Patho Test 2

Describe the alterations in immune function that occur in persons with AIDS.

-New uninfected CD4+ T cells created at a slightly slower rate than infected CD4+ cell are destroyed leading to a slow progressive decline in CD4+ cell counts. Thus there are lessened numbers of CD4+ T cells serve the normal immune functions such as, secreting cytokines to activate B cells, CD8+ T cells, and natural killer cells.

Understand the recognition systems for pathogens in innate immunity.

-Pattern recognition by Natural Killer cells: recognize evolutionarily retained patterns (pathogen-associated molecular patterns [PAMPs]) present on the surface of pathogens and in response bind to the pathogen and induce phagocytosis; PAMPs are made up of sugars, lipid molecules, proteins, and modified nucleic acids necessary for

Trace the process of hematopoiesis from stem cell to mature blood cell.

-after birth, hematopoiesis generally takes place in the bone marrow (liver & spleen before birth). -proliferation & differentiation are directed by cytokine action -pluripotent stem cell becomes lymphoid or myeloid stem cell -lymphoid stem cell become a NK, T cell or B cell progenitor -progenitor → actual NK, T cell or B cell -myeloid stem cell becomes a colony forming unit (CFU) of the following -monocyte CFU → monocyte -granulocyte CFU → eosinophil, neutrophil, or basophil -megakaryocyte CFU → megakaryocyte → platelets -erythrocyte CFU → reticulocyte → erythrocyte

Describe the mechanisms of HIV transmission and relate them to the need for public awareness and concern regarding the spread of AIDS.

-blood: blood transfusions before 1985 (when HIV screening was introduced); injection needle sharing and accidental needle sticks are a concern -sexual contact (most frequent mode of transmission): HIV infected body fluids coming into contact with mucosal membranes of the mouth, anus, and vagina; condoms are highly effective - mother to infant transmission through placenta, through breast milk, or via contact during birth; treatment with antiretrovirals decrease transmission rates here

State the virus responsible for AIDS and explain how it differs from most other viruses.

-human immunodeficiency virus (HIV): a retrovirus that attacks CD4+ T-cells (which are responsible for coordinating the immune response to infection), thus leaving the host immuno-incompetent and susceptible to severe infections caused by normally harmless organisms.

Discuss the vertical transmission of HIV from mother to child and recommended prevention measures

-mother to child HIV transmission can occur prenatally, during the L&D process through exposure to mucous membranes and blood, or postnatally through mucous membranes or breastfeeding; risk of transmission is higher if the mother has advanced HIV Dz (high viral load or low CD4+ count), prolonged rupture of membranes, or increased fetal exposure to maternal blood -women who are HIV+ should receive zidovudine (reverse transcriptase inhibitor) during pregnancy or at least during L&D; All pregnant women are recommended to be tested for HIV; should not use efavirenz (reverse transcriptase inhibitor) during first trimester (teratogen causing neural tube defects); information about risk of transmission with breast feeding (Note: the book stops short of saying the should breastfeed..just thought that was curious).

Compare the actions of the reverse transcriptase inhibitors (g., nucleoside/nucleotide analog reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors), protease inhibitors, and fusion inhibitors in terms of controlling HIV replication.

-reverse transcriptase inhibitors work to inhibit HIV replication by acting on the enzyme reverse transcriptase; some work by blocking the enzyme from adding nucleosides and some work by binding to the enzyme preventing it from acting -protease inhibitors bind to protease and inhibit its action preventing clevage of the polypeptide chain into individual proteins -fusion inhibitors are a type of entry inhibitor that blocks HIV from entering CD4+ cells all together -sense these classes all work on separate steps in HIV replication, they are often used in combinations

Describe the mechanisms and manifestations of GVHD

-three must have requirements: 1) graft contains immunologically competent cells; 2) host cells must express antigens that the graft does not have; 3) host must be immunologically compromised and incapable of mounting an effective immune response (all three of these happen when someone has a allogenic stem cell/bone marrow transplant) -donor T cells react to HLAs present on host cells (GVHD directly correlates with degree of HLA mismatching; develops in three step process- 1) activation of recipient APCs→ 2) activation, proliferation, differentiation, and migration of donor of donor T cells→ 3) target tissue destruction -40% of HLA-identical graft recipients (who were matched) develop some signs and symptoms of GVHD and require some treatment; acute GVHD develops in 1st 100 days, chronic sometime after that; CLINICAL MANIFESTATIONS: begins with maculopapular rash starting on hands and feet progressing to the entire body; GI involvement seen as nausea, anorexia, diarrhea, and abdominal pain; GI bleeding is an ominous sign; Liver Dz is common; venoocclusive Dz, drug toxicity, viral infection, iron overload, extrahepatic biliary obstruction, sepsis, and coma

Discuss the mechanisms of self-tolerance as they relate to the development of autoimmune disease.

-two fold process of central and peripheral tolerance central tolerance involves the selective elimination of autoreactive lymphocytes in the central lymphoid tissues (thymus for T cells); T cells that exhibit a high affinity to self-peptide MHC complexes are directed to undergo apoptosis (called negative selection); B cells that are autoreactive are eliminated by T cells peripheral tolerance: B cells same as central; autoreactive T cells that make out of central tissues are neutralized by a few different mechanisms: regulator type T cells are produced in the thymus that act to target and abolish the response of autoreactive T cells by interruption of IL-2 production and release autoreactive T cells in certain locations simply never come in contact with their antigen, so they remain immunologically inactive some actions by auto reactive T cells require costimulatory factors that are not strongly expressed in most normal tissues..thus in absence of a foreign material they are inert

opportunistic infections

: CD4+ cell counts less than 200/microliter place a person at a high risk of opportunistic infections involving common organisms. Illnesses become progressively more severe and more difficult to treat.

Compare normal and abnormal clotting

Abnormal clotting (hypercoagulability) comes in two basic forms, conditions leading to increased plt function and those leading to accelerated activity in the coagulation system. Predisposes you to thrombosis and vessel occlusion (art usually turbulence and plt related; ven usually flow stasis and coagulation pathway related)

Cite three general intervention methods that can be used in treatment of infectious illnesses.

