Exam Questions 2.pdf

the five cardinal signs of inflammation 2) rubor-redness tumor-swelling D Reilly thinks cheese does lines calor-heat Y dolor-pain loss of function (functio laesa) how do leukocytes adhere to the endothelium? bloo...

the five cardinal signs of inflammation 2) rubor-redness tumor-swelling D Reilly thinks cheese does lines calor-heat Y dolor-pain loss of function (functio laesa) how do leukocytes adhere to the endothelium? blood flow slows wall shear stress decreases this allows leukocytes to assume a more peripheral position this entire process is called margination = i.e. neutrophils adhering to and aligning to vessels the cells bind and detach = this is called a rolling Pantos, Ioannis & Georgios, Patatoukas & Efstathopoulos, the cells eventually adhere by complimentary Efstathios & Katritsis, Demosthenes. (2007). In vivo wall shear stress measurements using phase-contrast adhesion molecules MRI. Expert review of cardiovascular therapy. 5. 927-38. 10.1586/14779072.5.5.927. chemotaxis after crossing the endothelium, leukocytes pass through the basement membrane and enter the extravascular tissue the cells make their way to the agent by following a chemotactic gradient chemotaxis: continued the process of leukocytes exiting the circulation and moving towards the site of tissue injury is called chemotaxis. bacterial products are chemotactic. endogenous examples include cytokines. the type of leukocytes that infiltrate depends on the type of stimulus and the age of the inflammatory response. acute inflammation is dominated by neutrophils. in contrast… viral infections: lymphocytes are the first cell hypersensitivity reactions: lymphocytes and plasma cells predominate allergic reactions: eosinophils are the main cell type. Eosinophils are a type of white blood cell and a part of the body’s innate immune system. Eosinophils protect us from allergens and infections, like parasites. Allergy, hives, parasites, autoimmune, medication effect, etc. = eosinophils acute inflammation- some definitions of the major morphologic patterns serous inflammation fibrinous inflammation suppurative inflammation abscess ulcers serous inflammation this is cell poor fluid into spaces early stages of acute inflammation a skin burn results in a blister and accumulation of serous fluid- as an example fibrinous inflammation with increased vascular permeability, larger molecules can then seep through a fibrinous exudate develops when the vascular leaks are large meningitis and pericarditis are examples fibrinous exudates are usually dissolved and cleared by macrophages. fibrinous inflammation if these are not removed, it stimulates the growth of fibroblasts and blood vessels leading to scarring, known as organization. fibrinous pericarditis as an example It is the most common inflammatory response in acute pericarditis purulent inflammation this is characterized by pus pus is an exudate with neutrophils and necrotic debris and fluid purulent and suppurative inflammation are the same the most common cause is bacteria a common example would be acute appendicitis what are abscesses? abscesses are localized collections of purulent inflammatory tissue that is confined to a space the central portion is necrosis. at the periphery there is a zone of preserved neutrophils and fibroblast. Systemic effect might include LEUKOCYTOSIS A complication of acute bacterial pneumonia what are ulcers? a local defect of the surface of an organ or tissue due to the sloughing of inflamed necrotic tissue. ulcers occur when there is tissue necrosis. a classic example of peptic ulcer disease. morphologic features of chronic inflammation mononuclear cells such as macrophages, lymphocytes and plasma cells predominate lymphocytes (T cells specifically) secrete interferon gamma to activate macrophages interferon gamma is a cytokine (mediator of inflammation) tissue destruction ensues healing by way of fibrosis Mast cells Mast cells come on the scene during: insect bites medication/drug effect allergies reactions  Types of Cellular Adaptation: Hyperplasia and Hypertrophy  Cells respond to increased demand by hyperplasia or hypertrophy, or both Hyperplasia Cells respond with cellular proliferation Hypertrophy Cells respond with cellular enlargement + Metaplasia 5  Examples of Metaplasia The most common epithelial metaplasia is columnar to squamous:  Bronchial epithelium in response to toxin exposure with cigarette smoking  Biliary tree epithelium in response to presence of stones Example of squamous to columnar: esophageal epithelium in response to repeated exposure to acidic gastric contents 17  Lung Cancer Example Metaplasia Prove O E.g., Lung Metaplastic glandular Normal squamous epithelium epithelium: esophagus 18  Manifestations of Adaptation or Sub-lethal Cell Injury: (Reversible) Intracellular Accumulations (often linked with metaplasia) These substances (metabolites) may be:  Normal  Abnormal  Endogenous  Exogenous 19  Two Major Microscopic Changes Seen With Reversible Cell Injury  Cellular swelling - cytoplasm  Fatty change 1 things you'll Swelling see first.. 2 Fatty Deposit Important !! 