L12 Barriers, innate and complement

Question 1

What is barrier immunity? What 2 things can it be split into?

Answer 1

First line of defence against pathogens.
Can act as physical and active barrier.
Physical barrier is skin, lungs and gut mucosa
Active barrier is cilia, secretions e.g. tears and anti-bacterial peptides, commensal bacteria

Question 2

Where do we have mucous and how does it act as a barrier?

Answer 2

Lungs and gut mucosa. As they are one cell layer thick they need mucous to protect.
It traps bacteria, dust, anti-microbial peptides

Question 3

What happens when you have detects in the mucus?

Answer 3

cystic fibrosis

inflammation in asthma

Question 4

What are the 4 main ways pathogens can enter the body by?

Answer 4

Skin, GIT, respiratory tract, genito-urinary tract

Question 5

Why is irrigation important?

Answer 5

Inhibits infection as constant flow of tears, urine, salive, bile, sebaceous secretions and pancreatic secretions help protect from infection the surfaces which they flow over. If flow is obstructed they become nutritious sites for bacteria resistant to anti-bacterial mechanisms present in the fluid.

Question 6

What is chemical protection in barrier defence?

Answer 6

acid secretions of the stomach help sterilise partially digested food, lysozyme in tears is bacteriocidal and bile acids inhibit the growth of microorganisms.

Question 7

How do normal bacteria flora help in barrier defence?

Answer 7

lots of bacteria on skin, mouth and large intestine. They are non-invasive and dont cause disease. Loss of them due to antibiotics or excessive use of ati-septics–>opportunistic pathogens colonise

Question 8

What signs are there of an inflammatory response clinically?

Answer 8

Vasodilation, increased vascular permeability, heat and pain.

Question 9

What are the cells of the innate system?

Answer 9

APCs:

• dendritic cells
• macrophage/monocytes

Phagocytes:

• macrophages
• neutrophils

Granulocytes:

• neutrophils
• eosinophils
• basophils
• mast cells

Question 10

What are macrophages? Where do they come from? What are the different types?
What do they do?

Answer 10

Specialised cells involved in detection, phagocytosis and destruction of pathogen.
Macrophages originate from blood monocytes that leave the circulation to differentiation in different tissues.
Alveolar macrophages - lungs
Kupffer cells - liver
Microglial - CNS eliminate old or dead neurons
Splenic macrophages - spleen
Have PRRs
Get activated by Th1 CD4 in intracellular bacterial infection.

Question 11

What are dendritic cells?

Answer 11

DCs professional antigen presenting cells. Convert captured proteins into peptides. Put peptides onto MHC to present to T cells to stimulate the adaptive immune response

Question 12

What do neutrophils do?

Answer 12

Granulocytes and phagocytes. Contain inflammatory protein, toxic enzymes, oxygen radicals that kill pathogens.

Question 13

What are mast cells?

Answer 13

Granulocytes, important for acute phase response and allergic responses. Contain inflammatory proteins, toxic enzymes, oxygen radicals that kill pathogens.

Question 14

What are basophils?

Answer 14

Important for acute phase response and allergic responses. All contain inflammatory protein, toxic enzymes, oxygen radicals that kill pathogens.

Question 15

What do eosinophils do?

Answer 15

Granulocytes so contain inflammatory protein, toxic enzymes, oxygen radicals that kill pathogens. Important for parasite killing.

Question 16

What do innate cells use to recognise a pathogen?

Answer 16

PRRs, on every innate cell, recognise PAMPs that occur on microbes, but not on humans so distinguish self from non self.

Question 17

What are the 4 families of PRRs?

Answer 17

1) Toll-like receptors (TLRs)
2) Nucleotide oligomerisation receptors (NLRs)
3) C-type lectin receptors (CLR)
4) Rig-1 like receptors (RLR)

Recognise extracellular and intracellular pathogens

Question 18

What kinds of things do PRRs recognise on pathogens?

Answer 18

on bacteria can be: lipoproteins, DNA, flagellin, LPS-lipopolysaccharide, peptidoglycan, lipotechoic acid-LPA
on viruses can be:
different types of nucleic acid and coat proteins
on parasites can be:
GPI anchor
on yeast can be:
zymosan

Question 19

When PRRs bind to ligand what results from this?

Answer 19

Intracellular signalling cascade that stimulates the nucleus to produce cytokines.

Question 20

What happens in IRAK4 deficiency relating to PRRs?

Answer 20

This is why it’s important to recognise pathogens through PRRs. Defect in Toll like receptor pathway. Results in recurrent streptococcal and staphylococcal infection as a child. No fevers- dont get upregulation of inflammatory cytokines. Improves with age due to adaptive immune response.

Question 21

what the main proteins/processes of the innate system?

Answer 21

Cytokines: modulate cell activity or attract cells
Acute phase proteins: opsonise or present pathogens to the immune system
Complement: cascade proteins or opsonise, kill, activate or chemoattract

Question 22

What are cytokines?

Answer 22

Chemical network of signals released by cells of the immune system and other cells
Can be pro-inflammatory, anti-inflammatory, influence cellular differentiation and direct cellular migration.

Question 23

How can cytokines act with respect to cells?

Answer 23

Autocrine - on same cell
Paracrine - on nearby cell
Endocrine - on distant cell

Question 24

What are they key families of cytokines?

Answer 24

Cytokines: 
intereferon
chemokine
tumour necrosis factor
interleukin
haematopoietins
TGFβ

Question 25

Innate immune cell presenting pathogen can be enhanced by opsonisation. What is opsonisation and 3 ways in which microbes and antigen are opsonised?

Answer 25

Opsonisation is a way of coating a pathogen to make it more visible to the immune system.
They are opsonised by:
-Complement
-CRP and other acute phase proteins
-Immunoglobulin/ab

Question 26

How does opsonisation help macrophages recognise a bacterium?

Answer 26

Phagocytes can phagocytose unopsonised bacteria using PRRs but this process is slow.
Phagocytosis is initiated and completed faster when the bacteria is opsonised, e.g. with ab
The more points of recognition, the more effective the process of phagocytosis here with complement and IgG

Question 27

What are the 3 pathways in complement?

Answer 27

classical, lectin and alternative

Question 28

What initiates the classical pathway?

Answer 28

ab:antigen complexes binding

Question 29

What initiates lectin pathway?

Answer 29

carbohydrate sugars

Question 30

What initiates the alternative pathway?

Answer 30

spontaneous/direct contact with microbial polysaccharides

Question 31

What common protein do all 3 pathways cleave?

Answer 31

C3 –> C3a and C3b
C3b opsonises
C3a activates mast cells to release histamine

Question 32

What are the effects of complement activation?

Answer 32

1) inflammation - release of histamine from mast cells
2) cytolysis from MAC which punches holes in microbial membranes
3) opsonisation - complement components bind to microbial surface and promote phagocytosis
4) chemotaxis C5a is a neutrophil chemoattractant
5) inactivation of complement - regulatory proteins limit damage to host cells that may be caused by complement

Question 33

What are the 4 functions of complement activation?

Answer 33

1) Opsonisation - surface C3b and inactive C3b are recognised by complement receptors on neutrophils and macrophages promoting phagocytosis
2) cell lysis resulting from MAC
3) mast cell degranulation when C3 hydrolyses to C3b and C3a which acts on local mast cells to induce degranulation
4) neutrphil chemoattractant is able to attract neutrohpils to the site of complement activation