The invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present within the body. The nature of infection can vary with respect to severity, location, and number of organisms involved. 

These can be commensal or mutualistic. 

The structure and activity of many exotoxins;

the B subunit (domain) binds the toxin to a cell (tricks the cell into undergoing endocytosis),

the A subunit (domain) disrupts cell function when it enters the cell (via the induced endocytosis). 

Infectious Dose 50 and Lethal Dose 50

The number of organisms or dose that will infect or kill ≈ 50% of an experimental group of hosts within a specified time period.

A virus that does not kill its host cell by viral

release-induced lysis. 

Polymicrobial disease is:

A type of infection that persists in tissues for long periods, during most of which there are no symptoms.

Infectious organisms can enter a latent state in which the organism is not infectious at that time. 

1) The condition resulting from the presence of bacteria/pathogens, or their toxins, in blood or tissues.

2) Systemic (spread throughout the body) response to infection. 

(a) Direct contact- touching (b) Indirect contact, like microbes left on fomites. Droplet contact < 1m away,

Air-borne contact >1m away, like food and water.

(c) Vectors, like fleas, mice, ticks. Mechanical vectors include those where no change or reproduction of microbes occur during transmission. Biological vectors include those where there is a physiological change or reproduction cycle of microbes during transmission, like mosquitos/Malaria.

(a) Skin provides good protective barrier unless it's broken. (b) Epithelial tissue of the mucous membranes are easiest route inside the body cavity. This is the parental route/ preferred route.

How a pathogen invades is usually based on their own mode of transmission and is particular. If it enters in a way other than the preferred route, it can cause a different set of symptoms. 

____ converts fibrinogen in our blood into it's activated form, fibrin. Fibrin usually forms a clot in the blood. 

*One of the ways pathogens break down defenses while attaching and colonizing. 

*Can be used to detect/identify pathogenic Staphylococcus; if put in petri, looks like snot.

____ can be made in conjunction with coagulase; it's released by the bacteria so that the bacteria can break out of the clot that was made by the immune system or by the bacteria itself. 

*One of the ways a pathogen breaks down defenses while attaching and colonizing. 

Toxins that target and kill WBC's. 

*One of the ways pathogens break down defenses while attaching and colonizing. 

Produced by Mycobacteria, blocks phagocytosis so that the phagosome can't engulf it. 

*One of the ways a pathogen breaks down defenses while attaching and colonizing. 

 Outer membrane proteins of Neisseria gonorrhoeae and Neisseria meningitidis. Neisseria use these proteins and fimbriae to "trick" a cell into endocytosis so that the pathogen is taken inside. 

*Opa has 4-5 different versions so that it can get around the immune system. This is an example of antigenic varience, and also one of the ways a pathogen can break down defenses while attaching and colonizing. 

A site where there are no microbes found, ie) blood, liver, kidneys.

Axenic means "no strangers."

*Most pathogens are found to invade the mouth, esophogus, and GI tract. 

Microbes use to penetrate the Hyaluronidase acid, breaking it up.

Hyaluronidase acid is a sugar polymer that plays a role in holding connective tissue that layers cells, and cell-cell attachment.

*One way a microbe can make is easier to invade tissue.

Breaks down collagen, which is a protein found in basal membrane of epithelial tissue that helps with skin elasticity. 

*One of the ways a microbe can make it easier to invade tissues. 

Degrades elastin, which gives connective tissue elasticity. 

*One of the ways microbes make it easier to invade tissues. 

The addition of one or more ADP-ribose moieties to a protein.These reactions are involved in cell signaling.

It's responsible for the actions of some bacterial toxins, ie) cholera toxin, diphtheria toxin, pertussis toxin, and heat-labile enterotoxin. These toxin proteins are ADP-ribosyltransferases that modify target proteins in human cells. 

Genus Bordetellia (beta proteo)

Also ribosylates the adenyl cyclase of ADP ribose into cAMP, but in the lungs. 

Blocks the production of chemokines (signaling molecules to the immune system), blocks WBC from being able to receive messages, and stops phagocytosis. 

Genus Corynobacteria; high G+C

Another AB toxin, same activity of ribosylating Adenyl cyclase, but targets enzyme EF2 instead of cAMP.

gram+ bacteria

AB toxins are Class I 

___ are inserted into the cell membrane, causing a hole/pore to form. This kills the cell by allowing free diffusion of cell matter; it leaks out. 