24  *future of Health care? Basic Cellular And Molecular Factors That Contribute To Irreversible Cell Injury And Death A common underlying process leading to cell death: Hypoxia  Morphologic Changes With Necrosis * knowthis - Light Microscopy Kidney Coagulative Brain : + Heart Liquifactory : Lung : caseous Fat : Pancrease Breast Fibrinoid : Vessels  DIest Patterns of Tissue Necrosis When large numbers of cells undergo necrosis, the whole tissue or organ is described as necrotic Several morphologically distinct patterns of necrosis have been identified that may give clues about the underlying cause This is important ! * Cardic Coagulative Necrosis Cardiac myocytes The basic architecture of the tissue is preserved for a few days. The injury denatures structural and enzymatic enzymes. Eosinophilic, anucleate cells may persist for days to weeks. Ischemia frequently leads to coagulative necrosis. A localized area of coagulative necrosis is an infarct. ** Liquefactive Necrosis Digestion of the dead cells occurs, resulting in the replacement of tissue with a liquid, viscous mass. This type of necrosis is seen with bacterial and fungal infections, with transformation of the tissue into pus. This type of necrosis is also seen with ischemic damage to the brain, as shown above.  “Dry” Gangrenous Necrosis Term commonly applied in clinical practice for limbs or sections of bowel that have lost their blood supply and undergone coagulative necrosis. With infection and the formation of liquefactive necrosis, it is termed “wet gangrene”.  "Cheesey" Lung* Think - Caseous Necrosis Encountered most often with tuberculosis Infection. There is a friable white “cheese-like” area of necrosis containing foci of inflammation known as granulomas.  + Pancreas DFat Necrosis Breast A Focal areas of fat destruction. A common location for this to occur is in the inflamed pancreas (pancreatitis), where pancreatic enzymes leak from injured cells. Trauma to breast another example. Fat Necrosis With Dystrophic - Calcification - From injury Patient with prior breast biopsy resulting in fat necrosis D A Vessels Fibrinoid Necrosis Usually seen in immune reactions involving blood vessels  Two types of Immunity INNATE IMMUNITY ACQUIRED IMMUNITY (nonspecific) (specific) – Basic elements we are – More specialized elements that born with, which are we acquire after birth always available on – Present only in vertebrates short notice – Only present if the individual – Include body surfaces, has had prior contact with a mucous membranes, the given agent cough reflex, even pH – Initial contact represents and fever “immunization”, which triggers – phagocytic cells such as activation of lymphocytes and macrophages, production of antibodies granulocytes, natural – Results in immunity to killer (NK) cells subsequent attack by the same agent  Hematopoiesis: the developmentFigure 1-3 of blood and blood-derived cells o * xam Question cells - what void US. frommod lineage  Antigen-Presenting Cells Called antigen presenting cells because they can take up and digest antigens such as pathogens and foreign protein. The digested material result in peptides that are displayed on MHC class II molecules and are presented to CD4 slide Important positive T-cells. & Very S + adaptive immunity innate between APC-link Question Ex Q: How do immune cells find pathogens in order to respond to them? A: Lymphocyte Recirculation -Lymph picks up pathogens and debris as well as macrophages and/or DC that have phagocytosed pathogens -Bring them to the nearest lymph node (called the draining lymph node) -A specific immune response can ensue The Big Picture from innate ATransitions to adaptive out chew upt spit "APCs Immunogens and Antigens Requirements for Immunogenicity 1) Foreignness - Do not respond to self (except: autoimmune diseases). - More foreign --> more immunogenic 2) Sizes (molecular weight) - > 6kD are generally immunogenic - < 1kD are not (ie. penicillin, aspirin) 3) Chemical Complexity - Homopolymers of amino acid are not immunogenic. Immunogens and Antigens Requirements for Immunogenicity 4) Degradability Antigen Processing - Susceptibility to enzymatic degradation - Stability for antigen presentation 5) Dosages - Insufficient doses may cause tolerance Don't respond - - Repeated administration may be required for a sufficient immune response Immunogens and Antigens Major Classes of Antigens Carbohydrates (polysaccharides) - immunogenic as part of glycoproteins Lipid - rarely immunogenic Nucleic Acid - not immunogenic - systemic lupus erythematosus (SLE) Proteins, Glycoproteins - very immunogenic Immunogens and Antigens Cross-reactivity - ability of an antibody, specific for one antigen, to react with a second antigen. - most antibodies cross-react with closely related antigens Shared epitopes Tetanus Toxoid Function & Structure of Antibodies Five major classes of antibody X Function & Structure of Antibodies Five major classes of antibody values garded Function & Structure of Antibodies IgG - four subclasses (IgG1, IgG2, IgG3 and IgG4) - placental passage - opsonization Function & Structure of Antibodies IgG - Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) - activation of complement - toxin/viral neutralization - bacterial immobilization Function & Structure of Antibodies IgG Antibody levels early in life Function & Structure of Antibodies IgM - first immunoglobulin produced following infection/immunization - most efficient immunoglobulin for complement fixation Function & Structure of Antibodies IgA - mainly in secretions (tears, saliva, sweat and mucus) - abundant on respiratory and mucosal surfaces (first line defense) - antibacterial and antiviral activity Function & Structure of Antibodies IgE - mediates