Antimicrobials-which include antibiotics, antivirals, antifungals, and antiparasitics antibiotics-act in 1 of 4 ways: 1-interference with a specific step in bacterial cell wall synthesis (ex: penicillin) 2-inhibition of bacterial protein synthesis (ex:vancomycin) 3-interruption of bacterial nucleic acid synthesis (ex:ciprofloxacin) 4-interference with normal bacterial metabolism (ex:sulfaziazine) ***see table 12.4 on pg 271 intravenous immunoglobulin and cytokine therapy -supplementing or stimulating the host's immune response so that the spread of a pathogen is limited or reverse. -pathogen-specific antibodies given to the patient as an infusion to facilitate neutralization, phagocytosis, and clearance of infectious agents above and beyond the capabilities of the diseased host nonpharmacological intervention -surgical interventions: provide access to an infected site by antimicrobial agents (incision and drainage of an abscess)/cleaning of the site (debridement)/removed infected organs/tissue (appendectomy)

List the infectious agents considered to pose the highest level of bioterrorism threat.

Category A agents include: B. anthracis, Yersinia pestis (cause of the bubonic plague), Francisella tularensis (cause of tularemia), variola major virus (cause of smallpox), hemorrhagic fever viruses (ebola, marburg, etc), C. botulinum (cause of botulism)

Discuss the pathophysiology and clinical manifestations of complement disorders including hereditary angioneurotic edema

Complement system is a key part of the innate immune response. Activation occurs via one of three ways: classic, lectin-mediated, or alternative pathway. Complement system promotes chemotaxis, opsonization,and phagocytosis of pathogens and bacteriolysis; alterations to this process result in enhanced susceptibility to infectious Dzs and the development of a host of auto-immune processes Primary disorders can result from inheritance of defective autosomal recessive, autosomal dominant, or codominant traits. Most result from inappropriate activation and regulation of complement proteins (deficiencies in these proteins are rarely seen); deficiencies of complement proteins are usually seen in the lectin pathway; disorders can involve one or more proteins, receptors, and/or control molecules anywhere along the complement cascade; clinical presentation is dependent on the complement affected those from the classical pathway yield an increase of autoimmunity and infection with high-grade pathogens those from the lectin pathway are associated with increased infection from usual pathogens such as Cryptosporidium and Aspergillus Hereditary Angioneurotic Edema (HAE): rare, results from either a quantitative or qualitative deficiency of C1-inhibitor (C1-INH); autosomal dominant; C1-INH normally inhibits activated C1r and C1s as well as the early steps of the lectin pathway (also inhibits factor XIIa in the coagulation cascade; results in uncontrolled release of substances that promote vascular permeability→ spontaneous episodes of deep localized tissue swelling in sub-q tissues of the extremities, face, and torso, or submucosal tissues of the upper airway and GI tract; laryngeal edema→ airway obstruction; GI swelling→ severe nausea, vomiting and diarrhea; a macular nonpruritic erythematous rash may precede attach; HAE manifests in early childhood and severity increases into adolescence; symptoms peak after 1.5days and resolve by 3days; treatment is based on symptoms secondary complement deficiencies: occur as a result of rapid activation and turnover of complement components; manifestations depend on the components of the complement pathway that is affected

Describe the composition and functions of plasma.

Composition o A liquid, 90-91% water by weight. 6.5-8% proteins by weight, and 2% other small molecular substances. High water content allows it to hold a lot of heat. It serves as a transport mechanism vehicle for the material carried in the blood. o Albumin 54% of blood proteins § Most abundant. Does not pass through the pores in the capillary wall to enter the interstitial fluid and therefore contributes to the plasma osmotic pressure and maintenance of blood volume § Serves as carrier for certain subst and acts as a blood buffer o Globulins 38% § Alpha that transport bilirubin and steroids § Beta that transport iron and copper § Gamma constitute the antibodies of the immune system o Fibrinogen § 7% § Soluble protein that becomes the insoluble protein fibrin during blood clotting. § SERUM: plasma WITHOUT fibrinogen -Function o Plasma water serves as a transport vehicle for material carried in the blood o Transport medium, plasma carries nutrients from the GI tract and oxygen from the lungs to body cells while picking up waster products from the ells for delivery to excretory organs, o Transports hormones and facilitate the exchange of chemical mediators o Plasma can also absorb heat and distribute much of the heat that is generated in the body

State an important concept in containment of infections due to bioterrorism and global travel.

First known outbreak: October 2001 (after 9/11/2001 attack) o Contaminated envelopes delivered by US Postal Service o Bacillus anthracis à Anthrax · Pathogens categorized in three levels based risk of use, transmissibility, invasiveness and mortality rate · Aided by ease of international travel o Examples of diseases of recent concern (not necessarily bioterrorism threats) § SARS § WNV § Ebola · Rapidity with which novel or exotic diseases can be introduced into nonindigenous regions of the world and to a susceptible population. Need to maintain resources for public health surveillance and intervention.

Discuss the rationale for matching of HLA or MHC types in organ transplantation.

For a transplant to be successful, the host's immune system needs to recognize the tissue as "self." This is done through the identification of known self major histocompatibility complexes (MHC). Circulating B and T lymphocytes destroy unfamiliar peptide fragments on MHCs. HLA/MHC typing allows for an estimation of the likelihood of tissue rejection (generally, likelihood is inversely proportional to the matching of HLAs and MHCs.

Describe the purpose of blood coagulation.

Formation of a fibrin mesh network that cements platelets and other blood components together to form a clot.

type I (immediate hypersensitivity disorders)

IgE-mediated disorders; classic allergic response; allergens can be medical, environmental, or pharmaceutical; exposure through inhalation, ingestion, injection, or skin contact; severity depends on level of preexisting sensitivity and portal of entry; two cell type involved (type 2 helper T-cells [T2H] and mast cells; mast cells promote differentiation toward the T2H subtype (vs. T1H); T2H direct lymphocytes to switch class and produce IgE antibodies, they also have cytokines responsible for inducing inflammatory responses; Type I hypersensitivity reactions are dependent on IgE-mediated activation of mast cells and basophils and the subsequent release of chemical mediators of the inflammatory response initial exposure→ allergen specific IgE is produced (part of the normal humoral response)→ subsequent exposure→ multimetric cross-linkages create bridging b/t IgE antibodies→ this linking signals mast cell degradation and release of vasoactive chemical mediators

Erythrocytes

Most numerous o Small, biconcave o RBC have a large surface area and can easily deform into just about any shape to move through the small capillaries of the circulatory system. -Lifespan 120 days o Carry oxygen carrying protein, hemoglobin, that fxns in in the transport of oxygen o Have no orgranelles, they have soluble enzymes, including carbonic anhydrase, within their cytosol. This enzyme facilitates the formation of carbonic acid form carbon acid from carbon dioxide and water, which in turn dissociates into bicarbonate and hydrogen ions. Thus, erythrocytes also contribute to carbon dioxide transport and regulation of acid base balance and are considered a superior acid base buffer.

