Pathologic Consequences of Infection

Question 1

How does pathology results directly from a microbe?

Answer 1

Pathogens that multiply in the cell can directly cause cell damage by rupturing the cell.
Not all organisms do this; some viruses bud out of the cell without killing it

Question 2

What are exotoxins?

Answer 2

They are secreted proteins from parasites that can cause serious tissue damage. They can be used as a strategy for entry, spread or defence.
They are often encoded by plasmids or phages

Question 3

How can exotoxins be used to the advantage of humans?

Answer 3

By inactivating toxins (toxids), we can use them as powerful vaccines. Diphtheria toxin can be chemically inactivated to make a vaccine. Toxins are typically highly conserved, which is why we don’t get scarlet fever (Streptococcal erythrotoxin)

Question 4

What are the five general modes of action of exotoxins?

Answer 4

Enzymatic lysis
Pore formation
Inhibition of protein synthesis
Hyperactivation
Effects on nerve-muscle transmission

Question 5

What are hemolysins?

Answer 5

They are enzymes such as lecithinases, phospholipases, pore-forming molecules that destroy the integrity of the cell.
They affect many cells (not just red blood cells)
Clostridium perfringenes, which causes gangrene, secretes phospholipase C
Staphylococcus aureus secretes alpha-toxin

Question 6

How do toxins typically alter the metabolic machinery?

Answer 6

They typically two subunits: an A subunit and a B subunit
The A subunit is the active component
The B subunit is the binding component that interacts with the receptors on the cell membranes
The B subunit binds to the cell membrane, then A subunit (or the entire toxin) enters the cell via endocytosis and becomes activated

Question 7

How does the diphtheria toxin alter metabolic machinery?

Answer 7

The B subunit binds to the cell
The toxin-receptor complex is internalized
The A subunit passes into the cytosol
The A subunit inactivates the transfer of amino acids from tRNA to the polypeptide chain during translation of mRNA
This causes the death of mass cells, and the host is unable to breath

Question 8

How does the cholera toxin alter metabolic machinery?

Answer 8

The toxins has 5 B subunits surrounding one A subunit
The B subunits bind to intestinal epithelial cells
The A subunit is internalized
The A subunit is cleaved into A1 and A2
A1 inhibits the inhibition of cAMP production
The sodium/chloride flux is changed, resulting in large outflow of water and electrolytes form the epithelial cells causing profuse diarrhea

Question 9

How does tetanus interfere with nerve-muscle transmission?

Answer 9

The B subunit binds to ganglioside receptors on nerve cells
The A subunit is internalized and travels to the CNS
The A subunit interferes with synaptic transmission of inhibitory neurons by inhibiting neurotransmitter release
This causes the excitatory transmitters to continuously fire, causing spastic paralysis

Question 10

How does botulinum interfere with nerve-muscle transmission?

Answer 10

The botulinum toxin enters via the intestine
The toxin blocks the release of acetylcholine release from the presynaptic neuron at neuromuscular junctions of the peripheral nerve endings
This causes flaccid paralysis

Question 11

What is diarrhea?

Answer 11

It is an invariable result of intestinal infections
It can be considered as a way for the host to quickly get rid of infecting organisms
It can be considered as a way for a parasite to quickly spread to fresh hosts

Question 12

What causes diarrhea?

Answer 12

Often the result of a toxin

Microbial invasion and damage to epithelial cells can cause diarrhea

Question 13

Describe how well the immune response is controlled

Answer 13

The immune response is very well controlled with regards to distinguishing between self and foreign agents
It is not very well controlled with regards to the degree of immune response and over-activation. Overactivation of the immune response can lead to damage to the host tissues`
Endotoxins often utilize this inability of the immune system to control its degree of response

Question 14

What are endotoxins?

Answer 14

They are lipopolysaccharides (made up of lipid A, a core oligosaccharide, and O-polysaccharide, which is variable)
Integral parts of the microbial cell walls (characteristic of Gram-negative bacteria

Question 15

What are the most important effects of endotoxins?

Answer 15

Fever and vascular collapse (shock)

Fever is due to the release of cytokines IL-1 and TNF by macrophages, which affect the hypothalamus

Question 16

What is an example of another microbial molecule that can overstimulate the immune system?

Answer 16

Toxic shock syndrome, caused by Staphylococcus, toxic shock syndrome toxin (TSST1) activate a large portion of T cells, which produces enough cytokines to produce a toxic effect

Question 17

How can the complement system damage the tissue of the host?

Answer 17

The complement system plays an important role in the acute inflammatory response by producing the chemotactic factors C3a and C5a
LPS can activate both he classical (via lipid A) and alternative (via polysaccharide) C pathways and this could lead to shock induced by the toxic amounts of endotoxin
Polymorphonuclear leukocytes aggregate, adhere to vessel walls and release toxic molecules that damage the host

Question 18

What are the two types of allergic responses?

Answer 18

Antibody mediated (type I, II and III)
Cell mediated (type IV)

Question 19

What is type I hypersensitivity?

