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Pathology(Immune Dysfunction)*


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Hypersensitivity rxn. in w/c there is delayed hypersensitivity;proliferation of antigen-specific CD4+ memory T cells,with secretion of IL-2 & other cytokines,w/c in turn recruit & stimulate phagocytic macrophages; involves cytotoxic CD8+ T lympho
Type IV(cell-mediated)
-examples(tuberculin rxn.,contact dermatitis,tumor cell killing,virally infected cell killng)
Hypersensitivity rxn. in w/c antibodies react w/ antigens that are intrinsic components of cell memb. or other structures,such as basement memb.~ direct damage,complement-mediated inc. susceptability to phagocytosis, or antibody-dependent cell-mediated c
Type II(cytotoxic)
-examples(warm antibody autoimmune hemolytic anemia,hemolytic dse. of the newborn,Goodpasture synd.,Graves dse.)
Hypersensitivity rxn. in w/c insoluble complement-bound aggregates of antigen-antibody complexes are deposited in vessel walls or on serosal surfaces or other extravascular sites;neutrophils are chemotactically attracted & release lysosomal enzymes,p
Type III(immune complex)
-examples(serum sickness,Arthus rxn., polyarteritis nodosa,SLE,immune-mediated glomerular dse.)
Cells of the immune system w/c include B cells,T cells, & natural killer cells;identified by cell-surface glycoproteins specific for both cell type & stage of differentiation
Lymphocytes w/c originate from stem cells in the BM;differentiate in the BM & peripherally(cluster in the germinal centers of lymph nodes & in lymphoid follicles of the spleen;charact. by surface immunoglobulin;15% of circulating peripheral bld.
B cells
Lymphocyte w/c originate from stem cells in BM & differentiate in the thymus;populate the paracortical & deep medullary areas of lymph nodes & periarteriolar sheaths of the spleen; 70% of circl.peripheral bld.
T cells
-subclassified into:CD4+ Tcells(60% of circulating T cells)& CD8+ Tcells(30% of circl. T cells);ratio of 2:1
Lymphocyte w/c are also called large granular lymphocytes(LGLs);15% of cirl. lymphocytes;kill tumor cells,fungi,& cells altered by viral infxn.;can lyse cells by antibody-dependent cell-mediated cytotoxicity(ADCC)
Natural Killer(NK)cells
-does not involve specific sensitization or antibody in killing of cell
Cells of the immune system w/c are derivatives of peripheral bld. monocytes;members of the mononuclear phagocytic system(MPS),secrete cytokines;process & present antigens(along w/ HLA class II antigens) to CD4+ Tcells;participate in delayed hypersens
-can directly kill tumor cells
Cells of the immune system charact. by dendritic cytoplasmic processes;express large quantities of cell surface HLA class II antigens;poorly phagocytic
Dendritc cells of lymphoid tissue
-resemble macrophages in that they are antigen presenting cells
Cells of the immune system marked by presence of Birbeck granules(tennis raquet shaped cytoplasmic structures); express HLA class II antigens;antigen presenting cells
Langerhans cells of the skin
Soluble proteins secreted by lymphocytes(lymphokines),monocytes-macrophage(monokines),& NK cells;act as effector molecules influencing the behavior of B cells,T cells,NK cells,macrophages, hematopoietic cells
Consist of about 20 plasma proteins & their products,w/c can be activated by the classic or alternative pathway to form a final product(membrane attack complex)that lyses targeted cells
Complement System
Cytokine w/c come from monocytes, macrophages,& other cells;stimulate T cell proliferation & IL-2 production
Cytokine secreted from macrophages,T cells,& NK cells w/c stimulate proliferation of T cells,B cells,& NK cells;activate monocytes
Cytokine secreted by T cells w/c acts as growth factor for tissue mast cells & hematopoietic stem cells
Cytokine secreted by T cells w/c promote growth of B cells & T cells; enhances expression of HLA class II antigen
Cytokine secreted by T cells w/c promote end-stage maturation of B cells into plasma cells
Cytokines secreted by T cells,monocytes & other cells w/c promote maturation of B & T cells;inhibits growth of fibroblast
Cytokine secreted by B cells & macrophages w/c has antiviral activity
Cytokine secreted by T cells & NK cells w/c have antiviral activity;activates macrophages;enhances expression of HLA class II antigens
Cytokine secreted from fibroblast w/c have antiviral activity
Cytokine secreted from macrophages,T cells,& NK cells w/c stimulate T cell proliferation & IL-2 production: cytotoxic to some tumor cells
Tumor Necrosis factor-alpha(TNF-alpha, cachetin)
