Module 2 Lecture 5: Innate Immunity

Question 1

What is inflammation?

Answer 1

Innate, non-specific response to Tissue Injury

Phagocytes get recruited to isolate/destroy pathogens, clear debris and prepare for healing and repair

Question 2

What are the hallmarks of an inflammatory response?

Answer 2

Pain, Redness, Swelling and Heat

Four things you will either feel or see as a sign of inflammation

Question 3

Explain how inflammation occurs when you get a splinter?

Answer 3

1. A break in the skin allows for foreign pathogens to enter the site of injury and reproduce
2. Resident macrophages (in tissue) activate and engulf pathogens while releasing cytokines and chemokines from their sensors
3. Mast cells then release histamine (which prolongs inflammation and sends signals to other cells)
4. Histamine will cause vasodilation of blood vessels & permeability of capillaries allowing for more immune cells to squeeze through
5. Neutrophils and Monocytes squeeze through the blood vessel wall (endothelial cells) which is called diapedesis and go to the site of infection
6. Monocytes enlarge into macrophages and both macrophages and neutrophils will phagocyte the pathogens

• First responder of the inflammation response is resident tissue macrophages which will send signals to get more immune cells like neutrophils and monocytes to the site of infection
• Walling-off inflammed area means fibrinogen will come and clot up the wound

Question 4

Are B cells and T cells recruited in the site of inflammation?

Answer 4

No; they are not recruited by inflammation. Only monocytes and neutrophils are recruited during inflammation

Question 5

What are cytokines and chemokines?

Answer 5

• Signals released by resident tissue macrophages that have several jobs but mainly for killing microbes.
• Cytokine that only recruits cells (neutrophils & monocytes) to site of infection = chemokines

Multiple different types of cytokines; not specific to doing one thing

Question 6

What is Interleukin 1

Answer 6

Most powerful cytokine; produced between immune cells/leukocytes

Some cytokines can be made NOT by Immune cells
IL 6 is made by muscle cells because increases metabolism and produce heat

Question 7

What are things that Cytokines do?

Answer 7

• Endogyneous pyrogen induces fever on the body
• Decrease plasma concentration of iron (use of iron for pathogen metabolism and replication)
• Stimulate release of acute phase protein
• Trigger clotting and anti clotting

EP which starts localized due to cytokines can become systemic which allows for fat tissue to metabolize and produce heat (fever symptoms of body temperature increase)

Question 8

What is the ultimate goal of inflammation? What happens to tissue that become irreparable?

Answer 8

Tissue repair = ultimate goal
* Tissue that is unrepairable is replaced with scar tissue; fibroblasts which make proteins of ECM make collagen to replace that irreparable tissue

Question 9

What are side effects of chronic inflammation?

Answer 9

Alzheimers, atherosclerosis, asthma, diabetes, cancer

Treatment: NSAIDs or glucocorticoids (steroid treatment)
Interferons: Cytokine that is antiviral which interferes with virus hijacking the cell

Question 10

What is the complement protein system?

Answer 10

• Non-specific response
• Made of plasma proteins from the liver and circulate inactively

Inactive until they see a pathogen

Question 11

What are the mechanisms of activation for complement proteins

Answer 11

1. Spontaneously (once near the surface of the pathogen they attach and coat it) - Fastest way of activation
2. Binding to sugar molecules on the pathogen surface which complement proteins recognize and activate
3. Activation by antibodies binding to antigen on pathogens - Longest time to active b/c Adaptive

By coating the pathogen, they opsonize it; marks the pathogen for destruction via phagocytosis

Question 12

What do complement proteins do once activated

Answer 12

• Enhance the uptake of pathogens via phagocytosis due to opsonization (tagged/marked for destruction)
• Forms membrane attack complexes (Protein complexes) on the surfaces of the pathogen and punch holes through them

Question 13

What are dendritic cells?

Answer 13

One of the tissue resident macrophages that has a unique star shaped morphology

Known for being the bridge between innate and adaptive immunity

Question 14

How do dendritic cells work?

Answer 14

• Sit in the tissues immaturely doing macropinocytosis
• When they encounter a pathogen they go from immature to mature DC

Professional APC - They chop pathogen up and combine its peptides with the pathogens peptides and presents them to the leukocytes