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61 Cards in this Set

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What molecules are responsible for opsonization of pathogens, and act as a physiological barrier for innate immunity?
1) complement
2) Mannose-binding lectin
3) C-reactive protein (CRP)
Differences in neutrophils and macrophages:
Neutrophils - first cell to reach site of inflammation
Macrophages - longer lived than neutrophils, involved with MHC-II molecule presentation.
The barriers of the innate immune system.
1) Physical/anatomical
2) Physiological
3) Phagocytic
4) Inflammatory
What molecules play an important role in responding to viral infections?
Type 1 interferons
Cell in the innate immune response have WHAT receptors, which bind to common pathogenic "patterns", and what are some examples of these receptors?
Pattern recognition receptors (PRRs), which recognize PAMPs (pathogenic associated molecule patterns).
Example:
Toll-like receptors - membrane or endosome associated
NOD-like receptors - intracellular
What are the features of the inflammatory response:
1) Vasodilation: in capillaries, due to constriction further upstream
2) increased capillary permeability
3) influx of phagocytic cells
What are the differences in the two types of adaptive immunity?
1) Humoral - B cells and antibodies, principle defense against extracellular microbes
2) Cell mediated - T cells, defense against intracellular pathogens by promoting death of infected cell
The difference in active and passive immunity.
Active - induced by exposure of host to foreign antigen, confers response and memory
Passive - transfer of lymphocytes or antibodies to host serum. Useful for rapid resistance, does not confer memory.
Two types of passive immunity.
1) Passive humoral immunity - transfer of cell-free, antibody containing serum
2) passive cell mediated immunity - transfer of T cells
How many antigens can the adaptive immune system recognize?
10^9 - 10^11 distinct antigenic determinants
What does the BCR consist of? What is the important end?
two heavy chains and two light chains. The amino end, where the light/heavy chains pair, is the antigen binding site, making the BCR bivalent
What does the TCR consist of?
tow polypeptides (alpha and beta) that are disulfide linked, and recognizes MHC molecules.
What CD4+ T helper cells are activated, what happens?
Depends on the helper T:
TH1 cells produce cytokines that support inflammation
TH2 cells produce cytokines that promote B cell activation
Which cells are the APC cells?
Macrophages
Dendritic Cells
B cells
What are the two signals needed for lymphocyte activation?
1) binding of antigen to the BCR/TCR
2) ligand binding co-stimulatory receptor
Describe the cells that develop from hematopoietic stem cells.
1) Common Lymphoid Progenitor forms all lymphocyte cells (B, T, NK) immediately, along with dendritic cell precursor
2) Myeloid Stem cells produce colongy forming units, which go along to form monocyte, granulocytes, megakaryocyte, and erythrocyte.
Where hematopoiesis is found in different stages of development.
Early gestation - yolk sac
5th-6th week - liver and spleen
4th month - moves into bone marrow, by 7th month it's only found there
In hematopoiesis, which cells are multipotent and pluripotent.
HSC - pluriopotent
Myeloid and Lymphoid stem cells - multipotent
Antibodies against what will help you purify stem cells to inject into mice?
Sca-1
How does the body maintain stead state number of cells?
1) regulates input of cels to match attrition due to consumption or destruction
2) removal of aged, defective, or unneeded cells (necrosis or apoptosis)
Neoplastic cells that produce a single antibody are called what?
hybridomas
What are the common clusters of differentiation found on immune cells?
CD4 - T helper
CD8 - T cytoxic and sometimes NK cells
CD16/CD56 - NK cells only
CD45 - all lymphocyte types
How are TLR's activated?
Via TAK1 complex, which leads to activation to two systems: MAP kinase and NFkB, which turns on transcription of inflammation response genes.
What are 3 receptors found on macrophages?
1)LPS receptors - bind lipopolysaccharides on gram negative bacteria
2) Toll like receptors - many microbial components
3) NOD receptors - bacterial cell wall
What are the common domains in Toll receptors?
Extracellular domains - Leucine rich regions (LRR)
Intracellular domain - TIR domain because it looks similar to IL-1 receptor domain.
Describe the steps in ROS formation:
1) oxygen converted to superoxie
2) superoxide converted to hydrogen peroxide via superoxide dismutase
3) hydrogen peroxide converted to hypochlorite via myeloperoxidase
***also, NO can combine with superoxide to form peroxynitrite, very reactive.
Describe characteristics of the eosinophils and basophils.
1) Eosinophils - stain bright red with eosin, contains Charcot-Leyden crystals, important in parasitic infections and allergic response. Seen in response to some tumors
2) Basophils - stain blue with hematoxylin, have surface IgE receptors for allergic response, release granules of histamine and leukotrienes (involved in vasculature constriction)
What are the features of NK cells:
similar to T cells, but don't need to go to thymus, cytolytic, have unique cell markers (CD2, Cd16 aka IgG, CD56), produce cytokines
Where are B cells tested for self reactivity?
Stromal cells of the bone marrow, where 80-90% will be defective and undergo apoptosis. Called "negative selection" or "clonal deletion"
Where does class switching occur in B cells?
During affinity maturation of B cells, after they are activated by antigen, and in secondary lymphoid organ, like lymph nodes or spleen.
Differences in each Ab
IgA - put into secretions: saliva, tears, fluids of GI
IgG - put into blood circulation, smaller than IgM, allows it to get out into tissue
IgE - allergic response, antiparasitic
Describe stages of B cell development.
1) lymphoid progenitor
2) Pro-B cell - differentiates and binds to stromal cell with VLA$ on cell, and VCAM on stroma
3) Pre B cell forms from binding of c-Kit and SCF, and expression of IgM in
4) immature B cells - have IgM
How can B cells survive as autoreactive cells?