Type I hypersensitivity reactions - high levels during parasitic infection -  Relevant Inheritance of MHC genes = MHC genes are inherited as a set of MHC alleles (haplotype) from both parents, and they are inherited as a set. MHC gene products designated by numbers in humans eg. A1, B27, DR4. Example of a Haplotype class Answer is all genestheyall aa f m: A1; B8; Q DR3 Phenotype A1, 2; B8, 57; DR3, 4 p: 0A2; O B57; - DR4 I - Class MHC proteins are co-dominantly expressed (ie. ALL protein products are expressed) - Very important because it means some people have more diversity here than others based on the variation in the genes inherited - HLA genes can be associated positively or negatively with disease HLA-haplotypes transmitted as a block from parent to child Example Chance of 2 unrelated individuals sharing HLA identity: extremely low Chance of 2 siblings sharing HLA identity: 25% or 1/4 Both parents may have the 1 2 3 4 same allele at one locus: Child would be homozygous m: A3; B5, DR4 p: A3; B2, DR4 Child expresses 4 different HLA types HLA class I genes are expressed on all nucleated cells* Really important - Communicate to CD4 T cells ! HLA class I and II Are Expressed on professional Antigen-Presenting Cells (pAPCs) HLA class II expression can be induced by certain cytokines Interferon-gamma (IFN- ) (non-professional APCs deputized as APC) Important: polymorphism based on genes being expressed, but also in the combinatorial pairing in the class II genes Proteins are processed into peptides and said he loves this slide. loaded onto MHC molecules MHC Class I - Antigen Processing this !! and Presentation Pathway Need are making cells that Eliminatevirus CDS T Cells + the Endogenous Self-antigen antigen  * Important part MHC Class II – Exogenous Antigen Processing Pathway CD4 "T Exogenous antigen B. Association of exogenous peptide Only professional 1. Exogenous protein internalized APCs 2. Associates with acidic vessels containing proteases and peptidases 3. degraded into peptide fragments 4. CLIP out, peptide in: exchange catalyzed by HLA- DM 24  Question - Cross-presentation Dendritic cells can transfer exogenous Ag to MHC class I - allows them to activate cytotoxic T cells with antigens from extracellular sources.  that to kine CM mat * INfy : What are the causes of chronic inflammation? Persistent infections An example would be mycobacteria Mycobacteria evoke delayed type hypersensitivity reactions Mycobacteria cause a granulomatous reaction Viruses, fungi and parasites can also persist like mycobacteria Hypersensitivity diseases * allergy + autoimmune Defined as excessive and inappropriate activation of the immune system This leads to autoimmune disease An example would be multiple sclerosis Immune responses against an environmental substance are called allergic diseases Prolonged exposure to toxic agents that are either exogenous or endogenous An example would be silicosis for exogenous + asbestos  of activ. lymphos and Collection * macros. in giant cell granuloma = Other diseases where chronic inflammation Respone Immune plays a role Antibodies compliment cymphocytes Atherosclerosis Alzheimer’s soup reson A ~ Type 2 diabetes pink Macros-Biuzzing in Cancer I see mpho theliod * Rheumatoid arthritis Granulomas D "Langhan Giant Cell" X seen inTB Horseshoe shaped blue pink+ ↳ Equal Too much Pink = Dead cells = Necrosis  The cells and their mediators of chronic inflammation The main cells are macrophages, lymphocytes and plasma cells Macrophages are professional phagocytes Macrophages are activated via the classical and alternative pathways The classical pathway as activated by endotoxin The alternate pathway is activated by interleukins Once activated, macrophages secrete growth factors for angiogenesis and collagen synthesis and fibrosis. Aforegin body cells : regular nuclei scattered throughout cyto Epi macros whair/suture/filler = Foregin body giant cell rxn Lymphocytes Microbes, environmental antigens activate lymphocytes Lymphocytes amplify and propagate chronic inflammation Lymphocytes are the dominant population in chronic inflammation Lymphocytes interact with macrophages and co stimulate one another Other cells in chronic inflammation Eosinophils Question D A Parasites recruit eosinophils Eosinophils have granules that contain major basic protein Major basic protein is highly toxic to parasites Major basic protein also causes lysis of epithelial cells & Questions Mast * cell = Allergy Granulomatous inflammation Granulomas inflammation is a form of chronic inflammation It is characterized by collections of activated macrophages and lymphocytes Granulomatous inflammation sometimes has central necrosis (Doesn't have to Necrotizing or NOT Granulomatous inflammation is a cellular attempt to contain an offending agent that is difficult to eradicate Lymphocytes and macrophages are activated Macrophages gain abundant cytoplasm Macrophages begin to mimic epithelial cells Macrophages can fuse and form multinucleate giant cells * Question Tuberculosis is a granulomatous disease caused by infection with mycobacteria= necrotizing granulomas* Inflammation: General take a ways When inflammation is excessive, it can cause many diseases When inflammation is defective, it results in susceptibility to infections Inflammation recognizes malignant cells in our body and this is the target of multiple therapeutic interventions RA main cell type = lymphocytes