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Immunology (aimen n) - use these > Review of the Innate Immune System > Flashcards

Review of the Innate Immune System Flashcards

1
Q

Why do we need an innate immune response?

A

Adaptive Immune Response is too slow to protect us from some new pathogens

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2
Q

Describe the speed of action of the adaptive immune response

A

Adaptive Immune Response:
Cytotoxic T cells activated for new infection after 3-4 days and Antibodies after 5 days

Sufficient for slow growing bacteria (may take upto 6 days) before they start replicating at a dangerous level by which time the specific immune response will be under way

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3
Q

Why is adaptive immunity not sufficient for Influenza?

A

Influenza replicates every 4hrs = produces thousands of products rapidly

  • requires innate immunity to buy time for adaptive immune response to kick in
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4
Q

Which type of immunity is required to resolve infections?

A

Both adaptive and innate immune responses are required to resolve infection

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5
Q

How does adaptive immunity work?

A

Adaptive immunity involves very specific recognition of infectious agent (usually detects a protein = antigen)

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6
Q

Outline the specificity of innate immunity

A

Innate immunity involves recognition of broadly conserved features of different classes of pathogens (PAMPs)

  • no specific antigen recognition
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7
Q

What are the components of innate immunity?

A
  • Phagocytosis
  • Inflammatory Response
  • Cytokines, Interferons + Antimicrobial peptides (AMPs)
  • Complement
  • Intrinsic Defences – “the hostile cell”
  • NK cells
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8
Q

Which immune cells carry out phagocytosis?

A

Carried out in vertebrates by Dendritic cells, macrophages and neutrophils

(monocytes, granulocytes, neutrophils)

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9
Q

What is the role of phagocytosis?

A

Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development/reactivation of the adaptive immune response

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10
Q

How do macrophages carry out phagocytosis?

Brief

A

Macrophages destroy material in lysosomes

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11
Q

How do macrophages trigger an inflammatory response?

A
  1. Captured material triggers macrophage activation
  2. Activated macrophages produce cytokines and chemokines
  3. Stimulates both innate + adaptive immune responses
  4. Inflammatory response triggered; can promote a local antimicrobial state
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12
Q

What is an inflammatory response?

A

Generic defence mechanism

  • Localises + eliminates injurious agents
  • Removes damaged tissue components
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13
Q

What changes occur during an inflammatory response?

A
  • Enhanced tissue permeability + extravasation
  • Neutrophil recruitment
  • Enhanced cell adhesion
  • Enhanced clotting
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14
Q

What 2 hormones do activated macrophages release?

A

Infected macrophage releases 2 types of polypeptide hormones:

  • cytokines
  • chemokines
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15
Q

How does the bloodstream aid inflammatory response?

A

Bloodstream supplies neutrophils and macrophages as well as normal RBCs etc.

Allows breakdown of capillary wall to allow more immune cells to get in to help break down pathogens

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16
Q

What are chemokines and cytokines?

A

Glycoprotein hormones that affect the immune response

Produced by activated macrophages

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17
Q

What is the role of cytokines?

A

Cytokines modify the behaviour of cells in the immune response

Interleukins (eg. IL-1)

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18
Q

What is the role of chemokines?

A

Chemokines = chemotactic factors

i.e. create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection

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19
Q

How are pathogens recognised by phagocytes?

A
  • Detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
  • By Scavenger receptors
  • By some Toll-Like Receptors (TLRs)
  • By passive sampling

(= by detecting PRRs)

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20
Q

How do phagocytes recognise pathogenic patterns?

A

Pattern recognition is through Pathogen-Associated Molecular Patterns (PAMPs) present on the infecting organism (e.g. bacteria)

21
Q

Why is PAMP recognition a good way to recognise pathogens?

A

PAMP molecules present on pathogens only; not on host cells

PAMPs are Essential for survival of pathogens

PAMPs = Invariant structures shared by entire class of pathogens

22
Q

Outline common PAMPs

A
  • Gram-ve bacteria; LPSs
  • Gram+ve bacteria; teichoic acid, lipoteichoic acid, peptidoglycans
  • Bacterial flagellin
  • Abnormal protein glycosylation
  • Abnormal nucleic acids - viruses
23
Q

What are PRRs?