These toxins are Class II

____ create Phosphorus that "chews up" the cell membrane. An example is the alpha toxin of Chlostridium perfringes- the gas gangrene tissue damage. 

These toxins are Class II

___ are toxins made by some pathogenic forms of staphylococcus. They trigger an immune response by activating T cells, but in a non specific way. Normally, a T cell has to recognize a particular antigen shape. 

Superantigen toxins are Class III

Instead of recognizing a particular antigen shape, the T cell recognizes a tiny fragment of a small antigen %. A large amount of T cells just grab onto the MHC (Major Histocompatibility Complex) and activates a lot of T cells. 

The T cells then make Cytokines, releasing a lot at one time, causing a cytokine storm. This can result in dropped blood pressure and shock. 

(1) Passive: by normal bodily function

(2) Active: by mechanisms in place that make them leave

(3) Active: by organisms like snails, clams, and flukes

___ are signs that are subjective evidence of disease or physical disturbance observed by the patient; not visible to others.

Examples are: headache, visual disturbances, nausea, and pain. 

Immune responses that are not specific to a particular pathogen in the way that the adaptive immune responses are. They depend on a group of proteins and phagocytic cells that recognize conserved features of pathogens and become quickly activated to help destroy invaders. We are born with only an innate immunity from mom, it has to be built up. 

In the first critical hours and days of exposure to a new pathogen, we rely on our innate immune system to protect us from infection.

In vertebrates, they are also required to activate adaptive immune responses.

 The adaptive responses are highly specific to the particular pathogen that induced them. They can also provide long-lasting protection.

A person who recovers from measles, for example, is protected for life against measles by the adaptive immune system, although not against other common viruses, such as those that cause mumps or chickenpox.

____ are the type of cells that make up the majority of the epidermis layer. They make keratin, and are derived from stem cells. They form at the basal layer of the epidermis and are eventurally pushed up as they die and sluff off.

Sluffing off carries away potentially harmful bacteria. This is one mechanism of innate immunity. 

Innate. Sweat makes the skin too salty for many bacteria to survive on. It contains lysozymes= they break down the subunit bonds of peptidoglycan (NAG*NAM), so this is more effective against gram+ bacteria. 

This is one of the mechanisms of immunity. 

Eyes make tears @ the outer corner, which dilutes bacteria and washes them into the duct, and into the nasal passages. 

There's lysozymes in tears, and ciliated cells in the nasal passages and lungs. These ciliated cells help to move dump the bacteria into the stomach. 

____ provides some immunity, simply by competing with microbes for simple resources. It provides a layer of protection.

Recall the story of the "no normal flora" mouse infected with Shigella and E. coli- the E. coli won out and protected the mouse from getting Shigellosis, even when Shigella was intoduced days prior to E. coli.  

WBC, Eosin granulocytes= have granules that take up the red stain, and help with destroying parasitic infections, like worms, helminths, and protists. 

Part of the innate immunity response. 

WBC, Basophil granulocytes= have granules that take up the blue stain, tend to release a lot of chemical messengers that release hystamine (leads to allergies). 

Part of the innate immunity response. 

WBC, Neutrophil granulocytes= have granules that take up the purple stain. They're one of the phagocytic cells (capable of engulfing foreign material).

Part of the innate immunity response. 

WBC, they have granules, but they do not take up stain. These are part of the adaptive as well as innate immunity response. 

They consist of Lymphocytes and Monocytes- monocytes diversify into Macrophages and Dendritic cells, these 2 are phagocytic. 

A WBC, an agranulocyte. NKC kill cells that have become infected with bacteria or virus.

They use 2 enzymes to do this: Perforin (perforates cell membrane, makes holes, that allows granzymes to enter the cell), and Granzyme (triggers apoptosis). 

Phagocytic cells, (ie Neutrophils, Macrophages, and Dendritic cells).

They secrete pattern recognition receptors that look for molecules that microbes characteristically have (ie peptidoglycan, LPS, fungal cell walls, and flagellin). 

These receptors stick to foreign material and mark it for phagocytosis (process is called opsonization). 

A cytoplasmic body formed by the fusion of a phagosome, or ingested particle, with a lysosome containing hydrolytic enzymes (DNAases, RNAases, lipases, proteases).

