Immunology (part 3)

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Innate immunity

What are 3 other names for innate immunity?

natural, native, and non-specific

Do lower organisms have innate immunity too?

yes

____ immunity is always present in healthy individuals, is the first responder (has a rapid response), block entry of microbes, kills microbes that enter, and sends signals to alert adaptive immunity.

innate

Can innate immunity be triggered by damaged host cells?

yes

What are 5 things that innate immunity cannot/does not do?

1. does not recognize specific antigen structure
2. does not require prior exposure to antigen
3. does not become stronger (it will have the same reaction every time it encounters a pathogen)
4. does not react against noninfectious foreign substances or self-molecules/cells
5. does not form memory cells

What are epithelial barriers?

the first barrier that microbes encounter

What are 4 examples of epithelial barriers?

skin, respiratory mucosal epithelia, GI tract mucosal epithelia, and genitourinary tract mucosal epithelia

To cause infection, pathogens must cross ____ ____.

epithelial barriers

How can pathogens cross the epithelial barriers? (3)

1. they may adhere to the surface and infect the cell or cross the epithelial barrier
2. they may also colonize the epithelia
3. an unnatural breach in the epithelial surface may also let them in (ex: cut, wound, burn)

The ____ is a continuous physical and chemical barrier.

skin

Loss of integrity of the skin causes increased risk of ____.

infection

Epithelial cells produce ____ substances.

antimicrobial

There are ____ in sweat to prevent the entry of pathogens.

acids

The entry of normal flora is blocked by ____ ____.

dead keratinocytes

The common portal of entry through the skin occurs through ____ ____ with microbes.

physical contact

The respiratory tract has ____ and ____ that work together in the upper segment and surfactants in the lungs (lower segment).

mucus and cilia

The upper airway begins at the ____ and ends in the ____ and is protected by the ____ ____.

nose, bronchioles, mucociliary escalator

Mucus secreted by ____ ____ forms a fine layer lining the airway and trapping microorganisms

goblet cells

____ waft the mucus towards the mouth and nose, where trapped organisms are cleared by sneezing or coughing.

cilia

Mucus secretion is abnormal in ____ ____ and cilia are defective in ____ ____ ____.

cystic fibrosis, primary ciliary dyskinesia

The main defenses in lower respiratory tract are ____ secreted by ____ ____ ____.

surfactants, type II pneumocytes

There are about ____ m^2 of mucus membranes

400 m^2

Why might organisms trapped in mucus not be able to cause infection?

because they cannot adhere to cell surface

____ ____ move move in wave-like pattern toward mouth.

ciliated cells

The ____ ____ removes pathogens via coughing and sneezing

mucociliary elevator

____ is a substance that lowers surface tension and keeps alveoli from collapsing.

surfactant

What is the immune function of surfactant?

binds to components of the cell surface of pathogens and causes them to agglutinate. That leads to destruction by phagocytes.

Is normal flora immune to the antimicrobial substances in the saliva?

yes

The ____ motion of the GI tract helps clear things out of the system.

peristaltic

What common practice can disrupt the normal flora in both the GI tract and in the genitourinary tract, making these areas more prone to infection?

taking antibiotics

What are some features of the genitourinary system to keep microbes out?

1. Defensins and other antimicrobial products produced by epithelial cells and commensals
2. Constant flushing of urinary tract
3. Acidic vaginal pH and commensal bacteria
4. Spermine and zinc in semen are antibacterial (keeps the semen sterile)
5. Lactoperoxidase in milk (keeps milk sterile for the baby)

Are tears a feature of the innate immune system?

yes, because they wash away pathogens and contain antimicrobial substances

Epithelial cells produce antimicrobial chemicals called ____.

defensins

What are the 2 types of defensins and where else are they found?

alpha and beta; in neutrophil granules

Defensins have _____-spectrum antibiotic properties and have increased production in response to inflammatory _____.

broad, cytokines

_____ are alpha defensins that are produced by intestinal epithelial cells.

cryptocidins

What are three types of epithelia-associated cells that are also B cells and T cells that are exceptions to the rules?

intraepithelial T lymphocytes (IELs), B-1 cells, mast cells

Intraepithelial T lymphocytes are associated with ____ epithelial cells, express ____ ____ of limited diversity, and recognize ____ structures.

barrier, antigen receptors, shared

Intraepithelial T lymphocytes also secrete ____, activate ____, and kill ____ cells.

cytokines, phagocytes, infected

B-1 cells are located in the ____ cavity and are similar to IELs. They can respond to microbes and toxins that breach the walls of the ____, and they produce natural ____ (IgM).

peritoneal, intestine, antibodies

Where are mast cells located?

under many epithelia and in serosal cavities

What do mast cells do?

secrete substances that mediate inflammation or release granules

Both the IELs and B-1 cells have more similarities to the ____ immune system.

innate

____ and ____ are circulating phagocytes that are recruited to the site of infection.

monocytes and neutrophils

____ are phagocytes that are found in tissues.

macrophages

Phagocytes ____, ____, and ____ microbes.

recognize, ingest, and kill

Recognition by phagocytes occurs through ____ ____ ____.

pattern recognition molecules

Pattern recognition molecules are only found on ____, not on ____ cells.

pathogens, host

What are PAMPs?

pathogen-associated molecular patterns on pathogen

What are PRRs?

pathogen-recognition receptors on phagocyte

____ bind to ____ and the pathogen is internalized.

PRRs, PAMPs

_____ is the process of getting a cell from the blood stream to the site of infection.

diapedesis

What are the 7 steps of phagocytosis?