Answer 19

It is the most common
They are the result of a reaction to an allergen (antigen in the environment)
The symptoms occur at the location of the effector cells (which may be unrelated to the actual point of entry of the allergen e.g., hives from strawberries
Individuals with multiple allergies or severe allergies (could be due to genetic disorders) tend to have an overproduction of IL-4, which selects for IgE production of IgG, increased IL-4 receptors on B cells or even certain types of MHC-II

Question 20

Describe the type I allergic responses

Answer 20

Initial exposure to the allergen
IgE formation following the primary antibody-mediated immune response
IgE binds via the Fc portion to specific receptors of basophils (in blood) and mast cells (in tissues), both cell types contain histamine granules
Second and subsequent exposure to the same allergen causes the allergen to bind to the V region o the Fab and crosslink two adjacent IgEs on mast cell/basophil surface
Crosslinking triggers degranulation and release of histamine and other mediators
Immediate response (minutes after exposure)

Question 21

What are the symptoms of type I hypersensitivity?

Answer 21

Hay fever (watery eyes, runny nose from vascular permeability and oedema)
Swelling and itching (nasal congestion, hives, oedema)
Anaphylaxis (bronchoconstriction, shock, oedema)
Asthma (smooth muscle constriction)

Question 22

What are the key mediators of type I hypersensitivity?

Answer 22

Histamine

SRS-A

Question 23

What is histamine? What does it do?

Answer 23

Preformed molecules in granules
Binds receptors on target cells (lungs, skin, blood vessels)
Vasodilation (key response because of chemotaxis), capillary permeability, smooth muscle contraction
Antihistamines block histamine receptors

Question 24

What is SRS-A? What does it do?

Answer 24

Slow reacting substance of anaphylaxis
Produced after exposure to allergen, not preformed
Slow release and lag time
Bronchoconstrictor implicated in asthma

Question 25

How are chronic type I allergies treated?

Answer 25

Antihistmines (block histamine receptors on target cells)

Corticosteroids (block degranulation of mast cells)

Question 26

How are acute type I allergies (anaphylactic shock) treated?

Answer 26

Epinephrine (EpiPen)
Inject directly, increases cAMP levels which decreases mediator release
Immediate, short effect (around 20 minutes)
Results in an increase in blood pressure and prevents/counteracts shock
Followed by intravenous antihistamines

Question 27

What is hyposensitization?

Answer 27

Giving small doses of antigens and increasing over time can reduce the allergy

Question 28

What is type II hypersensitivity?

Answer 28

Antibody-mediated response is made of non self cells/autoantibodies
IgG is produced and binds to non-self cell surface and activates the classical pathway (MAC attack)

Question 29

What are examples of type II hypersensitivity?

Answer 29

ABO blood transfusion reactions: Rh incompatibility
Blood stage malaria (parasite antigen is picked pu by red blood cells)
Antimyocardial antibody GAS infection (cross0reacting carbodhydrate antigen

Question 30

What is type III hypersensitivity?

Answer 30

Large antigen-antibody complexes precipitate and induce inflammation
Activation of complement, attraction of phagocytes, general tissue damage
Sedimentation of these complexes in the kidney (malarial nephropathy) results in kidney toxicity (chronic glomerularnephritis)
Also occurs in the joints and lungs (Arthus reaction - Farmer’s lung, which can lead to extrinsic allergic alveolitis)

Question 31

What is Arthus reaction?

Answer 31

Microbial antigens enter the tissue (fungal antigens in the lung), encounter an antibody and form immune complexes. This activates the complement system and chemotaxis attract polymorphonuclear leukocytes (PMNs). There is degranulations of PMNs and tissue mast cells. The resulting inflammatory response is further potentiated by damaged induced by PMN-derived lysosomal enzymes.

Question 32

What is serum sickness?

Answer 32

Repeated doses of foreign proteins (passive immunization, injecting antibodies) leads to circulating complexes that deposit in the kidneys, joints and skin. This can cause glomerularnephritis and rheumatoid arthritis

Question 33

What is type IV hypersensitivity?

Answer 33

There is no antibody involvement
It it helper and cytotoxic T cell mediated
It is delayed and starts hours or days after contact and can last for for days

Question 34

What is the hygiene hypothesis?

Answer 34

Allergic reactions are more common than previous times. Some hypothesis that this is due to ‘microbial exposure deficiency syndrome’. There is evidence supporting this:
Children that are born by C-section are more likely to develop asthma and have more allergic reactions
People who live on farms tend to have less allergic reactions
Since the implementation of water treatment plans in developed countries, IBD rates have increased. In developing countries where there isn’t always access to clean water, there is no IBD

Question 35

What is the correlation between viruses and cancer?

Answer 35

Some viruses can cause cancer (or increase the risk)
HepB/C and liver cancer
EBV and Kurkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s disease
HPV and cervical cancer

Question 36

What is the correlation between bacteria and cancer?

Answer 36

Some bacteria can cause/increase the risk of cancer

H. pylori and stomach and duodenal cancer, MALT lymphoma,