Explain the transfer of passive immunity from mother to fetus and from mother to infant during breastfeeding.

Passive immunity is immunity transferred from another another source. Maternal IgG antibodies readily cross the placenta during fetal development. After birth the neonate also receives IgG antibodies from the mother in breastmilk or colostrum. Therefore, infants are provided with some degree of protection from infection for approximately 3-6 months. Maternal IgG is effective against most microorganisms and viruses that a neonate encounters. IgA is not transferred in utero but IS transferred to the breast fed infant in colostrum. IgA antibodies are associated with mucosal members and provide local immunity for the intestinal system during early life.

Identify the differences between primary and secondary immunodeficiency disorders.

Primary: are congenital or inherited; can be sex-linked, autosomal dominant, or autosomal recessive Secondary: acquired later in life; develop as a result of other pathologic states (malnutrition, disseminated cancers, infection of the cells of the immune systems (i.e. HIV), treatment with immunosuppressive drugs (chemo, corticosteroids, transplant rejection meds)

Discuss the possible mechanisms underlying autoimmune disease.

Results from a loss of self tolerance. Exact mechanisms are unknown. Seen as a combination of environmental and genetic factors. People with autoimmune disorders exhibit susceptibility genes that act in concert with environmental factors to increase a person's risk for developing a Dz process. These factors lead to situations of -a breakdown in T cell anergy: release of costimulatory factors, failure of regulatory T cells -release of sequestered antigens: could be treated as a foreign antigens if they were not known during T cell development -molecular mimicry: exposure to a foreign antigen that is immunologically similar to autoantigen (share the same epitopes) -the development of superantigens

Describe the criteria for establishing an autoimmune basis for a disease.

Serologic assays that demonstrate antibodies against tissue antigens or cellular components are compared/correlated with physical findings during a workup.

Describe the manifestations of thrombocytopenia.

Spontaneous bleeding most often in small vessels of mucous membranes and skin (nose, mouth, GI tract, uterine cavity). Abnormal menstrual bleeding. Petechiae (pinpoint hemorrhages) and purpura in dependent areas with increased capillary pressure. Petechiae= think low plt count (not plt dysfunction). With severe plt depletion intracranial bleeding. Spleen may be enlarged in ITP d/t it being the site of plt degradation. Primary ITP (idiopathic ITP) Secondary ITP: may be associated with AIDS, systemic lupus erythematosus, antiphospholipid syndrome, chronic lymphocytic leukemia, lymphoma, hep C, heparin, quinidine

Describe the changes in the immune response that occur during the normal aging process.

The ability of the immune system to protect the body from pathogenic organisms and environmental toxins declines as a result of an overall decline in immune responsiveness. This results from changes in both cell-mediated (Tcell) and humoral (B cell) immune responses. Older adults: More susceptible to infections Have more evidence of autoimmune and immune complex disorders Have a higher incidence of cancer than do younger people Have a weakened response to immunization Comorbid conditions impair normal immune function and compromise the immune response Multifactorial cause, size of thymus diminishes to 15% or less of its max size affecting T-cell production and function. Production: There may be a decrease in the number of lymphocytes in peripheral lymphoid tissue but most common finding is a slight decrease in the proportion of T cells to other lymphocytes and a decrease in CD4 and CD8 cells. Function: Lymphocytes exhibit altered responses to antigen stimulation with an increased proportion becoming unresponsive to activation. CD4 T lymphocytes most severely affected because theres is a decreased rate of synthesis of the cytokines that stimulate the proliferation of lymphocytes and expression of the specific receptors that interact with the circulating cytokines. Actual B cell function is compromised with age, the range of antigens that can be recognized by the B cells does not change.

Define the role of the complement system in immunity and inflammation.

The complement system is a powerful effector of both innate and adaptive (humoral) immunity that allows the body to recognize infection and destroy invading organisms. The complement system consists of a group of proteins (c1-c9) that are NORMALLY present in the plasma in an INACTIVE form. Activation of the complement system is a highly regulated process, involving the sequential breakdown of proteins to generate a cascade of cleavage products that are capable of proteolytic enzyme activity. tremendous amplification occurs because the activation of one molecule at one step allows for MULTIPLE activated enzymes at the next step. Comp. activation is inhibited by proteins that are present on normal host cells; thus it actions are limited to microbes and other antigens that lack these inhibitory proteins. -The reactions of the comp system can be divided into 3 phases: Initial activation- 3 pathways to activate comp system- 1. the alternative pathway, which is activated on microbial cell surfaces in the absence of antibody and is a component of innate immunity. 2. The classical pathway- activated by certain types of antibodies bound to antigen and is part of humoral immunity. 3. the lectin pathway- activated by a plasma lectin that binds to mannose on microbes and activates the classical system pathway in the absence of antibody. The early-step inflammatory process- A central component of complement for ALL 3 pathways is the activation of the C3 protein and its enzymatic cleavage to a LARGER C3b fragment and a SMALLER C3a fragment. The smaller C3a fragment stimulate inflammation by acting as a chemoattractant for neutrophils. The larger C3b fragment becomes attached to the microbe and acts as an opsonin (molecules that coat neg. charged particles on cell membranes and enhance the recognition and binding of phagocytic cells to microorganisms) for phagocytosis. -it also acts as an enzyme to cleave C5 into 2 fragments: C5a fragment that produces vasodilation and increases vascular permeability, and a C5b fragment , which leads to the late-step membrane attack response. The late step membrane attack responses- C3b binds to other complement proteins to form an enzyme that cleaves C5, generating C5a and C5b fragments. C5a then stimulates the influx of neutrophils and the vascular phase of inflammation. The C5b fragments that remains attached to the microbe, initiates the formation of complex comp proteins C6, C7, C8, and C9 into a membrane attack complex protein, or pore, that allows fluids and ions to enter and cause cell lysis. -pathological manifestations associated with comp def. range from increased risk for infections and inflammatory tissue and autoimmune disorders that are the result of impaired activated comp. clearance.

