An introduction to the Immune system (part 1)

Question 1

Why are we as humans not unique when it comes to our immune system?

Answer 1

All multicellular organisms have some kind of immune system.

Question 2

What is the role of the immune system?

Answer 2

The immune system identifies and eliminates microorganisms and other harmful substances as well as abnormal cancer cells.

Question 3

How does the immune system carry out it’s role?

Answer 3

By distinguishing “self” molecules from “non-self” molecules.
By identifying “danger” signals (e.g. from acute inflammation).
Or via a combination of the 2.

Question 4

What are the 2 arms to our immune systems?

Answer 4

Adaptive and Innate

Question 5

Why does a balanced immune system offer optimal effectiveness?

Answer 5

It protects a person from pathogens but does not reject donor tissues.

Question 6

If your immune system is not working properly what could you develop?

Answer 6

Autoimmunity
Allergies
Asthma
Sepsis
Chronic recurrent infections.

Question 7

What is an Immune over-reaction?

Answer 7

Reaction to self.

Reaction to innocuous substances.

Question 8

What methods can we use to manipulate the immune system to prevent or treat human diseases?

Answer 8

Immunization.
Anti-inflammatory and immunosuppressive drugs.
Cancer immunotherapy
- Immunotherapy enables the immune system to recognize, target and eliminate cancer cells, making it a potential “universal answer” to cancer.

Question 9

What methods can we use to manipulate the immune system to prevent or treat human diseases?

Answer 9

Immunization
Anti-inflammatory and immunosuppressive drugs
Cancer immunotherapy - Immunotherapy enables the immune system to recognize, target and eliminate cancer cells, making it a potential “universal answer” to cancer.

Question 10

What are the components of an Innate (Natural) Immunity?

Answer 10

Natural/physical barriers (they are there to stop us getting the pathogen in the first place).
Soluble factors
- Cytokinesis
- Acute Phase proteins
- Inflammatory mediators
- Complement proteins
Immune Cells
- Macrophages
- Mast cells
- Natural Killer cells
- Neutrophils

Question 11

What are the components of an Acquired (Adaptive) Immunity?

Answer 11

Soluble Factors
- Cytokines
- Antibodies
Immune cells
- B cells
- T cells

Question 12

Pathogens infect the body through a variety of routes.

What are 4 examples of points of entry and 2 routes of attack?

Answer 12

Each of these routes have specific "constitutive" barriers to infection.
Points of Entry
- Digestive System
- Respiratory system
- Urogenital system
- Skin damage
Routes of attack
- Circulatory system
- Lymphatic system

Question 13

Constitutive barriers to infection: skin
Why is it a physical barrier, what are the physiological factors and what are 4 examples of sebaceous glands in the skin?

Answer 13

Skin is the most important barrier to infection.
Phsical barrier
- Composed of tightly packed, highly keratinised, multi-layered cells.
- Constantly undergo renewal and replacement
Physiological Factor
- Low pH 5.5 (acidic)
- low oxygen tension
Sebaceous glands
- secrete hydrophobic oils
- Lysozyme
- Ammonia
- Antimicrobial peptides

Question 14

Constitutive barriers to infection: mucous

How does mucous act as a physical barrier, what enzymes does it contain and how does cilia work with the mucous?

Answer 14

Secreted mucous
- Mucous membranes line all body cavitites that come into contact with the environment
- Respiratory
- Gastrointestinal
- Urogenital tract
- The mucus traps bacteria which are subsequently removed by ciliated cells.
Physical barrier
- to trap invading pathogens
Secretory IgA
- prevents bacteria and viruses attaching to and penetrating epithelial cells
Contains enzymes: Lysozyme, defensins and antimicrobial peptides directly kill invading pathogens Lactoferrin acts to starve invading bacteria of iron.
Cilia directly trap pathogens and contribute o removal of mucous, assisted by physical manoeuvres such as sneezing and coughing.

Question 15

Constitutive barriers to infection: Commensal bacteria

What is the role of commensal bacteria?

Answer 15

100 trillion (10 to the power of 14) bacteria normally reside at epithelial surfaces
- >500 different microbial species
- Symbiotic relationship with the host
Commensal bacteria reside amongst the mucus and epithelial cells of a mouse small intestine.
Commensals compete with pathogenic microorganisms for scarce resources’ also produce fatty acid and bactericidins that inhibit the growth of many pathogens.

