innate immunity

Question 1

define the following

1. antigen
2. PAMP
3. PRR
4. Cytokine
5. Chemokine

Answer 1

1. antigen-a section of biological material that can be targeted by an aimmune response
2. PAMP-pathogen associated molecular patterns, motifs that are entirely unique to non-self microbes
3. PRR-Pattern recognition receptor, the cellualr receptors that recoginze PAMPs
4. cytokine-solube molecules that mudolate the immune response
5. chemokine-soluble molecules that set up a gradient of chemoattractants to the site of infection

Question 2

define the following

1. Type 1 IFN
2. TLR
3. IRF

Answer 2

1. Type 1 IFN- cytokines made in response to PAMP sensing that modulate the immune response to fight intracellular invaders. Important for viral attacks
2. TLR-toll like receptors, PRRs that primarily recognize PAMPs. Signal through MyD88(most) and TRIF(TLR3)
3. IRF-interferon regulatory factor. transcription factors that control interferon prodution and some interferon responses

Question 3

describe the components involved in the following parts of the innate immunity:

1. barriers-3
2. molecular-3
3. cellular-4

Answer 3

1. barriers
   
   1. physical
      
      1. skin, hair, nails
   2. chemical
   3. microbial
2. molecular
   
   1. complement
      
      1. cascade that leads to: inflammation, neutraphil, neutraphil recruitment, pore formation
   2. antimicrobial peptides
      
      1. defensins, cathelicidins, histatins
      2. activated by proteolysis
      3. amphipathic
      4. form pores in membranes
   3. antimicrobial enzymes
      
      1. lysozymes
         
         1. found in teasrs, saliva, phagocytes
      2. phosphodiesteraseA
         
         1. enters bacterial cell wall and hydrolyzes phospholipids
3. cellular
   
   1. NKcell
      
      1. induced apoptosis
      2. granules
   2. DC
      
      1. messenger
      2. resident in the tissues
      3. bridge between innate and adaptive
   3. Phagocytes-garbage colelctors, ROS & NOS, long lived phagocyte
      
      1. macrophages
      2. monocytes
   4. neutrophils
      
      1. kamikaze cells
      2. short lived phagocyte
      3. granules

Question 4

What component of the physical barriers are vulnerable?

Answer 4

mucosal membranes

1. in red
   
   1. have physiological function with the outside world and potential vulnerable exposure.

Question 5

top to bottom

Answer 5

physical barriers-tight junctions

Question 6

Name the locations in the skin and notable services to physical protection

Answer 6

Question 7

Fill in the blanks for the following components of barrier defense

Answer 7

Question 8

of the molecular defense mechanisms give detail about the components involved

Answer 8

Innate responses all lead to membrane disruption

1. antimicrobial peptides
   
   1. defensins, cathlicidins, histatins
      
      1. activated by proteolysis
      2. amiphipathic
      3. form pores in membranes
2. compement
   
   1. enzymatic cascade that leads to inflammation,
   2. neutrophil recruitment
   3. pore formation
3. antimicrobial enzymes
   
   1. lysozyme
      
      1. found in tears, saliva, phagocytes
      2. breaks peptidoglycan
   2. phospholipase A
      
      1. enters bacterial cell wall and hydrolyzes phospholipids

Question 9

Define the three cascade pathways for Complement. why doesnt complement attack self proteins?

Answer 9

1. alternative -spontaneous and the first to lead to C3
   
   1. does not depend on an antigen-antibody reaction in order to become active. biolodical activators of this pathway include bacterial endotoxins, yeast cell walls, aggregated immunoglobulins and snake venom.
2. classical
   
   1. activated by the Fc portion of an immunoglobulin in an antigen-antibody complex.
   2. also by enzymes (trypsin, plasmin) and a variety of substances which include endotoxins, cell membranes and viruses
3. Lectin
   
   1. the activation of the lectin pathway is dependent on the binding of a lectin to mannose on the surface of a pathogen

Self cells have “OFF” proteins which tell complement proteins not to attack. Microbes lack these proteins

Question 10

What are the three complement pathways, how are they initiated and where do they converge?

Answer 10

1. alternative pathway-spontaneous hydrolysis or pathogentic surfaces. does not depend on antigen-antibody reaction.
   
   1. C3 goes through a series of hydrolytic events. C3b interact with Factor B and D generating C3.
   2. poperdin is a medicine that is also used for this pathway
2. classical -activated by IgG/IgM binding
   
   1. C1q binds to Fc portion of the antibody, promoting the formation of the C1 complex
   2. C1 cleaves C4
      
      1. C4
         
         1. C4b-binds to closeto the membrane then to C2 exposing it to C1
   3. C1 cleaves C2->C3 convertase
      
      1. C3=C4b2a
3. the lectin pathway- activated by PAMPs (MBL look like C1q and bid to microbial surface
   
   1. bound MBL serve as docking sites for MBL-associated serine proteases(MASPs)
   2. MASPs cleave C4 and C2=C3 xonvertase

after C3 is initiated it will lead to the generation of C5 in the MAC system (pore formation in the wall of the cell)

Question 11

Describe the function of defensins

Answer 11

amphipathic molecule that disrupts the cell membrane.

cysteine rich peptides produced by spithelial barrier, actinb as a broad spectrum antibiotic(fungi and bacteria)

stimulation of innate immune system receptors such as TLRs and inflammatory cytokines =IL-1, TNF

Question 12

How does lysozyme assist with poreformation?