Describe the vascular changes in an acute inflammatory response

The vascular phase of acute inflammation is characterized by changes in the small blood vessels at the site of injury. It begins with momentary vasoconstriction followed rapidly by vasodilation. Vasodilation involves the arterioles and venules with a resultant increase in capillary blood flow, causing heat and redness (two of the cardinal signs of inflammation). There is an increase in vascular permeability with outpouring of protein rich fluid (exudate) into the extravascular spaces. The loss of proteins reduces the capillary osmotic pressure and increases the interstitial osmotic pressure. This, coupled with an increase in capillary pressure, causes a marked outflow of fluid and its accumulation in the tissue spaces, producing swelling, pain, and impaired function. As fluid moves out of the vessels, stagnation of flow and clotting of blood occur.

Describe the immune mechanisms involved in allogeneic transplant rejection.

Three mechanisms (but can also be in combined form) cellular rejection: T cell-mediated; most common; host T lymphocytes recognize donor antigens as foreign (whether presented by host APCs or donor APCs)→ cytotoxic T cells attack donor tissue and APCs, at the same time helper T cells secrete cytokines calling B cells, other cytotoxic T cells, macrophages, and natural killer cells to the area→ results in increased vascular permeability and eventually graft injury humoral rejection: B-cell mediated; involves proliferation of B cells that produce antibodies against donor (either before transplant or after transplant in response to tissue antigens); can be hyperacute, occurring immediately after reperfusion, or simple acute, rejection occurring days to weeks after the transplant chronic rejection: immune-mediated rejection occurring over an extended period of time; T cells and macrophages infiltrate graft and set up a chronic immune response→ causing cellular hypertrophy and subendothelial thickening→ impaired blood supply

hypersensitivity pneumonitis (farmer's lung, aka extrinsic allergic alveolitis)

a form of inflammatory lung disease resulting from exaggerated immune response to Actinomyces (bacteria found in moldy foliage); exact mechanism not known but possibly a role of both type III and type IV immune responses

clot dissolution (fibrinolysis):

allows; blood flow to reestablish and permanent tissue repair to take place; sequence of steps controlled by activators and inhibitors; circulating plasminogen is locally converted to the active form of plasmin by activators from the vascular endothelium, liver, and kidneys; Plasmin digests fibrin strands and some clotting factors (fibrinogen, factor V, factor VII, prothrombin, and factor XII). circulating plasmin is inactivated by alpha2-plasmin inhibitor to prevent fibrinolysis on a global scale. Large amounts of plasminogen are trapped in clot formations. tissue plasminogen activator (t-PA) is slowly released from injured tissues converting it to plasmin.

type II (antibody-mediated disorders)

also called cytotoxic hypersensitivity; mediated by IgG or IgM antibodies directed against target antigens on specific host cell surfaces or tissues; target tissue determines clinical manifestations; initiated by four different processes; always initiated by binding of IgG or IgM antibody to tissue-specific antigens; Type II hypersensitivity are mediated by IgG & IgM antibodies directed against target antigens on specific host cell surfaces or tissues and result in complement-mediated phagocytosis and cellular injury -complement activated cell destruction: results from activation of the classic pathway leading to influx of ions, small molecules, and water into the cell causing lysis (1st pathway); 2nd pathway is triggering of phagocytosis by macrophages (this is the process that happens in Rh incompatibility) -antibody dependent cell cytotoxicity: uses both the innate and adaptive immune responses; mechanisms rely in the activity of nonspecific NK cells; common antiviral mechanism -complement- & antibody-mediated inflammation: antigens that are normally expressed on vessel walls or are circulating plasma are deposited on the surface of endothelial or extracellular tissues —> antibody in the tissues activates the complement cascade—>this attracts neutrophils, which instead of destroying cells by phagocytosis, undergo degranulation and release of mediators involved in the inflammatory response -binding of antibody to target cell receptors (i.e. ntoward the receptor

commensalism

an interaction in which colonizing organisms acquire nutritional needs and shelter but the host body not affected EX: microflora of the skin

mutualism

an interaction in which the microorganism and the host both derive benefits from the interaction EX: certain inhabitants of the GI tract extract nutrients from the host and secrete essential vitamin by-products of metabolism such as vitamin K

Antigen

antigen detection incorporates features of culture and serology but reduces to a fraction of time required for diagnosis. The method relies on purified antibodies to detect antigens of infectious agents in specimens obtained from the diseased host. · Genomic sequences or metabolites produced by the pathogen DNA or RNA sequences may be unique to a single agent DNA probe hybridization - small fragments of DNA are cut from the genome of a specific pathogen and labeled with compounds that allow detection polymerase chain reaction real-time PCR includes a fluorescence-labeled probe that specifically binds a target DNA

host

any organism capable of supporting the nutritional and physical growth requirements of another organism

humoral (B-cell).

associated with B-cell (used for bacterial defence) dysfunction and decreased Ig production; see recurrent infections of S. pneumoniae, H. influenzae, Staph aureus, and gram-neg organisms (i.e. Pseudomonas); viral defense is unchanged; transient hypogammaglobulinemia of infancy: deficiency in usually IgG and IGA; symptoms seen as maternal IgG levels decrease in the first 6 months of life; upper resp tract infections, lower resp infections, allergies, & allergic asthma; usually resolve in first 3 yrs primary humoral immunodeficiency disorders: results from impaired differentiation and maturation of lymphoid stem cells in the bone marrow: X-Linked Agammaglobulinemia: unresponsive to abxs therapy w/o IVIG therapy Common Variable Immunodeficiency Selective Immunoglobulin A Deficiency: most common of these; reduction of IgA (involved in neutralizing intestinal pathogens); may go on to develop CVID (one above) later in life; usually no overt symptoms; circulating levels are so low that they can have allergic reactions to blood products with high levels of IgA Immunoglobulin G Subclass Deficiency secondary humoral immunodeficiency disorders: Ig loss or decrease secondary to other conditions (i.e. malnutrition, burns, GI loss, nephrotic syndrome, malignancy, and medication side effects);

microflora

bacteria inhabiting exposed surfaces of the body

nervous system manifestations

can be peripherally acting or centrally acting -HIV Associated Neurocognitive Disorders: general umbrella term with cognitive impairment, motor dysfunction, and behavioral/psychosocial symptoms; given after exclusion of all other etiologies -toxoplasmosis: usually a reactivation of a latent T.gondii parasite infection affecting the CNS -progressive multifocal leukoencephalopathy (PML): demyelinating Dz of the white matter cause by the JC virus that attacks oligodendrocytes