Cytokine secreted by T cells w/c stimulate T cell proliferation & IL-2 production;cytotoxic to some tumor cells
Tumor Necrosis factor-beta(TNF-beta)
Pathway in the complement system w/c is initiated by rxn. w/ antigen-antibody complexes
Classic Pathway
-final lytic form of activated complement is the result of a series of enzymatic cleavages & recombinations of cleavage products
Pathway in the complement system initiated directly by nonimmunologic stimuli(such as invading microorganisms)leading to cleavage products that cause cell lysis
Alternate Pathway
-bypasses the initial stages of the classic pathway
A group of related proteins coded by histocompatibility genes & are located in the region of the short arm of chromosome 6,known as major histocompatibility complex(MHC);play important role in organ transplantation
Human Leukocyte Antigen(HLA)Sytstem
-referred to as HLA antigens(class I & class II)
Principal antigen involved in tissue graft rejection;include the HLA-A,HLA-B & HLA-C antigens w/c are found in almost all human cells;identified by standard serologic techniques
Class I Antigens
-serologic testing of HLA-A & HLA-B antigens are used to predict the likelihood of long term graft survival
HLA antigen found in immunocompetent cells,macrophages,dendritic cells, Langerhans cells,B cells,& some T cells;include HLA-DP,HLA-DQ,HLA-DR antigens;identified by standard serologic testing or by mixed lymphocytic rxn.
Class II Antigens
HLA antigen assoc. w/ almost 90% of cases of ankylosing spondylitis
HLA-B27 Antigen
Hypesensitivity rxn. in w/c an antigen reacts w/ IgE bound to basophils or mast cells~degranulation~release of histamine~vasoactive,smooth muscle spasm-inducing,chemotactic effects
Type I(anaphylactic)
-examples(hay fever,allergic asthma, hives,anaphylactic shock)
Laboratory findings in SLE
LE test(positive 70% of cases;replaced by more sensitve determinations),(+)test result for ANA,dec. serum complement(assoc. w/ active renal involvement),immune complexes at dermal-epidermal junct.,biologic false-positive
(BFP)test for syphilis(due to anticardiolipins)
Clinical manifestations of SLE
Fever,malaise,lymphadenopathy,weight loss,joint symptoms,skin rashes(butterfly rash),Raynaud phenomenon(vasospasm of small vessels),serosal infl.(pericarditis,pleuritis),diffuse interstitial pulmonary fibrosis, endocarditis,immune complex vasculitis, glomerular changes,neurologic & psychiatric manifestations,eye changes(yellowish,cotton wool-like fundal lesions-cytoid bodies)
Type of transplant rejection w/c is antibody-mediated & occurs in the presence of preexisting antibody to donor antigens;occurs w/ in min. of transplantation;a localized Arthus rxn. marked by acute infl.,fibrinoid necrosis of small vessels & exte
Hyperacute Rejection
Type of transplant rejection w/c is T cell-mediated;occurs days to months after transplant;charact. by infiltration of lymphocytes & macrophages;may show evidence of arteritis w/ thrombosis & cortical necrosis(antibody-mediated mech.)
Acute Rejection
Type of transplant rejection caused by antibody-mediated vascular damage; occurs months-years after an otherwise successful transplantation;charact. by vascular fibrointimal proliferation~ small scarred kidney
Chronic Rejection
General considerations for a successful graft
Donor & recipient must be matched for ABO blood groups & for as many HLA antigens as possible;adverse immune response is suppressed by immunosuppressant drugs,radiation, or Tcell depletion
Graft-verses-host dse.
Problem in BM transplantation in w/c immunocompetent cells are transplanted; also occurs in whole blood transfusion in patients w/ severe combined immunodeficiency(SCID);charact. by the rejection of "foreign" host cells by engrafted T & B cells;CD8+ Tcells from graft directly damage host cell; clinical features(fever,rash, hepatosplenomegaly);target organs(liver,skin,gastrointestinal mucosa)
Prototype connective tissue dse. w/c often affects women(80% of px.)of child bearing age & is marked by the presence of a ANAs(antinuclear antibodies)& extensive immune complex-mediated inflammatory lesions involving multiple organ systems,joints
Systemic Lupus Erythematosus(SLE)
Most common inherited B cell defect due to the inability of IgA B cells to mature to plasma cells;charact. by anaphylactic rxn. to transfused bld. & infxn.(especially in mucosal surface)
Isolated IgA Def.
-all other immunoglobulins are normal
Diverse grp. of disorders caused by failure of terminal B cell maturation~dec. in plasma cells~hypogammaglobulinemia;manifested by recurrent bact. infxn.
