Innate Immune System pt.2

Question 1

Functions of Complement

(4)

Answer 1

1) Opsonization
2) Lysis
3) Chemotaxis
4) Inflammation

Question 2

Complement Pathways

• function

Answer 2

enhance ability of antibody & other cells

Liver proteins activate cascade of proteolysis rxns

• phagocytosis
• inflammation
• cell lysis

(3) pathways converge on C3 > cleaved

• C5 cleaved > Membrane Attack Complex
• C5a - soluble > activates mast cells
• C5b > opsonin > activates complement

Question 3

Classical Pathway

Answer 3

Antibodies bound to Antigen surface

• recognized by C1q/r/s complex
  
  • activated > cascade
  • C3 convertase cleaves:
    
    • C3a + C3b

COMMUNICATION

Question 4

Alternative Pathway

Answer 4

self-nonself discrimination

C3 spontaneously cleaved on pathogen surface

• initiated by microbial cell surface constituents (endotoxin?)

MAC formed > lysis

Question 5

C5a & C3a

Answer 5

role in anaphylaxis

activate mast cells - directly trigger degranulation

Question 6

Lectin Pathway

Answer 6

mediated by mannan-binding lectin > (opsonin)

(mannose polymerase)

• binds to certain C residues on some pathogen surface > cascade
• C3 cleavage > MAC formed > lysis

Question 7

Complement Activation & Negative Feedback

Answer 7

Host has many negative feedback mechanisms to prevent spontaneous / over-activation of complement

Some pathogens evolved > can escape complement pathway by mimic negative feedback

Question 8

Complement Activation & Disease Monitoring/Diagnosis

Answer 8

Certain diseases involve STRONG complement activation

• C3 & C4 levels measured
  
  • LOW levels may indicate Autoimmune disorders
• diseases resulting in Antigen-Antibody complex in blood > stuck

Question 9

Inflammation

Answer 9

RESPONSE to damage

process of recruiting leukocytes & plasma proteins (antibodies, complement, cytokines, acute phase reactants)

accumulation in tissue, activation to destroy microbes

Question 10

Leukocyte infiltration

Answer 10

presence of more than normal WBC

Question 11

Inflammation STEPS (6)

Answer 11

1) Cytokine release
2) attract cells involved in inflammation (neutrophils/monocytes)
3) also change vascular endothelial cells of BV

• vasodilation
• (4) capillary leakiness
  
  • ​paracellular transmigration
  • Plasma proteins migrate (Ab, Complement APRs)
• homing signal to recruit more inflammatory cells

5) migrated cells produce more mediators

ERYTHEMA (redness) & EDEMA (swelling)

Dendritic Cells take antigens & report to LN > Adaptive IS

• antigens also flow to draining LN to initiate

Question 12

Important Cytokines in Inflammation

Answer 12

IL-1

IL-6

TNFa (tumor necrosis factor alpha)

Type 1 Interferons - IFNa & IFNb

Question 13

IL-1, IL-6 & TNFa

• production
• functions (4)

Answer 13

produced by many different cell types

↑Production in presence of PAMPs

can act as chemokines - postcap v. > ↑ homing signal

PYROGENs - cause fever

stimulate liver production of acute phase reactants proteins

• ↓ BP > shock
• ^ thrombosis (clotting)
• ↓ appetite > cachexia (wasting of muscle/fat)

Question 14

NSAIDs

Answer 14

i,e. aspirin

inhibit pyrogens that act on hypothalamus to increase prostaglandin production to produce fever

Question 15

Acute Phase Reactants

• (2)
• (3) types

Answer 15

proteins produced by liver

stimulated by IL-1, IL-6, TNF

1. C-reactive protein (CRP)
2. Fibrinogen
3. Complement Proteins

Question 16

Acute Phase Reactants

1) C-reactive protein (CRP)

Answer 16

part of blood analysis to indicate inflammation or monitor disease activity

Question 17

Acute Phase Reactants ​

2) Fibrinogen

Answer 17

cause elevated ESR - marker for inflammation

involved in clotting

Question 18

ESR

Answer 18

erythrocyte sedimentation rate

• measure of blood precipation speed incubated 1hr

elevated ESR may indicate elevated fibrinogen levels

Question 19

Ferratin & Anemia

Answer 19

Ferritin(an iron storage protein) = APR made by a variety of cells in the body.

Increased Ferritin levels go up during inflammation

• can complicate anemia diagnosis

Question 20

Chronic Inflammation

Answer 20

severe tissue damage can cause

tissue remodeling & fibrosis (scarring of CT)

• results in granulomas
  
  • ​(nodule of activated macrophage/Tcells fused)

Question 21

Chronic Inflammation

• Granulomas

Answer 21

calcified or not

• found in prolonged Delayed Type Hypersensitivity (DTH)

or TB

• nodule of inflamm tissue → clusters of activated macrophages/T-cells

Question 22

Interferons

• functions (3)

Answer 22

Interfere viral replication → antiviral response

• ↑protein production that block viral replication (transcrip/translate)
• ↑ MHC-I expression
• ↑ sensitivity to apoptosis

Question 23

Types of INTERFERONs

Answer 23

IFNa

IFNb

IFNg

Question 24

Interferon production

• in response to?
• produced by?

Answer 24

Produced in response to PRR’s recognition of viral nucleic acids

by infected cells to act on surrounding cells

• to prevent spread of infection

→ infer resistance to infection

Question 25

Role of Innate Immune System in Infections

Answer 25

fast-acting & important in prevention

cytokines made by innate IS modify Adaptive response

Question 26

Describe self-nonself discrimination at Innate immune system level

Answer 26

↓ level of specificity

Since can’t distinguish between virus strains

Rely on germline encoded mechanisms in DNA to distinguish between self/non-self

Ex: stress, PRRs, negative feedback for complement activation (self vs. pathogen)

> all cells can produce MIC-A/B & ↓ MHC-I​