Mycoplasmas

capable of independent replication; do not produce peptidoglycan cell wall and are therefore highly resistant to abx such as penicillins and cephalosporins; 3 types: Mycoplasma, Ureaplasma, Acholeplasma; Mycoplasmas are commensals in human hosts but may produce diseases such as pneumonia, genital infections, and maternally transmitted respiratory infections to infants with low birth weight

convalescent period-

characterized by the containment of infection, progressive elimination of the pathogen, repair of damaged tissue, and resolution of associated symptoms. The time required to complete this period can be days, weeks, or months. The resolution is the total elimination of a pathogen from the body without residual signs or symptoms

thrombocytes (plts)

circulating cell fragments of megakaryocytes -function to form plt plug to help control bleeding -circulate 8-9 days before being degraded by phagocytic cells

Describe the functions of the various cytokines involved in innate immunity.

cytokines are low molecular weight proteins that serve as soluble chemical messengers and mediate the interaction the interaction between immune and tissue cells. -the cytokines involved in innate immunity include: TNF-a and lymphotoxin; interferons (IFN-y, IFN-a, INF-B), the interleukins IL-1, IL-6, and IL-12; and CHEMOKINES (table 13.2). These substances modulate innate immunity by stimulating the development of cells involved in both innate and adaptive immunity, producing chemotaxis within leukocytes, stimulating acute phase protein production, and inhibiting viral replication. -once an innate immune phagocyte is activated with a pathogen, cytokines are released into the the surrounding tissue where they exert their effects. -under normal circumstances the duration of activity of cytokines is relatively short so that a prolonged immune response does not occur.

Characterize the chemical mediators that orchestrate the immune response.

cytokines generated by cells of the immune systems; can be regulatory, pro-, or anti- inflammatory; generate responses by binding to specific receptors on target cells; classes are below interleukins (ILs): produced by macrophages and lymphocytes in the presence of invading microorganisms or inflammatory activation; work to enhance the acquired immune response interferons (IFNs): produced by macrophages and T lymphocytes; primarily protect against viral infections and help modulate the inflammatory response tumor necrosis factor alpha (TNF-a): produced by macrophages; important mediator of inflammation; endogenous pyrogen; with prolonged exposure it has the ability to produce coagulation chemokines: small protein molecules that function to direct WBC migration to primary site of immune action colony stimulating factors: subset of cytokines that stimulate hematopoiesis

Immunity

defined as the body's ability to defend against specific pathogens and/or foreign substances in the initiation of disease processes. The immune system can distinguish itself from foreign substances and discriminate potentially harmful from non harmful agents. It can also defend against abnormal cells and molecules that periodically develop.

combined T and B cell disorders

diverse group of disorders resulting from mutations in many genes that influence lymphocyte development or response; leads to impaired communication between the cells of humoral and cell-mediated immune systems and failure of the adaptive immune response; severity can range from mild to ultimately fatal severity SCIDs (severe combined...): infants are lymphopenic and lack T Cells (equates to ~70% loss of circulating lymphocytes); Dz course resembles that of AIDS (failure to thrive, chronic diarrhea, and severe opportunistic infections; fatal in the first 2yrs unless they get a bone marrow transplant; disorders that are less severe d/t only diminished T cell function and B-cell antibody production are grouped together as CID (combined immunodeficiency disorders); generally still presents with recurrent infections and failure to thrive

Differentiate the mechanisms of drug-induced thrombocytopenia and idiopathic thrombocytopenia.

drug-induced: drug induces an antigen-antibody response and formation of immune complexes that cause plt destruction by complement mediated lysis; rapid fall in plt count; quinine, quinidine, and some sulfa-containing abxs idiopathic: (primary-immune thrombocytopenic purpura [ITP]) formation of antiplatelet antibodies against glycoproteins in the plt membrane; the plts are then destroyed by phagocytosis in the spleen.

Class III MHC

encode for many components of the complement system and play a role in innate immunity. The first MHC molecules discovered were called human leukocyte antigens (HLA) and so named bc they were found on the surface of wbc. HLA are major target in organ transplant rejection.

Fungi

eukaryotes; contain a membrane-bound (organized) nucleus; Serious fungal infections are usually acquired through puncture wounds or inhalation *yeasts are single celled; reproduce by budding; EX: Candida albicans is a commensal flora of the skin and mucous membranes *molds produce long, hollow, branching filaments called hyphae; EX: dermatophytes (incapable at growing at core temp of 37C so infection is limited to cooler cutaneous surfaces) such as ringworm, athlete's foot, jock itch *dimorphic fungi are yeast at one temperature and molds at another temperature (EXAMPLE: blastomycosis, histoplasmosis, coccidiomycosis)

saprophyte

free-living organisms obtaining their growth from dead or decaying organic material from the environment

Spirochetes

gram negative rods that are unique due to helical shape and long length; anaerobic; 3 types: Leptospira, Borrelia, and Treponema -Leptospires gain access to host through broken skin or mucous membranes; EX: Weil syndrome -Borrelia gain access to host through bite of an arthropod vector such as lice or ticks; EX: lyme disease, relapsing fever -Treponema spread person to person through direct contact; EX: syphilis

Leukocytes

granulocytes (neutrophils, basophils, eosinophils) Neutrophils -50-60%of all WBCs; maintain normal host defenses against invadeing substances -first to arrive at injury, originate as myeloblasts in bone marrow; move through out blood for 1-2days then into tissues for 4-8days; die after phagocytic function of cell senescence Eosinophils -1-3% of WBCs; increase in number during allergic reactions and parasitic infections -attach themselves to parasites using surface markers and then release hydrolytic enzymes to kill the parasite\ Basophils - 0.3-0.5% of WBCs -has granules that contain heparin, histamine, and other inflammatory mediators -similar to mast cells; both cell types thought to be involved in allergic and hypersensitivity reactions agranulocytes (lymphocytes, monocytes [macrophages]) lymphocytes -20-30% of WBCs function in lymph nodes and spleen in immune responses -three types (B cells, T cells, and natural killer cells [NK cells]) monocytes and macrophages - largest WBC (3-8% of WBC count) -circulates in blood 1-3days, can live in tissue for months to years -may have different name once in tissue (Kuppfer in liver, microglial in brain, histiocytes in loose connective tissue) -important in chronic inflammation and during the immune response involved in activating lymphocytes and presenting antigens to T cells

