Term
| what is clonal deletion? explain the process. |
|
Definition
| Clonal deletion is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes |
|
|
Term
| what is humoral mediated immunity? explain the process |
|
Definition
| antibody mediated immunity. Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation and memory cell generation |
|
|
Term
| explain the IGM-IGG acquired immunity response. |
|
Definition
IgM serves as the B cell receptor for antigen attachment and is produced in the early stages of plasma cell
response. IgG,the most abundant immunoglobulin in the blood, is
produced copiously when the body is subsequently exposed to the same antigen. |
|
|
Term
| So an antigen is seen by a B cell. Does it just start pumping out antibodes right away, or does it need some assistance? |
|
Definition
T-dependent antigens,which are typically protein antigens, do not directly stimulate the production of antibody without the
help of a special type of T cell known as a helper T cell. The majority of antigens to which B cells respond are T-dependent antigens. |
|
|
Term
| when t helper cells get turned on, what do they do? |
|
Definition
| they pump out t cell clones and memory cells. |
|
|
Term
| what is cell mediated immunity? |
|
Definition
| consists of t helper cells and cytotoxic t cells. helper cells recognize MHC II on APC, and then pump out t cell clones, memory cells, and cytokines. Cytotoxic t cells, however, recognize MHC I which can cause the activation of perforin or apoptosis. |
|
|
Term
| what are the two types of T-cells? what do they primarily do? |
|
Definition
| t helper cells recognize MHC II on APC, and then pump out t cell clones, memory cells, and cytokines. Cytotoxic t cells, however, recognize MHC I which can cause the activation of perforin or apoptosis. |
|
|
Term
| Which type of cells are calssified as APC's? |
|
Definition
| dendritic cells, macrophages, and b cells. |
|
|
Term
| When t helper cell releases cytokines, what are some possible effects? |
|
Definition
| assist in production of antibodies, activate macrophages and NK cells, activate cytotoxic t cells |
|
|
Term
| where are MHC 1 platforms? |
|
Definition
|
|
Term
| what do cytotoxic t cells recognize? |
|
Definition
| antigens on MHC 1 platforms |
|
|
Term
| what can happen when a cytotoxic t cell recognizes an abnormal MHC I? |
|
Definition
| transplant rejection, activation of perforin, or induction of apoptosis |
|
|
Term
| how do cytotoxic t cells help in fighting cancer? |
|
Definition
| cancer can cause a fucked up MHC I, which if a cytotoxic t cell sees, it will destroy. |
|
|
Term
| difference of NK cell vs cytotoxic t cell |
|
Definition
| NK are not specific, Tc cells are very specific |
|
|
Term
| what is a suppressor T cell and what is its function? |
|
Definition
| it disarms Th, Tc, and B cells. This prevents autoreactivity. it is thought that dysfunction of suppressor t cells could initiate development of autoimmune dissorders |
|
|
Term
| when a virus infects a cell, and it starts making virus proteins, how do we recognize that? |
|
Definition
| some viral proteins will attach to MHC I |
|
|
Term
| pg 324 fig 12-13. exposure to a |
|
Definition
|
|
Term
| when a B cell recognizes a pathogen, it does 2 things. what are they? |
|
Definition
| produces plasma cells (which generate antibodies) and memory B cells ( future long term immunity.) |
|
|
Term
| What are dendritic cells? are they APC's? do they have MHC II. |
|
Definition
they are APC's with MHC II.
1.bone-myeloid, monocyte, lymphoid derivatives
maturation - stellate in peripheral tissues
activation with antigen contact
follicular dendritic cells -whole AB-antigen complex
presentation
T-cell tolerance - eliminate auto-reactive cells |
|
|
Term
| what is the general structure and function of the lymphoid tissues? |
|
Definition
compartmentalized tissue.
