What are cellular bags of granules in the loose connective tissue close to the blood vessels?
When does caseous necrosis occur?
-Combination of coagulative and liquefactive necrosis
After cell damage the free calcium released activates what 4 things?
2.Phospholipases (membrane damage)
3.Proteases (cycloskeletal disassembly)
4.Endonucleases (chromatin damage)
Describe the 3 processes of cellular autodigestion?
1.Pyknosis=clumping of the nucleus
2.Karyolysis=Dissolution of nuclear structure
3.Karyohexxis=Fragmentation of the nucleus
List the cell surface receptors which chemical can bind to?
1.Pattern Recognition Receptors (PRR)
2.Pathogen Associated Molecular Patterns (PAMP)
What is a good cellular marker of cell death? What is a bad marker?
Bad=Lactate Dehydrogenase or PSA
Explain the stages of emigration of neutrophils during a SECONDARY immunity response?
2.Pavementing=to endothelial cells causing increase in permeability
3.Emigration=through diapedesis, the PMN's squeeze through to extracellular space
4.Exudating=is continuing to injury through chemotaxis
How can an immune injury occur?
-Through an inflammatory reponse
-If the cells membrane becomes altered the immune system may not recognize it and attack it (autoimmune disease)
What is the cellular response to low oxygen (hypoxia)?
-Decrease in ATP b/c mitochondria need O2
-Results in Na/K and Na/Ca pumps to fail b/c they need ATP
-Sodium accumulates within the cell causing water to go with it swelling out the cell
How does lead injure cells?
-Shuts down Vit D production
-Inhibits bone formation in children
(Could be irreversible damage b/c bone and nervous are injurred)
If a test has a high specificity, what defect could result and why?
More false negatives, especially if it is a milder form of the disease, because it is designed to test for absence of disease
What is fatty necrosis due to?
Lipases (calcification also occurs)
Where does fat necrosis occur?
Breast, Pancreas, and abdominal organs
What can cause liquefactive necrosis?
What is liquefactive necrosis due to?
Where does liquefactive necrosis occur?
Neurons and glial cells of the brain?
What is the most common type of necrosis?
What is coagulative necrosis due to?
Where does coagulative necrosis occur?
Kidneys, heart, adrenal gland
What are the consequences of necrosis?
-Loss of Fxn
-Release of intracellular proteins
What does necrosis typically result from?
What is athracosis?
Deposition of carbon dust in the lung
Where does iron come from in faulty infiltration?
RBC breaking down and forming iron
What is the Prussian blue reaction specific for?
Iron, it makes it appear blue
What do cellular accumulations result from?
Infiltration of certain molecules
What is the function of Eosin
-Stains cytoplasm of normal cells pink
What is the difference between endogenous and exogenous cellular accumulations?
Endogenous=comes from inside the cell
Exogenous=comes from outside the cell
What happens when a cell is introduced to ionizing radiation? (2 ways)
1.Penetrate through to the DNA
2.Interact w/ H2O to form free radicals which eventually bind to DNA and cause cancer
Is metaplasia pathologic?
What is an example of metaplasia?
Change from one normal cell type to another normal cell type.
Ex=simple cuboidal to simple squamous in esophagus of smokers
What cells can hyperplasia never occur in?
What is the difference between hypertrophy and hyperplasia?
-Hypertrophy is tissue enlargement resulting from an increase in cell size
-Hyperplasia is tissue enlargement resulting from an increased number of cells
What are the GENERAL steps in inflammation?
-Tissue injury occurs
-Inflammatory mediators are produced
-Emigration of neutrophils to injury
What triggers the 2nd line of defense?
Injured cells (infection, ischemia, poor nutrition)
What is the second line of defense in an immune response?
What are the examples of the physical and biochemical barriers for the first line of defense for inflammatory responses?
-Biochemical=sweat,earwax,tears (must be synthesized and secreted)
-Antimicrobial peptides and flora in the gut
In general, what is the first line of defense in an immunity response?
-Use physical and mechanical barriers and biochemical barriers
What causes atrophy
-Diminshed blood supply
Which type of cellular adaption occurs to the skeletal muscles during/after a workout?
When does hyperplasia become pathological?
When the overgrowth obstructs or interrupts normal function and development
During pregnancy, which cellular adaptation occurs to the breast epithelial cells?
Which cellular adaptation occurs when and individual has hepatectomy?
If the left ventricle is enlarged due to high blood pressure, is this hypertophy or hyperplasia?
