Innate Immunity Flashcards
What are defensins?
Antibacterial enzymes on the skin
What line of defense are urinary and GI tract?
First, because they flush away unwanted materials
Lyzozyme:
nonspecific bacterial enzyme in saliva and tears
Why does oral medication (antibiotics) cause Clostridium difficile or other types of diarrhea?
Damage of non-invasive bacteria that prevent other bacteria from colonizing
Events occurring during the innate response
-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
How is a threat recognized? PRR:
Pattern recognition receptors are looking for PAMP (infectious agents) or DAMP (host)
PAMP: pathogen associated molecular patterns
DAMP: damage associated molecular patterns
PRR cont.
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
PRR cont.
Can be intracellular, on the cell surface, or soluble/secreted
TLR: toll-like receptors (kinds of PRR)
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)
Step 2 of innate response after binding PRR and PAMP
genes are activated that will transcribe cytokines, adhesion molecules, antimicrobial molecules
Step 3: Acute phase response
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)
What part of inflammation causes heat and redness?
increased blood flow to site
Five cardinal signs of inflammation:
Heat, redness, swelling, pain, loss of function (due to tissue damage)
Complement system (See white board image!)
Group of plasma proteins produced in the liver which help destroy pathogens (complement the work of antibodies)
3 complement pathways: classic, alternative, lectin
MAC (membrane attack complex)
protein complex poking a hole in gram negative bacterial membranes
complement activation
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
Why are NK cells considered innate despite being active during adaptive responses?
No memory
Dendritic cells activate which type of cell?
T cells
Which innate immune cells produce inflammatory mediators?
Eosinophils, basophils, mast cells
What’s unique about follicular dendritic cells?
cannot engulf, no phagocytosis, just named for dendritic appearance
How are neutrophils and monocytes moved from blood into tissues?
Adhesion molecules bind them to the endothelium
once they enter insterstitium, they are attracted to the site of infection by chemotactic factors
Fc receptors on phagocytic cells
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
Do i need to know slide 25?
probably not
What are NET’s in phagocytosis?
Neutrophils/phagocytes can release substances in the vicinity to kill microorganisms (helps other cells nearby)
NETS contain lysozyme, elastase, defensins, etc
Know differences between dendritic and follicular dendritic cells?
slide 29
where are inflammatory mediators found?
Eosinophil: blood and tissues
basophil: blood
mast cells: mucosal and connective tissues
Complement system (for real this time)
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
Describe the 3 pathways:
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!!!!!!!)
define opsonization
coating a microorganism to make it more readily detected by a phagocytic cell
in general, the complement system:
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)
When are interferons produced?
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
What are microglia?
types of macrophages in the CNS
what type of macrophage is in skin?
Langerhans
MHC 1 vs MHC II
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
PRR summarized
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
Two types of PRR
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
where are TLR’s found?
all WBC, epithelial and endothelial cells
NK cells logically summarized
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
What happens in response to release of histamine?
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.
