Innate Immunity

Question 1

Endotoxins

Answer 1

Heat-stable (pyrogen) cell-associated toxin
NOT directly TOXIN
Induces body to produce toxic molecules

Question 2

LPS

Answer 2

Endotoxin on gram - bacteria

Question 3

Pathology of LPS

Answer 3

LPS responsible for many of the body’s responses to gram negative bacteria

• profound inflammatory response
• infiltration of neutrophils and MOs
• increases permeability
• swelling

Question 4

Septic shock

Answer 4

Endotoxin shock - associated w/ gram - infection

• lethal
• can lead to DIC, necrosis, ARDS

Question 5

How to avoid Endotoxins

Answer 5

Test for pyrogen using LAL

-if dev DIC - there is LPS present

Question 6

What toxic about LPS?

Answer 6

Proteins produced by LPS-stimulated MOs are the endogenous mediator (inflammatory cytokines)

• *IL-1
• *TNF-Alpha

Question 7

TNF-Alpha

Answer 7

Important cytotoxic molecule produced by MO and is an important immunoregulator molecule

• Has overlapping function w/ IL1
• -stimulating B and T cells
• -inducing fever

Question 8

IL-1

Answer 8

Cytokine secreted by activated and stimulated MOS
_produced as a pro-cytokine (must be cleaved prior to release)
_cleavage often by caspase 1 activated by inflammation sensitive complex (inflammasome)

Question 9

Super Agtigenic Toxins

Answer 9

TSST-1 - endotoxin causing toxic show syndrom
-In response to the binding of toxin
__both T cells and APC produce many cytokines
–>TNF-alpha and IL1

Question 10

Complement System

Answer 10

• Much more than lead to cell lysis
• Imp inflammatory mediators
• Role in opsonization
• Imp in clearing immune complexes
• Terminal complement imp in killing Neisseria

Question 11

Complement

Answer 11

Is the collective term for a complex of sequentially interacting serum proteins

Question 12

What occurs as a result of complement activation cascade?

Answer 12

Cell lysis
Increased phagocytosis
Increased vascular permeability
Enhance leukocyte chemotaxis
Functional stimulation of MOs

Question 13

What are the two PWs for complement?

Answer 13

Classical PW
Alternative PW
**both lead to cleavage of C3 –>C3a and C3b
C3b attaches to surface of pathogen

Question 14

Classical PW

Answer 14

• Initiation by IgM or IgG binding to Ag on a pathogen surface
• C1 binds single molecule of IgM (pentamer) or 2 or more IgG
• Activated C1s cleave C4 and C2
• C2a binds to surface C4b - forming C3b convertase (C4b2a)
• binds to C3b and cleaves it
• C3b binds covalently to microbial surface

Question 15

Alternative PW

Answer 15

Formation and action of the soluable C3 convertase iC3Bb that initiates this PW

• -formation and action of the C3 convertase (C3bBb) at a pathogen surface
• -C3 continuously cleaved and C3b put on pathogen surface

Question 16

Inactivation of C3b

Answer 16

• Inactivation of C3b by factor H and factor I to give fragments iC3b
• DAF and MCP disrupt C3 convertase C3bBb on a human cell surface

Question 17

How are bacteria recognized by INNATE immune response?

Answer 17

By Endotoxins and Complement

–w/o them you DON’T get ADAPTIVE immune response

Question 18

What do phagocytes do when react with bacteria?

Answer 18

Release cytokines

-too many is bad

Question 19

Release of cytokines

Answer 19

Locally - its good

Systemically - its bad–> they become part of pathology

Question 20

What are the receptors that interact with LPS ?

Answer 20

Recognized by the complex TLR4, MD2, and CD14 (part of LPS receptor - TLR4)

• leads to engulfment and digestion of bacteria
• lead to transcription of inflammatory cytokines

Question 21

TLR’s

Answer 21

Diff TLRs are recognize diff things and respond differently

Question 22

Why is inflammasome important?

Answer 22

Important for IL1 production

Question 23

Both complement PWs lead to C3b on pathogen surface in order to…?

Answer 23

Amplify C3b

Question 24

What does C3b lead to?

Answer 24

Binding to complement receptors

• ->Opsonization
• ->Clearance of immune complexes

Question 25

What occurs when IgG binds to SOLUABLE multivalent Ag?

Answer 25

- C1 binds to soluable immmune complex (Ag:Ab) and initiates complement rxn - Immune complex coated with covalently bound C3b - C3b binds to receptor on erythrocyte surface - Erythrocyte takes them to spleen/liver where they are removed by phagocytic cells * *classical PW clears complex

Question 26

What imp role does classical PW play?

Answer 26

Clear immune complexes out of blood

Question 27

C5 Convertase

Answer 27

Activated by both PWs | **IMP Chemotactic Factor (attracts MO, nuetrophills, etc)

Question 28

Lytic PW

Answer 28

Contains C5-C9 - Components binds to surface of pathogen or RBC coated w/ Ab - Forms pores - Cell dies

Question 29

What are the biological active peptides?

Answer 29

C3a and C5a = anaphylatoxins - make cell leaky - draw monocytes/nuetrophils to site

Question 30

What are ANAPHYLATOXINS?

Answer 30

Make blood vessels leaky around where complement being fixed - causes them to be more fluid - complement, Ab, and more cells come to site of infection

Question 31

Inhibitors of complement system?

Answer 31

- C1INH inhibits C1 - C4BP binds to C4 in classical PW and makes it a target for factor I inhibition - Factor H binds C3b and makes it target for factor I - inactivates C3b --> iC3b - DAF and MCP disrupt C3 convertase C3bBb

Question 32

What is C59?

Answer 32

Binds to C5b678 complex and prevents recruitment of C9 to form pore

Question 33

C1, C2, C4 deficiency causes?

Answer 33

Immune-complex disease | -cant clear immune complex from blood

Question 34

C3 deficiency causes?

Answer 34

Susceptible to capsulated bacteria

Question 35

C5-C9 deficiency causes?

Answer 35

Susceptible to Neisseria

Question 36

Factor D and Factor P deficiency causes?

Answer 36

Susceptible to capsulated bacteria and Neisseria but not immune-complex disease

Question 37

Factor I deficiency causes?

Answer 37

Susceptible to capsulated bacteria

Question 38

DAF or CD59 deficiency causes?

Answer 38

Auto-immune like conditions

Question 39

C1lNH deficiency causes?

Answer 39

HANE