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Principles > Immunology - Innate Immune Response > Flashcards

Immunology - Innate Immune Response Flashcards

1
Q

Two methods of communication in the immune system

A

Direct contact

Indirect

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2
Q

Direct contact communication

A

Receptor (e.g. immune cell)

Ligand (e.g. pathogen, immune cell, tissue cell)

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3
Q

Indirect communication

A

Injured tissue cells and activated immune cells can produce and secrete cytokines
Autocrine signal acts on immune cells or injured tissue
Paracrine signal acts on nearby cells

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4
Q

Phases of Innate Immune Cell Response

A

Recognition
Activation
Effector

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5
Q

Recognition Phase

A

Pathogens express PAMPs (pathogen associated molecular patterns)
Innate immune cells express PRRs (pattern recognition receptors) specific to PAMPs

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6
Q

Activation and Effector Phase

A

Acute inflammation and pathogen killing

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7
Q

Role of Macrophages

A

Induction of apoptosis

Recognition and removal of dying cells by phagocytes

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8
Q

Clearance of apoptotic cells

A

Apoptotic cells release signals to attract and activate macrophages
Macrophages recognise the signals
Macrophages rearrange their cytoskeleton and internalise apoptotic cells
Digestion of apoptotic cells
Secretion of anti-inflammatory mediators

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9
Q

Phagocytosis

A

Receptor binds to signals of apoptotic cell - forms a phagocytic cup
Cup extends round and pinches off the target, forming a phagosome
Fuse with lysosomes to form a phagolysosome
Contents are degraded
Debris released into extracellular fluid

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10
Q

Innate Immune Response of Macrophages

A

Kill pathogens
Produce inflammatory mediators
Cannot kill infected tissues

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11
Q

Innate Immune Response of Mast Cells

A

Produce inflammatory mediators by degranulation (released of preformed) and gene expression (production of new)
Cannot kill infected tissues or pathogens

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12
Q

Innate Immune Response of NK Cells

A

Kill infected tissue
Produce inflammatory markers
Cannot kill pathogens

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13
Q

Systemic Effects of Cytokine Release

A

Fever
Acute Phase Response
Increased neutrophil production

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14
Q

Acute Phase Response

A

Alters pasma concentrations of specific proteins in response to inflammation
Driven by cytokines
Due to altered protein synthesis in the liver

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15
Q

C Reactive Proteins

A

Acute phase protein
Marker of inflammation
Enhance phagocytosis
Activate complement system

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16
Q

Innate Immune System - Cells of Early Response

A

Macrophages
Mast Cells
NK Cells

17
Q

Innate Immune System - Cells of Late Response

A

Neutrophils

Complement

18
Q

Inflammation Steps

A

Increased vascular permeability (Macrophages - TNFa, IL-1 & Mast Cells - TNFa)
Vasodilation and increased blood flow (Macrophages - TNFa & Mast Cells - Histamine)
Endothelial cell activation and expression of selections and ICAM-1/VCAM-1 (Macrophages - TNFa, IL-1 & Mast Cells - Histamine)
Transendothelial migration and chemotaxis of neutrophils (Macrophages & Mast Cells - chemokine gradient)

19
Q

Transendothelial Migration

A

Neutrophils bind weakly to selectins
Selectin mediated rolling of neutrophils
Neutrophils bind strongly to ICAM-1/VCAM-1 ligands
Neutrophils squeeze between the endothelial cells
Neutrophils migrate to site of inflammation within affected tissues (chemotaxis)

20
Q

Neutrophils - Characteristic Features

A

Intracellular granules + multi-lobed nucleus

21
Q

Innate Immune Response of Neutrophils

A

Kill extracellular pathogens

Produce pro-inflammatory cytokines (e.g. TNFa)

22
Q

Neutrophils Killing Mechanisms

A

Phagocytosis
Degranulation
NETs

23
Q

Neutrophils - Phagocytosis

A

Chemokine like signals and PRRs
Neutrophils encapsulate pathogen in phagosome
Kill pathogens by Antimicrobial proteins (granules filled with these)
OR
NADPH oxidase-dependent mechanisms (respiratory burst = production of toxic reactive oxygen species)

24
Q

Neutrophils - Degranulation

A

Release of anti-bacterial proteins form neutrophil granules directly into extracellular milieu
Direct killing of extracellular pathogens
Tissue damage and potentially systemic inflammation

25
Q

Neutrophils - NETs

A

Activated neutrophils release intracellular structures into the extracellular environment
NETs immobilise pathogens, preventing them from spreading and facilitating their phagocytosis

26
Q

Complement System

A

Should only triggered by pathogens

When triggered, specific complement proteins can enzymatically activate other complement proteins in cascade reaction

27
Q

Complement Activation - Mannose Binding Lectin Pathway

A

Mannose on invading battery acts as a ligand for MBL

Activates C4b/C2a, which cleaves C3 to C3a + C3b and activates downstream events

28
Q

Complement Activation

A

C3 is cleaved to C3b + C3a

This activates downstream complement proteins and leads to the response

29
Q

Innate Immune Response of Complement

A

Pathogen killing
Pathogen opsonisation
Leukocyte recruitment and inflammation

30
Q

Complement Activation - Alternative Pathway

A

Spontaneous breakdown of unstable C3 to C3a and C3b
C3b rapidly degraded, or binds to the bacterium
When blinded to bacterium, factor B attaches, forming a new complex
This complex further cleaves C3 to C3b + C3a and causes downstream events
ACTS AS AN AMPLIFICATION LOOP

31
Q

Complement - Downstream Events

A

C3a causes innate immune response
C3b cleaves C5 to C5a + C5b
C5a causes innate immune response
C5b binds with C6-C9 giving a membrane attack complex, which causes innate immune response

32
Q

Complement - Pathogen killing

A

Membrane attack complex binds to pathogens

Inserts into target cell walls and causes osmotic lysis of cells

33
Q

Complement - Opsonisation

A

C3b acts as an opsonin, binding to the bacteria and flagging it up for phagocytes to bind

34
Q

Complement - Leukocyte Recruitment and Inflammation

A

C3a and C5a promote inflammation
Act directly on blood vessels
Activate mast cells to release pro-inflammatory mediators and chemokines

35
Q

Role of Dendritic Cells

A

Bridge between innate and adaptive immune systems
Present in peripheral tissues in an immature state
Phagocytose antigens, cell debris, particles
Mature and migrate into secondary lymphoid tissues where they play a key role in antigen presentation

Principles (13 decks)

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