Question 16

Describe the story of an infection

Part 1: early Innate Immune Response?

Answer 16

Tissue-resident innate immune cells
Macrophage
- Phagocytosis
- Pro/Anti-inflammatory
- Bacterial killing mechanisms
- Antigen presentation
- Wound healing/ tissue repair
Mast Cell
- Pro-inflammatory
- Parasitic killing mechanisms
- Linked to allergy and asthma
The tissue-resident innate immune cells and complement system combine to result in pathogen killing and acute, local inflammation.
A combination of tissue-resident innate immune cells and complement system results in pathogen killing and acute, local inflammation.

Question 17

What happens when the physical (natural) barriers are breached?

Answer 17

Pathogens invade and the Innate immune responses are initiated?

Question 18

What happens when tissue-resident innate immune cells recognise pathogens as “non-self” and dangerous?

Answer 18

Phagocytic ("eating" cells)
- Macrophages and Dendritic cells (DCs)
Other cells
- Mast cells
are all initiated.

Question 19

Infection of extracellular bacteria and fungi result in extracellular Bacteria and Fungi ingested by Macrophages. What are the modes of ingestion?

Answer 19

Modes of ingestion are:
- Pinocytosis:
- Ingestion of fluid surrounding cells
- Receptor-mediated endocytosis:
- Molecules bound to membrane receptors is internalized.
- An important step in the generation of adaptive immunity.
Phagocytosis: (Key for macrophages)
- Intact particles (e.g. bacteria) are internalized whole.
- These are facilitated by “Opsonisation”.
Extracellular bacterial pathogens do not invade cells and proliferate instead in the extracellular environment which is enriched with body fluids.

Question 20

Mast cells step in….

Answer 20

1. Degranulation
   - Release of pre-formed inflammatory substance
2. Gene expression
   - Production of new pro-inflammatory substances.

Question 21

Summary - Early Innate Immune Responses:

Answer 21

Pathogens send out PAMPs and injured tissue cells send out “danger” signals which stimulates the Macrophages and Mast cells. These perform a variety of roles.
Pathogens Killed.
Infected cells killed.
Production of pro-inflammatory mediators.
Nitric Oxide
Prostaglandins/ leukotrienes
Histamins
Pro-inflammatory cytokines (TNFalpha)
These cause localised, acute inflammation.

Question 22

What is a person’s innate immunity?

Answer 22

Innate immunity is present continuously, it is a defence mechanism that is present from birth and is generally non-specific (i.e. the same generic response occurs towards many different types of material).

Question 23

What is a person’s acquired immunity?

Answer 23

Acquired immunity is induced by the presence of “foreign” or “non-self” material (including infectious micro-organisms). he response that occurs is (usually) unique to the specific substance or pathogen that induced the response.

Question 24

What arms of the immune system work together to form an overview of the immune system?

Answer 24

Both innate and acquired immune systems work closely together to eliminate disease-causing micro-organisms.

Question 25

What are examples of physical barriers,
Traps,
Elimination,
Unfavourable pH,
Lysozyme Enzyme?

Answer 25

Physical barrier
- Skin and mucous membranes lining digestive, urinary, respiratory and reproductive systems.
Traps
- mucous, cilia (in nose and trachea), hair ( covering body and in nose/ears), earwax
Elimination
- Coughing, sneezing, urination, diarrhoea
Unfavourable pH
- Stomach acid, sweat, saliva, urine
Lysomzyme Enzyme
- in tears, sweat
- digests bacterial cell walls

Question 26

How does our Immune System protect us if anatomical/ chemical barriers fail?

Answer 26

Innate Immunity is present continuously, it is a defence mechanism that is present from birth.
The same generic response occurs to many different microbial species.
Rapid response (mins-hrs).
(Innate immunity is present continuously, it is defence mechanism that is present from birth. It responds in the same generic way to many different types of pathogen).
Acquired (adaptive) immunity is induced by the presence of foreign materials.
A unique response is generated to each individual pathogen. Slow response (days).
(Acquired immunity is induced by the presence of foreign material and is usually quite specific. He fundamental properties of adaptive (acquired) immunity are specificity, adaptiveness, discrimination between self and non-self, memory).
The defence of a host towards foreign bodies can be divided into innate immunity and adaptive (acquired) immunity.

