Innate Immunity

Question 1

What are defensins?

Answer 1

Antibacterial enzymes on the skin

Question 2

What line of defense are urinary and GI tract?

Answer 2

First, because they flush away unwanted materials

Question 3

Lyzozyme:

Answer 3

nonspecific bacterial enzyme in saliva and tears

Question 4

Why does oral medication (antibiotics) cause Clostridium difficile or other types of diarrhea?

Answer 4

Damage of non-invasive bacteria that prevent other bacteria from colonizing

Question 5

Events occurring during the innate response

Answer 5

-Threat recognition
-innate immune cell activation and complement system
-production of cytokines, chemokines, acute phase proteins and defensins
-upregulation of cell adhesion molecules
-attraction of cells to site of damage
-elimination, resolution, tissue repair

Question 6

How is a threat recognized? PRR:

Answer 6

Pattern recognition receptors are looking for PAMP (infectious agents) or DAMP (host)

PAMP: pathogen associated molecular patterns
DAMP: damage associated molecular patterns

Question 7

PRR cont.

Answer 7

Recognition is structurally-specific

Common to whole groups of organisms or host cells

Example: LPS: lipopolysaccharide: sound on all gram-negative bacteria

How is PRR diff from antigen receptor? nonspecific

Question 8

PRR cont.

Answer 8

Can be intracellular, on the cell surface, or soluble/secreted

Question 9

TLR: toll-like receptors (kinds of PRR)

Answer 9

Not expected to know these in depth, they are new to A&P, just know some are on the cell surface and others are intracellular, and they cause vasodilation, leukocyte attraction, fever (intracellular response releases interferons which interrupt viral replication)

Question 10

Step 2 of innate response after binding PRR and PAMP

Answer 10

genes are activated that will transcribe cytokines, adhesion molecules, antimicrobial molecules

Question 11

Step 3: Acute phase response

Answer 11

proinflammatory cytokines (like histamine, prostaglandins, etc.) act on the liver which increases 1000x secretion of acute phase proteins (a variety of proteins which have various important roles in the innate immune response)

Question 12

What part of inflammation causes heat and redness?

Answer 12

increased blood flow to site

Question 13

Five cardinal signs of inflammation:

Answer 13

Heat, redness, swelling, pain, loss of function (due to tissue damage)

Question 14

Complement system (See white board image!)

Answer 14

Group of plasma proteins produced in the liver which help destroy pathogens (complement the work of antibodies)

3 complement pathways: classic, alternative, lectin

Question 15

MAC (membrane attack complex)

Answer 15

protein complex poking a hole in gram negative bacterial membranes

Question 16

complement activation

Answer 16

C3a, C4a and C5a

These are substances that cause mast cells and basophils to release inflammatory mediators such as histamine

Mediators released from mast cells: histamine, leukotrienes, prostaglandins

Neutrophil adhesion to endothelium (then roll)

Vasodilation: bradykinin (acts on pain receptors)

Increased vascular permeability: edema

Recruitment of neutrophils into tissues

Question 17

Why are NK cells considered innate despite being active during adaptive responses?

Answer 17

No memory

Question 18

Dendritic cells activate which type of cell?

Answer 18

T cells

Question 19

Which innate immune cells produce inflammatory mediators?

Answer 19

Eosinophils, basophils, mast cells

Question 20

What’s unique about follicular dendritic cells?

Answer 20

cannot engulf, no phagocytosis, just named for dendritic appearance

Question 21

How are neutrophils and monocytes moved from blood into tissues?

Answer 21

Adhesion molecules bind them to the endothelium

once they enter insterstitium, they are attracted to the site of infection by chemotactic factors

Question 22

Fc receptors on phagocytic cells

Answer 22

An antibody can be on the surface of the pathogen and the phagocytic cell will recognize the Fc (Y body)portion of the antibody and then engulf the pathogen and destroy it

Question 23

Do i need to know slide 25?

Answer 23

probably not

Question 24

What are NET’s in phagocytosis?

Answer 24

Neutrophils/phagocytes can release substances in the vicinity to kill microorganisms (helps other cells nearby)

NETS contain lysozyme, elastase, defensins, etc

Question 25

Know differences between dendritic and follicular dendritic cells?