Hypertrophy, b/c cardiac cells don't divide
(Nor do neurons skeletal muscle)
Why is dysplasia NOT etiology to cancer?
B/c it doesnt always cause cancer, it is a risk factor
In smokers, why might metaplasia occur?
-Normal cuboidal cells may not be enough to handle the smoke so they will undergo metaplasia into stratified
-Not pathological but if harmful stimulus continues dysplasia may occur
What is the difference between dystrophic and metastatic calcification?
Dystrophic=necrotic tissue attracts calcium
Metatstatic=hypercalcemia and calcium gets deposited into normal tissues
What is the cause and give an example of dystrophic and metastatic calcification?
Dystrophic= cause is necrosis
Metastatic= cause is hypercalcemia
What is fibrinous exudate and what does it indicate?
-Thick clotted exudate
-Indicates advanced inflammation
What is purulent exudate and what is it indicative of?
-Indicates a bacterial infection
What is hemmorhagic exudate and what does it indicate?
-Exudate containing blood
What is serous exudate and what is it indicative of?
-Indicative of early inflammation
Redness (vasodilation) as a sign of inflammation?
Swelling (increase in permeability and emigration) as a sign of inflammation?
Heat (vasodilation) as a sign of inflammation?
Pain (vasoactive chemicals) as a sign of inflammation?
Which phagocytic cell functions to recognize and eliminate cells infected with viruses?
Natural Killer (NK) cells
Which phagocytic cell defends against parasites and regulates vascular mediators?
What is the purpose of monocytes and macrophages?
Monocytes are produced in bone marrow and migrate to the inflammatory site, where they develop into macrophages (3 to 7 days)
What are neutrophils and when are they predominate during inflammation?
They are phagocytes that are predominant in the early inflammatory response and become a component of the purulent exudate.
What is the role of phagocytosis in the inflammatory response?
Since the purpose of inflammation is to limit the extent and severity of injury and initiate the repair process, phagocytes get rid of debris and clean the place up for this to occur
What is the process of phagocytosis?
-Margination of cells to endothelium
-Diapadesis through endothelium
-Recognize cell to be engulfed
-Engulf cell and form phagosome
-Lysosomal granules destroy target cell
What is the function of the kinin system?
-Blood vessel dilation
What is the function of the coagulation system?
-Forms fibrinous meshwork at injured or inflammation site
Which protein system in inflammation can lyse cells directly?
What is the function of monocytes?
Clean up cellular debris
What are the general functions of all the interleukins?
-Stimulate WBC production in marrow
-Growth factors for B/T cells
What form of allergy is caused by pre-exposure?
What is the deleterious effects of hypersensitivity?
What immunopathy is caused by the immune system no longer recognizing self-antigens?
What is an immune reaction to tissues of another individual?
IgE mediated-anaphylactic hypersensitivity?
Immune complex mediated hypersensitivity?
Tissue-specific reactions-cytotoxic Ab hypersensitivity?
Cell mediated-delyaed hypersensitivity?
What is Anaphlaxis the most severe response to?
What are activated to release histamine?
H1 and H2 receptors
What causes the most immediate response?
-IgE in response to environmental antigens.
When activated IgE binds to...
Fc receptors on the surface of mast cells (cytotropic antibody)
What is caused by increased dilation?
What is a nerve ending mediated response?
What is the release of histamines causing the release of fluids?
(Antihistamines help mild symptoms but NOT congestion)
What is a histamine reaction where water moves out of the vascular system at a high rate?
What causes dysrhythmias to occur in Type 1 hypersensitivity?
-Sudden increase in blood pressure causes this (Hypotension)
-NOT caused by IgE or histamine because there are no receptors on the heart
What are the 2 theories of Type 1 hypersensitivity?
2.Abnormal environmental considerations (Ex. Over protection of immune system=food allergy increase in developed countries)
What are the 3 types of type 1 hypersensitivity tests?
3.Laboratory Tests (measure of IgE circulation)
What causes desensitization to Type 1 hypersensitivity?
IgG-blocking antibodies prevent IgE from binding by blocking site
Why does it take 2 exposures for Type 1 to be activated?
1.Macrophage has to engulf antigen
2.This is presented to a lymphocyte
3.Which is presented to a plasma cell which will release antibodies and they will be systemic for 2nd exposure.
4 diseases caused by Type 1
3.Atopic Dermatitis (rashes)
How does epinephrine work to treat Type 1 reactions?