Answer 12

Lysozymes clear the peptidoglycan layer from the bacteria clear a pathe to the membrane for any one of the hole poking pathways to occur.

Question 13

What is the defensin and how does it work

Answer 13

a byproduct of the complement pathway. Non-selective, can imbed in the lipid bylayer, and break up the lipids like a soap.

Question 14

list function of

1. neutrophils
2. monocytes/macrophages
3. natural killer cells
4. dendritic cells

Answer 14

1. neutrophils
   
   1. short lived
   2. throw EVERY thing at the antigen
   3. granulocytes
2. monocytes/macrophages
   
   1. can stick around for long time
   2. barbage collector
   3. uses ROS and NOS
3. natural killer cells
   
   1. induces apoptosis
   2. need a signal from the cell stopping the NK cell from sending apoptotic signal to the target cell
4. dendritic cells
   
   1. messenger, runs away with information and bring it to the lymph node for the adaptive immune system
   2. senntinal cell that live in the skin, bridge between adaptive and innate immune system

Question 15

which cells phagocytize? Describe the step wise process.

Answer 15

Macrophages and neutrophils

1. recognize PAMPs or antigen on APC presents it the the response cells
2. antigen is phagocytized and structure insie cell with foreign item= phagosome
3. put into lysosomes: contains molecules that break down structures
4. phagocyte is then activated to generate the ROS and NOS
   
   1. NADPH oxidase is activated to create radical Oxygen O-

Question 16

describe structures and function of PMNs

1. how does it move?
2. describe the nucleus
3. how are chemokines used?
4. what is a neurtaphil extracellular trap?

Answer 16

Question 17

what does a monocyte do as it relocates to the site of infection? hint differentiation

Answer 17

monocytes locate into the tissue and differentiate into macrophage or dendritic cell

macrophages

1. garbage collectors, pick up the debris
   
   1. if everything is cleaned up then no inflammation is sent
2. if a pathogen is encountered
   
   1. MHC2 present antigen and inflammatory responses are initiated

denritic cells - replenished b/c the previous ones left to the lymph node for APC to adaptive immune system

Question 18

explain NKcell operation.

Answer 18

The NKcells are always in a state of send an apoptotic signal. so they must be told to stop sending the signal by healthy cells.

1. Inhibitory<<<activatinr signal sent>
   <li>inhibitory&gt;&gt;&gt;&gt;activating=cell lives</li>

</activatinr>

The steps to signal transduction

1. degranulation
   
   1. pokes holes in membrane
2. induction of death receptors
   
   1. tells cell to apoptos
3. ADCC-atibody dependent cellular cytotoxicty
   
   1. tumor, infected…
   2. Ab attach to the cell surface and Fc region communicates with NKc

Question 19

list the location of receptor and what it recognizes. relativly broad picture.

Answer 19

1. TLR
   
   1. endosomal-DNA
   2. extracellular-LPS, and alike
2. C type lectins
   
   1. looking at sugars that are different from mammalian cell
3. cytosolic
   
   1. NLR
      
      1. good at sensing bacterial sugars in the cytosol
      2. tend to favor the inflammatory gene response
   2. RLR
      
      1. look for non mammalian RNA
   3. CDS
      
      1. look for DNA, mammalian DNA should not be in the cytosol

Question 20

How does interferon work? What cells can synthesize it?

Answer 20

all cells make interferon (except RBC)

1. virus induces an interferon response
   
   1. IFN tells neighboring cells to get away
   2. IFN autostimulates to shut down normal state and go into antiviral state

Question 21

After stimulation, what does NF-kB and INF produce? what are the actions of these chemokines?

Answer 21

leads to increase expression of

1. NFkB
   
   1. cytokines, adhesion molecules, costimuators
      
      1. acute inflammation
      2. stimulation of adaptive immunity
2. IRF
   
   1. IFN-1
      
      1. antiviral state

Question 22

What is a PRR?

Answer 22

receptor that recognizes PAMPs.

adaptor molecules links the immune response to the anitgen presentation.

1. IRF
   
   1. type 1/3
      
      1. innate
   2. type 2
      
      1. adaptive

Question 23

What is happening in this image?

Answer 23

The neutraphil is acting in last attempt to stop antigen by throwing its nucleus at the antigen.

1. nucleus is sticky and slows the growth.

Question 24

Some pathogens evade the immune system. Complete the list of possible infection prevention/contianment options.

1. pathogen->gets on skin
   1.

Answer 24

if you dont get rid of the infection their are two possibilites:

1. die
2. chronically sick