large collection of lymphocytes
sample plasma/lymph for invading
pathogens
communication to blood/lymph |
|
|
Term
| what are the primary lymphoid tissues? |
|
Definition
B- and T-cell production (almost
to maturity)
Thymus - T-cell replication
weak self MHC recognition
elimination of strong self MHC |
|
|
Term
| what are the secondary lymphoid structures? |
|
Definition
peripheral aggregation (lymph
nodes, spleen, MALTs)
lymphocyte-antigen interaction |
|
|
Term
| do t cells have strong or weak MHC recognition? what happens when it is strong? |
|
Definition
| weak. if its strong, it gets deleted. |
|
|
Term
|
Definition
| mucosal associated lymphoid tissue. |
|
|
Term
| explain the general concept of blood typing. |
|
Definition
| antigens are produced on RBC's. |
|
|
Term
| if you have type A blood, what type of antibodies do you have circulating? |
|
Definition
|
|
Term
| if you have type AB blood, what type of antibodies do you have circulating? |
|
Definition
| neither A nor B antibodies |
|
|
Term
| if you have type O blood, what type of antibodies do you have circulating? |
|
Definition
|
|
Term
| what happens if you get the wrong blood type? |
|
Definition
| your antibodies will attach and agglutinins are formed. |
|
|
Term
|
Definition
- Positive (+) if present on RBCs
Negative (-) if not
Operates similar to regular antibodies
No ABs generally developed if Rh+ or Rh-
ABs formed with transfusion of Rh+ blood to someone
with Rh- |
|
|
Term
| if you are Rh positive, do you have the protein? if you are negative ? |
|
Definition
|
|
Term
| antibodies get formed for Rh factor when? |
|
Definition
| it happens when Rh+ blood is seen by an Rh- person, they will form antibodies to it. |
|
|
Term
|
Definition
|
|
Term
| what are the two types of cell death? |
|
Definition
necrosis - swelling, protein denaturation, organelle breakdown "explode"
apoptosis - cell fragmentation, chromatic condensation, programmed "implode" |
|
|
Term
| subthreshold stressors initiate "positve" adaptations. what happens if the stress is above the threshold? |
|
Definition
| suprathreshold challeneges may cause visible cell damage, repeated may cause irreversible damage or death |
|
|
Term
| cell injury cause: primary hypoxia. this can cause what? |
|
Definition
| decreased blood supply - ischemia |
|
|
Term
| can immunological reactions cause hypoxia? |
|
Definition
| i think so? nearly all inflammation accompanied by healthy tissue destruction |
|
|
Term
| what are the 4 general principles of cellular injury? |
|
Definition
Four intracellular systems are vulnerable
Cell membrane (maintenance of intracellular environment)
ATP generation
Protein synthesis
Genetic integrity |
|
|
Term
| what are reactive oxygen species? |
|
Definition
| they are chemically reactive molecules containing oxygen. they are a normal product of O2 metabolism, however,during times of environmental stress, ROS levels can increase dramatically and cause significant cell damage. |
|
|
Term
| what would high intracellular CA+2 cause injury? |
|
Definition
|
|
Term
| would morphological changes happen before or after function is lost? |
|
Definition
|
|
Term
| if we lose the Na/K pump because we don't have ATP, what happens? |
|
Definition
| we get a net inflow of water into the cell because we have open ion flow. our membrane is depolarized, so all those voltage gated channels are just wide open. |
|
|
Term
| if cytochrome c leaks out of the mitochondria into the cytoplasm, what happens? |
|
Definition
| can cause apoptosis, protease activation, or lipid peroxidation |
|
|
Term
Due to ischemia, what are some consequences of cessation of ATP
generation? |
|
Definition
decreased Na-K pump,
cell size increases because we can't power the pump. membrane is depolarized, voltage gated channels stay open, and Na+ comes into the cell, bringing water with it.
