Innate Immunity 1

Question 1

What happens when the immune system over or underreacts to internal or extrernal threats ?

Answer 1

Unbalanced response means immune system goes wrong
-Autoimmune disease is a response to self antigens
-Under-reaction leaves you vulnerable to cancers caused by viruses, they can cause mutations in infected cells which benefit themselves in terms of replication

Question 2

What does the immune system do ?

Answer 2

Provides:
-Protection from pathogens
-Elimination of abnormal host cells
-Rejection of donoe tissues

Immune system balanced between killing things and collateral damage for optimal effectivity

Question 3

What are points which microbes can enter the body and routes through which they can attack ?

Answer 3

Each of these routes have specific “constitutive” barriers to infection

These anatomical (physical) and chemical barriers are the first line of defense against pathogenic microorganisms

Answer 4

Question 5

What are examples of physical barrier to microbes ?

Answer 5

Skin and mucous membrane

Question 6

What is the role of the skin in the immune system ?

Answer 6

Skin is the most important (physical) barrier to infection
-Composed of tightly packed, highly keratinised, multi-layered cells (impenetrable to water and microbes)
-Constantly undergo renewal and replacement

Physiological factors
-Low pH (acidic)
-Low oxygen tension, upper layers far from blood supply to limit growth of aerobes)

Sebaceous glands secrete hydrophobic oils (hard to stick on)

Chemical defenses;
-Lysozyme (hydrolytic enzyme present in tears, saliva, sweat, breast milk - attacks pepticoglyacn cell wall of bact and fung)
-Ammonia
-Antimicrobial peptides (AMPs) -Pos charge and hydrophobic so attracted to neg charge of evil membranes so imbed

Question 7

What is the role of mucous membranes in the immune system ?

Answer 7

Form a (physical) barrier and line all body cavities that meet the environment

Physical barrier
-Mucus; sticky to trap microbes to be expelled by coughing/sneezing
-Respiratory tract: cilia (particularly in upper bronchi) help to expel trapped mucous

Physiological factors
-Secretory IgA (sIgA)
-Low pH (acidic) - stomach, urogenital tract

Chemical defenses
-Lysozyme
-Antimicrobial peptides (AMPs)
-Lactoferrin - found often in mucous secretions, traps iron

Question 8

What are commensal microorganisms ?

Answer 8

Compete with pathogens for resources and produce fatty acids and bactericidins that stop pathogens growing

Many in a symbiotic relationship with the host

Provide protective actions

(e.g. Staphylococcus epidermidis; Lactobacillus species; Clostridium sci

Question 9

What protective actions do commensal microbes provide ?

Answer 9

Protective functions against bacteria and fungi:
-Competition for resources (nutrients, space)
-Secretion of antimicrobial peptides (AMPs)
-Increased mucus production
-Maintenance of epithelial barrier integrity (e.g. by supporting cell growth, tightening cell junctions)

In gut also aid with digestion

Question 10

What are the innate and adaptive immune systems ?

Answer 10

Innate immune responses present from birth;
- same generic response occurs to many different microbial species.
-response occurs quickly
-natural immunity

Adaptive immune responses are induced in response to specific foreign/non-self antigen
-Unique response generated to each individual microbe and their antigen
-response delayed as time needed for tailoring

Both work closely together to eliminate pathogenic microbes from the body to prevent colonisation and disease.

Question 11

What parts make up the innate immune system ?

Answer 11

Phagocytic and degranulating cells (tissue-resident and circulating)
Physical Barriers
Acute Phase Proteins
Inflammatory Mediators
Compliment proteins

Secreted proteins
-Complement (induced)
-Chemokines
-Cytokines

Its job is to kill and control pathogen while alerting other innate and acquired system

Question 12

What is the role of phagocytic cells (tissue-resident and circulating) in the innate immune response ?

Answer 12

-Orchestrate initiation of response
-Recognise, ingest and kill bacteria and yeasts
-e.g. Macrophages, Neutrophils, Dendritic cells

Question 13

What is the role of degranulating cells (tissue-resident and circulating) in the innate immune response ?

Answer 13

-Damage and kill multicellular parasites (and virally infected cells)
-Empty granules of acid and stuff onto bad things but can also cause collateral
-e.g. Mast cells, Neutrophils, Eosinophils, Basophils

Question 15

Which lukeocytes respond first to invasion ?

Answer 15

Tissue-resident innate immune cells are the first responders to recognise invading microorganisms as ‘non-self’
-Macrophages
-Mast Cells
-Natural Killer Cells

Mast cells found in superficial tissue

Question 16

How do innate immune cells recognise pathogens ?

Answer 16

Pathogens express ‘signature’ molecules not found on/in human cells: Pathogen associated molecular patterns (PAMPS)
Shared by many different pathogenic species
-e.g. gram-negative bacterial lipopolysaccharide
-e.g. bacterial/fungal cell wall β-glucans
-e.g. viral dsRNA

Innate immune cells (and some other cell types) express partner receptors for these PAMPS: Pattern-recognition receptors (PRRs
-Found on the cell surface and in the cytosol (for detection of extracellular and intracellular pathogens, respectively)

Question 17

Describe the stages of the early innate immune response

Answer 17

1) Physical (natural) Barriers Breached, pathogens Invade, innate Immune Responses Initiated
2) Tissue-resident innate immune cells are the first responders to recognise invading microorganisms as ‘non-self’
3) Extracellular bacteria and fungi are ingested and killed by macrophages via the process of phagocytosis
4) Tissue damage caused by large extracellular pathogens (e.g. parasites) leads to Mast cell activation
5) Macrophages and Mast cells produce pro-inflammatory mediators which lead to acute inflamation

Question 18

Describe the role of macrophages within an invasion

Answer 18

Extracellular bacteria and fungi are ingested and killed by macrophages via the process of phagocytosis
1) Macrophages PRRs bind to microbial PAMPs, macrophage activated and change in cytoskeleton forms phagocytic cup
2) Cup extends around the target and pinches off, forming a phagosome (microbe inside)
3) Fusion with lysosomes forms a phagolysosome where microbes are killed and degraded (acidic environment, lysosomal hydrolases and proteases)
4) Microbial debris (including antigens) is released into extracellular fluid
5) Peptides from microbial proteins are expressed on special cell surface receptors (MHC-II molecules)
6) Pro-inflammatory mediators are released (e.g. TNFα, is a cytokine)

Question 19

How are mast cells activated ?

Answer 19

Tissue damage caused by these large extracellular pathogens leads to Mast cell activation

This is same as allergy pathway

Question 20

What are interferons ? ?

Answer 20

A type of cytokine inolved in defence against viruses

Interferons released by virally infected cells signal to neighbouring uninfected cells:
-Destroy RNA and reduce protein synthesis
- Undergo apoptosis
Interferons also activate immune cells e.g. NK cells

Question 21

What do mast cells do ?

Answer 21

Part of the early innate immune resposne
-Deal with pathogens too large for phagocytosis
-When PRRs on mast cell bind to PAMPs on pathogen, the mast cell is stimulated to release pre-formed pro-inflammatory substances such histamine and tryptase – degranulation
-As this happens, the mast cell also begins to produce pro-inflammatory substances (histamine, TNF, chemokines, leukotrienes)
-Associated with allergy

HOW DOES THIS LEAD TO KILLING/EXPULSION???

Question 22

How many PAMPs are there ?

Answer 22