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What does an elevated WBC count mean?
infection
What does high C-reactive protein in the blood mean?
complement system is activated
Which is a rapid response: innate or adaptive?
innate
Which is a delayed response: innate or adaptive?
adaptive
True/False. The innate immune system has memory.
False
Is innate specific or non-specific?
non-specific
What is the cytokine-mediated fever mechanism?
1. Pathogen
2. Cytokines (IL-1, IL-6, TNF-alpha)
3. Hypothalamus
4. PGE2
5. Fever
What is the lymph node activation pathway?
1. Antigen-presenting cell
2. T-helper cell
3. B-cell activation
4. Dendritic cells migrate to nodes
5. T helper cells stimulate B cells -> antibody production
What does node swelling mean?
immune cell proliferation
What does IL-6 lead to?
fever and acute-phase proteins being activated
What is the link between innate and adaptive immunity?
It is sequential: innate -> adaptive
It is cooperative (they work together)
What makes mealses special with immunity?
It wipes out all the memory cells for every virus the pt has been exposed to before
What are the natural defense mechanisms of the oral cavity?
1. Oral mucosa
2. Nasopharynx-associated lymphoid tissues (tonsils)
3. Tongue
4. Saliva and salivary glands
5. Tooth plaque fluid and adjacent GCF
What are the two major mechanisms of innate immunity in the oral cavity?
1. Immune exclusion (inactivation, clearance of microbes from oral mucosa+enamel)
2. Inflammation (occurs when we need to remove infectious agent after mucosal penetration)
What is the difference between immune exclusion and inflammation?
- Immune exclusion is the inactivation and clearance of microbes from the oral mucosa/enamel BEFORE any mucosal penetration
-Inflammation is the next step that occurs when we need to remove the infectious agent AFTER mucosal penetration.
For the innate immunity in the oral cavity, what are ways that we use inflammation to remove the infectious agent?
1. Phagocytosis
2. Recognition of PAMPS by PRR
3. Inflammatory mediators
What do epithelial desolation, saliva flow, and mucin/agglutinins function for?
physical removal or microbes
What is the function of lysozyme?
causes cell lysis
What is lactoferrin's/ apolactoferrin function?
iron sequestration
What does the complement system function for?
activates neutrophils
What is secretory IgA's function?
prevents microbial adhesion and metabolism
What are IgG, IgA, and IgM's functions?
prevent microbial adhesion; opinions; complement activators
What parts of the oral mucosal epithelium help prevent penetration of microbes into deeper tissues?
- saliva
- keratin
- granular layer
- basement layer
What do cells in the oral mucosa express ______ for immune surveillance?
PRRs
What can some pathogens do to avoid being detected by the immune system?
- Some periodontal pathogens hide within buccal epithelial cells as a protective niche
What are some antigen-nonspecific denfense chemicals in oral secretions?
1. Calprotectin
2. Antimicrobial actions of saliva
3. Defensins
4. Gingival crevicular fluid
How can antigen-nonspecific defense chemicals in oral secretions help for an immune response?
- they can aggregate or agglutinate microbes
- they can promote or inhibit microbial adhesion
- they can directly kill or inhibit the growth of microbes
- they can contribute to microbial nutrition
How does calprotectin work?
- it is produced by nonkeratinized oral epithelial cells
- deprives microbes of essential divalent ions
- present in neutrophils, monocytes, macrophages
How does saliva act as an antigen-nonspecific defense?
- The flow of saliva and swallowing removes debris and unattached microbes
- It replenishes fluids in the oral cavity, which dilutes/clears microbes and acid from plaque
- Contains neurophils and antigen-nonspecific defense chemicals (secretory IgA, IgA, IgG) and other enzymes
How does defenses act as an antigen-nonspecific defense?
- it forms pores that cause osmotic instability and cell lysis
- It can be found in saliva
- it is active aganist fungi
- causes degranulation of mast cells
- chemotactic for neutrophils, dendritic cells, memory T cells
How does GCF act as an antigen-nonspecific defense?
- contains blood components including leukocytes are in the junctional epithelium
-
Normally, the flow of GCF is high or low?
low
What causes an increase of flow of GCF?
increases with inflammation to flush oral surfaces that are vulnerable to penetration by microbes
When does the composition of GCF change?
changes during inflammation increasing in the number of lymphocytes and neurophils
What is immune exclusion/colonization resistance?
bacteria that normally live in our oral cavity complete aganist pathogenic bacteria
What is an example of when a potential pathogens proliferate?
infection by the fungal pathogen Candida albicans after most of the commensal bacteria are killed by broad-spectrum antibiotics such as tetracycline
What is microbial antagonism?
one species harms, and can exclude, the other
What is synergism?
two species cooperate to benefit both
What is symbiosis?
one species benefit, other may be unaffected or harmed
What is commensalism?
one species benefit, the other is unaffected
What is mutualism?
both species benefit
What is parasitism?
one species benefits, the other is harmed
Where is MALT located and what is it responsible for?
MALT lies beneath the oral mucosal epithelium and contains phagocytes and APCs, which sample antigens in the oral mucosa and provide the link between innate and acquired immune response
What drives adaptive immunity?
MALT
What is found around the basement membrane to help eliminate pathogens that overcome innate immune exclusion and pass through the intact oral mucosal epithelium?
lymphoid cells
What are the extraoral lymph nodes and intraoral lymphoid tissues present in the mouth?
- palatine and lingual tonsils
- salivary gland lymphoid tissue
- gingival lymphoid tissue submucosal lympoid cells scattered in the submucosa
What and where does the lymph tissues drain from the oral cavity?