Class I & II MHC molecules

hese are responsible for encoding human leukocyte antigens (HLAs)., which are proteins found on cell surfaces and define the individual's tissue type. these surface glycoproteins that form the basis for human tissue typing. MCH polymorphisms affect immune responses as well as susceptibility to a member of diseases. It is nearly impossible for 2 people to have the same MHC profile. MHC I and II also play a role in antigen presentation, protein frags from inside the cell are displayed by MHC complex on the cell surface, allowing the immune system to differentiate between the bodies own tissue and foreign substances (unfamiliar peptide frags) and the foreign are attacked by B and T cell lymphocytes. MHC1 contain a groove that accommodates a peptide frag.

type III immune complex mediated disorders

hypersensitivity is caused by the formation of antigen-antibody immune complexes in the bloodstream, which are deposited in the vascular epithelium or extravascular tissues and which activate the complement system and induce massive inflammatory response- type III; an excessive amount of antigen leads to the formation of insoluble antigen-antibody immune complexes and subsequent generalized deposition in tissues such as blood vessels, joints, heart and kidneys→ complement cascade activation→ increased vascular permeability→ recruitment of phagocytic cells leading to generalized tissue damage and edema

Characterize the significance and function of MHC molecules.

in order for the adaptive immune response to function properly, it must be able to discriminate between self and nonself (foreign and harmful) molecules. The T-lymphocytes are designed to respond to a limitless number of of antigens and at the same time ignore self-antigens expressed on tissues. the MHC molecules allow the lymphocytes to do just this. The MHC is a large cluster of genes located on the short arm of chromosome 6. the complex occupies approx. 4 million base pairs and and contains 128 different genes , only some of which play a role in immune response. The MHC are divided into 3 classes ( I, II, III) based on their underlying function.

Describe the causes and effects of increased platelet function.

increased plt function: causes- disturbances in flow, endothelial damage, increased sensitivity of plts to aggregation and adhesion factors; smoking, atherosclerosis hyperlipidemia, elevated cholesterol, hemodynamic stress, and diabetes mellitus can predispose to vessel damage-> plt adherence-> thrombosis Thrombocytosis (plt count >1,000,000; actually getting a plt cnt this high is rare): can be reactive (secondary) or primary process; thrombopoietin in an unbound form stimulates the differentiation of megakaryocytes into plts; thrombopoietin is normally bound to circulating plts; when plt count falls more thrombopoietin is released to circulate causing differentiation (negative feedback loop); secondary-any Dz process that causes increased thrombopoietin will lead to increased plt count (tissue damage d/t surgery, infection, cancer, chronic inflammatory conditions such as Crohn's); can occur concurrently with other blood-proliferative dz such as polycythemia vera and myelogenous leukemia. primary- thrombopoietin receptor and platelet binding abnormalities can cause increased free circulating thrombopoietin levels although actual amounts of thrombopoietin in the body are normal

malignant tumors

increased risk likely d/t impaired cell-mediated immunity; as people are living longer with AIDS there are reports of increased incidence of age and gender specific malignancies (non-AIDS-defining malignancies); Kaposi Sarcoma, non-hodgkin lymphoma, HPV leading to the development of either cervical or anal carcinoma

stages of infectious disease

incubation, prodromal, acute, convalescent

Serology

indirect means of identifying infectious agents by measuring serum antibodies in the disease host. This is helpful in organisms that are difficult to culture ( M. Leprae and T. Pallidum ). A tentative diagnosis can be made if the antibody titer against a specific pathogen rises during the acute phase and falls during the convalescence phase.

Compare the progress of HIV infection in infants and children with HIV infection in adults.

infants of infected mother will usually test HIV+ when using an antibody test for ~18 months d/t lingering maternal antibodies (usually antibodies perset for only 6 months); Polymerase chain reaction (PCR) test that detects presence of the virus can be used under 18mths and requires 2 + tests to confirm the Dx. -clinical presentation in children is seen by failure to thrive, CNS abnormalities, and developmental delays; infants weigh less and are shorter; a major cause of mortality in HIV+ infants is cotransmission of pneumocystis jiroveci pneumonia (PCP)

Parasites

infect and cause diseases in humans or other animal either directly or indirectly; infected animals may then transmit disease to animals; 3 types: protozoa, helminths, arthropods *Protozoa-single celled animals with well defined nucleus and organelles; EX: amebic dysentery, malaria, giardiasis passed directly from host to host through sexual contact, contaminated water or food, or by an arthropod vector. *Helminths-worms, roundworms, tapeworms, flukes; trichinosis transmission occurs through ingestion of fertilized eggs (ova) or the penetration of the infectious larval stages through the skin, directly or with the aid of an arthropod vector. *Arthropods-ticks, mosquitos, biting flies; ectoparasites infest external body surfaces--EX: scabies, chiggers, lice, fleas--may carry bubonic plague, endemic typhus, epidemic typhus

State two conditions that contribute to increased clotting activity.

inherited defect in factor V causing the inability of the factor Va to be inactivated by protein C (making an important antithrombotic counterregulatory mechanism in effective). ~2-25% of white people carry the mutation; in people with recurrent DVT frequency of the defect can be as high as 60% increased thrombosis and coagulation can can stem from venous stasis (bed rest, immobility), MI, cancer, hyperestrogenic states, anc oral contraceptives. Cancer- many tumor cells are thought to release tissue factor molecules (combined with increased immobility and sepsis)--> increased thrombosis antiphospholipid syndrome (associated with autoantibodies (mostly IgG) directed against protein-binding phospholipids-> increased coagulation activity; mechanisms are unknown; treatment is geared at removing/reducing factors that predispose to thrombosis (smoking, estrogen-containing contraceptives, etc.)

prodromal stage

initial appearance of symptoms in the host, but the clinical presentation may be vague, including malaise, mild fever, myalgia, headache and fatigue.

