Innate Immunity

Question 1

First line of defense in innate immunity

Answer 1

• Anatomical
  
  • Skin
  • Mucous membranes
• Mechanical
  
  • Cilia in respiratory tract
  • Tight jxns between cells
  • Tears
• Physiological
  
  • Lysozymes
  • Fatty acids on skin
  • Low pH/digestive enzymes in the gut
  • Antibacterial peptides

Question 2

Second line of defense in innate immunity

Answer 2

• Phagocytosis - neutrophils (PMNs), monocytes, macrophages
• Immune surveillance - natural killer cells’ cytotoxic activity

Question 3

Neutrophils (PMNs) are short-lived and fast-acting.

Function

Answer 3

• Phagocytosis releases hydrolytic enzymes responsible for other processes that effect acute inflammation
• Also involved in the complement system
• Releases cytokines for cell-cell communication
• Neutrophil extracellular traps (NETs): neutrophil vomits out its own DNA (suicide), which sticks to bacteria and traps them from moving

Question 4

Overview of innate immuner response when there is a barrier breach of skin

Answer 4

1. Bacteria enter through the breach
2. Cytokines recruit neutrophils to the site of invasion
3. Neutrophils create redness, heat, swelling

Question 5

Recall from acute inflammation:

How do neutrophils and other leukocytes leave the bloodstream and enter the intersitial space?

Answer 5

1. Cytokines at the site of injury signal endothelial cells to present selectins –> margination
2. Selectins weakly bind to leukocytes –> rolling
3. Adhesion to the postcapillary venule (veins thinner than arteries)
   
   1. TNF and IL-1 upregulate CAMs
   2. C5a and LTB4 upregulate integrins (interacts w CAMs)
4. Transmigration across the endothelium
5. Chemotaxis - leukocytes move toward chemical attractants
   
   1. Neutrophils are attracted by bacterial products, IL-8, C5a, and LTB4

Question 6

Macrophages are long-lived mononuclear phagocytes. Like neutrophils, they undergo diapedesis to leave the blood.

No recognition of self vs non-self, only uses ___

Answer 6

toll-like receptors

Question 7

Describe the process of macrophage phagocytosis

Answer 7

1. Opsonins (IgG & C3b) target microbe for phagocytosis
2. Pseudopods extend to ingest the microbe
3. Phagosome is formed and merged with lysosomes –> phagolysosome
4. Digestion by enzymes
5. Discharge residual bodies containing indigestible materials (waste), which flows through nodes to interact w lymphocytes

Question 8

Naural killer cells

Answer 8

Large, granular lymphocytes that are involved in cytotoxicity against virus-infected cells and tumor cells.

Question 9

How do NK cells know which cells to kill?

Answer 9

They recognize cells that lack MHC-1. However, overproduction of a stimulatory ligand can also cause an NK cell to kill it, even in the presence of MHC-1 (normally inhibits NK cell)

Question 10

Many viruses and tumors downregulate ___ to

Answer 10

MHC-1

to protect from killing by cytotoxic T cells, but then NK cells recognize this loss of MHC, and kill these cells

Question 11

___ are a pattern recognition receptor (PRR) on immune cells that allow recognition of pathogen-specific molecules called PAMPs.

It is the main way that the innate immune system identifies foreign vs self

Answer 11

Toll-like receptor

Question 12

Dendritic cells recognize __ through TLRs, then travel to the lymph nodes ot recruit the ___

Answer 12

Recognize PAMPs through TLRs –> travel to lymph nodes to recruit the adaptive immune response

This is why vaccines contain PAMPs - they want to stimulate the innate immune response, then the adaptive immune repsonse

Question 13

TLR4

Answer 13

recognizes LPS (lipopolysaccharides), a component of gram-negative bacteria cell walls

present on macrophages, dendritic cells, mast cells, and eosinophils

Question 14

Complement system

Answer 14

Serum enzymes (“complements antibody activity”) that…

• Recruitment of inflammatory cells
• Opsonization of pathogens for phagocytosis
• Perforation of pathogen cell membranes

Question 15

Complement system consist sof classical, alternative, and lectin pathways. What are they and what is the order in wihch they occur?

Answer 15

Alternative > lectin > classical

• Alternative: pathogen surfaces activate complement; continuously activated in a low level
• Lectin: mannose-binding lectin binds to pathogen surface (low yield)
• Classical: C-reactive protein or antibody binds to a specific antigen on pathogen surface -> activate complement

Question 16

Complement proteins C1-9 are activate din numerical order, but the system converges on ___, which will __

Answer 16

Converge on C3, which sticks to the surface of bacteria

Question 17

C3, 4, and 5 are all cleaved into two piece: a and b

What happens?

Answer 17

The b piece binds to bacteria for opsonization (tag bacteria for killing)

The a piece is an anaphylatoxin that activates mast cells and attracts neutrophils

–> forms a pore in teh bacterial surface

Question 18

Malfunction of ___ would devastate the immune system.

Answer 18

C3

Question 19

FUNCTIONS OF CYTOKINES

Answer 19

o T cell activation

o B cell activation

o Hematopoiesis

o Toxicity

o Antiviral defense: Interferons (esp IFN-a & IFN-B)

o Inflammation: Pro-inflammatory cytokines, IL1, IL6, TNF-a

Question 20

Interferons

Answer 20

confer viral-infection-resistance to nearby uninfected cells.

Question 21

Type 1 vs Type 2 inteferons

Answer 21

• Type 1 interferons : IFN-a , IFN-B
  
  • ​Produced by virally infected cells
  • Strong anti-viral activity:
    
    • Increases MHC-1 expression –> cytotoxic T cell response
    • Increases ligands for NK cells’ receptors
    • Induces resistance to viral replication
• Type 2: IFN-y
  
  • ​Produced by leukocytes (Th1, Tc1, NK)
  • Weak antiviral activity
    
    • Enhance adaptive immunity
    • Activate macrophages to better kill bacteria
    • Increase expression of MHC I and MHC II