(I) Lecture 4: Innate Immunity Part III

Question 1

Immune Proteins

Answer 1

Cytokines
Complement Proteins (C3a and C3b)
Antibodies (Adaptive Immunity)

Question 2

Types of Cytokines

Answer 2

Interleukins
Interferons
Tumor Necrosis Factors
Chemokines

Question 3

Cytokines

Answer 3

Chemical messages (proteins that communicate w/ cells)

• target cells can only respond if they have a receptor for it
• cytokine receptors have HIGH AFFINITY = powerful biological responses
• regulates hematopoiesis
• have a role in BOTH innate and adaptive immunity

Question 4

Responses induced from interaction btwn cytokines and their receptors

Answer 4

• changes in expression
• increase/decrease enzyme activity
• induce differentiation
• modulate effector functions
• cell survival/death

Question 5

Mode of action of cytokines

Answer 5

secreted cytokine binds SPECIFIC receptors

signal transduction pathway
- stimulus triggers cell to translate stimulus into expression of cytokine –> cytokine binds receptor –> biological response

Pleiotropy, redundancy, cascade induction

Question 6

Pleiotropy

Answer 6

SAME cytokine act on DIFFERENT cells to evoke different responses

Question 7

Redundancy

Answer 7

DIFFERENT cytokines evoke SAME response in cells

Question 8

Cascade induction

Answer 8

action of a cytokine INDUCES PRODUCTION of one or more additional cytokines

Question 9

Pro-inflammatory cytokines

Answer 9

Their presence triggers inflammation

Interleukins (IL): IL-1 and IL-6

Tumor Necrosis Factor (TNF): TNF alpha

Question 10

Chemoattractant cytokines

Answer 10

Chemokines

cell recruitment to site of infection

Question 11

Antiviral response cytokines

Answer 11

Interferons (IFN): Type I IFN

Question 12

Homeostasis and cytokines

Answer 12

Cytokine networks moderate the cross-talk btwn epithelial cells w/ innate and adaptive immune cells to maintain homeostasis

Question 13

Disruption of cytokine-guided cross-talk

Answer 13

Leads to initiation of inflammation (mostly by innate derived pro-inflammatory cytokines)

leads to IBD (inflammatory bowel disease)

If unresolved, it can lead to chronic inflammation since immune cells attack epithelia

Question 14

Phagocytosis and inflammation

Answer 14

Phagocytosis results in inflammation

1. Sensing PAMP/PRR (PAMP binding to PRR also triggers production of cytokines = inflammation)
2. Phagocytosis
3. Starvation/Intoxication
4. Killing
5. Signaling

Question 15

Chemokines

Answer 15

chemoattractant cytokine

attracts immune cells to infected tissues

BOTH immune and epithelial cells secrete chemokines

immune cells w/ chemokine receptors are recruited from blood into specific tissue

inflammatory trigger causes release of chemokines = neutrophils go to site of infection

Question 16

PAMP-PRR binding

Answer 16

Leads to phagocytosis and cytokine secretion

Question 17

Signs of Inflammation

Answer 17

DOLOR: pain
RUBOR: redness
CALOR: heat
TUMOR: swelling
FUNCTIO LAESA: loss of function

Question 18

Inflammation

Answer 18

dilation and increased permeability of endothelial cells

• increased local blood flow
• leakage of fluids and blood proteins into tissues
• extravasation (leakage) of immune cells into tissues
• results in heat, redness, and swelling

leads to increase in immune cells and enhanced clearance of pathogens

Question 19

Neutrophils in the immune system

Answer 19

1. Neutrophil sense bacteria
2. Neutrophil slows and squeezes through blood vessel
3. Neutrophil moves towards bacteria which have been marked by antibodies for ingestion
4. Neutrophil engulfs and destroys marked bacteria

Question 20

Pathogens and inflammation

Answer 20

1. bacteria/viruses trigger macrophages to release cytokines and chemokines
2. vasodilation and increased vascular permeability cause redness, heat and swelling
3. inflammatory cells migrate into tissue and release inflammatory mediators that cause pain

Question 21

Why is inflammation a good thing?