Question 27

How do both the innate the innate and acquired immunity work together to defence against pathogenic micro-organisms?

Answer 27

Both arms detect and destroy pathogens:
- Both are essential for maximal protection but they work in different ways
- Innate immune responses attack all microorganisms indiscriminately.
- Acquired immune responses are specifically tailored to individual microorganisms.
Innate Immunity
- Rapid first response to infection (0-96 hours)
- NO immunological memory
- Non-specific
- Can distinguish SELF from NON-SELF and should only react against non-self
Acquired Immunity
- Lag time from exposure to response (>96 hours)
- Immunological memory thus subsequent responses are faster and more powerful; basis for protective vaccination against infectious diseases.
- Specific for each antigen encountered
- Self regulating through Regulatory T-cells
- Can distinguish SELF from NON-SELF and should only react against non-self.

Question 28

How is the body infected by extracellular bacteria and fungi?

Answer 28

Extracellular bacterial pathogens do not invade cells and proliferate instead in the extracellular environment which is enriched with body fluids.

Question 29

What is the 7 step process of phagocytosis?

Answer 29

1. Macrophages express a set of “PRRs”.
2. Receptor binding to “PAMPs” signals the formation of a phagocytic cup.
3. Cup extends around the target and pinches off, forming a phagosome.
4. Fusion with lysosomes to form a phagolysosome - killing of pathogens and degradation of contents (acidification, lysosomal hydrolases).
5. Debris (including antigens) is released into extracellular fluid.
6. Pathogen - derived peptides are expressed on special cell-surface receptors (MHC-II molecules).
7. Pro-inflammatory mediators are release (e.g. TNFalpha)

Question 30

What is the role of phagocytosis?

Answer 30

Phagocytosis is a specific form of endocytosis by which cells internalise sold matter, including apoptopic cells and microbial pathogens.
While most cells are capable of phagocytosis, it is the professional phagocytes of the immune system, including macrophages, neutrophils and immature dendritic cells, that truly excel in this process.
Macrophages recognize specific PAMPs expressed on the surface of many different extracellular pathogens.
Macrophages rearrange their cytoskeletal - the cell membrane then extends around the target, eventually enveloping it and pinching-off to form a discreet phagosome.
This vesicle can mature and acidify through fusion with late endosomes and lysosomes to form a phagolysosome, in which degradation and digestion of the cargo occurs.
Killing occurs because the phagolysosomes contain hydrolytic enzymes, proteases and they also have a highly acidic pH.
Release of cellular debris in the form of small soluble molecules is the final step.
At the same tie, pro-inflammatory mediators such TNF alpha are being secreted to promote acute inflammation and peptides derived from the pathogen are expressed on special cell surface receptors.
Not that a single phagocyte can ingest more than one cellular “corpse”, (multiple, probably in succession) this is essential for secretion of pro-inflammatory cytokines.

Question 31

What is the definition of opsonisation and what are some examples of opsonins?

Answer 31

The coating of pathogens by soluble factors (opsonins) to enhance phagocytosis.
Examples
- C3b
- c-reactive protein (CRP)
- IgG/IgM

Question 32

Opsonisation enhances phagocytosis. What is the process by which opsonised bacteria are engulfed and destroyed by phagocytes?

Answer 32

A bacterium opsonised with complement attaches to the complement receptor on the phagocyte. This opsonised bacteria are engulfed and destroyed by phagocytes.

Question 33

What are the 5 types of natural barriers and what are examples of each?

Answer 33

Physical barrier
- Skin and mucous membranes lining digestive, urinary, respiratory and reproductive systems.
Traps
- mucous, cilia (in nose and trachea), hair (covering body and in nose/ears), earwax
Elimination
- Coughing, sneezing, urination, diarrhea
Unfavourable pH
- Stomach acid, sweat, saliva, urine
Lysozyme Enzyme
- In tears, sweat
- Digests bacterial cell walls

Question 34

What is acute inflammation?

Answer 34

Acute inflammation is the tissue response to infection (or injury).
The onset can be immediate or take some days.
This is an important response t cellular injury or infection. It has both a rapid innate phase as well as a prolonged phase that is an important component of acquired immunity. Immediately after injury of infection a number f proteins are released. These lead to the physiological characteristics of inflammation: swelling, redness, heat, and pain.