It is a B2 receptor agonist that is a very potent vasoconstrictor
What are the 2 types of histamine blockers?
How do steroids treat Type 1 reactions?
These help to calm down the immune system
What do leukotriene blockers do?
These help to shutdown the leukotriene mediators released from mast cells to reduce bronchoconstriction and prohibit the chemotaxis of inflammation
What is indicative of Type 2?
A specific cell or tissue is the target of an immune response
What are the 5 mechanisms of Type 2?
1.Cell is destroyed by antibodies and complement
2.Cell destruction through phagocytosis
3.Antigens enter systemic circulation and deposit on tissues
5.Causes target cell malfunction
What is ADCC?
Antibody-dependent cell-mediated cytotoxicity: a mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies
What is target cell malfunction?
Ex. Myasthenia gravis: autoantibodies to ACh receptors on the neuromuscular endplates block the action of ACh
What is opsonization?
This is the coating of microbes for more efficient recognition by phagocytes
What is hemolytic anemia?
Disease caused by Type 2 where antibodies target RBC's and leads to complement destruction
What Goodpasture's syndrome?
Disease caused by Type 2 that is a kidney disease where antibodies attack basement membrane proteins and inflame the merlisk
What is Graves disease?
Type 2 disease where antibodies act to release T4 by targeting the thyroid gland
What is the difference between Types 2 and 3?
Type 2: antibodies circulate freely and are tissue specific by binding to cellular antigens
Type 3: does NOT exhibit organ specificity, instead it forms intermediate immune complexes for deposition in tissues
What is serum sickness?
This is a systemic immune complex disorder that is triggered by the deposition of insoluble antigen-antibody complexes in blood vessels, joints, heart and kidney tissue.
What is the mechanism of serum sickness?
-Deposited complexes activate complement
-Increase vascular permeability
-Recruit phagocytic cells
(All of which can promote local tissue damage and edema)
What is the arthus reaction?
-It is a localized immune-complex mediated response
-It is a term used to describe localized tissue necrosis caused by immune complexes in the skin
What is SLE?
Systemic Lupus Erythematosus: multi-organ auto immune disease caused by Type 3 that causes vasculitis
What are the 4 steps of Type 3?
1.Formation of blood borne immune complexes
2.Deposition of complexes in tissues
3.Complement activation at the site of complex deposition
4.This leads to attraction of leukocytes that injure tissue/vessel
What is Poststreptococcal Glomerulonephritis?
After strep infection the bacteria secret proteins that live in the blood stream and antigens attack and can clog up the nephritis
What is Polyarteritis Nodosa?
Complexes that work on endothelial cells in blood vessels and can break off and cause embolisms
What is the major identifier of Type 4?
Does NOT involve antibodies
What is direct cell-mediated cytotoxicity?
Cytotoxic T cells (CTL's) directly kill target cells that have signal proteins from antigens and MHC's
What is the mechanism of Type 4?
-Antigen starts reaction -Macrophages and lymphocytes emigrate to the site
-Macrophages engulf antigen
What is caseating granuloma?
Caseous necrosis that has become calcified by macrophages surrounding it and adding lymphocytes until a dense membrane of connective tissue encapsulates it.
What are epithelial and giant cells indicators of?
ALWAYS chroni inflammation
What are the diseases caused by Type 4?
-Infections with mycobacterium (TB and Leprosy
What is contact dermatitis?
It is an inflammatory response of the skin that is initiated by reexposure to an allergen that a person is already sensitive too.
What is sarcoidosis?
It is a disease in which abnormal collections of chronic inflammatory granulomas form as nodules in multiple organs.
What is the mechanism of contact dermatitis?
-Skin proteins react with biologics
-First exposure takes 7-10 days to create T memory cells (NO signs)
-Second exposure takes 1-2 days to activate macrophages and lymphocytes (Signs of reaction)
What is an allergy?
Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals that are NOT normally harmful
Ex. Pollen, molds, fungi, foods, animals
What is an allergen?
Weak antigens that are non-parasitic substances that can cause a type 1 allergic reaction
What are the 2 types of allergen protection?
1.It can be contained within a particle to large to be phagocytosed
2.Protected by non-allergenic coat
What causes damage from allergies?
It is NOT the allergen, but the response that causes damage
What mediates an immediate allergic response?
1.IgE attaches to mast cells and basophils
2.These cells release histamine
What helps to combat anaphylaxis?