The enzymes digest most of the material within the phagosome. After fusion, the food particles or pathogens contained within the phagosome are usually digested by the enzymes contained within the lysosome.

Phagolysosome formation follows phagocytosis. It is common in immunological functions of neutrophils, macrophages, and dendritic cells. 

Neutrophils "spit them out," but Macrophages and Dendritic cells: they become antigen representing cells, by using the engulfed foreign material (microbe particles) as a way to identify these same microbes.

This information is then taken to the lymphocytes (WBC that need this information to identify futute invaders). 

The 30+ proteins circulating in blood respond to foreign material and act in a "complement cascade." 

1 protein will recognize foreign material, get activated, and this copy will activate other multiple protein. This happens in sequence: a trigger starts the cascade, which amplifies the signal, allowing for a massive immune response. 

Complement cascade can have 3 different effects that all end the same: 1) Cytolysis 2) Opsonization, and 3) Infammatory response (in absence of tissue damage). 

Complement cascade can have 3 different pathways of initiation: 1) Classical 2) Alternative, and 3) Lectin

Complement protein C3 gets activated, it breaks into subunits C3a and C3b. 

C3b can act as an obstinant, sticking to a microbe and tagging it for phagocytosis (especially sticks to LPS). C3b also activates complement protein C5, which breaks into subunits C5a and C5b. 

C5b activates C6789 (10-16 copies of C9). 

C6789 together form the Multi-membrane Attack Complex. This pore-forming complex destroys the cell. 

                    C3a→     MAST cell

          ↑

        C3 →                          C5a

                    C3b→      C5→

                                         C5b→    C6789

                                                     ↑MAC

From the end result of Complement System, the C3 has cascaded into the formation of C6789. These complement proteins together form the MAC. 

The multiple copies of C9 form a ring, which is a pore-forming ring made on a cell membrane. The rest of the complex inserts itself into the pore, creating a large hole that leads to cytolysis.

This is most effective against Gram- bacteria due to their thin peptidoglycan layer. 

C3a and C5a:

Both stimulate a specialized WBC (MAST cell) that releases  hystamine and other inflammatory mediators (signals that cause and inflammatory response= inflammation).

In addition, C5a is also chemotactic for macrophages. That is, they call in macrophages which mark for phagocytosis. 

1 of the 3 ways a Complement System can be initiated. Both innate and adaptive immunity cross paths here. 

Some foreign object is recognized by antibodies (proteins made by the adaptive immunity response). The antibodies bind to the foreign body, which then can activate complement protein C1.

C1 activates C2 and C4. Both C2 and C4 self cleave into subunits (C2 into C2a and C2b) (C4 into C4a and C4b).

The C2a and C4b subunits come together and form a heterodimer. This heterodimer complex activates C3, which is the beginning of the end process of Complement System cascade. 

C1

activates

↓          ↓

C2                 C4

                           ↓                   ↓

C2b    C2a       C4b   C4a 

heterodimer

↓ 

C3

1 of the 3 pathways to the initiation of the Complement System. This pathway is more innate, because it's not specific. 

Foreign matter is recognized by complement proteins: Properdin, factor B, and/or factor D.

Once these proteins have bonded to the bacterium in some sort of combination, they form a comlex that acivates C3.

The complement protein C3 is the beginning to the end of Complement System cascade. 

(‾‾‾)

B  P  D

↓

C3

 1 of the 3 pathways of initiation of the Complement System cascade.

Lectin (a protein that binds with sugar- Glucose here) is made by the liver in response to released cytokines by active macrophages (actively phagocytized).

Lectin in this case is mannose-binding, with mannose being a protein that most bacteria have on their cell surface, either on proteins or lipids.

Mannose-binding protein (MBP) also recognizes a carb (mannin) that is a structural component of the fungal cell wall, so the Lectin pathway is useful against fungal pathogens. 

   (Glucose)

                                    (MBP)     → bind

  ↓

 activates

  C2        C4 

  ↓         ↓

  C2a ↔ C4b

heterodimer

↓

 activates

C3

The Lectin Pathway: 1 of 3 pathways of initiation of the Complement System.

MBP binds to Glucose, which activates C2 and C4, that split into subunits C2a and C4b that form a heterodimer- a complex that activates C3, which is the beginning of the end process of Complement System cascade.