exhaustion of intrinsic
cellular/tissue
substrates
Anaerobic glycolysis –
decreased pH -reduced protein
synthesis |
|
|
Term
| what is an ischemic reperfusion injury? |
|
Definition
| Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function |
|
|
Term
| what are the free radical special, why are they bad, and what does your body have to combat them? |
|
Definition
Single unpaired electron (unstable)
Attack nucleic acids, crosslink proteins/membrane
structures
Mitigated by Superoxide Dismutase, Antioxidants |
|
|
Term
| what happens when you have mercury in your cell? |
|
Definition
| inhibits ATPase transport |
|
|
Term
| What are p-450 mixed function oxidases (smooeth ER in liver). |
|
Definition
| cranked up in reaction to benign chemicals like alcohol or barbituates. if their levels are high, membrane phospholipids can be peroxidized, decreased protein ER,sER swelling, rER breakdown. inability to facilitate lipoprotein secretion which leads to fatty liver disease |
|
|
Term
|
Definition
| cell shrinkage/loss of cell substance. this is a change in balance between synthesis and degradation. so we get increased lysosomal degradation, ubiquitin-proteasome pathways, and autophagic vacuoles (lipofuscin). |
|
|
Term
| what are some causes of atrophy? |
|
Definition
| loss of blood supply, denervation, immobilization, loss of hormonal stimulation |
|
|
Term
|
Definition
| a stress or heath shock protein that tags proteins that get broken down by proteosomes. |
|
|
Term
|
Definition
| Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments. |
|
|
Term
| what is hypertrophy vs hyperplasia? |
|
Definition
| increase in cell size vs increase in cell number |
|
|
Term
| does skeletal muscle undergo hyperplasia? |
|
Definition
|
|
Term
| skeletal muscle hypertrophy, what are some factors involved? |
|
Definition
| more proteins/myofilaments but no increase in workload per unit, reactivate quiescent genes, mechanical or trophic triggers |
|
|
Term
| what is one example of metaplasia? |
|
Definition
| from columnary to squamous transformation of epithelial cells in the lining of the lungs in response to smoking. the cell wanted to get more protection (which it did) but it decreased function. |
|
|
Term
| subcellular responses - what is lysosomal catabolism? heterophagy vs autophagy |
|
Definition
|
|
Term
| what are some smooth ER/mitochondrial changes in response to hypertrophy or atrophy? |
|
Definition
|
|
Term
| when do we get Cytoskeletal abnormalities? |
|
Definition
Architecture, transport, cell
motility, phagocytosis |
|
|
Term
| when do we get Induction of heat shock proteins? |
|
Definition
Protein folding, disaggregation,
Tagging injured proteins
Misfolded proteins |
|
|
Term
| what happens when a stress protein sees a misfolded protein? |
|
Definition
| if ubiquitin sees it, it gets tagged and sent to the proteosome for COMPLETE AND UTTER DESTRUCTION |
|
|
Term
| what happens when ubiquitin sees a protein that is beyond repair? |
|
Definition
| ubiquitin tags it and then sends it to the proteosome for degradation. |
|
|
Term
| what are some misfolded protein diseases? |
|
Definition
| alzheimers and mad cow disease (ceutzfeldt-Jakob disease) |
|
|
Term
| what are some examples of intracellular accumulations? |
|
Definition
| a normal cell becoming a fatty cell, a cell filling up with a misfolded or mistransported protein. ingestion of idigestable material (tar). lysosomal disease causing accumulation of endogenous cell waste. |
|
|
Term
| what are some qualities of reversible cell damage vs irreversible cell damage? |
|
Definition
----------Reversible
Cell and mitochondrial swelling
Lipid vacuoles
Membrane blebbing, loosening
of attachments
Rribosomal detachment
Disaggregation of granular
nuclear elements
------- Irreversible
Extensive membrane damage
Lysosomal swelling
Vacuolization/ Ca2+
accumulation in mitochondria |
|
|
Term
|
Definition
| morphological changes that follow cell death. there is enzymatic digestion, protein denaturation, eventual vacuolization and calcification. |
|
|
Term
| what is coagulative necrosis? |
|
Definition
Basic structure preserved, eventually
removed
hypoxic injury |
|
|
Term
| what is liquefactive necrosis? |
|
Definition
Focal bacterial/fungal infection
(leukocyte attraction)
Central nervous system death |
|
|
Term
