Unit 7 - Pathologic Consequences of Infection

Question 1

What 2 types of pathology can result directly from the microbe?

Answer 1

1) Directly cause cell damage. Multiplication within host cell and usually causes tissue damage by causing host cell to rupture
2) Dormant viruses bud out without killing (Pt will show no signs or symptoms)

Question 2

Describe endotoxins

Answer 2

• Can cause serious tissue damage
• Secreted proteins
• Can be encoded on plasmids/phages
• Can be part of a vaccine (toxoid)

Question 3

Explain how endotoxins can be part of a vaccine (toxoid)

Answer 3

1) Chemically inactivated toxin (formaldehyde) ex. diphtheria
2) Effective, highly conserved ex. scarlet fever (Streptococcal erythrotoxin)

Question 4

List the modes of action of endotoxins

Answer 4

1) Hemolysins
2) Alteration of metabolic machinery
3) Interference with nerve-muscle transmission
4) Botulinum

Question 5

Describe Hemolysins (A mode of action of endotoxins)

Answer 5

• Many cells affected beyond RBC
• Enzymatic lysis
• Pore formation

Question 6

Describe enzymatic lysis

Answer 6

Clostridium perfringenes

• an alpha toxin (PLC) hydrolyses phophorylchlorine in cell membrane
• causes lysis of cell membrane and death of cell

Question 7

Describe pore formation

Answer 7

Staphylococcus aureus

• an alpha toxin forms a pore and causes K+ to leak out of the cell membrane
• pore formation causes loss of nutrients and leads to cell death

Question 8

Describe Alternation of metabolic machinery (A mode of action of endotoxins)

Answer 8

-A and B subunits
A = active
B = binding
ex. Diphtheria toxin 
blocks protein synthesis

-Cholera toxin
5 B subunits
1 A subunit

Question 9

Describe “inhibition of protein synthesis”

Answer 9

C. diphtheriae

• B binds to the membrane
• A enters the cell through the membrane
• Inactivates elongation factor-2
• Prevents protein synthesis by ribosome
• Causes cell death

Question 10

Describe “hyper activation”

Answer 10

V. cholera

• 5 B subunits
• A1 and A2 subunit
• Attach to ganglioside receptor

A1 and A2 enter through the cell membrane

• Cause increased adenylate cyclase activity
• Increase cAMP
• Loss of cell nutrients through cell membrane (Na, H2O, Cl, K, Bicarbonate)
• Causes diarrhea

Question 11

Describe Interference with nerve-muscle transmission (A mode of action of endotoxins)

Answer 11

Ex. tetanus and botulinum toxins

• Extremely potent
• A-B toxins
• B subunit binds to ganglioside receptors on nerve cells
• Tetanus
• B-unit binds to nerve cell receptor, A-subunit internalized area ?
• X synaptic transmission and neurotransmitter release
• Continuous stimulation of motor neurons, spastic paralysis

Effects on nerve-muscle transmission:

• Cl. tetani
• Tetanospasmin blocks inhibitory transmitter release
• Results in continuous stimulation by excitatory transmitter

Question 12

Describe botulinum (A mode of action of endotoxins)

Answer 12

• Via intestine
• Peripheral nerve endings at neuromuscular junction
• X acetylcholine release - flaccid paralysis

Cl. botulinum

• toxin blocks release of Each from vesicles
• excitatory stimulation blocked
• plastic surgery
• people who sweat a lot

Question 13

List some points about diarrhea

Answer 13

• Invariable result of intestinal infections
• Allows host to get rid of infecting organism
• Allows parasite spread to fresh hosts
• Toxin/microbial invasion
• Results in loss of fluid that can be very bad

Question 14

Immune response is very ______ with respect to distinguishing self vs. foreign

Answer 14

controlled

Question 15

Immune response is not so well controlled with respect to degree of immune response and ____-______

Answer 15

over-activation

*this can cause host tissue damage

Question 16

Endotoxins are produced by gram-_____ organisms. They are not secreted, always attached to pathogen

Answer 16

negative

Question 17

Describe endotoxins

Answer 17

• Integral parts of microbial cell wall
• Released when cells die
• Lipopolysaccharides
  
  • Lipid A
  • Core oligosaccharide
  • O-polysaccharide - variable
• Fever and shock
  
  • Fever causes a release of cytokines by macrophage (IL-1 and TNF effect hypothalamus)
• Other microbial molecules stimulate cytokines
  
  • TSST-1 (T cells release cytokines)

Question 18

T or F: LPS can activate both the alternative (polysaccharide) and classical (lipid A) C pathways

Answer 18

True

Question 19

Gram ____ organisms (ex. septicemia) leads to “toxic amount of endotoxin”

Answer 19

negative

Question 20

Allergic responses 1, 2, and 3 are ____ mediated

Answer 20

antibody

B cells

Question 21

Allergic response 4 is ___ mediated

Answer 21

cell

T cells

Question 22

Describe allergic response Type 1

Answer 22

• Most common (runny nose, eyes, itchy skin)
• Reaction to an allergen (Ag in the environment)
• Symptoms
  
  • Location of the effector cells (cells which respond to presence of allergen)
  • May be unrelated to the actual point of entry of the allergen (ex. hives from ingesting strawberries)
• Individuals with multiple allergies or severe allergies
  
  • Genetic disorders
  • Overproduction of IL-4 selects for IgE production over IgG, increased IL-4 receptors on B cells, or even certain types of MHC-2

