OBC 231 General Pathology

Diseases of the Immune System
Dr. Huda Hammad Dr. Wael Swelam

11/23/2011

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury
 Individuals who mount immune responses against an antigen are said to be

“sensitized” to that antigen.

 When these responses are pathologic or excessive, the manifestations are called

“hypersensitivity”.

 Normally, a system of checks and balances optimizes the eradication of infecting

organisms without serious injury to host tissues.

 However, immune responses may be inadequately controlled or inappropriately

targeted to host tissues.

 In these situations, the normally beneficial response is the cause of disease.

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Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury
Causes of Hypersensitivity Diseases
 Pathologic immune responses may be directed against different

types of antigens, and may result from various underlying abnormalities: Autoimmunity. 2. Reactions against microbes. 3. Reactions against environmental antigens.
1.

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the immune system does not react against an individual's own antigens (self-tolerance). Autoimmunity:  Normally. self-tolerance fails.  Sometimes.  The diseases caused by autoimmunity are referred to as autoimmune diseases. 4 11/23/2011 . resulting in reactions against one's own cells and tissues that are called autoimmunity.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases 1.

Reactions against microbes:  Many types of reactions against microbial antigens may cause disease.  In some cases.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases 2. the reaction may be excessive or the microbial antigen is unusually persistent. 5 11/23/2011 .

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases Reactions against microbes Antibodies produced against microbial  immune complexes T-cell responses against persistent microbes  sever inflammatory response Antibodies / T cells cross-react with a host tissue During the process of eradicating the infection host tissues injury Inflammatory Poststreptococcal glomerulonephritis Granulomas. and this normal immune response damages liver cells e.g. Tuberculosis Rheumatic heart disease Cytotoxic T cells try to eliminate infected cells. e.g. Viral hepatitis 11/23/2011 6 .

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases Tuberculos granuloma Viral hepatitis Poststreptococcal glomerulonephritis 7 Rheumatic heart disease 11/23/2011 .

animal dander. pollen. or dust mites). but almost 20% of the population is "allergic" to these substances. 8 11/23/2011 ..g.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases 3. Reactions against environmental antigens:  Most healthy individuals do not react strongly against common environmental substances (e.

and pose therapeutic challenges.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Causes of Hypersensitivity Diseases  These hypersensitivity diseases tend to be chronic. 9 11/23/2011 . they are sometimes grouped under the term immune-mediated inflammatory diseases.  Since chronic inflammation is a major component of these disorders. often debilitating.

4. 10 11/23/2011 .  The first three are variations on antibody-mediated injury.  This classification of immune-mediated disease is not perfect.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases  Hypersensitivity reactions are traditionally subdivided into four types. T-cell-mediated (type IV) hypersensitivity. 2. because several immune reactions may coexist in one disease. whereas the fourth is cell mediated. Immediate (type I) hypersensitivity. 1. Immune complex-mediated (type III) hypersensitivity. Antibody-mediated (type II) hypersensitivity. 3.

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are within minutes from sensitized mast responsible for the inflammation seen cells causing the intense immediate in late-phase reactions. . reactions associated with conditions 11/23/2011 12 such as systemic anaphylaxis.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immediate (type I) hypersensitivity  Some of these mediators are released  Others. such as cytokines.

D4.Sequence of events in immediate (type 1) hypersensitivity Action Mediator Vasodilation. TNF) Leukotriene B4 Eosinophil and neutrophil chemotactic factors (not defined biochemically) 11/23/2011 Smooth muscle spasm Cellular infiltration 13 . D4.. chemokines. E4 Histamine Prostaglandins PAF Cytokines (e. E4 Neutral proteases that activate complement and kinins Prostaglandin D2 Leukotrienes C4.g. increased vascular permeability Histamine PAF Leukotrienes C4.

such as mucosal epithelial cell damage.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immediate (type I) hypersensitivity  Often. inflammation and tissue destruction. (2) a second. late-phase reaction: in 2 to 8 hours later and may last for several days. the IgE-triggered reaction has two well-defined phases: (1) the immediate response: vasodilation. and smooth muscle spasm. within 5 to 30 minutes after exposure to an allergen and subsiding by 60 minutes. Dominated by neutrophils. 14 11/23/2011 . eosinophils. and lymphocytes. vascular leakage. especially TH2 cells.