| what is gangregnous necrosis? |
|
Definition
–ischemic,
coagulative with liquefaction |
|
|
Term
| what is caseous necrosis? |
|
Definition
Found with tuberculosis (“cheesy”
appearance)
Obliterated structure |
|
|
Term
|
Definition
Typically with pancreatitis
Destruction of cell membranes
with enzyme release |
|
|
Term
| what is fibrinoid necrosis? |
|
Definition
Fibrin-like appearance
(coagulation)
antigen-antibody deposition in
vascular walls
Apoptosis
Cellular suicide, “pre-programmed”
cell death
normal development
hormonal, growth factor dependent
deletion of autoreactive or tumor
cells
mild injuries (heat shock protein
mediated)
Typical single cells, clusters of cells
DNA condensation, fragments
endonuclease, protease activation
no inflammation
cytoplasmic buds (apoptotic bodies)
- Phagocytosis
Cellular Aging
Progressive accumulation of sublethal injury
and diminished function
Decreased mitochondrial oxidative phosphorylation
Decreased protein synthesis, structural abnormalities
Intrinsic cellular aging
Finite number of replications
Incomplete replication of chromosome ends
Clock gene
“Wear and tear”
free radical damage
post-translation |
|
|
Term
| where do the parts of the apoptotic cell eventually go? |
|
Definition
| they get eaten by phagocytes. |
|
|
Term
| what are some times we see apoptosis in the body? |
|
Definition
| in normal development and.... |
|
|
Term
| is there inflammation with apoptosis? |
|
Definition
|
|
Term
| what are three factors in cellular aging? |
|
Definition
progressive accumulation of sublethal injury and diminished function
intrinsic cellular aging
"wear and tear" |
|
|
Term
| Afterhyperpolarization - whats up with that? |
|
Definition
| well we get potassium flowing in, but calcium flows in as well, which binds to some potassium channels and keeps them open. |
|
|
Term
| cascade for hypoxic damage? |
|
Definition
| decease in O2 --> decrease ATP generation --> decrease in Na-K pump function (leading to more Na+/ca ions flowing in) --> cell swelling AND depolarization leading to activation of voltage gated Na+ and Ca+2 channels as well. --> intracellular messengers are turned on by Ca+2 --> mitochondrial damage (cytochrome c, apoptosis) --> decreased ATP |
|
|
Term
| what are the phases of inflammation? |
|
Definition
| initiation, amplification, termination |
|
|
Term
| what happens during the initiation phase of inflammation? |
|
Definition
Structural changesleading to increased blood flow and extravasation
Emigration of immune cells to neutralize damage(chemotaxis) |
|
|
Term
| what happens during the amplification phase of inflammation? |
|
Definition
lification
Elevated cellular metabolism, release of inflammatory mediators
Inflammatory mediators can also cause elevated temperature, damage
tissue |
|
|
Term
| what happens during the termination phase of inflammation? |
|
Definition
nhibition, dissipation of mediators
Growth factors will promote cell proliferationand repair |
|
|
Term
| what are some difference between acute and chronic inflammation? |
|
Definition
| acute tends to be an immediate and early response to tissue injury. vasodilation and vascular leakage and edema, then leukocyte emigration (mostly PMN's - 2 to 6 hours). chronic inflammation tends to include Macrophage accumulation(24-48 hrs) and lymphocytes (5-7 days);Proliferation of fibroblasts and angiogenesis(weeks to months |
|
|
Term
| what are the cardinal signs of inflammation? |
|
Definition
Rubor - increased blood flow
Tumor - fluid accumulation
Calor - increased blood flow-cytokine release (increase body temp)
Dolor - (pain)chemical mediators, nerve compression?
functio laesa - loss of function |
|
|
Term
|
Definition
| transudate is protein poor (mainly water) exudate is protein rich |
|
|
Term
|
Definition
| for every 10 degree celsius increase in temperature, you get 2x the reaction rate in your body. |
|
|
Term
| Describe the process of inflammatory vasodilation |
|
Definition
| actually its brief vasoconstriction followed by vasodilation. this is caused by chemical triggers, mainly histamine produced by degranulating mast cells (basophills in CT). Open microvascular beds |
|
|
Term
| describe vascular leakage caused by the immediate transient response |
|
Definition
Initiated by histamines,
bradykinins, leukotrienes within
15 – 30 min.
