Pathologic Consequences of Infection Flashcards
What are the 3 categories of pathogens?
- direct
- indirect
- immune mediated
Can viruses bud out in the absence of tissue damage?
Yes- in this case you would not see any signs and symptoms of infection
Where does the tetanus vaccine come from and how does it work?
tetanus vaccines are made from the inactivated toxins of the bacteria - the toxin is denatured so that it cannot bind to the cell’s receptor and cause a toxic response
- it still, however, has antagonist that evokes an immune response in the body– this causes immunity to the toxin
Why is heat not enough to stop the spread of food poisoning?
- not enough to stop the spread of food poisoning because intense heat is enough to kill the bacteria but not enough the denature the toxins
Exotoxins are secreted ____ that can be encoded on ____/____
Proteins
plasmids/phages
What is an example of a chemically inactivated toxin?
diphtheria
What is an example of an effective/highly conserved toxin?
- scarlet fever
What kind of cells do hemolysin affect?
- ## they affect both red blood cells, as well as numerous other cells
What are the two different mechanisms of lysis via hemolysin?
- enzymatic lysis an pore formation
How goes enzymatic lysis of hemolysins occur? What is an example?
- clostridium perfringenes is an example, and it occurs via phospholipase C, causing hydrolysis in the cell membrane
How does pore formation occur as an action of hemolysin?
- pore formation occurs primarily in Staph aureus and occurs via the alpha toxin
- there is an alpha subunit (active one) and a beta subunit (binding one)- the alpha subunit is the thing we use to protect ourselves from the toxin, while the beta subunit is the subunit that finds and binds to the cell, allowing the suability to go into the cell and cause the infection
How does the diphtheria toxin work?
- it blocks protein synthesis
What does the beta subunit decide?
- decides the specificity of binding, and decides what cell the toxin will bind to
What is the action of cholera in the body?
- cholera has an ab subunit and binds to epithelial cells in the GI tract
- increases production of cAMP in the GI tract- this results in a loss of salt
- more salt is secreted into the lumen and this results in diarrhea via osmosis - water chases the salt and host cells lose water inorder to maintain osmotic balance
What are 2 examples of toxins that interfere with nerve-muscle transmission
tetanus and botulinum toxin
Toxins that interfere with the nerve-muscle transmission are known as ____ toxins and the B subunit bids to the ganglioside receptors on____
AB toxins
nerve cells
How does the tetanus toxin work in the body?
- the B unit of the toxin binds to the nerve cell receptor, with the A subunit internalized (inhibits transmission of the NT at the synapse)
- X synaptic transmission and NT release
- continuous stimulation of motor neurons leads to a spastic paralysis
How does the botulinum toxin work in the body?
Botulinum works in the body via the intestine
- has peripheral nerve endings at the neuromuscular junction and cause Ach release that causes a flaccid paralysis
Botulinum and tetanus both work at the nervous system but have _______
opposite actions
Botulinum toxin is frequently used as what?
- used in cosmetic surgery, as botox, used to treat crossed eyes as well as overactive sweat glands
What is the host advantage as well as the parasite advantage of diarrhea?
- host: allows the host to get rid of the organism causing the intestinal infection
- bacteria: allows the parasite to spread to a new host
The immune response is very controlled with respect to ______, but is NOT very controlled with respect to what?
The immune system is very controlled at distinguishing self vs foreign
However, it is not very good at distinguishing the degree of immune response and over activation - this can cause host tissue damage
_____ can be secreted, but ____ cannot be secreted
Exotoxins
Endotoxins
Describe endotoxins
- always part of a cell, not secreted by a cell unless the cell dies- part of the cell wall
- endotoxins are lipopolysaccharides
What are some of the effects of endotoxins?
- endotoxins can cause systemic shock and bottom out blood pressure that can cause multiple organ failure
What effects do exotoxins have on the body?
- they cause a localized effect in the body- ie. a GI infection that is localized and can have the effect of diarrhea
Why are endotoxins so much more toxic to the body than exotoxins?
- they product different cytokines that in small concentrations have a very large effect on the body (can clump platelets, cause liver failure and damage the endothelial tissue in the body - all of these factors lead to shock
What is the only treatment for infections that are caused by endotoxins?
have to select an antibiotic very carefully - cannot kill the bacteria because it will release more endotoxins
Describe LPS?
- lipid A
- core oligosaccharide
- O-polysaccharide which is variable
How do endotoxins cause fever?
- causes a release of cytokines by macrophages
- IL-1 and TNF effect in the hypothalamus
- other microbial molecules stimulate cytokines
- T cells-> cytokines
What pathways can the LPS activate to stimulate tissue damage?