Formation of the Platelet Plug

initiated when plts come into contact with the vessel wall; glycoprotein GPIIb/IIIa binds to fibrinogen and bridges plts to one another; Plt plug forms by adhesion and plt aggregation; plt receptors bind to von Willebrand factor (vWF) and to exposed collagen fibers; after activation plts shape changes to a spiny sphere allowing for aggregation; platelet aggregation inhibitors (asprin, plavix, ticlid) work here Platelets: half life of 8-12days; normal serum count is 150,000-400,000/microliter; production controlled by thrombopoietin (a protein from liver, kidneys, smooth muscle. and bone marrow); cell membrane is coated in glycoproteins (such as GPIIb/IIIa), glycosaminoglycans, and coagulation proteins; contains enzymes needed for synthesis of prostaglandins -Platelets also contain alpha and delta granules that release mediators for hemostasis after plt activation further perpetuating plt aggregation -alpha- express P-selectin (an adhesive protein) and contain fibrinogen, vWF , fibronectin, factors V and VIII, platelet derived growth factors (PDGF) and transforming growth factor-alpha. These growth factors encourage proliferation of endothelial cells, smooth muscle, and fibroblasts that help in vessel repair -delta- granules contain ADP, ATP, ionized Ca, histamine, serotonin, and epinephrine that contribute to vasoconstriction

clot retraction

is squeezing of the clot, expelling serum and joining the edges of the broken vessel. The action of actin and myosin in plts helps in this retraction. This process requires large numbers of plts. process occurs within 20-60min after clot formation.

Rickettsiaceae

live in but do not infect arthropods which then infect humans through a bite; EX: typhus and Rocky Mountain Spotted Fever

Kaposi Sarcoma

malignancy of the endothelial cells that line the blood vessels; associated with herpesvirus 8; opportunistic malignancy (seen in immunosuppressed people); most common HIV related malignancy

List the systemic manifestations of an infectious disease.

may be specific and reflective of the site of infection (i.e. diarrhea, rash, convulsions, hemorrhage, pneumonia); or they can be global manifestations and non-Dz-specific (i.e. fever, myalgia, headache, and lethargy -symptoms can be obvious (chickenpox lesions) or covert (increased white cell count)

pathogen

microorganisms so virulent that they are rarely found in the absence of disease

Western Blot test

more sensitive than the EIA; can be indeterminate during the window period before seroconversion; HIV antigens are separated based on weight and arranged on nitrocellulose paper→ serum sample is added to paper where HIV antibodies (if present) bind with the antigens→ a substrate and an enzyme are added to produce a color reaction→ colored bands corresponding to different weights of the antigens appear (if antibody present); certain combinations of these colored bands indicate a positive result; color change without meeting the combination criteria indicate indeterminate results (possibly in the window period)

wasting syndrome

nonspecific presence of chronic weakness, diarrhea, and fever; Dx of exclusion of other causes; contributing immune factors include inflammation of the GI associated lymph tissues, and cytokine dysfunction

Rickettsiaceae/Anaplasmataceae/Chlamydiaceae/Coxiella

obligate intracellular pathogens like viruses but have a peptidoglycan cell wall, reproduce asexually and contain RNA and DNA like bacteria

parasitic

only the infecting microorganism benefits from the relationship ***All microorganisms, even saprophytes and members of the normal flora, can be opportunistic pathogens when the health and immunity of the host have been severely weakened by illness, malnutrition, or medical therapy

incubation period

pathogens begin actively replicating without producing symptoms. This period can be long or short depending on certain factors: general health of the host, portal of entry and degree of infectious dose of pathogen. EX- Salmonellosis (6-24 hours), Hep. B (50-180 days)

bacteria

prokaryotes; lack an organized nucleus; primitive; contain both DNA and RNA;many transiently harbor plasmids which are circular pieces of DNA(may contain genetic info that increase virulence or abx resistance); contain both cytoplasmic membranes and cell walls-composed of peptidoglycan which is a target for many abx; bacteria prefer to stick together and produce communities called biofilms (causes 80% chronic infections); classified based on microscopic appearance--bacilli (rods), cocci (spherical), spirilla (helical); also classified according to staining of the cell: gram-positive organisms stain purple by a primary basic dye (usually crystal violet) and gram-negative organisms are NOT stained purple but are counterstained red by a second dye (safranin)

Culture

propagation of a microorganism outside of the body, usually on or in artificial growth media such as agar plates or both. Bacterial pathogen: identification is based on microscopic appearance and Gram stain reaction, shape, texture and color (morphology) of the colonies and by a panel of biochemical reactions. Chlamydiaceae and Rickettsiaceae and all human viruses are obligate intracellular pathogens and require cell culture.

Prions

protein particles that lack any kind of demonstrable genome and are able to transmit infection; slow progression, non-inflammatory neuronal degeneration leading to loss of coordination (ataxia), dementia, and death over a period ranging from months to years; Examples include: Creutzfeldt-Jakob disease, kuru, mad cow disease in bovines; they lack reproductive or metabolic functions, so current antimicrobial agents do not work

Cellular (T-cell)

result from deficiencies in one or more of the components of the cell-mediated immune response; T-cells subgroups work together to protect against fungal, protozoan, viral, and intracellular bacterial infections, to control malignant cell proliferation, and coordinate the overall immune response..defects here can lead to a wide range of responses; primary cell-mediated disorders: most sever of the primary immune disorders; produce severe viral, fungal, and opportunistic infections within the first few months of life (maternal antibodies offer no protection); from defective expression of the TCR complex, defective cytokine production, and defects in T-cell activation secondary cell-mediated disorders: more common than primary cell-mediated disorders; mostly associated with acute viral infections (i.e. measles, cytomegalovirus) and certain malignancies such as Hodgkin Dz and other lymphomas; viral infections can infect specific T-cell subgroups depleting that particular subtype leading to a loss of immune function associated with the subgroup; malignancies can lead to unregulated or depletion of a particular cell type; can also be idiopathic occurring later in life; these secondary disorders usually put people at risk from normally harmless pathogens;

Viruses

smallest obligate Bacintracellular pathogens have no organized cellular structure; consist of a protein coat (capsid) that surrounds a nucleic acid core (genome) of DNA or RNA (but never both); single stranded or double stranded; incapable of replication outside of a living cell; some viruses may be enclosed in a lipoprotein envelope--EX: herpesvirus group and paramyxoviruses (influenza and poxviruses); also categorized by size, physical characteristics, mechanisms of replication (EX: retrovirus), mode of transmission (EX: arthropod-borne virus, enterovirus), target tissue, or type of disease produced (EX; hepatitis A, B, C, D, E); viral replication Figure 12.3 on pg 256 shows various methods of viral replication: viruses may replicate in 3 ways: 1-cell lysis and death during replication EX:polio virus virus enters host cell>inserts genome into host cell chromosome>virus remains latent for a period of time>stimulus causes virus to undergo active replication and produces symptoms EX:herpesvirus oncogenesis: for example, HPV can be a precursor to cervical cancer retrovirus (HIV) replication: virus enters host cell>viral RNA genome is translated into DNA by viral enzyme, reverse transcriptase>viral DNA copy is integrated into host chromosome, and becomes latent>reactivation and replication require reversal of process>cell lysis occurs occasionally

