Module 1B Flashcards
1
Q
Are immune responses and inflammation the same
A
- No we can have both at the same time
- An immune wo a inflammation and opposite
2
Q
What do all blood cells come from
A
Pluripotent hematopoietic stem cells (HSCs)
3
Q
Hematopoiesis (what are the cells differentiated into)
A
- When blood cells are exposed to cytokines and surrounding stromal cells they differentiate into
- Megakaryocytes
- Erythrocytes
Leukocytes
4
Q
Megakaryocytes
A
Thrombocytes (platelets)
5
Q
Erythrocytes
A
Red blood cells
6
Q
Leukocytes
A
- White blood cells
-Includes lymphocytes, granulocytes, monocytes, macrophages, neutrophils, eosinophils
7
Q
Innate immunity
A
- Refers to the host defense mechanisms that are immediately available on exposure to pathogens because they are always present
-Includes epithelial barriers, mucous membranes
8
Q
What cells are in the innate immune system
A
- Granulocytes
- Mononuclear phagocytes
- Natural killer cells
-Dendritic cells
9
Q
Granulocytes
A
- Neutrophils, eosinophils, basophils, mast cells
- Often the first cells to arrive at the site of injury
- Characterized by granules in their cytoplasm and their varying shapes of the nucleus
- Engulf and kill pathogens in their cytoplasmic granules to kill the pathogen and also enhance inflammatory response
10
Q
Neutrophils
A
Phagocytize microbial invaders
11
Q
Eosinophils
A
- Phagocytize parasites, boost immune signal
12
Q
Mast cells
A
- Know for histamine release
Found in mucous membranes exposed to environment
13
Q
Basophils
A
- A lot like mast cells
-Boost immune signal
14
Q
Mononuclear phagocytes
A
- Monocytes and macrophages
- Monocytes are baby macrophages
- Monocytes circulate in the blood and when they go into tissue they can grow 5-10x into macrophages
- Remain motile and reside in reticular connective tissue
- Also release pro inflammatory molecules like cytokines or eicosanoids
15
Q
Natural killer cells
A
- Cytotoxic lymphocytes that target tumour and virus infected cells not a specific antigen
- (check other white blood cells to see if they are damaged or infected
-Selectively pick damaged or infected host cells as there is an abnormal expression of surface molecules on damaged cells
16
Q
Dendritic cells
A
- Connection between innate and adaptive immunity
- Reside in tissues and stimulate adaptive immune response
- Immature ones patrol peripheral tissues and capture pathogens through phagocytosis
-Mature ones then migrate to the lymphoid organs to present the antigens they discovered to the T-cells
17
Q
Adaptive immune system
A
- Characterized by antigen specificity and immunological memory
-More complex process as requires antigen processing and recognition
-Takes days to develop a response
18
Q
Cells in the adaptive immune system
A
- B cells
-T cells
19
Q
B cells
A
- A naïve b cell encounters a pathogen ad binds to it through immunoglobin (b cell receptor)
- The B cell multiplies
- Its offspring differentiate into plasma cells or memory cell cells (guided by interleukins
20
Q
Plasma cells
A
Short lived and secrete antibodies
21
Q
Memory B cells
A
- Long lived (years) and express the same immunoglobin as the parent B cell
-Responsible for a quick secondary response when coming into contact with the same pathogen
22
Q
T cells
A
- Express receptors that only recognize antigens that are expressed by the dendritic cells or other antigen presenting cells (memory B cells)
- Three types: Tc, Th, Memory T cells
23
Q
Cytotoxic CD8+ T cells
A
- Tc cells
- Destroy host cells that are infected
24
Q
Helper CD4+ T cells
A
- Th cells
- Secrete cytokines that enhance the function of other cells to help in getting rid of the pathogen
25
Memory T cells
- Can persist for years and mount a quick response on re exposure
26
Antibody
- Is not on a plasma membrane
- Y shaped glycoprotein created by the body in response to a specific antigen
27
Immunoglobulin
- On the transmembrane
- Y shaped glycoprotein created by the body in response to a specific antigen
- 5 types - different heavy change poly peptide sequence that behave differently
28
IgG, IgM, IgA, IgD, IgE
IgG
- 75% of Ig
- Secondary response
- 4 subclasses
- Passes through placenta
- Studied to judge immune response
IgM
- On B cells or a pentamer
- Primary response
- Involved in autoimmune dx
IgA
- Epithelial surfaces and mucous membranes
- 2 subclasses
- Makes pathogen weaker
IgD
- Unknown function
- Transmembrane
IgE
- Allergic response to pollen, fungus, spores, and parasites…
- Fast response
- Involved in asthma, eczema….