Question 23

List the 6 steps involved in Type 1 Allergic Response

Answer 23

1) Initial exposure to the allergen
2) IgE formation following the primary Ab-mediated immune response
3) IgE binds via the Fc portion to specific receptors of basophils (in blood) and mast cells (in tissues), both cells types contain histamine granules
4) Second and subsequent exposure to the same allergen. Allergen binds to V region of the Fab and crosslinks two adjacent IgE’s on mast cell/basophil surface
5) Crosslinking triggers degranulation and release of histamine and other mediators
6) Immediate response (minutes after exposure)

**May not show sins of symptoms in first encounter.

Question 24

List some symptoms of a Type 1 Allergic Response

Answer 24

• Hay fever (allergic rhinitis): Watery eyes, runny nose from vascular permeability and edema
• Swelling and itchiness: Nasal congestion, hives, and edema
• Anaphylaxis: Bronchoconstriction, shock, edema
• Asthma: smooth muscle contraction

Question 25

List the 2 Key mediators of Type 1 Allergic Responses

Answer 25

1) Histamine | 2) SRS-A (slow reaction substance of anaphylaxis)

Question 26

Describe the role of histamine as a key mediator in Type 1 Allergic Responses

Answer 26

- Preformed molecules in granules (present in granules in mast cells at all times) - Binds receptors on target cells (lungs, skin, blood vessels) - Vasodilation, capillary permeability, smooth muscle contraction - Antihistamines block histamine receptors (prevents binding)

Question 27

Describe the role of SRS-A (slow reacting substance of anaphylaxis) as a key mediator in Type 1 Allergic Responses

Answer 27

- Produced after exposure to allergen, not preformed - Slow release and lag time - Bronchoconstrictor implicated in asthma (asthma rxn mediated by SRS-A)

Question 28

What do you need to treat in Type 1 Allergic Responses?

Answer 28

1) Chronic allergies 2) Acute allergies (anaphylactic shock) 3) Hyposensitization

Question 29

How do you treat chronic allergies?

Answer 29

Antihistamines - block histamine receptors on target cells Corticosteroids - block degranulation of mast cells (using corticosteroids long term can suppress immune system and make you more prone to infections)

Question 30

How do you treat acute allergies (anaphylactic shock)?

Answer 30

Epinephrine (EpiPen) - Inject directly, increases cAMP levels which decreases mediator release - Immediate, short effect (20 min) - Results in an increase in blood pressure and prevent/counteracts shock - Followed by IV antihistamines

Question 31

How do you treat hyposensitization?

Answer 31

- Reducing sensitivity to particular antigen | - Long term treatment option has to be done in controlled setting

Question 32

Describe Type 2 Cytotoxic Hypersensitivity

Answer 32

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

Question 33

Give some examples of IgG produced binds to non-self cell surface and activates the classical complement pathway (MAC attack)

Answer 33

- ABO blood transfusion reactions, Rh incompatibility - Blood stage malaria (Parasite Ag picked up by red cells) - Antimyocardial antibody of GAS (Group A streptococci) infection (cross-reacting carbohydrate antigen)

Question 34

Describe Type 3 Immune Complex Hypersensitivity

Answer 34

- Large Ag-Ab complexes precipitate and induce inflammation - Activation of complement, attraction of phagocytes, general tissue damage - Lungs, kidneys, joints - Arthus Reaction - Serum sickness

Question 35

Describe Arthus Reaction

Answer 35

"Farmer's lung" Microbial antigens that enter the tissues (ex. fungal particles in the lung) encounter antibody and form immune complexes. These activate complement and initiate chemotaxis of polymorphonuclear leukocytes (PMNs) and degranulation of these and tissue mast cells. The resulting inflammatory response is further potentiated by damage induced by PMN-derived lysosomal enzymes.

Question 36

Describe serum sickness

Answer 36

- Repeated doses of passive immunization - Circulating complexes - Deposition in kidneys, skin and joints (Glomerulonephritis, rheumatoid arthritis)

Question 37

Describe how glomerulonephritis occurs

Answer 37

-Glomerulonephritis is caused by immune complex-mediated tissue damage. Type 3 hypersensitivity results in the deposition of immune complexes in the blood vessels walls, particularly at sites of high pressure, filtration of turbulence such as the kidney. Large complexes deposit on the glomerular basement membrane, while small ones pass through the basement membrane and then deposit on the epithelial side of the glomerulus.

Question 38

Describe Type 4 Delayed of Cell-mediated Hypersensitivity

Answer 38

- No Ab involvement - Th and Tc cell-mediated - Delayed as starts hour/days after contact and can last for days

Question 39

What is The Hygiene Hypothesis?

Answer 39

- Allergic reaction more common than previously - Microbial exposure deficiency syndrome (expose young children to antigens early on, eat dirt) - C-section vs. vaginal birth (more chance of asthma in c-section because they are not exposed to antigens that they would be in vaginal birth) - Pets (grow up with pets, less likely to form a reaction) Basically, need to be exposed to antigens when you are young, so that the initial reaction is small and can form immunity. Versus if they were exposed when older and used to a clean environment, the antigen response is much bigger.

Question 40

What bacteria is linked with stomach cancer?

Answer 40

Helicobacter pylori

Question 41

How can infectious agents cause tissue damage in various ways?

Answer 41

- Direct destruction of cells - Toxin production - Overstimulation of immune system