Innate Immunity

Question 1

what are the 3 overall aspects of the innate immune response (+ hrs)

Answer 1

1. Intrinsic barriers (prevent entry)
2. Immediate response (0-4h)- recognition of microbes or alarmins by broadly specific receptors
3. Early induced innate response (4-6h)- Leukocytes are recruited from the blood into tissues and provide key innate responses

Question 2

How does the epidermis and dermis act as a barrier

Answer 2

epidermis- Tightly packed desmosomes, top layers composed of dead cells w low water content and no receptors

Dermis- Sebacecous glands produce a low pH environment

Question 3

how does the mucus membrane act as a barrier

Answer 3

• Epithelial cells tightly packed by tight junctions
• lamina propria contains various immune cells
• Goblet cells secrete mucans which traps particals from entry

Question 4

where is the mucocillary escalator found and what does it do

Answer 4

-found in respiratory areas with epithelial cells with cilia that beat in synchronized rythm to move musus up and out

Question 5

what is dysbiosis and examples (2) `

Answer 5

Alteration in the normal constituents of tissue microbiota

1. C diff–> associated w antibiotic use
2. Bac vaginosis–> gardnerella vag> lactobacilli spp.

Question 6

what are AMPs

Answer 6

Released by immune/tissue cells to trigger immune respone/ kill microbes

Question 7

What are 4 examples of AMPs

Answer 7

1. Lysosome- degrades peptidoglycan (gram pos bac)
2. Defensins- + charged peptides that form pores on microbial cell membranes (causing eflux)
3. Surfactant pros- act as oposins (phago beacons)
4. Complement pros

Question 8

What do complement proteins lead to (3)

Answer 8

1. Inflamation + chemotaxis
2. Opsonization of microbes
3. Disruption of microbial membranes

Question 9

what happens in the compliment protein classical path, lectin path and alternative path

Answer 9

Classic- C1q binds directly to pathogen surface

Lectin- lectins(MBL) bind to mannone on pathogen

Altern- Spontaneous activation of compliment pro 3 on path

Question 10

What happens when c1q/lectin bind to the pathogen surface + what is made in the end

Answer 10

Serine pros are activated which break down compliment pros

All pathways produce an important structure called C3 convertase**

Question 11

what does c3 convertase make and what do they do

Answer 11

C3a,C5a- promote inflamation/chemotaxis

C3b- opsonin

C5b,c6,7,8,9- membrane attack complex (make pores so int contents of microbe leak out)

Question 12

What type of pathogen is most susceptible to actions of complement pro

Answer 12

Bacteria and fungi

Question 13

What type of cells initiate the intermediate immune response and how do they detect it

Answer 13

tissue resident cells found @ the site of injury

• using broadly non specific receptors called pattern recognition receptors (PRRs)

Question 14

What 2 things do PRRs recognize

Answer 14

PAMPs (found on microbes; LPS/dsRNA/RNA virus)

DAMPS/alarmins (due to damage; intracellular structures)

Question 15

examples of DAMPS

Answer 15

• Free DNA, histone pros
• Heat shock pros
• Uric acid
• HMGB1
• S100 pros

Question 16

What are the inflammatory PRRs and what do they do

Answer 16

• Toll like receptors
• RAGE

-cell signaling cascade that results in activation of proinflammatory genes+ mediators +interferons

Question 17

What do embeded TLRs sense compared to endosomal TLRs

Answer 17

embeded membrane- ext microbe structures

Endosomal- recognize int microbe structures

Question 18

What TLR receptor recognizes: DAMPs, peptidoglycan/zymosan, dnRNA, LPS, ssRNA, Flagelin, CPG DNA

Answer 18

DAMPS- TLR2+4
pep/zym- TLR 1+2
DsRNA- TLR 3
LPS- TLR4
ssRNA- TLR 7+8
Flagenlin- TLR5
CPG DNA- TLR9

Question 19

Examples of cytokines that inflamatory PRRs release

Answer 19

IL1
TNFa
IL6
IL8
IL12
type 1 interferons

Question 20

what are the type 1 interferons and wht do they do

Answer 20

-IFNa and IFN b

• induce resitence to viral replication in cells not affected
• increase MHC class 1 (for t cell function)
• Activate dendridic cells and macrophages and NKcells

Question 21

what is the physiological roles of acute inflamation

Answer 21

• antimicrobial responeses for regen + repair

- Fever- triggers body temp increases and increases phagocyte activity, heat shock pros and inhib of microbe growth

Question 22

Other than inflammatory PRRs what is the other PRR + exmaples (3)

Answer 22

Phagocytic PRRs

1. Mannose receptor
2. Scavenger receptors
3. complement receptor
   - if ant of these receptors bind its associated ligand phagocytosis occurs

Question 23

How do phagosomes destroy phagocytized material

Answer 23

phagosome fuses with lysosome forming phagolysosome (has hydrolytic enzymes + low ph, increased prod of ROS/RNS and antimicrobial peptides)

Question 24

What starts the induced innate response and what is its goal

Answer 24

Inflammatory mediators produced as a result of recognition of PAMPS/DAMPS

-Facilitates extravasion of leukocytes and blood components into injured area

Question 25

what are the steps that proinflammatory mediators do to facilitate extraversion

Answer 25

1. Edothelia activation (icams/selectins)
2. Capillary endothelial cell tight junctions weaken making blood vessels leakier
3. Arteriole smooth muscle relaxes (vessel dialation)

Question 26

What happens in rolling adhesion

Answer 26

E selections on membrane binds to slex on blood leukocytes that roll along vessel wall

Question 27

What happens in firm adhesion

Answer 27

Integrens on leakucytes bind to ICAM molecules on endothelial cells; anchors them firmly

Question 28

What happens in diapedesis and migration

Answer 28

diapedesis- leukocytes squeeze between epithelial cells

Migration- Chemokines (IL8) attract leukocytes to site of injury

Question 29

What are the 3 main antigen presenting cells

Answer 29

cDCs
macrophages
B cells