They can undergo receptors editing, by recombining DNA.
Describe the two classes of HLA (human leukocyte associated antigen) molecules?
MHC-I: Heavy chain with 3 domains (alpha 1/2 helices bind antigen), and alpha 3 that interacts with cell membrane. THe Beta chain is very conserved. Class 1 first small Ag
MHC-II: alpha 1 & 2 and beta 1 & 2. Fits longer Ab
What transmembrane peptides in the T cells help transduce the signal into the cell?
CD3 complex - has 2 dimeric parts and intracellular tyrosine kinase domain
What are the steps of T cell development?
1) becomes lymphoid progenitor, which becomes T cell precursor and moves to thymus
2) T cell precurosor doesn't have CD4 or CD8
3) thymus eptihelium signals T cell to become double positive (CD4/8)
4) T cell tested in thymus for the MHC it binds to most strongly
5) cell then loses one CD, becomes helper or cytoxic.
What accessory molecules bind to each other when a T cell binds to its antigen/MHC? What is there is no co-stimulatory signal?
CD28 (on T cell) and B7 (on the APC). No signal --> T cell undergoes anergy
What are present in the thymus that help prevent T cell from being autoreactive?
AIRE (autoimmune regulatory epithelium). Macrophages that digest apoptotic cells from AIRE form Hassall's corpuscles.
Difference in cortical and medula area of thymus?
cortical - sites for positive selection of t cells
medullary - sites for negative selection of t cells
What cells are important in developing mucosal immunity in Peyer's patches?
M cell
What is unique about the spleen compared to other lymph organs?
1) It has no afferent lymphatics, only receives antigens from blood
2) contain white pulp follicles with inner T cell and outer B cell ring.
3) these follicles can develop germinal centers between T/B cell border rings, and are then considered secondary follicles
4) without the spleen, we are sensitive to polysaccharide capsular bacteria
What type of endothelium do naive lymphocytes use to get into lymph nodes?
high endothelial venule
Describe parts of lymph node.
Follicles - mostly B cells, and follicular dendritic cells
Paracortical region - T cell zones
What is found in mast cells?
1) histamine
2) enzymes - tryptase, chymase ,protease
3) Lipid derived mediators - prostaglandins and leukotrienes
4) Cytokines - IL-1, IL-3, IL4, TNFa
What cells produce histamine, and how much do they make per cell?
Basophils and mast cells - they produce about 3-6 pg/cell
What pharmacodynamic effects are mediated by each histamine receptor?
H1: Pruritus, vascular permeability/vasodilation. Most antihistamines block this
H2: Gastric acid secretion. Bocked to treat gastritis
H3: Neurotransmitter
H4: Itch and Th2 cells produce cytokines that trigger allergic reaction. Up and comming immunomodulator
What is the Triple Response of Lewis?
All seemed to be caused by H1 receptor
1) Flush - local erythema causing BV dilation, red skin
2) Flare - axon reflex from direct stimulation of sensory nerves
3) Wheal - produced by increased microvascular permeability
Common allergic diseases.
Allergic rhinitis - hay fever
Atopic dermatitis - allergic eczema
Urticaria - hives
Asthma
Anaphylaxis
What are symptoms that antihistamine drugs can't treat?
can't treat late phase reactions like anaphylaxis. they are better at treating inflammation (sneezing, itching, congestion)
What are the 1st generation antihistamines mentioned? What are the downsides?
Downsides - they tend to cause sedation
1) Ethylenediamines
2) Ethalnolamines (benadryl) - rhinitis
3) Alkylamines - rhinits
4) Peperazines (atarax) - urticaria, very sedating
5) Piperidines (periactin) - rhinitis and weight gain
6) Phenothiazines (Phenegran) - antiemetic
2nd generation antihistamines mentioned?
1) Cetirizine (Zyrtec)
2) Loaratadine (Claratin)
3) Fexofenadine (allegra)
What are the topical antihistamines mentioned?
Nasal:
1) Azelastine (Asteline) - aa. bitter taste
2) Olopatadine (patanase)
Ocular
Olopatadine (patanol) - contraindications, contacts
Levocabastine (Livostin) - contraindicaitons - contacts, aa - stinging
What are H2 gastric acid antogonist drugs mentioned?
1) Ranitidine (Zantac)
2) Cimetidine (Tagamet)
What type of receptor are serotonin receptors?
Most are 7-transmembrane g-protein linked
BUT
5-HT3 is an Na-K ion channel
What is the triple response of blood pressure after serotonin infusion?
10 rapid chemoreceptor response - bradycardia and hypotension
2) hypertension due to vascular smooth muscle (5HT3 recepotrs)
3) Hypotension due to 5-HT receptors releasing NO
What is ergotism?
when alkaloids from grain infected by Claviceps cause allergic response by binding to 5-HT (serotonin) and alpha adrenergic receptors.
What ergot alkaloid medicines are used?
Migranes:
1) ergotamine
2) dihydroergotamine (DHE)
Hyperprolactinemia from pituitary turmos
1) Bromocriptine
What are some serotonin receptor agonist and antogist?
Agonist:
1) Prokinetic agents (metoclopramide) - increaes GI motility and emptying
antogist
1) Cyproheptadine - H1 antihistamine
2) Ondansetron (Zofran) - anti-nausea
What causes hereditary angiodema?
Mutation in C1-esterase inhibitor, so you get overactive complement system, minor trauma (dental surgery) leads to swelling. Mistaken for anapylaxis and given epinephrine/steroids that don't help.
What do leukotrienes do?
1) slow acting bronchioconstirctor
1) areteriolar constriction
3) increase vascular permeability, edema
What are some luekotriene inhiibotrs mentioned?
Zileuton, CysLt recpeotr antonist (singulair)