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Immuno mikro eng > Innate Immunity and Complement > Flashcards

Innate Immunity and Complement Flashcards

1
Q

What are the three main barriers of the innate immune system?

A

Mechanical - i.e. fluid / mucus
Chemical - i.e. lysozyme / defensins
Microbiological - normal flora

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2
Q

List some receptor types used by the host cells to recognize invading pathogens after barriers have been broken? What do they recognize

A

TLRs - recognize PAMPs (pathogen-associated molecular patterns)

C-type Lectin Receptors - recognize sugars

NOD-like - intracellular nucleic acid detecting

RIG-1 like - recognize RNA

f-Met-Leu-Phe - detect chemotaxic moeity on bacteria

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3
Q

What cytokine do dendritic cells produce in response to viral invasion?

A

Type 1 interferon

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4
Q

How does a monocyte entering the tissue know to differentiate into a macrophage or DC?

A

Depends on cytokine environment

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5
Q

What is an opsonin?

A

A protein that binds a microbial cell surface and aids in immune system targeting for phagocytosis (opsonization)

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6
Q

What syndrome results from being unable to make superoxides in phagocytes?

A

Chronic granulomatous disease

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7
Q

What is an important sugar to bind on bacteria?

A

Mannose - includes Mannose binding lectin (MBLs) and receptors for mannose

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8
Q

Where are TLRs located?

A

Some are on outer cell membrane, some are intracellular

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9
Q

What are the two most important TLRs and what do they bind? These receptors give some specificity to innate immune system

A

TLR4 - binds bacterial LPS (part of gram(+)) and leads to activation of defends genes by activating NFkB

TLR3- binds viral dsRNA, triggers interferons synthesis, preventing viral replication

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10
Q

What are examples of other TLR specificities?

A
  1. Flagellin
  2. Unmethylated CpG (human DNA is methylated)
  3. Peptidoglycan
  4. Zymosan - yeast
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11
Q

What are three proinflammatory cytokines released by activated macrophages? What do they do?

A

IL-1 - activates endothelium and lymphocytes, induces fever and IL-6 production

IL-6 - activates lymphocytes and induces liver APPs

TNF-alpha - induces fever and activates endothelium, increases permeability of endothelium for diapedesis

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12
Q

What is an important new treatment for rheumatoid arthritis?

A

Antibody for TNF-alpha in synovial fluid

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13
Q

What are the functions of IL-8 and IL-12?

A

IL-8 - chemokine for attracting PMNs

IL-12 - activates NK cells, and induces Th0 cells to become Th1

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14
Q

What is the positive feedback loop between macrophages and NK cells?

A

Macrophages produce IL-12, inducing NKs. NKs produce IFN-y, further inducing macrophages.

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15
Q

What are acute phase proteins in general?

A

Produced in liver in response to infectious agents, especially IL-6 induction. Can also induce clotting in inflammatory response via fibrinogen

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16
Q

List the two major APPs and their function?

A

C-reactive protein - sign of inflammation, binds bacteria as an opsonin and also activates complement

Mannose-binding lectin (MBL) + SPs A&B - opsonin and complement activation

17
Q

What are the major actions of the inflammatory response?

A

Increased blood flow by dilation of capillaries, expresion of adhesion molecules for leukocyte binding, secretion of vasoactive peptides for diapedesis (IL-1/TNFa), clot formation to prevent spread of pathogen

18
Q

What are selectins and what is their function?

A

A type of lectin, an adhesion receptor on endothelium which binds carbohydrates on leukocytes and slows them

19
Q

What are integrins and ICAMs?

A

Adhesion molecules. Integrins are expressed on leukocytes and bind the ICAMs (intracellular adhesion molecules) on the endothelium and DCs strongly to stop their movement

ICAM = receptor, Integrin = ligand

20
Q

What induces the production of IFN-alpha and beta, and what is their three functions?

A

Induced by viral dsRNA binding by TLR3

Functions

  1. Inhibit translation of viral mRNA
  2. Activate NK cells which kill virus infected cells
  3. Increase expression of MHC1 to promote cytotoxicity of CD8-T cells towards them
21
Q

What is the function of NK cells?

A

kill virus-infected and tumor cells which are deficient in MHC Class 1, due to downregulation via mutant DNA

22
Q

What are the three main functions of the complement (C) system?

A
  1. Attracting phagocytes via anaphylatoxins
  2. Assisting phagocytosis via opsonization
  3. Direct killing of pathogens
23
Q

In what way does complement interact with both innate and adaptive immune systems?

A

Innate - activated by microbial products or APPs (lectin / alternative pathway)

Adaptive - activated by Ag-Ab complexes - classical pathway

24
Q

Which two Ig types can activate complement?

A

IgM and IgG (classical pathway)

25
Q

What are the steps up to C3 in the classical pathway?

A
  1. Ab binds the pathogen.
  2. C1 binds the Fc of the Ab.
  3. C1s cleaves C4 into C4a and C4b
  4. C4b is attached to pathogen, cleaves C2 to C2a and C2b.
  5. C4b2b complex is C3 convertase
26
Q

What is the only change between classical and lectin pathway?

A

Lectin - MBL replaces the antibody as what ultimately binds the C1.

Mannose binding lectin binds the mannose residues of the pathogen

27
Q

What is the alternative pathway up to C3?

A

C3 is spontaneously hydrolyzed and sticks to pathogen surface. C3b works with Factor B to be activated by factor D (activated factor B = Bb).

C3bBb = C3 convertase

28
Q

What is the classical / lectin pathway through C5?

A
  1. C4b2b cleaves C3 into C3a and C3b.
  2. C3b attaches and makes C5 convertase
  3. C5 convertase cleaves C5 into C5b and C5a.
  4. C5b initiates assembly of membrane attack complex of C6-9
  5. C3a / C5a are vasoactive, and C5a attracts PMNS
29
Q

What is the alternative pathway through C5?

A

All the same steps since its a C3 convertase, except the C3bBb complex is stabilized by Properdin and leads to extra deposition of C3b and amplification of alternative pathway on pathogen

30
Q

How is complement regulated?

A

Host cells have regulatory proteins as well as in plasma to prevent accidental activation of the cascade, which are not present on pathogens

31
Q

What is hereditary angioneurotic edema and what causes it?

A

Lack of C1 inhibitor which causes C1 to dissociate and prevents excessive activation of complement. Too much C2b causes swelling in these patients

32
Q

What are some other regulatory proteins of complement?

A

DAF, Factor I, and Factor H which inactivate C3b

C4b binding protein

33
Q

What is factor P?

A

Factor which stabilizes the MAC for full lysis

34
Q

What does a mutation in CD59 cause?

A

Paroxysmal nocturnal hemaglobinuria - mutation lets immune system attack RBCs due to lack of CD59

Immuno mikro eng (56 decks)

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