Module 1B Flashcards
Are immune responses and inflammation the same
- No we can have both at the same time
- An immune wo a inflammation and opposite
What do all blood cells come from
Pluripotent hematopoietic stem cells (HSCs)
Hematopoiesis (what are the cells differentiated into)
- When blood cells are exposed to cytokines and surrounding stromal cells they differentiate into
- Megakaryocytes
- Erythrocytes
Leukocytes
Megakaryocytes
Thrombocytes (platelets)
Erythrocytes
Red blood cells
Leukocytes
- White blood cells
-Includes lymphocytes, granulocytes, monocytes, macrophages, neutrophils, eosinophils
Innate immunity
- Refers to the host defense mechanisms that are immediately available on exposure to pathogens because they are always present
-Includes epithelial barriers, mucous membranes
What cells are in the innate immune system
- Granulocytes
- Mononuclear phagocytes
- Natural killer cells
-Dendritic cells
Granulocytes
- 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
Neutrophils
Phagocytize microbial invaders
Eosinophils
- Phagocytize parasites, boost immune signal
Mast cells
- Know for histamine release
Found in mucous membranes exposed to environment
Basophils
- A lot like mast cells
-Boost immune signal
Mononuclear phagocytes
- 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
Natural killer cells
- 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
Dendritic cells
- 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
Adaptive immune system
- Characterized by antigen specificity and immunological memory
-More complex process as requires antigen processing and recognition
-Takes days to develop a response
Cells in the adaptive immune system
- B cells
-T cells
B cells
- 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
Plasma cells
Short lived and secrete antibodies
Memory B cells
- 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
T cells
- 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
Cytotoxic CD8+ T cells
- Tc cells
- Destroy host cells that are infected
Helper CD4+ T cells
- Th cells
- Secrete cytokines that enhance the function of other cells to help in getting rid of the pathogen
Memory T cells
- Can persist for years and mount a quick response on re exposure
Antibody
- Is not on a plasma membrane
- Y shaped glycoprotein created by the body in response to a specific antigen
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
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….
The lymphatic system
A network of lymphatic vessels connected to lymph nodes
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\
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
Which way does the lymphatic system flow
- Only flows upwards toward the neck with rhythmic contractions of smooth muscle
Where do B and T cells travel
Both the blood and lymph
What are primary lymphoid organs responsible for
- For lymphocyte maturation and development
-Bone marrow and thymus
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
What are the maturation processes of B and T cells guided by
Interleukins
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
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
Lymph nodes
Are round specialized structures positioned along the lymphatic vessels like beads on a chain
What do swollen lymph nodes mean
sign of infection
How does lymphocyte recirculation occur
- B and T cell development in bone marrow and thymus enter blood stream
- 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
- When they reach a secondary lymphoid order they enter it
How are pathophysiology and pharmacology connected
Many different infections or diseases will all have anti inflammatory and sometimes immuno-suppressants in treatment
Type 1 diabetes mellitus
Immune mediated destruction of B cells in pancreas that secrete insulin
Rheumatoid arthritis
Immune mediated destruction of joints
Hashimoto’s thyroiditis
Immune mediated destruction of the thyroid gland
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)
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
How are antibiotics classified
Either by their structure or mechanism of action (MOA)
MOA
- Mechanism of action
-The process by which a molecule such as a drug functions to produce a pharmacological effect
Bactericidal
Drugs that kill/ destroy the bacteria entirely all by themselves
Bacteriostatic
- Drugs that slow down the growth of the bacteria
-Need to bodies immune system to dispose of the bacteria
If an individual is immunosuppressed what would they take (bacteriostatic or bactericidal)
Bactericidal
Broad spectrum antibiotics
- Drugs that are effective against a wide variety of bacteria
-Prescribed empirically when we don’t know specific pathogen
Narrow spectrum antibiotics
- Drugs that are effective against very specific microorganism or restricted group
-Prescribed when pathogen is clear
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
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
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
How do bacteria defend against penicillin
- Produce a beta lactamase (penicillinase) that breaks the beta lactam ring leaving It ineffective and causes penicillin resistance
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
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
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)
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)
What is Allergic rhinitis
- Common abnormal immune response to harmless environmental allergens
-Mediated by IgE–> histamine release from mast cells
Symptoms of allergic rhinitis
- nasal, ocular, and palatal pruritus(itching)
- paroxysmal sneezing
- Rhinorrhea
-nasal congestion
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
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
How is allergic rhinitis treated
- Through the use of drugs that target histamine
-Antihistamines block histamine receptors
What does blocking mean
Binding to a receptor with no biological response
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
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
- H2: the lining of stomach, produce gastric acid
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
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