Answer 25

slide 29

Question 26

where are inflammatory mediators found?

Answer 26

Eosinophil: blood and tissues basophil: blood mast cells: mucosal and connective tissues

Question 27

Complement system (for real this time)

Answer 27

Important soluble component of the innate immune system, is a series of plasma enzymes, regulatory proteins, and proteins that are activated in a cascading fashion, resulting in cell lysis. Punch holes in the cell walls of bacteria, making them osmotically unstable (MAC) Still nonspecific (despite antibody involvement) because it can’t be modified to target a specific organism over others

Question 28

Describe the 3 pathways:

Answer 28

Classic pathway: -C1, C4, C2, C3b -(C3b is a great flag for phagocytosis of pathogen) -C3a and C5a break away and stimulate release of histamine and leukotrienes, enhancing inflammation -C5b-C9 breaks off and is called a membrane attack complex (impact on white board image) -Goal of compliment is cell lysis (Caused by MAC and neutrophils for ex.) Alternate pathway: C3b binds directly to Ag on bacteria (less steps) -don’t really understand why the other C’s are not there to begin with, ruzga says C3b just has very high affinity and doesn’t know where others went -Similar to classic except not antibody-mediated (attaches directly to pathogen) and no C1-4 Lectin pathway: same as alternate but with all other C’s (except for C1)!! (Alternate and lectin do not rely on antibodies!!!!!!!)

Question 29

define opsonization

Answer 29

coating a microorganism to make it more readily detected by a phagocytic cell

Question 30

in general, the complement system:

Answer 30

In general, the cleavage products of complement components facilitate microbe or damaged cell clearance (C1a, C4, C3)... promote activation and enhancement of inflammation (anaphylatoxins, C3a, C5a)... and promote microbe or opsonized cell lysis (MAC)

Question 31

When are interferons produced?

Answer 31

By cells infected with viruses they are proteins that prevent viral replication Upregulate MHC class I and II molecules, resulting in increased antigen presentation and better detection decrease permeability of these cells responsible for flu-like symptoms: malaise, tiredness, muscle soreness, fever

Question 32

What are microglia?

Answer 32

types of macrophages in the CNS

Question 33

what type of macrophage is in skin?

Answer 33

Langerhans

Question 34

MHC 1 vs MHC II

Answer 34

MHC Class I: Found on all nucleated cells (even platelets) (not mature RBC) Present antigens from inside cell, can help eliminate cancer cells early Cytotoxic and NK cells recognize this complex MHC Class II: Only found on antigen presenting cells (APC): macrophages, dendritic cells and B cells Presents antigens from outside the cell (exogenous) Present to CD4 T cells

Question 35

PRR summarized

Answer 35

Macrophages, neutrophils, eosinophils, basophils, mast cells and dendritic cells also have special receptors known as Pattern Recognition Receptors (PRR) PRR are able to recognize the category of the invader (bacterium, virus, fungus or parasite) This allows for the production of appropriate cytokines to recruit the right type of immune cells

Question 36

Two types of PRR

Answer 36

Phagocytic: don’t release cytokines Inside the phagocyte, the bacteria is in a phagosome, which fuses with a lysosome and causes death of the pathogen This process kills about 2% of pathogens The other 98% are killed by oxidative burst: but this kills the macrophage also Mostly in the neutrophils Signaling: These kick in when there is a large number of pathogens They cause the macrophage to release cytokines This recruits more cells to the area to help with phagocytosis

Question 37

where are TLR's found?

Answer 37

all WBC, epithelial and endothelial cells

Question 38

NK cells logically summarized

Answer 38

Able to detect the down regulation of MHC (caused by the invading organism which makes it harder for T-cells to recognize the presence of infection) and induce apoptosis in these virally infected cells Cancer cells may also down regulate MHC production : so NK cells also offers protection from growth of cancer as well

Question 39

What happens in response to release of histamine?

Answer 39

Results in vasodilation and increased leakiness of the blood vessels allowing additional immune cells (especially macrophages and neutrophils) to move out of the bloodstream and into the tissue.