Endothelial cell contraction
widens intercellular gapsof
venules (not arterioles,
capillaries)
Cytoskeleton reorganization
through TNF, IL-1 (both cytokines)
4 – 6 hrs post injury |
|
|
Term
| describe vascular leakage through immediate sustained responses |
|
Definition
| direct endothelial damage from heath or UV injury causes leakiness |
|
|
Term
| describe vascular leakage by delayed prolonged leakage |
|
Definition
| caused by bacterial toxins |
|
|
Term
| describe vascular leakage by leukocyte dependent injury |
|
Definition
Mostly in venules of
pulmonary capillaries
Release of toxic oxygen
species and proteolysis |
|
|
Term
| describe vascular leakage by transcytosis |
|
Definition
| intracellular vesicular pathways (VEGF) |
|
|
Term
| describe vascular leakage by angiogenesis |
|
Definition
| new blood vessels may be leaky (late) |
|
|
Term
| leukocyte emigration happens through the sequence of what 4 events? |
|
Definition
margination and rolling
adhesion
transmigration (diapedesis)
chemotaxis and activation |
|
|
Term
| what happens during margination and rolling of leukocytes? |
|
Definition
| leukocytes migrate towards the sides of post capillary venules. then expression of complementary surface adhesion molecules (selectins)caused by histamine and thrombin allow them to stick |
|
|
Term
| where do selectins get expressed? |
|
Definition
| on the surface of endothelial cells AND on the surface of WBCs. selectins bind to selectins and we get ROLLING |
|
|
Term
| describe the process of leukocyte adhesion. |
|
Definition
| so the leukocyte has p-selectin expressed on its membrane, but these proteins need to bind to the endothelial wall to adhere and stop. luckily, release of cytokines at the injury site cause expression of p-selectin in the endothelial wall. the rolling finally stops and the leukocyte has Cell Adhesion Molecules (CAMS) that bind to integrins. |
|
|
Term
| describe the process of transmigration or diapedesis |
|
Definition
One type of CAM – (platelet
endothelial cell adhesion
molecules or PECAM –1) initiates
transmigration
Must then cross basement
membrane |
|
|
Term
| describe leukocyte chemotaxis. |
|
Definition
Leukocytes follow chemical gradient to site of injury(chemotaxis)
Soluble bacterial products
Complement components (C5a)
Cytokines (chemokine family e.g., IL-8)
Chemotactic agents bind surface receptors
calcium mobilization, assembly of cytoskeletal contractile elements
extend pseudopods with surface adhesion molecules (integrins) |
|
|
Term
| describe leukocyte activation. |
|
Definition
1.. Cytokine binding to Gprotein receptor
2. Phospholipase C (PIP2
to
DAG and IP3
)
3. IP
3
-induced increased IC
Ca2+from ER
4. DAG activation of PKC –
phosphorylation
5. Net effects:
Pseudopodia
Increased integrin
affinity
Secretion/degranulation
Arachidonic aci |
|
|
Term
| describe phagocytosis and degranulation in inflammation |
|
Definition
BCs recognize and
attach bacteria
use of opsonins
complement system or
antibodies
Engulf (form phagocytic
vacuole)
Triggers an oxidative
burst
formation of vacuole
which fuses with
lysosome (phagolysosome) |
|
|
Term
| describe degradation and clean up of the inflammatory response |
|
Definition
Reactive end-products typicallyonly active within
phagolysosome –can overflow
Hydrogen peroxide broken down to water and
oxygen by catalase
Dead microorganisms degraded by lysosomal acid
hydrolases
Lysozyme destroys cell walls
Lipases, proteases, RNAases, DNAases
Residual body with indigestible material remains |
|
|
Term
| what are some chemical mediators of inflammation? |
|
Definition
Plasma-derived:
Complement, kinins, coagulation factors
Many in “pro-form” requiring activation (enzymatic
cleavage)
Cell-derived:
Preformed, sequestered and released (mast cell –
histamine, platelet - serotonin)
Synthesized as needed (prostaglandin, cytokines,
leukotrienes) |
|
|
Term
| what are some properties of histamine? |
|
Definition
causes vasodilation, EC contraction
Released by mast cells, platelets, immune reactions |
|
|
Term
| what are some properties of serotonin? |
|
Definition
Vasodilatory
Triggered by platelet aggregation |
|
|
Term
| what are some properties of the neuropeptides like substance P? |
|
Definition
Regulates vascular tone, permeability
Mediate pain responses at spinal cord dorsal horn |
|
|
Term
| describe plasma proteases and their effects on inflammation? |
|
Definition
|
|
Term
|
Definition
| converts fibrinogen to fibrin |
|
|
Term
|
Definition
| dissolves fibrin blood clots. |
|
|
Term
| what does arachadonic acid do? |
|
Definition
| forms prostaglandins and thromboxone via cyclooxygenase pathway. causes vasodilation and prolong edema. .............. |
|
|
Term
|
Definition
|
|
Term
| describe prostaglandins and thromboxane and leukotrine synthesis |
|
Definition
| prostaglandins and thromboxanes are derived arachadonic acid in the body. these are very inflammatory compounds, and many NSAIDS try to stop either prostaglandin synthesis or thromboxanes in order to stop inflammation. |
|
|
Term
| describe some properties of cytokines |
|
Definition
| polypeptides of lymphocytes, macrophages. have autocrine, paracrine, and endocrine effects. they increase endothelial cell adhesion molecule expression. theiy are endogenous pyrogens |
|
|
