Cytokines And Complement

Question 1

Cytokine

Answer 1

Control immune system

• (+) and (-) feedback loops, agonist is and antagonistic relationships, redundant fxns
• can be harmful if over/under active
• intercellular regulatory proteins
• allow immune cells to communicate
• made as needed, not stored
• cells w/ receptors respond
• receptor affinity/ number affects response

Question 2

Cytokine targets

Answer 2

1. Autocrine- acts on self
2. Paracrine - acts on neighbor
3. Endocrine - acts far away

Question 3

Cytokine general properties

Answer 3

1. Targets
2. High affinity for receptors - measurable effect from small amt.
3. Macrophages and CD4 + T cells -> inc. production/secretion
4. Adaptive and innate immunity

Question 4

Activation of JAK/Stat Pathway

Answer 4

1. Bind receptor -> JAK activation
   * phosphorylate receptor for STAT proteins
   * phosphorylates STAT
2. STAT activates/inhibits transcription of specific genes

Question 5

Types of cytokines

Answer 5

1. Interferons (IFN)
2. Chemokines
3. Interleukins (IL)
4. Tumor necrosis factor (TNF)
5. Growth Factors
6. Colony stimulation factor (CSF)

Question 6

Interferons

Answer 6

Type 1 (alpha and beta)

• viral infections
• autocrine and paracrine
  1. Activate antiviral mech
  2. Inc. MHC I expression -> adaptive response
  3. Inc. NK activity
• Antiviral state
  1. IFNs stimulate neighbor cells
  2. RNAse activated
  3. RNAse chops viral RNA
  4. Stops viral replication
• Fxn: innate antiviral response

Question 7

Chemokines

Answer 7

MCP-I, IL-8

*chemotaxis, proinflammatory

Question 8

Interleukins

Answer 8

IL-6, IL-10

*Fxn: Leukocyte development

Question 9

TNF-alpha

Answer 9

Acute response coagulation

Question 10

Growth Factors

Answer 10

VEGF, GM-CSF, TGF-beta

*Fxn: growth differentiation

Question 11

Acute phase response

Answer 11

Inflammation cytokines: IL-1, IL-6, and TNF- alpha

• innate response
• change in metabolism, vasculature, and plasma proteins
• effects occur w/in hours
• can caused damage if prolonged

Question 12

Interferons Gamma (IFN-Gamma)

Answer 12

• Adaptive component
• Released by T cells and NK cells
• inc. macrophage activity
• inc. NK cytotoxicity
• inc. B cell antibody production
• takes a couple of days

Question 13

Communication and cooperation via cytokines

Answer 13

1. Macrophage infected w/ resistant microbe
2. Macrophages secrete IL-12
3. IL-12 activates NK cells
4. NK cells secrete IFN-gamma
5. IFN-gamma -> macrophage makes more ROS and lysozyme
6. Macrophages can kill microbe
7. IFN-gamma from NK- autocrine effect

Question 14

Membrane attack complex (MAC)

Answer 14

• C5-C9, poly C9

* makes holes in infected cell membrane -> allow H2O in and changes osmolarity

Question 15

Inflammation

Answer 15

• C3a, C4a, C5a = anaphylatoxins

* ensures microbes that escape MAC are phagocytosed by leukocytes

Question 16

Opsonization

Answer 16

C3b binds complement receptor 1 (CR1) expressed by phagocyte cell -> phagocytosis

Question 17

Antibody production

Answer 17

C3d recognized by CR2 on B cells -> inc. antibody production

*complement proteins bound to immune complexes recognized by dendritic cells

Question 18

Regulation of complement

Answer 18

Necessary to prevent auto-immunity

*plasma and cell membrane associated proteins can stop complement cascade at various points

Question 19

Complement deficiencies

Answer 19

1. Hereditary angioedema
2. Paroxysmal nocturnal hemoglobinuria
3. C1-C4 deficiencies
4. C5-C9 deficiencies

Question 20

Hereditary angioedema

Answer 20

C1-Inh deficiency -> dec. C4 protein -> inc. vascular permeability
*recurrent episodes of severe swelling

Question 21

Paroxysmal nocturnal hemoglinuria

Answer 21

DAF and CD59 deficiency -> mediated RBC lysis

Question 22

C1-C4 deficiencies

Answer 22

Recurrent bacterial infections and immune complex diseases (SLE)

Question 23

C5-C9 deficiencies

Answer 23

Recurrent meningococcal and gonococcal infections

Question 24

Complement pathways

Answer 24

1. Classical
2. Lectin
3. Alternative

Question 25

Classical complement pathway

Answer 25

1. Activation: IgG antibodies bind to microbes 2. C1 formation and activation -> cleavage of C2 and C4 3. C2b + C4a -> C3 convertase 4. C3 cleaved -> C3a + C3b * C3a = inflammatory mediator * C3b = opsonin 5. C3 convertase + C3b -> C5 convertase 6. C5 cleaves -> C5a + C5b * C5a = inflammatory mediator * C5b = MAC initiator 7. MAC formation * C5B + C6 + C7+ C8 + mult. C9 8. Microbial lysis

Question 26

Lectin Pathway

Answer 26

1. MBL binding to pathogenic mannose 2. C2 and C4 cleaved 3. C2b + C4a -> C3 convertase 4. C3 cleaved -> C3a + C3b * C3a = inflammatory mediator * C3b = opsonin 5. C3 convertase + C3b -> C5 convertase 6. C5 cleaves -> C5a + C5b * C5a = inflammatory mediator * C5b = MAC initiator 7. MAC formation * C5B + C6 + C7+ C8 + mult. C9 8. Microbial lysis

Question 27

Alternative Pathway

Answer 27

1. Spontaneous cleavage of C3 on microbial surface 2. C3b + Bb -> C3 convertase 3. C3 cleaved -> C3a + C3b * C3a = inflammatory * C3b = opsonin 4. 2(C3b) + Bb + C5 -> C5 convertase 5. C5 cleaves -> C5a + C5b * C5a = inflammatory mediator * C5b = MAC initiator 6. MAC formation * C5B + C6 + C7+ C8 + mult. C9 7. Microbial lysis

Question 28

Differences between complement pathways

Answer 28

1. Activation | 2. Classical involves adaptive immune system, other 2 do not

Question 29

Cytokine properties/actions

Answer 29

1. Pleiotropism: one cytokine stimulates several responses 2. Redundancy: CD4 -> several cytokines -> single response 3. Synergy: 2 sets result in same result 4. Antagonism: work against each other