- network of lymph capillaries and lymph vessels links the oral mucosa, gingivae, and pulp to other structures, such as the tongue, and drain into the submandibular, retropharyngeal, and other lymph nodes
What are the two ways microbes can enter the lymphatic system?
1. Microbes have to overcome the innate immune system and penetrate through the oral mucosa
2. Transported to the lymphatics by phagocytes
When is an immune response elicited?
When the microbial antigens reach the lymphocytes in the MALT
What happens after the lymphocytes that have encountered an antigen is activated?
The lymphocytes leave the MALT via the efferent lymphatics and enter the circulation, after which they relocate to the lamina propria to drive the acquired immune response
What are the types of T cells in the lamina propria?
CD4 and CD8 but some intraepithelial lymphocytes (IELs
What is the most predominant T cells in the lamina propria?
CD4 and CD8 types
What are the B cells in the lamina propria associated with?
acini of the major and minor salivary glands and they synthesize IgA
What are some clinical connections to look out for in the oral cavity defense?
Reduced saliva -> xerostomia -> candidasis (easier for things to grow well in a dry environment
Neutrophil defects -> aggressive periodontitis
IgA deficiency -> recurrent infections
What is immunity?
state of protection against foreign pathogens or substances (antigens)
What is the first example of the first concept of immunity?
Thucydides 430 BC
What are some examples of when vaccinations worked?
smallpox
What is variolation?
take a pustle of someone who had the disease and scratched into the skin (early vacination)
What did Edward Jenner do for smallpox?
He used material from cowpox lesions to protect people against smallpox
What is attenuation?
When you use a weakened or aged culture that has lost its virulence to allow the body to mount a resistance but you do not get sick from it.
Who played with chickens and realized that if you used an attenuated culture then the subject didn't die?
Pasteur
When was the first human vaccination and on who?
1885 on Joseph Meister
Who made the rabies vaccination?
Pasteur
What is innate immunity?
"anatomic, physical barriers"
- mucous,
- tears,
- skin,
- cilia
- membranes
- chemicals (acid, enzymes)
- inflammation/fever
- phagocytosis
What immune cells are used in innate immunity?
Phagocytes and Natural Killer cells
What is aquired immunity?
"Physiologic and cellular barriers"
- T cells and B cells
- antibodies
- memory part of immune system
What are the defense chemicals in oral secretions?
1. Calprotectin
2. Defensins
3. Cathelicidins
4. Saliva
5. Lysozyme
6. Peroxidase
7. Histatins/Cistains
8. SLPI, PRP
9. Mucins
What is calprotectin?
starves microbes
What are defensins?
membrane pore forming peptide
What are Cathelicidins?
lysosomal antimicrobial polypeptide
What is in saliva that is used for the innate immune system?
Ig, lysozyme, lactoferrin, periodases
What is lysozyme?
aggregates microbes and amphipathic sequences
What is peroxidase?
oxidizes bacterial enzymes in glycolytic pathway
What are mucins?
aggregates bacteria, various effects
What is GCFs?
GCF: Gingival crevicular fluid
- Found in the sulcus under the gingiva (different than saliva) and is full of Igs, and other enzymes for protection
What immune cells use phagocytosis?
neutrophils, monocytes, and macrophages
What are pathogen associated molecular patterns (PAMPs)?
conserved patterns on the cells that the immune system can recognize as NOT our own (bacteria or pathogens)
What are some examples of PAMPs?
LPS, bacterial DNA, double-stranded RNA (viruses), glucans (cell wall of fungi) , flagellin
How do we recognize PAMPs?
with pattern recognition receptors (toll like receptors)
What are natural killer cells
nonphagocytic lymphocytes that kill virus infected cells, if it does not have MHC1 it kills the cell
What are the two receptors on a NK cell? How does it know when to kill a pathogen?
1. Antigen receptor
2. MHC I receptor
- If a cell does not express MHC1, the NK will kill the cell
What are acute phase proteins? What organ produces it?
serum proteins that are produced in the liver in response to tissue-damaging infections and other inflammatory stimuli
What is a C reactive protein?
acute phase protein that binds to bacteria to promote phagocytosis and activates the complement system
How does acute phase proteins work?
activates classical complement system resulting in increased clearance from a pathogen
What is the complement system?
has at least 30 components which interact in an ordered and tightly regulated manner to cause phagocytosis of target cells
What does opsonin do?
promote phagocytosis
What are the three important outcomes of activation?
1. Inflammation: anaphylatoxins promote the inflammation
2. Lysis: Membrane Attack complexes punches holes in membrane
3. Opsonin: enchange phagocytosis
What are the two lines of hematopoietic stem cells (HSC)?
myeloid line and lymphoid line
What are some characteristics of hematopoietic stem cells?
pluripotent and self-renewing
Cells from which HSC lineage are the first responders to infection?
myeloid
Cells from which HSC lineage lead to T and B cells?
lymphoid
What are the four main types of myeloid-erythroid progenitors?
granulocytes, macrophages, red blood cells, megakaryocytes (form platelets)
What are the the types of granulocytes?
neutrophils, eosinophils, basophils
What is the main circulating WBC, highly phagocytic, and usually first responder to infection?
Neutrophil
What is NETosis?
neutrophil exocytosis trap (traps microbes) that causes cell dealth without phagocytosis
What is the least abundant WBC that is a nonphagocytic cell involved with antiparasite defense and allergies?
basophil
What is similar to basophils but not found in blood only tissues, nonphagocytic?
mast cells
What cell is involved in parasitic infections and allergies, they have both phagocytic and extracellular killing?
eosinophil
What are some non granulocyte cells?
monocytes, macrophages, and dendritic cells
What do monocytes differentiate into?
Macrophages