followed in short order by profound respiratory difficulty caused by pulmonary bronchoconstriction and accentuated by hypersecretion of mucus. 15 11/23/2011 . urticaria (hives).  Laryngeal edema may exacerbate matters by causing upper airway obstruction. and skin erythema appear.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immediate (type I) hypersensitivity Clinical and Pathologic Manifestations : Systemic anaphylaxis:  Within minutes of an exposure in a sensitized host. itching.

with resultant vomiting. and the patient may progress to circulatory collapse and death within minutes. and diarrhea. abdominal cramps.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immediate (type I) hypersensitivity Clinical and Pathologic Manifestations : Systemic anaphylaxis:  The musculature of the entire gastrointestinal tract may be affected. 16 11/23/2011 . there may be systemic vasodilation with fall in blood pressure (anaphylactic shock).  Without immediate intervention.

skin (contact. or 3.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immediate (type I) hypersensitivity Clinical and Pathologic Manifestations :  Local reactions generally occur when the antigen is confined to a particular site. 17 11/23/2011 . such as : 1. lung (inhalation. 2. gastrointestinal tract (ingestion. causing urticaria). causing bronchoconstriction). causing diarrhea).

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or they may be adsorbed exogenous antigens (e.g.  The antigens may be normal molecules intrinsic to cell membranes or extracellular matrix.. a drug metabolite).Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Antibody-mediated (type II) hypersensitivity  Caused by antibodies directed against target antigens on the surface of cells or other tissue components. 19 11/23/2011 .

4. 20 11/23/2011 . 6. 7. 1. Acute rheumatic fever. 2. Goodpasture syndrome. 10. 9. Autoimmune thrombocytopenic purpura.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Antibody-mediated (type II) hypersensitivity  Antibody-mediated abnormalities are the underlying cause of many human diseases. 3. Pemphigus vulgaris. examples include: Autoimmune hemolytic anemia. Graves disease (hyperthyroidism). Insulin-resistant diabetes. Myasthenia gravis 8. Vasculitis caused by ANCA. 5. Pernicious anemia.

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Antibody-mediated (type II) hypersensitivity Mechanisms of Antibody-Mediated Diseases: A. 21 11/23/2011 .

g. 22 11/23/2011 . myasthenia gravis. e. Grave’s disease (hyperthyroidism).Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Antibody-mediated (type II) hypersensitivity Mechanisms of Antibody-Mediated Diseases: C. and cause functional derangements (either inhibition or unregulated activation) without cell injury. Antibodies can bind to cell surface receptors or essential molecules.

 Tissue injury in these diseases is the result of the inflammation. 23 11/23/2011 . such as nucleoproteins.  It is only when these complexes are produced in large amounts.  The antigens in these complexes may be exogenous antigens. or endogenous antigens. such as microbial proteins. persist. typically secondary to complement activation.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immune complex-mediated (type III)  Caused by antibodies binding to antigens to form complexes that circulate and may deposit in vascular beds and stimulate inflammation. and are deposited in tissues that they are pathogenic.

thus initiating 3) An inflammatory reaction in various sites throughout the body Excess amount of initial antibody  immune complexes  precipitated at the site of injection and trigger the same inflammatory reaction as in systemic immune complex disease Local 24 11/23/2011 . Immune complex-mediated (type III) Systemic 2) Deposition of the immune complexes in various tissues.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases 1) Formation of antigen-antibody complexes in the circulation.

vasculitis.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases Immune complex-mediated (type III) Disease Systemic lupus erythematosus Poststreptococcal glomerulonephritis Antigen Involved Nuclear antigens Streptococcal cell wall antigen(s). nephritis foreign serum protein (horse anti-thymocyte globulin) Various foreign proteins Cutaneous vasculitis 11/23/2011 Arthus reaction (experimental) 25 . such as Arthritis. arthritis. may be "planted" in glomerular basement membrane Clinicopathologic Manifestations Nephritis. skin lesions. others Nephritis Polyarteritis nodosa Reactive arthritis Serum sickness Hepatitis B virus antigen Bacterial antigens (Yersinia) Hepatitis B virus antigen Acute arthritis Various proteins.

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases T-cell-mediated (type IV) hypersensitivity Mechanisms of T-cell-mediated (type IV) hypersensitivity reactions: 26 11/23/2011 .

27 11/23/2011 . mediated by CD8+ T cells.Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases T-cell-mediated (type IV) hypersensitivity Mechanisms of T-cell-mediated (type IV) hypersensitivity reactions: B. Direct cell cytotoxicity.

