Innate Immunity II (1/7)

Question 1

What are sentinel cells?
What do they do?

Answer 1

Includes macrophages & neutrophils

They do phagocytosis

Question 2

What is phagocytosis

Answer 2

Means of destroying pathogenic bacteria & fungi

Initiates antigen presentaiton

Part of both innate & acquired immunity

Question 3

What is the difference between opsonic and non-opsonic phagocytosis?

Answer 3

Opsonic: typically mediated by deposition of proteins (antibodies) on microbes that target them for recognition by specific phagocytic receptors on leukocytes

Nonopsonic: mediated by cell surface receptors on leukocytes that recognize molecular patterns on microbes i.e. PAMPs

Question 4

What systems in the innate immune system recognize PAMPs?

Answer 4

TLRs, complement, collectins (surfactant), scaventer receptors, pentraxins (CRP), lectins, CD14, NLRs, RIG1-1-like receptors

Question 5

What is the scavenger receptor superfamily?

Answer 5

They recognize PAMPs of bactieria, are present in macrophages

Question 6

What are collectins?

Answer 6

Proteins that can bind phagocytes, serve as opsonins, protect in general against bacteria

Includes surfactant proteins in the lungs

Question 7

What is the phagosome-lysosome fusion?

Answer 7

A post-phagocytic event in which the phagosome fuses with the lysosome so it can degrade the phagosome’s contents

Question 8

What happens after pathogen ingestion?

Answer 8

NADPH oxidase (Phox) is activated & converts O2 to superoxide (ROS) in the phagosome. Reactive nitrogen species also form

Note that superoxides cannot leave the phagosome nor cross the membrane but H2O2 is freely diffusible and can exit the cell

Question 9

How do bacterial virulence factors subvert host defenses in the phagosome-lysosome fusion event?

Answer 9

Modify phagocytic receptors, impair ingestion phase, escape from phagosome into cytosol, stall phagosome maturation, resist lysosomal degradation

Question 10

What is CGD?

Answer 10

Chronic granulomatis disease

It is an interited defect of the NADPH oxidase complex

Results in a block in generation of ROS in phagosome

Symptoms = recurrent infections with catalse-positive organisms (including staphylococcus) –> lymphadenitis, absecces, granuloma formation

Question 11

What are non-oxidative killing mechanisms of phagocytes?

Answer 11

Principally proteins within granules that are released upon cell stimulation i.e. proteases, lysozyme, defensins, etc

Question 12

What else besides infection is phagocytosis used for?

Answer 12

Disposal of apoptotic corpses, which is accompanied by an anti-inflammatory signal via production of TGF-beta.

Because apoptotic corpses contain many potential self antigens, the lack of an appropriate anti-inflammatory signal has the potential to trigger autoimmunity

Question 13

How does the innate response affect the acquired immune response? (in general)

Answer 13

Innate response is first (cytokines, TLR, physical barriers) & mounts the acquired response if it isn’t cleared with innate only

Question 14

What are chemokines?

Answer 14

Like hormones but the only direct cell motion i.e. leukocytes, which have receptors for chemokines & cytokines

Leukocytes increase the level of adhesion molecules in response to a high concentraiton of cytokines & chemokines, which makes them stick & begin to respond –> inflammation

Question 15

What are dendridic cells?

Answer 15

Monocyte lineage derived cells

Have dendrites that can take up & present antigen to lymphocytes in lymph nodes

They are the most important antigen presenting cells

Question 16

What is dendridic cell maturation?

Answer 16

The process by which dendridic cells change fom skin form to the lymph form

DC maturation is characterized by a change in function (from antigen capture to antigen presentation) and a change in which cell surface receptors are expressed

Question 17

What triggers DC maturation? What directs it?

Answer 17

Once the TLRs recognize pathogens, take up antigen, which leads to their activation –> chemokine receptors expressed on DC surface –> allows them to migrate to site of production. **chemokines direct where they need to go

Question 18

What are the 3 types of antigen presenting cells?

Answer 18

Dendridic cells: most important

Macrophages (can also phagocytose)

B cells

The 3 are used in different contexts

Question 19

How do DC sample antigens?

Answer 19

1. ICAM-1 on antigen presenting cell (APC) binds LFA-1 on T cell - “kiss and touch”

If the interaction is tight, it sets in motion signalling events that lead to a more stable interaction between LFA-1 & ICAM-1 & other adhesion molecules

You need an additional signal for proper activation “costimulatory signal” - without it, T cell is inactivated; helps prevent recognition of self antigens

Note that costimulatory signal is not antigen nonspecific & occurs between the APC and T cell

2. MHC peptide presents Ag on Ag presenting cell