Immunology 2 Flashcards

1
Q

What are the three components of the innate immune system?

A

The activation of the complement system, phagocytosis by macrophages, and neutrophils and destruction by natural killer cells.

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2
Q

What are the functions of the complement system?

A
  1. To produce MACs – Membrane Attacking Complexes which pierce the membrane of pathogen.
  2. Produce anaphylatoxins – important to increase vascular permeability and act as chemo-attractors for neutrophils and macrophages to the site of infection.
  3. Prime pathogens for phagocytosis through opsonisation
  4. Attract neutrophils to the site of injury
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3
Q

What are the three pathways in which the complement cascade can be activated?

A
  1. Classical pathway
  2. Lectin-Mannose binding pathway
  3. Alternative pathway
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4
Q

How is the classical pathway initiated?

A

The production of an antigen-antibody complex. It therefore is not the first pathway to occur as it requires activation of the adaptive immune system.

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5
Q

What type of protease enzymes are complement proteins?

A

Serine proteases (serpins). They are highly specific – one complement protein cleaves another in a specific site.

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6
Q

What is the product of the classical pathway?

A

Opsins, anaphylatoxins and MACs.

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7
Q

What is the classical pathway?

A

C1 binds to the antigen-antibody complex and cleaves C2 into C2a and C2b. This complex also cleaves C4 into C4a and C4b. C2a and C4b form a complex to cleave C3 into C3a and C3b. C2a/C3b/C4b all work together to cleave C5 into C5a and C5b. C5b works with C6, C7, C8 and C9 to form MACs.

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8
Q

What anaphylatoxins are produced in the classical pathway?

A

C5a, C3a, C4a and C2b.

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9
Q

What is the lectin-mannose binding pathway?

A

The MBL (mannose binding lectin) – opsins – bind to mannose. This is a group of sugars only found on the surface of pathogens – not mammalian cells. MBL binds to mannose on the pathogen surface, this binds to MASP 1 (MBL associated serine protease) and MASP 2 activate C2 and C4. The rest of the pathway is identical to the classical pathway.

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10
Q

What does MASP stand for?

A

MBL Associated Serine Protease

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11
Q

Give examples of pathogens that have mannose on their surface?

A

Bacteria such as Streptococci and Salmonella
Fungi such as Candida albicans
Viruses such as Influenzas and HIV

Parasites such as Leishmania

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12
Q

What is the alternative pathway?

A

There is always a small amount of auto-activation. C3 can be auto activated to form C3a and C3b. This is very slow. Upon contact with bacteria, auto-activated C3b binds with Factor B and properdin which rapidly activates more C3 and C5. The rest of the pathway is the same as the classical pathway.

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13
Q

Which complement pathway is most likely to be activated upon a first infection with Candida albicans?

A

Lectin mannose-binding pathway

Alternative pathway

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14
Q

What is the role of anaphylatoxins?

A
  1. Increase permeability of the blood vessels and increase smooth muscle contraction
  2. Chemoattraction of phagocytes (C3a and C5a)
  3. Act as opsins – C3b
  4. Trigger degranulation of endothelial cells, mast cells and phagocytes
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15
Q

How does C3b act as an opsin?

A

C3b is cleaved to iC3b. The macrophage contains receptors for iC3b, facilitating phagocytosis of the bacteria by the macrophage.

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16
Q

Which cells are professional macrophages?

A

Macrophages, Dendritic cells and neutrophils

17
Q

What are the stages of phagocytosis?

A
  1. Chemotaxis and adherence of the pathogen to the phagocyte.
  2. The pathogen is ingested
  3. A phagosome is formed
  4. The phagosome fuses with lysosomes to form phagolysosomes
  5. The lysosomes secrete lysozymes into the phagolysosome causing the digestion of the pathogen.
  6. The products of digestion are absorbed.
  7. Other fragments of the pathogen are displayed on the phagocytes (if antigen-presenting).
18
Q

What are the three phases of a macrophage?

A

Resting macrophage, primed macrophage and hyperactive macrophage

19
Q

What is a resting macrophage?

A

Express low number of MHC Class II. Collect debris from tissues and eliminate apoptotic cells.

20
Q

What is a primed macrophage?

A

Macrophages are primed by the cytokine INF-g produced by NK cells and T helper cells. Express increased levels of MHC Class II. Can take up larger pathogens.

21
Q

What is a hyperactive macrophage?

A

Expresses lots of MHC Class II. The cell has stop proliferating, it is larger and can phagocytose larger cells. Become hyperactive when stimulated with both IFN-g and lipopolysaccharide (LPS).
Hyperactive macrophages produce cytokines: tumour necrosis factor – can combat tumour cells and virus infected cells - and IL1.

22
Q

Which cytokines cause macrophages to become hyperactive?

A

Gamma interferon IFN-g (produced by macrophages, B cells, T helper cells)

Lipopolysaccharide LPS (produced by bacteria)

23
Q

Which cytokine causes macrophages to become primed?

A

Gamma interferon INF-g

24
Q

Where are macrophages found?

A

In areas exposed to the environment for example just under the skin, lungs, GI tract

25
Q

How long do neutrophils last?

A

5 days

26
Q

Where to neutrophils reside?

A

Blood

27
Q

How do neutrophils bind to blood vessel walls in the inflamed tissue?

A

Use a ‘double key mechanism.’ Normally neutrophils express selectin and endothelial cells express ICAM. When inflamed endothelial cells express selectin also. It is only when neutrophils receive cytokines that cause them produce Integrin, that there is a double key. The Selectin ligand on the neutrophil van bind to the selectin receptor in endothelial cells. The ICAM in endothelial cells can bind to the Integrin on neutrophils. This causes the neutrophils to slow down, roll and bind when it stops.

28
Q

What is ICAM?

A

Intercellular Adhesion Molecule

29
Q

What stimulates the production of selectin on endothelial cells?

A

IL1 and TNF from macrophages

30
Q

What is SLIG?

A

Selectin Ligand

31
Q

What caused Integrin production on the neutrophil?

A

LPS from the bacteria and C5a.

32
Q

How do neutrophils know where to go when circulating in the blood?

A
  1. Double-key interaction: ICAM-Integrin and SLIG-Selectin

2. The neutrophil follows the concentration of f-Met

33
Q

How do Natural Killer Cells kill cells?

A

Induce apoptosis in infected cells. They do this as the Fas ligand bind to Fas on the target cell.

34
Q

Which proteins do neutrophils use to induce apoptosis?

A

Granzyme B and perforin