Hypersensitivity Diseases: Mechanisms of Immune Mediated Injury Types of Hypersensitivity Diseases T-cell-mediated (type IV) hypersensitivity  This group of diseases has received great interest because many of the newly designed biologic therapies developed to target abnormal T-cell reactions. 28 11/23/2011 .  Several autoimmune disorders. are now known to be caused by T cells. as well as pathologic reactions to environmental chemicals and persistent microbes.

. others) Protein antigens in CNS myelin (myelin basic protein. often with granulomas. ocular lesions Chronic inflammation of ileum and colon.g. e. ocular lesions Demyelination in CNS with perivascular inflammation. stricture Dermatitis. with itching. glutamic acid decarboxylase. glutamic acid decarboxylase. role of antibodies? Protein antigens of peripheral nerve myelin Unknown antigen. paralysis. GuillainBarré syndrome? Inflammatory bowel disease (Crohn's disease) Contact dermatitis 29 Environmental chemicals. may be derived from intestinal microbes Antigens of pancreatic islet βcells (insulin. poison ivy (pentadecylcatechol) . paralysis. usually 11/23/2011 short-lived. proteolipid protein) Unknown antigen in joint synovium (type II collagen?). paralysis. ocular lesions Demyelination in CNS with perivascular inflammation. may be chronic with persistent exposure Multiple sclerosis Rheumatoid arthritis Peripheral neuropathy. others) Demyelination in CNS with perivascular inflammation.Disease Specificity of Pathogenic T cells Clinicopathologic Manifestations Type 1 diabetes mellitus Antigens of pancreatic islet βcells (insulin. fibrosis.

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Rejection of transplants Transplantation problems  Surgical difficulties  Graft rejection  Organ shortage 31 11/23/2011 .

and destroys it Within same person Isograft Allograft Xenograft Between identical twins Between genetically different people Between different species 32 11/23/2011 .Transplant Immunology Outline: Graft compatibility Rejection = Autograft Recipient recognizes graft as foreign.

Histocompatibility  Histocompatible: antigenically similar to the host  Histoincompatible: antigenically different from the host  MHC antigens are the most important  ABO antigens are also important  Minor histocompatiblity antigens are less important 33 11/23/2011 .

DR • expressed on antigen-presenting cells • present antigen to TH cells 34 11/23/2011 .Compatibility: HLA complex  Gene collection on chromosome 6  Three regions: class I. DQ. HLA-B. HLA-C • expressed on nearly all cells • present antigen to TC cells  Class II gene products • DP. class III  Class I gene products • HLA-A. class II.

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BF TNF- proteins TNF- C' DP DQ DR 37 11/23/2011 .Compatibility MHC class I II III Region Gene products A HLAA B HLAB C HLAC DP DQ DR C4. C2.

Compatibility ♂ parents a/b c/d ♀ four possible haplotype combinations of children a/c a/d b/c b/d 38 11/23/2011 .

Compatibility HLA alleles A a b haplotypes 1 2 B 7 8 C w3 w2 DR 2 3 DQ DP 1 2 1 2 c d 3 11 44 35 w4 w1 4 7 1 3 3 4 39 11/23/2011 .

Compatibility ice cream pop fruit cookie veggie yum yum a haplotypes b De w c Vault d 40 11/23/2011 .

Compatibility: HLA inheritance  The more matching alleles between donor and host. the better!  Matching the class II antigens is more important than matching the class I antigens.  One or two class I mismatches = no big deal  One or two class II mismatches = big deal  Mismatches in both class I and II = very big deal 41 11/23/2011 .

number of mismatches 100 Class I Class II 0 1 or 2 3 or 4 graft survival. months 42 11/23/2011 . % 0 0 0 1 or 2 1 or 2 1 or 2 50 0 1 or 2 3 or 4 3 6 12 time after transplant.

Transplant Immunology Outline  Introduction  Graft compatibility  Graft rejection 43 11/23/2011 .

with lots of killing mechanisms. and react against. at least some foreign antigens in the graft  Rejection is complex. 44 11/23/2011 .  Every recipient will recognize.Rejection  Any two people (except identical twins) will express some HLA proteins that are different.

Rejection How do recipient cells know which cells to kill? 45 11/23/2011 .

Rejection Two mechanisms of rejection  T-cell-mediated rejection  Antibody-mediated rejection 46 11/23/2011 .

T-cell mediated rejection  CD8+ CTLs kill graft cells directly  CD4+ cells trigger a delayed hypersensitivity reaction 47 11/23/2011 .

CTL Killing Delayed Hypersensitivity 48 11/23/2011 .