29
The lymphatic system
A network of lymphatic vessels connected to lymph nodes
30
What are lymph capillaries made up of
- Smaller ones are made of Single endothelial layers
-Larger vessels are surrounded by layers of smooth muscle cells\
31
What does the lymphatic system do
- Collects plasma continuously leaking out from blood vessels into the interstitial spaces and returns the fluid (lymph) to the blood
32
Which way does the lymphatic system flow
- Only flows upwards toward the neck with rhythmic contractions of smooth muscle
33
Where do B and T cells travel
Both the blood and lymph
34
What are primary lymphoid organs responsible for
- For lymphocyte maturation and development
-Bone marrow and thymus
35
Where does B cells and T cells mature and develop
- B cells completely differentiate and mature in the bone marrow
- T cells originate in the bone marrow but mature in the thymus
36
What are the maturation processes of B and T cells guided by
Interleukins
37
What are the secondary lymphoid organs and what do they do
- Where mature lymphocytes interact with antigen presenting cells (APCs), antigen is localized so that it can be exposed to mature lymphocytes
-Spleen, lymph nodes, tonsils, appendix, peyers patch, adenoids
38
Spleens job within the immune system
- Has a red pulp where old or injured erythrocytes are recycled
- White pulp which consists of lymphocytes
-Connected via blood vessels rather then lymphatic vessels
39
Lymph nodes
Are round specialized structures positioned along the lymphatic vessels like beads on a chain
40
What do swollen lymph nodes mean
sign of infection
41
How does lymphocyte recirculation occur
1. B and T cell development in bone marrow and thymus enter blood stream
2. When they reach a secondary lymphoid order they enter it
a) If antigen is detected: stays in the tissue and becomes activated
b) No antigen detected: exits through lymph and re enters bloodstream
3) Allows continuous monitoring of the secondary lymphoid organs for infection
42
How are pathophysiology and pharmacology connected
Many different infections or diseases will all have anti inflammatory and sometimes immuno-suppressants in treatment
43
Type 1 diabetes mellitus
Immune mediated destruction of B cells in pancreas that secrete insulin
44
Rheumatoid arthritis
Immune mediated destruction of joints
45
Hashimoto's thyroiditis
Immune mediated destruction of the thyroid gland
46
How does bacteria cause disease (2)
- Bacteria grow rapidly and cause disease by sheer numbers (usually)
-Bacteria produce toxins that cause disease (e.g. botulinum toxin --> botulism)
47
How do antibiotics target bacteria
- Depending if they are gram positive or negative (Gram negative has an outer membrane and peptidoglycan while gram positive only has peptidoglycan
- Bacilli cocci or spirilla
- Aerobic or anaerobic
48
How are antibiotics classified
Either by their structure or mechanism of action (MOA)
49
MOA
- Mechanism of action
-The process by which a molecule such as a drug functions to produce a pharmacological effect
50
Bactericidal
Drugs that kill/ destroy the bacteria entirely all by themselves
51
Bacteriostatic
- Drugs that slow down the growth of the bacteria
-Need to bodies immune system to dispose of the bacteria
52
If an individual is immunosuppressed what would they take (bacteriostatic or bactericidal)
Bactericidal
53
Broad spectrum antibiotics
- Drugs that are effective against a wide variety of bacteria
-Prescribed empirically when we don’t know specific pathogen
54
Narrow spectrum antibiotics
- Drugs that are effective against very specific microorganism or restricted group
-Prescribed when pathogen is clear
55
When choosing an antibiotic to prescribe what do we need to consider
- C & S = culture and sensitivity
- Local epidemiological info = the geographic area
- Site of infection
- Immune system status
- Kidney and liver function
- Variables affecting pharmacokinetics (must keep above min concentration or resistance can occur)
- Patient allergies or intolerances
