Advanced Patho Edapt Notes

Advanced Patho Edapt Notes

Week 1: Immune System

Hypersensitivity Reactions oThe immune system functions to eliminate pathogens from the body using various mechanisms Pathogens are bacteria, viruses, and other microorganisms oThese mechanisms typically create a localized inflammatory response that effectively eliminates the pathogen with minimal damage to the surrounding tissues oIndividuals also come in contact with numerous foreign bodies (plant pollen, food) oContact with these environmental antigens does not normally elicit an immune response in a majority of individuals oHowever, in predisposed individuals the immune system can mount a response to environmental antigens, resulting in tissue damage that ranges from mild irritation to life threatening anaphylactic shock oThese immune responses are referred to as allergic reactions or hypersensitivity reactions oHypersensitivity reactions can be divided into 4 categories

Type I: Allergic Reaction

oOn initial encounter with an allergen, the individual will produce IgE antibodies oOnce the allergen is cleared, the remaining IgE bind to mast cells, basophils, and eosinophils that contain receptors for IgE This process is referred to as sensitization oWhen re-exposed to to the allergen the IgE located on the sensitized cells induce immediate degranulation oDegranulation causes the release of inflammatory mediators, such as histamine, leukotrienes, and prostaglandins that result in vasodilation, bronchial smooth muscle contraction, and mucus production oType I reactions can be local or systemic Systemic reactions can result in anaphylaxis Local reactions can produce rash, hives, itching oAllergic asthma is an example of a type I reaction Type II Hypersensitivity oTissue-specific and usually occurs as a result of haptens that cause an IgG or IgM antibody mediated response oThe antibodies are specifically directed to the antigen located on the cell membrane oHaptens are small molecules that can cause an immune responses when it attaches to a protein oMacrophages are the primary effector cells of type II responses NR 507 Advanced Patho Edapt Study Guide 1 / 4

oThe type II response begins with the antibody binding to the antigen and may

cause the following:

The cell to be destroyed by the antibody Cell destruction through phagocytosis by macrophages Damage to the cell by neutrophils triggering phagocytosis Natural killer cells to release toxic substances that destroy the cell Malfunction of the cell without destruction oExamples of type II reactions Drug allergies Hemolytic anemia Blood transfusion mismatch with resulting transfusion reaction and Rh hemolytic disease Type III Immune-Complex Reaction oThe type III hypersensitivity reaction is also an antigen-antibody response oMajor difference between type II and type III responses is that in a type II response the antibody binds to the antigen on the cell surface, but in type III responses the antibody binds to the antigen in the blood or body fluids and then circulates to the tissue oType III reactions are not organ specific and use neutrophils as the primary effector cell oImmune-complex deposition (ICD) causes autoimmune diseases, which is often a complication oAs disease progresses more accumulation of immune-complexes occurs and when the body becomes overloaded the complexes are deposited in the tissues and causes inflammation as the mononuclear phagocytes, erythrocytes, and complement system fail to remove immune complexes from the blood

oExample of type III reactions: serum sickness

Type IV cell-mediated, delayed reaction oType IV hypersensitivity reactions are known as cell-mediated responses and use lymphocytes and macrophages as primary mediators oUnlike the first three type of responses, which are humoral immune functions, type IV responses are mediated by t-lymphocytes and does not use antibodies oA typical reaction from a type IV cell mediated response would be a localized contact dermatitis oWhen an individual comes in contact with the antigen, t-cells are activated and move to the area of the antigen oThe antigen is processed and presented to macrophages, leading to epidermal reactions characterized by erythema, cellular infiltration and vesicles Immunodeficiency oPrimary vs secondary immunodeficiencies Primary Less common Occur due to a defect of the development of the immune system 2 / 4

Could involve antibody deficiencies, B and T-cell deficiencies, defects in the phagocytic cells and deficiency of complement Secondary Conditions in which the immune systems become compromised because of something else Could be caused by cancer, effect from a drug (chemo that suppresses the immune system), or infections that compromise the immune system in a profound way Common secondary immunodeficiency in the US is HIV oHIV is a RNA virus that invades the body through an cell by direct contact with an individual’s blood or body secretions oHIV has a strong affinity for cells of the immune system, especially CD4+ T cells oOnce the virus invades, it replicates to cause extensive damage to the immune system oWithout a normally functioning immune system the individual becomes susceptible to opportunistic infections, cancer, neurological disease, wasting and death oBiology of cancer Cancer is another type of secondary immunodeficiency Tumor is abnormal growth resulting from uncontrolled cellular proliferation (neoplasm) Any type of cell that is capable of cell division has potential for tumors Benign or malignant Benign oGrow slowly, non invasive, well differentiated cells, grow in a well contained capsule Malignant oGrow rapidly, invasive into other tissues, poorly differentiated, not encapsulated, can spread distantly (metastasis) Carcinoma 90% of malignant tumors Epithelial cells of organ surfaces and linings Sarcomas Connective tissues (bones and muscle) Lymphomas Involve blood or lymphatic systems 4 stages

Stage 1: no evidence of metastases

Stage 2: evidence of localized invasion

Stage 3: cancer cells have spread to regional structures

Stage 4: evidence of distant metastases 3 / 4

TNM

T refers to primary tumor N = the size of the tumor (the larger the number the bigger the tumor) M refers to the extent of metastases oFormation of cancer The formation of cancer begins with cell transformation and other factors Transformation is the process whereby a normal cell becomes a cancer cell Controlled (normal) cellular proliferation involves stem cells and the cell cycle A stem cell is an immature undifferentiated cell that is capable of infinite cellular division when stimulated The cell cycle is the process whereby the stem cell undergoes the process of cell division

Cell cycle has 2 parts: interphase (23 hours) and mitosis (1 hour cycle)

Interphase oG0 quiescent phase – resting, nondividing, inactive stem cell capable of growth and proper stimulus oG1 prepatory phase – stimulated, stem cells are starting to become metabolically active oS phase – high rate of DNA replication in stimulated stem cells oG2 – preparation of cell structures for cell division Mitosis oM phase – active cell division to form 2 genetically identical daughter cells oDaughter cells can then undergo differentiation to become a mature, end-stage specialized and functional cell with a finite life span oOnce a cell has differentiated it can not normally regress Apoptosis oAging, injured, or defective cells are eliminated from the body by a natural cell death process all apoptosis Cell division, proliferation, differentiation and death (apoptosis) are strictly controlled by a number of regulatory genes to maintain and balance between cell birth rate and cell death rate Chromosomes of normal cells contain two types of regulatory genes which have necessary function in normal cells

Proto-oncogenes: code for synthesis of growth factors or GF

receptors to promote cell growth = accelerator system

Tumor suppressor genes: stop further cell growth via triggering

cellular differentiation or apoptosis = braking system

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