A

Pattern Recognition Receptors are host factors that specifically recognise a particular type of PAMP

24
Q

How are PRRs encoded?

A

PRRs are germ-line encoded

25
Q

What are the the different functional classes of PRRs?

A

There are several classes of PRR, but functionally they are either:

  • Extracellular
  • Intracellular (cytoplasmic)
  • Secreted
26
Q

How do extracellular PRRs work?

A

Recognise PAMPs outside of a cell and trigger a coordinated response to the pathogen

27
Q

How do intracellular PRRs recognise PAMPs?

A

Recognise PAMPs inside a cell and act to coordinate a response to the pathogen

28
Q

How do secreted PRRs recognise PAMPs?

A

They act to tag circulating pathogens for elimination

29
Q

How do Toll-like receptors recognise pathogens?

A

Toll-like receptors recognise pathogens and flag them for cytokine and inflammatory cell release

30
Q

Where are NOD-like / RIG-like receptors found?

A

NOD-like and RIG-like receptors are cytoplasmic

31
Q

What is the complement system?

A

Effector mechanism for development of adaptive response

An adaptation grafted onto the original purposes of complement as a vital part of innate immunity

32
Q

How are complement proteins activated?

A

Complement proteins act as secreted PRRs and are activated by a range of PAMPs

Can also be activated by “altered self”

33
Q

What are interferons?

A

Secreted factors (type I and type III)
Induced by viral infection
Offer cross-protection

34
Q

Outline the interferon system

A
  1. During primary infection IFN produced and secreted
  2. IFN binds to neighbouring cells that has receptors for it
  3. Antiviral state triggered
  4. Virus ineffective in infecting other cells when undergoes apoptosis
  5. IFN causes expression of antiviral genes
35
Q

How do interferons produce an antiviral state?

A

IFN arrives from infected cell, binding a receptor and sets up a signal transduction system causing lots of gene expression

36
Q

Which protein is upregulated by IFNs?

A 
Protein Kinase R (PKRI) not expressed at high levels but is upregulated by IFN (at protein level) 
Requires cofactor (dsDNA) to activate it.
37
Q

Describe the effect of virus on IFN upregulated PKR

A

If virus gets in and replicates, it produces lots of dsDNA that is now able to activate PKRa - immediately switches off ribosome function

38
Q

What are AMPs?

A 
Antimicrobial Peptides (AMPs)
E.g. Defensins
Secreted short peptides (18-45 amino acids)
39
Q

How do AMPs work?

A

Usually work by disrupting cell wall leading to lysis
Some are induced by bacterial infection
Offer broad protection

40
Q

Outline the intrinsic defences of cells

A

The hostile cell contains biochemical mechanisms that discourage viral replication

  • Apoptosis
  • Restriction factors / Intrinsic Immunity
  • Epigenetic silencing
  • RNA silencing
  • Autophagy/Xenophagy
41
Q

What are NK cells?

A

Natural Killer (NK) Cells
> large granular lymphocytes
4% white blood cells
Lymphocyte-like but larger with granular cytoplasm

42
Q

What is the role of NK cells

A

Kill certain tumour & virally infected cells

Target cell destruction is
caused by cytotoxic molecules called granzymes & perforins

43
Q

How are NK cells activated?

A

Natural Killer (NK) cells are activated by loss-of-self

44
Q

What effect do NK cells have on infected cells?

A

NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells

45
Q

How do NK cells obtain selectivity for infected cells?

A

Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands

46
Q

Innate immunity detects ……….

A

PAMPs

47
Q

PRRs recognise ……..

A

PAMPs

48
Q

PRRs are ………. encoded

A

germline

= the same arrangement in all body cells, don’t change

(Antibodies and T-cells are rearranged somatically
The gene for an antibody is rearranged in B-cells)

Immunology (aimen n) - use these (14 decks)

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