Lecture 20 - Immunity to Microbes

Question 1

What are CRP, SAP, and MBP?

L20 S6

Answer 1

Acute phase proteins:

• C-reactive protein
• serum amyloid protein
• both activate complement

Mannose-binding lectin:
-activate lectin complement pathway

Question 2

What are the most potent chemoattracants for neutrophils?

L20 S9

Answer 2

• C5a
• C3a
• IL-8

Question 3

What effect does C3a and C5a have on mast cells?

L20 S7

Answer 3

Cause mast cells to degranulate releasing histamine and bradykinin which enhances blood flow and increase capillary permeability.

Question 4

What is fMLP?

L20 S9

Answer 4

Formyl-methionyl-leucyl-phenylalanine tripeptide

Bacterial product which acts as chemoattractant for neutrophils

Question 5

What is responsible for lymphocyte homing to lymph nodes?

L20 S11

Answer 5

Constitutively expressed L-selectin on lymphocytes and constitutively expressed PNAd (peripheral lymph node addressin) on HEVs

Question 7

What is the difference in mature and immature DC responses?

L20 S10

Answer 7

Mature:
-migrate to LNs with engulfed bacteria

Immature:
-engulf and internalize bacterial Ags

Question 8

Where are long lived memory cells and plasma cells located?

L20 S15

Answer 8

• bone marrow
• LNs
• spleen

Question 9

What are the different types of bacterial toxins?

L20 S16

Answer 9

Endotoxins:

• components of bacterial cells walls
• e.g. LPS of gram-negative bacteria

Exotoxins:

• secreted by bacteria
• e.g. diptheria toxin, cholera toxin, and tetanus toxin

Question 10

What mechanisms are used to kill phagocytized bacteria?

L20 S20

Answer 10

iNOS (inducible NO synthase):
-produces NO

Phagocyte oxidase:
-produces ROS

Question 11

What mechanisms are used by bacteria to evade humoral immunity? (5)

L20 S21

Answer 11

• change in surface antigens
• sialylation of LPS
• formation of decoy membrane blebs
• pili with variable regions
• IgA protease

Question 12

What mechanisms are used by bacteria to evade innate immunity? (3)

L20 S22

Answer 12

• inhibition of complement
• resistance to phagocytosis
• scavenging of ROS

Question 13

What are the mechanisms are used by the adaptive humoral immune system against extracellular bacteria?

L20 S23

Answer 13

Direct Ab response:

• neutralization (prevention of function by Ab binding
• opsonization (Fc receptor mediated phagocytosis)

Indirect Ab response (compliment activation via classical pathway):

• phagocytosis of C3b-coated bacteria
• inflammation (anaphylatoxins)
• lysis (MAC)

Question 14

What mechanisms are used by bacteria to evade adaptive immunity?

L20

Answer 14

Variation of surface Ags

Question 15

What are septic shock and septic shock syndrome?
What causes them?

L20 S26

Answer 15

Septic Shock:
-severe pathological response to disseminated bacterial infection

Septic Shock Syndrome:

• circulatory collapse
• intravascular coagulation

Caused by cytokines produced by Mφ and neutrophils that result in the production of acute phase proteins in addition to ROS/release lysosomal enzymes

Question 16

What Mφ products play a role in its activity and tissue damage?

L20 S27

Answer 16

TNF-α:
-upregulates TF and iNOS

IL-18:
-induces IFN-γ roduction which increase Mφ activation

Question 17

What is the function of superantigens (SAgs) and what are examples of disease caused by SAgs?

L20 S30-31

Answer 17

Binds class II MHC to variable region of TCR β chains causing activation.

Food poisoning:
-staphylococcal (mostly) SAgs

Toxic shock syndrome (TSS):

• S. aureus causes capillary leak
• S. pyogenes causes severe reaction

Kawasaki disease:
-active multi-system vasculitis of unknown etiology

Some autoimmune diseases

• via bystander effect cause by SAgs activating T cells
• e.g. rheumatic fever

Question 18

What occurs in response to a primary viral infection?

L20 S35

Answer 18

Production of type I interferons (e.g. IFN-α and IFN-β) which can be made by none immune cells

Type I interferons stimulate class I MHC presentation of viral Ag and inhibit viral gene replication.
Also activates NK and Mφ viral response.

Question 19

How are viral Ags transported to the LNs?

L20 S37

Answer 19

Virus infected cells die and release viral components.

Viral components (such as ssRNA) activate DCs which I turn activate APCs.

APCs, such as skin Langerhans cells, transport Ag to LN via lymphatics.

Question 20

Differentiate between endogenous and exogenous Ag presentation.

L20 S52

Answer 20

Endogenous:

• intracellular pathogens (primarily viruses)
• can display processed exogenous Ags (cross-presentation)
• Ag enters ER via TAP where it is loaded to class I MHC

Exogenous:

• extracellular pathogens
• degraded in phagolysozome where it is also loaded onto class II MHC

Question 21

By what mechanisms do bacteria evade intracellular immune responses?

L20 S53

Answer 21

Inhibition of phagolysosome formation:

• Mycobacterium tuberculosis
• Legionella pneumophila

Inactivation of ROS and nitrogen species:
-Mycobacterium leprae (phenolic glycolipids)

Disruption of phagolysozome membrane:
-Listeria monocytogenes (hemolysis protein)

Question 22

How are fungal infections recognized and cleared?

L20 S55-56

Answer 22

Recognition:

• PRRs binding PAMPs
• dectin-1 binding β-glucan

Th1 response:

• phagocyte activation (IFN-γ)
• most potent

Th2: response:

• Ab production
• inhibits Th1 which leads to increased susceptibility

Th17 response:
-neutrophil activation (IL-17 and IL-22)