Review of the Innate Immune System

Question 1

if we have an adaptive immune system, why do we need the innate immune system?

Answer 1

because the adaptive immune response is too slow to protect us from some pathogens, and the innate response is immediate

-adaptive: nothing really happens for about 3 1/2 days, antibodies start at about day 5. This is okay if your microbe replicates relatively slowly, but it is a problem if it replicates very quickly (eg. influenza virus)

Question 2

resolution of infection requires what?

Answer 2

both adaptive and innate immune responses

Question 3

does everything have an innate and adaptive immune response?

Answer 3

no, everything has innate immune responses

+ most things in nature survive without an adaptive immune response

Question 4

what is the role of specificity in the 2 immune responses?

Answer 4

adaptive involves specific recognition of an infectious agent, usually sees an antigen (MHC presentation, T cells)

immune has no specific antigen recognition, involves recognising broadly conserved features of different classes of pathogens

Question 5

components of innate immunity?

Answer 5

Phagocytosis
The Inflammatory Response
Cytokines, Interferons and Antimicrobial peptides (AMPs)
Complement (enhances ability of antibodies to work)
Intrinsic Defences – “the hostile cell”
NK cells

Question 6

Phagocytocis

Answer 6

specialise cells recognise something that shouldn’t be there and engulf it

carried out in vertebrates by dendritic cells, macrophages and neutrophils, and amebocytes in horseshoe crabs

1. clears pathogens
2. presents peptides on MHCs – promotes development/reactivation of adaptive immune response

Question 7

Dendritic cells

Answer 7

detect a pathogen and take it up, then they stop phagocytosis and traffick to the lymph nodes

at the lymph nodes they break down the pathogen they have engulfed and present peptides to MHC class II (and class I), and help select and stimulate naïve T and B cell division

Question 8

Macrophages

Answer 8

stay in the tissues (tissue resident) and present antigens - never involved in triggering a new immune response but they can reactivate one from memory

2 distinct roles in innate immunity:

1. Phagocytosis - material is destroyed in lysosomes
2. Captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses – this triggers the inflammatory response and can promote a local anti-microbial state

Question 9

activated macrophages producing cytokines and chemokine stimulates what?

Answer 9

a local anti-microbial state and progression towards an adaptive immune response

Question 10

Neutrophils

Answer 10

rarely tissue resident - they circulate, and when you trigger an infection they are recruited to the site of infection, and there is a massive increase in neutrophils

chronic inflammation will lead to tissue damage

Question 11

The Inflammatory Response - what is it?

Answer 11

generic defence mechanism

purpose is to localize and eliminate injurious agents and remove damaged tissue components (stops pathogen leaving the site of infection)

1. Enhanced permeability and extravasation
2. Enhanced cell adhesion and clotting - create a restricted environment to prevent pathogen spread
3. Neutrophil recruitment - breakdown in blood vessel so neutrophils and more macrophages can get to site of infection

Question 12

what are Cytokines and Chemokines?

Answer 12

Glycoprotein hormones that affect the immune response

Question 13

what are cytokines?

Answer 13

secreted by macrophages and dendritic cells, modify behaviour of cells in the immune response
-most of these are interleukins (eg. IL-1)

Interleukin 1 = major enhancer of the immune response
Interleukin 8 - chemoattractant
TNF-alpha

Question 14

what are chemokines?

Answer 14

chemotactic factors – create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection

Question 15

How do Phagocytes know what to eat?

Answer 15

detecting phosphatidylserine on exterior membrane surface - cells undergoing apoptosis

scavenger receptors

Toll-Like Receptors (TLRs, type of PRR)

passive sampling - neutrophil taking stuff up at random and destroying it, this can be damaging to the host

Question 16

what are Pathogen-associated Molecular Patterns (PAMPs)?

Answer 16

molecules present only on pathogens, not on host cells, essential for pathogen survival 
-shared by entire class of pathogens

examples:
Gram-negative bacteria: LPSs in outer membrane

Gram-positive bacteria: teichoic acid, peptidoglycan in outer membrane

Bacterial flagellin

Abnormal protein glycosylation

Abnormal nucleic acids - viruses

Question 17

what are Pattern recognition receptors (PRRs)?

Answer 17

Host factors that specifically recognise a particular type of PAMP, germ-line encoded

several classes of PRR, but functionally they are either:

1. Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen (lectin, scavenger, TLRs)
2. Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen (RIG-like, NOD-like)
3. Secreted – they act to tag circulating pathogens for elimination

Question 18

The Complement System

Answer 18

vital part of innate immune system

Complement proteins act as secreted PRRs

can be activated by a range of PAMPs or by “altered self”

3 pathways:
classical (C1q recognises LPS)
lectin (MBL recognises atypical glycosylation)
alternative

Question 19

Interferons - what are they?

Answer 19

species specific secreted factors (type I and type III) that play a major role in innate immunity - offer cross-protection

induced by viral infection - not expressed in tissues most of the time, so they require the thing they are going to eliminate to turn them on

Question 20

mechanism of action of interferons?

Answer 20

Virus enters and infects cells and replicates, in the first infected cells there’s no viral response, cells will apoptose and die, releasing lots more virus which will spread to neighbouring cells.

During the primary infection you produce interferon, which gets secreted binds to neighbouring cells via a receptor

causes an anti-viral state in those cells by turning on anti-viral response genes - one example: Double stranded viral DNA convert PKRi to PKRa, switching off ribosome function so you cannot make any proteins, but its also bad for the virus because it cannot make any proteins either.

Question 21

Anti-microbial peptides (AMPs)

e.g. Defensins

Answer 21

Secreted short peptides (18-45 amino acids)
Usually work by disrupting bacterial cell wall leading to lysis
Some are induced by bacterial infection
Offer broad protection

Question 22

name some intrinsic defences the host cell has to resist viral replication?

Answer 22

Apoptosis
Restriction factors/Intrinsic Immunity
Epigenetic silencing
RNA silencing
Autophagy

ebola has got a specific mechanism to block apoptosis

Question 23

Natural Killer (NK) cells

Answer 23

4% white blood cells

Major components of innate immune response, particularly against herpes viruses

Lymphocyte-like but larger with granular cytoplasm
Kill certain tumour & virally infected cells

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

Question 24

mechanism of action of NK cells

Answer 24

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

Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces - recognises the absence of an MHC class I/II, and injects perforins into an infected cell to kill them

Question 25

receptors of innate and adaptive immune system?

Answer 25

innate - Germ-line encoded receptors evolved by natural selection

adaptive - Receptors generated randomly within individual; cannot be inherited