Antibody-mediated rejection  Preformed antibodies • Anti-HLA or anti-ABO • Rejection occurs immediately (“hyperacute”) • Antibodies cause thrombosis • Rare these days  Newly-made antibodies • Appear within days to years • Usually directed against graft endothelium • Cause damage by:  Helping complement kill graft cells  Opsonizing graft cells (yummy!) 49 11/23/2011 .

Antibody-dependant cell-mediated cytotoxicity (ADCC)
   
Target cell is coated with IgG
Effector cell* has receptors for Fc fragment Effector cell binds to target cell Target cell is lysed

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Macrophage, Neutrophil, or NK Cell

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Clinical types of Rejection
Hyper-acute rejection • Within hours • Preexisting anti-donor antibodies • Rare these days • “Accelerated” is similar Chronic rejection • Months to years after transplant • Humoral and cell-mediated mechanisms • Hard to prevent • Hard to treat

Acute rejection • Starts at about 10 days • Cellmediated

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Acute cellular (t)

Acute humoral

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Chronic

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Autoimmune Diseases
 The immune reaction to self-antigens, or autoimmunity, is

the cause of certain human diseases.
 A growing number of entities have been attributed to

this process (see table in next slide).

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Organ-Specific Hashimoto thyroiditis Autoimmune hemolytic anemia Autoimmune atrophic gastritis of pernicious anemia Multiple sclerosis Autoimmune orchitis Goodpasture syndrome Autoimmune thrombocytopenia Insulin-dependent diabetes mellitus Myasthenia gravis Graves' disease Primary biliary cirrhosis*

Systemic Systemic lupus erythematosus Rheumatoid arthritis Sjögren syndrome Reiter syndrome Inflammatory myopathies* Systemic sclerosis (scleroderma)* Polyarteritis nodosa*

Autoimmune (chronic active) hepatitis* Ulcerative colitis
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*The evidence supporting an autoimmune basis of these disorders is not strong.
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these autoantibodies can be identified within lesions by immunofluorescence and electron-microscopic techniques.  For example. the presence of multiple autoantibodies accounts for many of the clinical and pathologic manifestations of SLE.Autoimmune Diseases  The evidence that the diseases listed in the previous table are the result of autoimmune reactions is more persuasive for some than for others.  Moreover. 57 11/23/2011 .

the response may be directed against an exogenous antigen.  In the systemic diseases.Autoimmune Diseases  In many other disorders. These diseases are often referred to as "collagen vascular" or "connective tissue" disorders. such as a microbial protein.  In some cases of apparent autoimmunity. 11/23/2011 . an autoimmune etiology is 58 suspected but is unproven. to multisystem diseases. the lesions affect principally the connective tissue and blood vessels of the various organs involved.  Autoimmune diseases range from those in which specific immune responses are directed against one particular organ or cell type.

Autoimmune Diseases: Self-Tolerance  Autoimmunity implies loss of self-tolerance.  Immunological tolerance is unresponsiveness to an antigen that is induced by exposure of specific lymphocytes to that antigen. 59 11/23/2011 .  Self-tolerance refers to a lack of immune responsiveness to one's own tissue antigens.

 Several mechanisms work in concert to prevent immune reactions against one's own antigens. receptors are produced that can recognize self-antigens.Autoimmune Diseases Self-Tolerance  During the generation of billions of antigen receptors in developing T and B lymphocytes.  These mechanisms are broadly divided into two groups: central tolerance and peripheral tolerance. 60 11/23/2011 .

• In the B-cell lineage. • Or die by apoptosis. 11/23/2011 .Autoimmune Diseases Self-Tolerance Central tolerance • Immature lymphocytes that recognize self-antigens in the central (generative) lymphoid organs are killed by apoptosis. some of the self-reactive lymphocytes switch to new antigen receptors that are not self-reactive 61 Peripheral tolerance • Mature lymphocytes that recognize self-antigens in peripheral tissues undergo one of the following: • They become functionally inactive (anergic). • Or are suppressed by regulatory T lymphocytes.

altering the recognition of self-antigens. Infections and tissue alterations that may expose selfantigens and activate APCs and lymphocytes in the tissues.Autoimmune Diseases Self-Tolerance  The variables that lead to a failure of self-tolerance and the development of autoimmunity include: 1. 2. Inheritance of susceptibility genes that may disrupt different tolerance pathways. 62 11/23/2011 .

and tissue injury.Pathogenesis of autoimmunity Autoimmunity arises from many causes. 63 11/23/2011 . including: 1) Inheritance of susceptibility genes that may interfere with selftolerance. other inflammatory stimuli) that promote lymphocyte entry into tissues. 2) Environmental triggers (inflammation. 3) Activation of self-reactive lymphocytes.

