune regulators)
1. Have roles in stimulating what two things?
2. Do they activate cells; such as dendritic cell maturation and stimulating mast cell degranulation?
1. innate immune cells and T cell chemotaxis
1. what are they
1.4. - limitied distribution in what and what?
2. toxic to what?
3. chemotactic for what?
4. Do pathogens utlilize similar resistance strategies as for defensins?
5. what are some ways bacteria protects itself?
* they basically do the same things as defensins
1. short, basic, cationic peptides (a lot like defensins)
1.4. mice and humans (only one gene expressed)
2. bacteria, fungi, some viruses
3. mast cells and neutrophils
5. makes membrane not negative, prevents binding, bumps them off when bound
(Defensins and cathelicidins)
1. expressed where?
2. are they induceible?
1. sites of environmental contact
1. How are cathelicidin and vitamin D related and sun related?
2. altered defensin gene expression is assocaited with what?
1. sun leads to vitamin d production --> vit D binds another protein that becomes transcription factor for cathelicidin --> enhanced microbial protection
(helps prevent tuberculosis)
2. skin diseases
1. protects from what?
2. by doing what?
3. what part of bacterial cell wall does lysozyme celave?
4. expressed where?
5. human milk vs cow milk?
1. bacterial infection
2. attacks the cell walls of bacteria
4. most mucosal membranes and within endosomes of phagocytes (tears, mucous, milk)
5. high in human, low in cow
1. Found where?
2. what is the main antimicrobial action? then what happens?
3. very important in what?
1. milk, mucosal secretions, neutrophil granules
2. bind iron with high affinity; reaquired by phagocyes and epithelial cells to sequester it from extracellular bacteria
3. neonate immunity in gut