1. chemotaxis and adherence of microbe to phagocyte
2. ingestion of microbe by phagocyte
3. formation of a phagosome
4. fusion of the phagosome with a lysosome to form a phagolysosome
5. digestion of ingested microbe by enzymes
6. formation of residual body containing indigestible material
7. either some of the peptides are held for antigen presentation or discharge of waste materials

Do antibodies kill anything?

no, but they will coat an organism (opsonization)

NK cells are a subset of ____. They are neither __ cells nor __ cells.

lymphocytes, T cells, B cells

What do NK cells do? (3)

kill infected cells, kill tumor cells, secrete cytokines

What is the main role of NK cells?

to protect against intracellular pathogens (mainly viruses)

NK cell recognition is mediated by ____ and ____ receptors.

activation and inhibition

Do NK cells kill immediately? Why or why not?

no, because they don't want to accidentally kill the wrong things.

What are some of the effector functions of NK cells? (7)

1. kill infected cells
2. operate in a similar manner to CTLs
3. have granules
4. eliminates reservoir of infection
5. can kill sooner than CTLs
6. IFNγ secreted by NK cells activates macrophages to destroy microbes/cells (positive feedback loop)
7. controls infection to allow T cell-mediated immunity to develop

What do the granules in NK cells contain and what do they do? (2)

1. contain perforin (creates pore)
2. contain granzyme (induces apoptosis)

____ consists of several plasma proteins.

complement

In a ____, one protein is activated by another and so on.

cascade

The complement cascade is activated directly by ____ and promote ____ and ____ of microbes.

microbes; inflammation and destruction

What are the 3 pathways of complement?

1. classical pathway
2. alternative pathway
3. lectin pathway

In the ____ pathway, C1 recognizes antibodies bound to microbes.

classical

The classical pathway is part of ____ immunity and needs ____ so it won't work until it has those.

adaptive, antibodies

The ____ pathway directly recognizes microbial structures and is part of innate immunity.

alternative

In the ____ pathway, mannose binding lectin (MBL) recognizes mannose residues on microbial glycolipids and glycoproteins.

lectin

The lectin pathway leads to activation of the ____ pathway and is part of ____ immunity.

classical, innate

Activation of any pathway leads to assembly of the ____ ____.

protease complex

In complement, the protease complex creates ____ that lead to ____ ____.

pores, cell lysis

Does cascade cause apoptosis?

NO!! It forms holes in the cells, which cause cell lysis.

Mammalian cells express ____ proteins that protect uninfected cells. This keeps us from putting holes in our own cells.

regulatory

Cytokines recruit and activate _____. They also regulate ____ ____.

leukocytes (WBCs); immune response

What are the sources of cytokines in innate immunity?

macrophages, neutrophils, NK cells, endothelial cells, and epithelial cells

Mannose-binding lectin and C-reactive proteins are both types of ____ proteins.

plasma

Mannose-binding lectin serves as an ____, which makes the microbe a ____ for ____.

opsonin, target, phagocytosis

Mannose-binding lectin (an opsonin) binds to ____ that are unique to microbes. ____ then bind to the attached MBL.

motifs; macrophages

Macrophages that bind to MBL increase the likelihood of ____.

phagocytosis

Mannose-binding lectin and C-reactive protein both activate ____ and act as ____.

complement, opsonin

What does C-reactive protein bind to?

capsules of pneumococcal bacteria and bacterial phospholipids

Because of C-reactive protein, ____ levels increase during the acute stages of many infections.

plasma

Innate immunity stimulates ____ ____.

adaptive immunity

Innate immunity signals to activate ____ ____ __ and __ ____. This is a ___ signal activation.

antigen specific T and B cells; 2

Innate immunity MUST have two signals to be activated. The first signal is ____ and the second signal is ____ ____ or ____ of ____ ____.

antigen, microbial product or component of innate immunity

The second signal of innate immunity could be a ____, ____, or ____ (on APCs).

complement, cytokines, or costimulators

The ____ signal of innate immunity will activate the response. The ____ of signal dictates the type of response.

second, type

The two types of second signal that dictates type of response are:

intracellular microbes and extracellular microbes

With ____ ____ as the second signal, cytokines lead to macrophage activation, leading to destruction of microbes and presentation to T cells, leading to T cell-mediated immunity.

intracellular microbes

With ____ ____ as the second signal, there is complement activation, which leads to activation of B cells and increased production of antibodies

extracellular microbes

Innate immunity and adaptive immunity have ____ communication with each other.

bidirectional (this allows innate to stimulate adaptive and adaptive to communicate with the innate as well)

Microbes that can avoid ____ immunity may also fail to stimulate ____ response.

innate, adaptive

The inflammatory response is an ____ response, where ____ are recruited to the site of infection in order to eliminate the ____.

early, leukocytes, infection

Cytokines (TNF, IL-1, chemokines), microbial products, and coagulation proteins act on ____ cells and ____.

endothelial cells and leukocytes

Cytokines stimulate expression of ____ molecules on endothelial cells.

adhesion

In the innate response, large numbers of ____ migrate to site, which are then large numbers of ____/____.

neutrophils; monocytes/ macrophages

Are neutrophils long-lived or short-lived?

short-lived

Recruited macrophages are activated by ____.

IFNγ

Inflammation usually causes little damage to ____ tissue, but prolonged inflammation can add to damage caused by ____.

host, microbe

In innate immunity, an ____ ____ response is a systemic change.

acute phase

What are some examples of systemic changes in innate response?

1. increased production of leukocytes
2. fever
3. changes in plasma protein levels
4. shock, DIC, multiple organ failure, and death (these are only in extreme cases)

Plasma protein levels in the innate response increase in ____ and ___. These levels all play direct roles in ____ ____.

complement proteins and C-response protein; host defense

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