Blood Coagulation:

stepwise process resulting in conversion of the soluble plasma protein, fibrinogen, to fibrin. Most coagulation factors are proteins synthesized in the liver. Vit K is used in synthesis of factors II, VII, IX, X, and prothrombin. Liver failure or Vit K deficiencies can lead to decreased prothrombin. Ca (factor IV) is involved in the first 2 steps in the clotting cascade. Citrate acts to deactivate Ca in stored donor blood. Coagulation is activated by either an intrinsic pathway or an extrinsic pathway; however, both are needed for normal coagulation. intrinsic pathway: slow (clots in 1-6min); activated when blood comes into contact with collagen in the injured vessel wall; begins with activation of factor XII (converts to XIIa)-->XI converts to XIa-->IX (Ca) converts to IXa-->common pathway extrinsic pathway: fast (15sec); activated when blood is exposed to tissue extracts; VII converts to VIIa-->common pathway; defects in this pathway result in less sever3e bleeding common pathway starts at activation of factor X to Xa-->prothrombin to thrombin-->fibrinogen to fibrin

Anaplasmataceae

targets immune system through WBCs; EX: sennetsu fever in Japan, Ehrlichia chaffeensis

Innate Immunity

the body's first line of defense. It is the natural resistance with which a person is born. Innate immunity consists of the skin and epithelial layers combined with the inflammatory response

infectious disease

the disease state brought about by the interaction with another organism that causes harm to the host

virulence

the disease-inducing potential

acute stage

the host experiences the maximum impact of the infectious process corresponding to rapid proliferation and dissemination of the pathogen. Toxic by-products of microbial metabolism, cell lysis, and the immune response mounted by the host combine to produce tissue damage and inflammation. Symptoms are more pronounced.

colonization

the presence and multiplication of a living organism on or within the host; does not cause harm to the host

Adaptive Immunity

the second line of defense, develops slowly over time but results in antibody development (more rapid, efficient, and targeted response) in case of continued initial exposure or subsequent exposure -both involve nonself recognition;

Vascular Constriction

transient vessel spasm constricts the vessel and reduces blood flow (can last minutes to hours). Neural reflex combined by thromboxane A2 (prostaglandin released from plts)

Chlamydiaceae

transmitted directly then replicate; EX: chlamydia the STD, chlamydia in the eye, etc

Coxiella

transmitted through contaminated milk or when animal tissue is aerosolized such as in meat processing; EX: Q fever, which is a nonspecific febrile illness with muscle aches and fever

allergic rhinitis

type 1; allergen is inhaled and deposited in the nasal mucosa→ antigen presented to T-cells by antigen presenting cell (APC)→ B-cell class switching occurs leading to increased levels of IgE→ allergen-IgE complex causes infiltration of the nasal mucosa by T2H cells, mast cells, basophils, eosinophils, and Langerhans cells causing a full cell-mediated immune response

food allergies

type I; specific food antigen comes in contact with IgE antibody present in the intestinal mucosa and stimulates local and systemic release of histamine and other cytokines producing the allergic responses

serum sickness

type III; an excessive amount of antigen leads to the formation of insoluble antigen-antibody immune complexes and subsequent generalized deposition in tissues such as blood vessels, joints, heart and kidneys→ complement cascade activation→ increased vascular permeability→ recruitment of phagocytic cells leading to generalized tissue damage and edema

Arthus reaction

type III; localized immune complex reaction associated with tissue necrosis (usually skin); caused by repeated local exposure to antigen where high levels of circulating antibodies exist; mechanisms not clearly understood; but believed to involve IgG; this is like a localized injection reaction to a drug

contact dermatitis

type IV; two phase inflammatory response; Sensitization phase- hapten captured by dendritic cells→ migrate to regional lymph nodes and stimulate T cell production, at the same time keratinocytes sense haptens and amplify local immune response→ elicitation phase- reexposure to haptin results in rapid recruitment and activation of memory-specific T cells

enzyme immunoassay (ElISA)

uses detection of antigen-antibody complexes that by and anti-human IgG antibody that binds to an enzyme..the enzyme then produces a color reaction; high false positive rates→ must be confirmed with the Western Blot test

three stages of homeostasis

vasoconstiction, platelet plug, coagulation

Describe the structure of HIV and trace its entry and steps in replication within the CD4+ T lymphocyte.

viral core of protein 24 (p24) containing two copies of the RNA genome, and enzymes (protease, reverse transcriptase, and integrase) → all surrounded by protein 17 (p17) matrix → surrounded by viral envelope of glycoproteins gp120 and gp41 viral replication sequence Attachment: gp120 binds to the CD4+'s binding site plus other surface molecules (chemokine coreceptors) → Uncoating: viral envelope fuses with CD4+ membrane uncoating the virus and releasing the viral core → DNA synthesis: RNA converted to DNA via reverse transcriptase (enzyme makes copy of RNC then makes a reverse copy leading to a double stranded DNA copy of the RNA that carries the instructions of replication) → Integration: DNA enters the nuclear envelop of the CD4+ cell with the help of the integrase enzyme and is inserted into the host cell DNA → Transcription: host cell activation causes transcription of the new DNA segment leading to a mRNA instruction form viral replication → rRNA uses mRNA to create chain of proteins and enzymes (called polyprotein); polyprotein contains components needed to construct new virus → Cleavage: protease enzyme cuts the polyprotein chain into individual proteins that make up the virus → proteins and viral RNA are released through cell budding or cell-cell fusion

metabolic disorders

wide range of metabolic and morphologic disorders are associated with HIV infection (lipoatrophy, mitochondrial disorders, lipohypertrophy, hypercholesterolemia, hypertriglyceridemia, insulin resistance, and impaired glucose tolerance; may be related to antiretroviral therapy

Describe the components of a complete blood count with differential.

•A complete blood count provides information regarding the number of blood cells and their structural and functional characteristics. •The white cell differential count is the determination of the relative proportions (percentages) of individual white cell types. -CBC: determines the number of red blood cells (RBCs), white blood cells, and platelets per unit of blood. Hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) are usually included in the CBC. MCV, MCHC, and MCH are called RBC indices.