Answer 21

inflammation quickly recruits circulating immune cells into infected tissue to enhance immune defenses

1. cytokines produced by macrophages cause dilation of local small blood vessels
2. leukocytes move to periphery of blood vessel as a result of higher expression of adhesion molecules
3. WBCs extravasate at site of infection

Question 22

Fever

Answer 22

an early response to infection

pathogens activate phagocytes
phagocytes release cytokines
cytokines stimulate hypothalamus
hypothalamus produces prostaglandins
prostaglandins trigger fever

may help to combat infection by reducing growth rate of microbes (highly debated)

Question 23

Liver and infection

Answer 23

Cytokines can act on liver to promote release of acute phase proteins like CRP and Complement 3 protein

Question 24

CRP

Answer 24

C-reactive protein

used clinically to quantify inflammation

Question 25

Complement System

Answer 25

50-plus serum proteins that cooperates w/ both innate and adaptive immune systems to ELIMINATE PATHOGENS

Question 26

Complement proteins

Answer 26

- directly kill microbes by forming the MAC (Membrane Attack Complex) = target pathogens for cell lysis and activation - decorate pathogens to promote phagocytosis (opsonization) - recruit immune cells/inflammation

Question 27

Complement Protein 3

Answer 27

Cleaved into C3a and C3b

Question 28

C3a

Answer 28

Maintains inflammation - recruits phagocytes to site - acts a cytokine

Question 29

C3b

Answer 29

helps w/ opsonization (coating of a surface of a pathogen with antibodies and complement proteins to promote PHAGOCYTOSIS) - bacterium is coated w/ C3b - when only C3b binds to CR1, bacteria are not phagocytosed - C5a can activate macrophages to phagocytose via CR1 - helps phagocytes recognize pathogen faster and better

Question 30

Interferons

Answer 30

type of cytokine that are important in directing ANTIVIRAL responses Type I Interferon: IFN alpha and IFN beta - critical to antiviral immune response - rapidly secreted by virus-infected cells

Question 31

Cytokine release and IFNs

Answer 31

Type I IFN is RAPIDLY secreted after a viral infection after cytokine release, a wave of NKC follows they control viral replication together

Question 32

Virus-infected cells and PRRs

Answer 32

Have PRRs expressed on the surface and inside of cells Viruses have BOTH extracellular and intracellular phases Endosomal PRRs recognize components released during intracellular viral replication/degradation (ex. nucleic acids) Surface PRRs recognize components on the outside of the virus Viral particles bind PRR and triggers rapid expression of IFN by infected cell

Question 33

IFNs and NKCs

Answer 33

Type I IFNs promote NK cell killing of virus-infected cell Virus-infected cell secretes chemokines (attracts NKCs) and Type I IFN (activates NKCs) NKCs release toxic enzymes (perforin and granzye) to target infected cell for apoptosis

Question 34

Viral Survival

Answer 34

some viruses can block IFN secretion and signaling - express effectors that act to suppress IFN expression (ex. hepatitis, polio, SARS-CoV2) - Need To cell immunity to fight them off Type I IFN are used to treat SOME viral infections (ex. herpes and hep B)

Question 35

Cytokine Therapy

Answer 35

Cytokine inhibitor industry continues to grow used for asthma, rheumatoid arthritis and some cancers to reduce inflammation IFNs are used as therapy for MS

Question 36

Effector Function of Cytokines

Answer 36

- phagocytosis (extracellular) - NK-mediated apoptosis (intracellular viruses) - inflammation

Question 37

Innate immunity response time

Answer 37

Rapid (seconds, minutes, hours)

Question 38

Innate immunity specificity

Answer 38

Broad (conserved molecular patterns only found in pathogens)

Question 39

Innate immunity diversity

Answer 39

Limited diversity Germline-encoded receptors

Question 40

Innate immunity main cells

Answer 40

Phagocytes, NK cells, epithelial cells

Question 41

Innate immunity proteins

Answer 41

Proinflammatory cytokines, type I IFNs, tumor necrosis factors, chemokines

Question 42

Innate immunity mechanism of pathogen destruction/inactivation

Answer 42

- Phagocytosis - Apoptosis - Chemical attack by antimicrobial peptides

Question 43

Innate immunity immune response

Answer 43

Non-adaptive = same response for every exposure to identical pathogen

Question 44

Innate immunity memory

Answer 44

NO memory is formed

Question 45

Innate immunity efficiency

Answer 45

Rarely malfunctions

Question 46

Innate immunity intracellular viruses