- Dosage forms available
-Ease of administration and adherence issues
56
Penicillin's
- Also known as beta lactams
- Disrupt bacterial cell walls
- Bactericidal
-Contain a beta lactam ring needed to bind to the penicillin binding protein and destroy it
57
Penicillin binding protein
- A protein only in bacterial cell walls that penicillin binds to and weakens the cell wall which allows fluid to enter and destroy the cell
58
How do bacteria defend against penicillin
- Produce a beta lactamase (penicillinase) that breaks the beta lactam ring leaving It ineffective and causes penicillin resistance
59
How can we still use penicillin against bacteria that have a beta lactamase
- Can add other drugs such as clavulanic acid (amoxiclav)
-This drug inhibits B- lactamases of some microorganisms
60
What is cyclosporine
- Inhibits production and release of interleukin II and inhibits interleukin II-induced activation which inhibits the self activation of T- lymphocytes
- Not specific
-Suppresses entire immune system
61
What is methotrexate
- Folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication
- How does it do this: inhibits dihydrofolate reductase, inhibiting the formation of reduced folates, and thymidylate synthetase, resulting in inhibition of purine and thymidylic acid synthesis, thus interfering with DNA synthesis, repair and cellular replication; it is cell cycle specific for the
S phase of the cycle
-actively proliferative tissues (ones that undergo rapid cell division) are more susceptible (target)
62
What diseases/ conditions is methotrexate used in
- Rheumatoid arthritis: unknown how
- Psoriasis: target rapidly proliferating epithelial cells in the skin
- Crohn's disease: may have immune modulator and anti inflammatory activity
-First introduced to treat leukemia (blood cancer)
63
What is Allergic rhinitis
- Common abnormal immune response to harmless environmental allergens
-Mediated by IgE--> histamine release from mast cells
64
Symptoms of allergic rhinitis
- nasal, ocular, and palatal pruritus(itching)
- paroxysmal sneezing
- Rhinorrhea
-nasal congestion
65
Early phase of allergic rhinitis
- Within 5 mins of exposure to allergen due to histamine (sneezing, increase in nasal secretions)
-Leads to: swelling of mucosa and reduced airflow, release of mediators that vasoconstrictors
66
Late phase of allergic rhinitis
- Occurs 2-4 hours after exposure, resolves after 12-24 hours after allergen is not present
- Symptoms: erythema, induration (hardening of tissue), heat, burning, and itching and microscopically by a significant influx of mainly eosinophils and mononuclear cells
- Can develop into sinusitis, auditory tube dysfunction, hyposmia (loss of smell), sleep disturbances, chronic mouth breathing, asthma exacerbations
67
How is allergic rhinitis treated
- Through the use of drugs that target histamine
-Antihistamines block histamine receptors
68
What does blocking mean
Binding to a receptor with no biological response
69
Histamine
- A bioactive amine packaged in dense intracellular granules
- Mast cells are known to release it
- When released bind to histamine receptors
-H1, H2, H3
70
Three types of histamine receptors
- H1: smooth muscle of vascular system, bronchial tree, digestive tract, nasal glands
Causes allergies, allergic reactions
- H2: the lining of stomach, produce gastric acid
Blocking the receptors reduces acidity of gastric contents
- H3: found in CNS, involved in releasing neurotransmitters like dopamine…
No current therapeutic products
71
1st generations antihistamines
- Block H1 receptors
- Shorter acting, cause more drowsiness, and work faster then 2nd gen
- Used mostly to treat allergic response but can be used for sleep aid
- Diphenhydramine and chlorpheniramine are most common
- Significant sedation
72
2nd Generation antihistamines
- Block H1 receptors
- Longer acting (12-24h), less sedating, take longer to start working then gen 1
- Safe to use daily for years
- Take daily to prevent symptoms during troubling season
- Not specific for antigen