Common variable immunodeficiency
Congenital Tcell def. due to aberrant embryonic development of 3rd & 4th branchial arches~hypoplasia of thymus & parathyroid glands,abn° of manbible, ear,& aortic arch;charact. failure of T cell maturation~lymphopenia(B cell remain unimpaire
DiGeorge Synd(thymic hypoplasia)
-manifest as recurrent viral & fungal infxn.;tetany(due to hypoparathyroidism w/ hypocalcemia);CATCH 22(Cardiac effects,Abn° facies,Thymic hypoplasia, Cleft palate,Hypocalcemia,deletion of chromosome 22)
Def. of both B & T cells~profound lymphopenia,humoral & cell-mediated immunity defects;occurs in autosomal recessive & X-linked forms(Adenosine deaminase def.-50%);a.k.a Swiss-type aggamaglobulinemia
Severe Combined Immunodeficiency dse(SCID)
-manifest as:severe infxn(bact.,viral, fungal),inc. incidence of malignancy, failure to thrive,Graft-versus-host dse. due to bld. transfusion
Autosomal recessive immunedeficiency w/c leads to accumulation of deoxyadenosine & deoxy-ATP(toxic to lymphocytes);causes 50% of autosomal recessive cases
Adenosine Deaminase(ADA)Def.
Clinical & anatomic manifestations & treatment for SCID
Clinical(severe infxn.,inc. incidence of malignancy,failure to thrive,Graft-versus-host dse. due to bld. transfusion);Anatomic(thymic hypoplasia,hypoplasia of lymph nodes, tonsils,& other lymphoid tissue);Tx.(BM & stem cell transplantation,ADA gene transplantation)
Immunodeficiency X-linked disorder charact. by eczema, thrombocytopenia, recurrent infections & poor antibody response to polysaccharide antigens; most often displays normal total immunoglobulin
Wiskott-Aldrich Synd.(Immunodef. w/ thrombocytopenia & eczema)
Mechanism of HIV infxn.,the virus w/c causes AIDS(Acquired immunodeficiency synd.)
Cell surface protein(gp120)of HIV viron binds to CD4+ cell types(Tcells most common;monocytes & macrophages w/c serve as reservoirs & vehicles for entry into CNS;dendritic,Langerhans cells,& microglial)~internalization of HIV into host cell~synthesis of proviral DNA~remains latent until activated by an infxn.(EBV,CMV)
Samples in w/c the HIV can be found in an infected person & test done to diagnose presence of the virus
Samples(blood,semen,vaginal secretions,breast milk,& saliva); Diagnostic test(ELISA test is presumptive;followed up by Western blot & direct assessment of viral RNA)
High risk populations for HIV infected people
Homosexual or bisexual men(75%), Intravenous drug abusers(15%), Heterosexual partners of persons in high risk groups(4%),px. recieving multiple transfusion(2%),Hemophiliacs(1%),Infants of high risk parents
Pathogenesis of AIDS
Infection w/ HIV~depletion of CD4+ Tcells(dec. in lymphocytes;dec. CD4+:CD8+ ratio to <1)~failure of humoral & cell-mediated hypersensitivty rxn.;despite dec. antibodies,px. can demonstrate hypergammaglobulinemia due to polyclonal B cell activation
Clinical manifestations of AIDS
Opportunistic infxn. by Pneumocystis carinii,CMV,Mucor species,typical & atypical mycobacteria(Mycobacterium avium-intracellulare);inc. incidence of malignancy(Karposi sarcoma,B cell non-Hodgkin lymphoma);CNS & PNS manifestations
Stages in HIV infection
May be symptomatic for several years~acute illness(infectious mononucleosis),lymphadenopathy,& AIDS-related complex(ARC)marked by chronic fever,weight loss & diarrhea;HIV seropositivity~AIDS
Connective tissue dse. occuring often in young women;widespread fibrosis & degenerative changes that affect the skin,GIT(especially the esophagus), heart,muscle,lungs & kidney;presence of the ANA anti-Scl-70(1/3 of cases)
Progressive Systemic Sclerosis(PSS, Scleroderma)
-CREST synd.(Calcinosis,Reynaud phenomenon,Esophageal dysfunction, Sclerodactyly,Telangiectasia)
Connective tissue dse. charact. by hypertrophy of collagen fibers of the subcutaneous tissue~tightening of facial skin,fixed facial appearance; sclerodactyly;Raynaud phenomenon(75%); visceral organ involvement(esophagus, GIT,kidneys,lungs,heart)~dysphagi
Progressive systemic sclerosis(PSS, scleroderma)
-due to widespread fibrosis & degenerative changes
Connective tissue dse. often affecting women in late middle age manifesting a triad(xerostomia,keratoconjunctivitis sicca,1 of several connective tissue/ autoimmune dse.);Sicca synd.(xerostomia & keratoconjunctivitis); involvement of salivary gland(b
Sjögren synd.