- can activate both the alternative (polysaccharide) and the classic (lipid A) C pathways
What kind of organism leads to a toxic amount of endotoxin?
- gram negative organisms
Activation of the complement pathway in the body makes the cells ___
sticky
How does septicemia occur via the complement pathway?
- C3a and C5a are produced, which are chemotactic factors
- polymorphnuclear leukocytes adhere to the vessel walls and release toxic molecules- this causes damage to the host cells
Allergic responses type 1,2, and 3 are all considered ____ mediated
antibody
Allergic responses type 4 is considered ______ mediated
cell
What is a type 1 allergic reaction?
- most common
- reaction to an allergen (antigen is in the environment)
What are the symptoms of a type 1 allergic reaction?
- location of the symptoms are the effector cells
- may be unrelated to the actual point of entry of the allergen (e.g. hives from ingesting strawberries)
Individuals with multiple allergies or severe allergies often have what?
genetic disorders
- overproduction of IL-4 -> selects for IgE production over IgG, increased IL-4 receptors on or even certain types of MHC-II
What are the stages of a type 1 allergic reaction?
- initial exposure to the allergen
- IgE formation following the primary Ab- mediated immune response
- IgE binds via the Fc portion to the specific receptors of basophils (in blood) and mast cells (in tissue). Both cell types contain histamine granules
- second and subsequent exposure to the same allergen
- allergen binds to the V region od the Fab and crosslinks two adjacent IgEs on mast cell/basophil surface
- crosslinking triggers degranulation and release of histamine and other mediators
- immediate response (minutes after exposure)
What are some of the most common responses to a type 1 allergic reaction?
- hay fever (allergic rhinitis)
- swelling and itchiness - nasal congestion, hives and edema
- anaphylaxis (bronchoconstriction, shock and edema)
- asthma
How does histamine work as one of the key mediators of a type 1 allergic reaction?
- preformed molecules in granules
- binds receptors on target cells (lungs, skin, blood vessels)
- vasodilation, capillary permeability, smooth muscle contraction
- antihistamines block histamine receptors
How do SRS-As act as a key mediator in a type 1 allergic response?
- produced after exposure to allergen, not preformed
- slow release and lag time
- bronchoconstrictor implicated in asthma
What are the most common treatments of allergic reactions? (type 1 chronic )
- antihistamines (block histamine on the target cells)
- corticosteroids (blocks degranulation of mast cells)
What is the most common treatments to cut allergies?
- epinephrine
(inject directly, increased cAMP levels which decreases mediator receptors. Has an immediate, short effect and should always be followed by intravenous antihistamines)
What is hyposensitization and what does it help?
- introducing small amounts of the allergen to a person early on to allow the body to get used to the allergen and not mount an allergic response to it
What is type 2 cytotoxic hypersensitivity?
Ab mediated response is made of non-self cells/autoantibodies
- IgG produced binds to non-self cell surface and activated the classical complement pathway (MAC attack)
- – ABO blood transfusion reactions, Rh incompatibility
- – blood stage malaria (parasite Ag picked up by red blood cells)
- antimyocardial antibody of group A streptococci infection
- – cross reacting carb antigen
How does plasmodium infections affect the red blood cells?
- plasmodium infections hide inside the RBCs and presents on the receptors of the RBCs
- antibodies in the cell is recognizing the antigens on the outside of the RBC and the body is mounting a response against the red blood cells
Describe a type 3 immune complex hypersensitivity?
Large Ag-Ab complexes precipitate and induce inflammation
- activation of complement attraction of phagocytes, general tissue damage
- lungs, kidneys, joints
- – arthus reaction- farmers lung
What does precipitation of blood on a slide indicate?
- an antigen- antibody complex is what is going on
An accumulation of the antigen- antibody complex in the joints can lead to what?
- arthritis and inflammation of the joints
Type 3 immune complex hypersensitivity in the lungs, kidneys and joints leads to what?
- serum sickness
- repeated doses of passive immunization
- circulating complexes
- deposition in kidneys, skin and joints
- — this can lead to glomerulonephritis as well as rheumatoid arthritis
Type 4 delayed or ell mediated hypersensitivity can lead to what?
- no antibody involvement
- Th and Tc cell mediated
- delayed as starts hour/days after contact and can last for days
Describe the hygiene hypothesis
- people aren’t exposed to antigens the same way that they were 100 years ago
- anytime the body sees the antigen, the response is much bigger than it was previously
- thought to be because of microbial deficiency syndrome- need to expose children to antigens early on in order to allow them to build their immune system
- people that were born vaginally and have pets growing up have a lower incidence of allergies
- a lot more cases of inflammatory bowel disease in countries where the water is clean
Seems to be a high incidence between ____ and some cancers
- viruses