Epinephrine helps to shutdown vasodilation (Benadryl does NOT work)
What type is a delayed allergic response?
Ex.Skin test of tuberculosis, contact dermatitis
What regulates delayed allergic responses?
Cytokines secreted by T cells and macrophages
What is an autoimmune disease?
Cytotoxic T cells or antibodies mistakenly attack the bodies own cells
What are examples of autoimmune diseases?
Myasthenia gravis, MS, SLE, rheumatoid arthritis
What are possible explanations of autoimmune disorders?
-Genetic predisposition (related to MHC 2)
-Sex: more common in women
What are the 3 possible "triggers" of autoimmunity?
-Trauma with exposure of a self-antigen that has been hidden from immune system
-Malfunction of regulatory T cells
What is an epitope?
This is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.
What is molecular mimicry?
This is when a microbe shares an immunologic epitope (doppleganger) with the host
What is a neoantigen?
This is a tumor antigen that is presented by MHC 1/2 molecules on the surface of tumor cells
What is a hapten?
Is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein
What is a regulatory T cell?
A specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens.
What is a forbidden clone?
Lymphocytes that might have a flawed receptor that reacts with self-antigens
What autoimmune disease affects more than one organ?
SLE: Autoantibodies are attacking Nucleic acids, erythrocytes, etc.
-Deposition of complexescontaining antibodies in the cell
What is the autoimmune disease that affects the CNS?
Multiple Sclerosis (demyelination)
What are the autoimmune diseases that affect the thyroid?
Hashimoto thyroditis and Graves disease (antibodies stimulating thyroid)
What is the autoimmune disease that affects the blood?
Autoimmune hemolytic anemia
What is the autoimmune disease that affects the skin?
Pemphis vulgaris (huge pustules all over)
What is the autoimmune disease that affects the muscle?
Myasthenia Gravis (Type 2, blocks ACh in motor end plate)
What are sings of SLE?
Butterfly rash over nose, renal disease, hematologic changes
What part of drugs can show symptoms similar to SLE?
Sulfur in drugs
(Isoniazid, hydralazine, methyldopa,quinine)
What are immunosuppresive therapies?
Corticosteroids, Cytotoxic drugs, Methotrexate and Cyclosporine
What is the mechanism of AIDS?
-HIV RNA retrovirus invades T helper cells CD4+
What is alloimmuntiy?
Immune system reacts with antigens on the tissues of other genetically dissimilar members of the same species
What is tissue rejection?
This occurs when cytotoxic T cells bring about the destruction of foreign tissue in the body.
Ex. organ transplant
What is used to combat tissue rejection?
Immunosuppressive drugs that inhibit the response of T cells to cytokines
What is hyperacute graft rejection?
An immediate transplant reaction (rare)
What is Acute graft rejection?
-Cell-mediated immune response against unmatched HLA antigens.
-T cells start rejecting it
What is HLA antigens?
The human leukocyte antigen (HLA) system is the name of the major histocompatibility complex (MHC) in humans
What is chronic graft rejection?
Months or Years later, acquired damage that leads to a rejection of an organ caused by weak cell-mediated reactions against minor HLA's
What is Type A blood?
If you belong to the blood group A, you have A antigens on the surface of your red blood cells and B antibodies in your blood plasma.
What is Type B blood?
If you belong to the blood group B, you have B antigens on the surface of your red blood cells and A antibodies in your blood plasma.
What is Type AB blood?
If you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells and no A or B antibodies at all in your blood plasma.
What is Type O blood?
If you belong to the blood group 0 (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma.
What is Rh factor?
-Rh+ can accept EITHER Rh+/Rh-
-Rh- can ONLY accept Rh-
What type of of injection is given to suppress Rh+ cells from producing antibodies?
What is a primary (cogenital) immunodeficiency?
Gentic anomaly that are disorders in which part of the body's immune system is missing or does not function properly.
What is secondary (acquired) immunodeficiency?
Caused by another illness and it is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent.
Ex. chemotherapy, AIDS
What is SCID?
Severe combine immunodeficiency disorder: stem cell failure to produce T/B cells
What is DiGeorge syndrome?
T cell failure
What is selective IgA deficency?
______ are gamma globulins produced by beta-lymphocytes when antigens enter the body.
Which type of hypersensitivity reactions is IgE mediated against environmental antigens?
Type I hypersensitivity
What receptor on mast cells does IgE bind to to cause histamine release?
Everytime there is an antibody mediated tisue damage, it is always __________ damage.