-assoc. w/ Rheumatoid arthritis(most common),SLE,PSS,polymyositis, Hashimoto thyroiditis
Laboratory findings in Sjögren synd.
Polyclonal Hypergammaglobulinemia(broad-based elevation of serum gamma globulins demonstrated by electrophoresis);ANAs,including highly specific anti-SS-B & less specific anti-SS-A
Connective tissue dse. often affecting women charact. by a chronic inflammatory process involving the proximal muscles of the extremities & skin(reddish-purple rash over neck & face-Dermatomyositis);inc. serum creatine kinase & ANAs;assoc. w/
-confirmed by muscle biopsy,w/c demonstrates necrotic muscle cells & a lymphocytic infiltrate
Connective tissue dse. charact. by specific ANAs(high-titer anti-nRNP & an immunoflorescent speckled nuclear appearance on morphologic ANA analysis);manifest as arthralgia, Reynaud phenomenon,esophageal hypomotility,myositis;dec. renal involvement
Mixed Connective Tissue Dse.(MCTD)
-mainly in women(80% of cases;peak incidence 35-40yrs)
An immune complex vasculitis charact. by segmental fibrinoid necrosis in the walls of small & med. art. of almost any organ;predominant in men;antigens are often unknown(Hep. B antigen implicated 30% of cases);drugs(sulfonimides,penicillin)may form i
Polyarteritis Nodosa
Clinical manifestations of Polyarteritis Nodosa
manifested as abd. pain,HPN,uremia, polyneuritis,allergic asthma,urticaria or rash, splenomegaly,fever, leukocytosis,proteinuria;may involve the lung(chest pain,cough,dyspnea, hemoptysis)
Group of disorders w/c feature fibrinoid change in connective tissue; may be of autoimmune origin;presence of antinuclear antibodies(ANAs) & various other autoantibodies
Connective Tissue(Collagen)Dse
-examples(SLE,Scleroderma,Sjögren synd.,Polymyositis,Mixed Connective Tissue dse.,Polyarteritis Nodosa)
Caused by deposition of amyloid fibrils derived from immunoglobulin light chains,referred to as AL(amyloid light chain)protein;marked by amyloid deposition in tissues of mesodermal origin(heart,muscle,tongue);may involve the kidney;assoc. w/plasma cell d
Primary Amyloidosis(immunocytic dyscrasia amyloidosis)
Amyloidosis marked by deposition of fibrils consisting of amyloid protein called AA protein(formed from amyloid-associated-protein,SAA);involves the kidney,liver,adrenals,pancreas,lymph nodes,spleen;complication of chronic inflammatory dse.(rheumatoid ar
Secondary Amyloidosis(reactive systemic amyloidosis)
Amyloidosis in w/c the amyloid is derived from a protein,transthyretin(serum protein that transports thyroxine & retinol);charact. by severe peripheral involvement caused by amyloid deposits
Portuguese type of polyneuropathy
Amyloidosis charact. by deposits of amyloid protein(A4 amyloid,amyloid B-protein);gene that codes for the protein precusors of A4 amyloid has been localized to chromosome 21
Alzheimer Dse.
Amyloidosis of autosomal recessive disorder charact. by episodic fever & polyserositis;distribution & type of amyloid similar to that of secondary amyloidosis(AA amyloid)
Familial Mediterranean Fever
Amyloidosis charact. by prominent amyloid deposits w/in the tumor, apparently derived from calcitonin
Medullary Carcinoma of the thyroid
Amyloidosis charact. by deposits of amyloid in islet cells;amyloid(amylin or islet amyloid polypeptide,IAPP)is derived from insulin or glucagon & interferes w/ insulin sensing by beta cells
Diabetes Mellitus
Amyloidosis charact. by minor deposits of amyloid found at autopsy in the very elderly;involves the brain,heart,& other organs;amyloidosis involving the heart is derived from transthyretin
Senile amyloidosis
Amyloidosis charact. by amyloid deposits in the joints of px. who have undergone hemodialysis for several yrs.;amyloid is derived from B-microglobulin(protein not readily filtered by dialysis memb.
Dialysis-associated amyloidosis

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