 A large number of autoantibodies is produced. 64 11/23/2011 .that can damage tissues either directly or in the form of immune complex deposits. classically including antinuclear antibodies (ANAs).Autoimmune Diseases Systemic Lupus Erythematosus  The fundamental defect in SLE is a failure to maintain self-tolerance.

Lupus erythematosis pathogenesis Genetic factors B cell reactivity alter the function of T cells. antigen-presenting cells & cytokines production B cells to enhance the function of other cells autoantibody production Organ damage 65 11/23/2011 .

Autoimmune Diseases Systemic Lupus Erythematosus 1997 Revised Criteria for Classification of Systemic Lupus Erythematosus Malar rash Oral ulceration Malar rash Photosensitivity 66 Discoid rash Arthritis 11/23/2011 .

Autoimmune Diseases Systemic Lupus Erythematosus 1997 Revised Criteria for Classification of Systemic Lupus Erythematosus Serositis Neurologic disorder Renal disorders 67 11/23/2011 .

5 ×109 cells per liter (1500 cells per mm3) on two or more occasions • Thrombocytopenia: <100 ×109 cells per liter (100 ×103 cells per mm3) in the absence of offending drugs 68 • Anti-DNA antibody to native DNA in abnormal titer • Anti-Sm: presence of antibody to Sm nuclear antigen • Positive finding of antiphospholipid antibodies 11/23/2011 .0 ×109 cells per liter (4000 cells per mm3) total on two or more occasions • Lymphopenia: <1.Autoimmune Diseases Systemic Lupus Erythematosus 1997 Revised Criteria for Classification of Systemic Lupus Erythematosus Hematologic disorder Immunologic disorder • Hemolytic anemia: with reticulocytosis. • Leukopenia: <4.

69 11/23/2011 . Antinuclear antibody:  An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome.Autoimmune Diseases Systemic Lupus Erythematosus 1997 Revised Criteria for Classification of Systemic Lupus Erythematosus 11.

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etc. immunosuppression.Immune Deficiencies: Basic Concepts  Immune deficiencies  primary (inherited)  secondary (to infection. C’ or phagocytic cell defect: bacterial infection  T cell defect: viral and fungal infections 71 11/23/2011 .)  Patients more susceptible to infections and cancer  Type of infection varies:  Ig.

NK cells) Typical patient: infant with recurrent infections Primary importance for our class: boards 72 11/23/2011 .Primary Immune Deficiency Diseases: Basic Concepts Rare! Genetic Can affect any part of immune system:  Adaptive (humoral or cellular)  Innate (C’. phagocytes.

SCID SCID DiGeorge syndrome X-linked agammaglobulinemia SCID Hyper-IgM syndrome IgA deficiency 73 11/23/2011 .

Primary immune deficiencies  X-Linked Agammaglobulinemia  Common Variable Immunodeficiency (CVID)  Hyper-IgM Syndrome  Selective IgA Deficiency  Combined T-cell and B-cell (antibody) deficiencies 74 11/23/2011 .

X-linked Agammaglobulinemia       Pre-B cells can’t differentiate into B cells Patients have no immunoglobulin Affects males Presents at 6 months of age (maternal Ig gone) Recurrent bacterial infections Treatment: intravenous pooled human Ig 75 11/23/2011 .

Common variable immunodeficiency  Group of disorders characterized by defective antibody production  Basis of Ig deficiency is variable (hence the name) and often unknown  Affects males and females equally  Presents in teens or twenties  Patients more susceptible to infections. but also to autoimmune disorders and lymphoma! 76 11/23/2011 .

Severe Combined Immunodeficiency 77 11/23/2011 .

Pneumocystis carinii Severe intestinal giardiasis Candida. sepsis. Pseudomonas Complement Defect Neisserial infections. Epstein-Barr Enteroviral virus. staphylococci.Examples of Infections in Immunodeficiencies Pathogen Type Bacteria T-Cell-Defect Bacterial sepsis B-Cell Defect Streptococci. other pyogenic bacterial infections Viruses Cytomegalovirus. severe varicella. Nocardia. Aspergillus Special features Aggressive disease with Recurrent opportunistic pathogens. Haemophilus Granulocyte Defect Staphylococci. failure sinopulmonary to clear infections infections. chronic meningitis 11/23/2011 78 . chronic encephalitis infections with respiratory and intestinal viruses Fungi and parasites Candida.

A good way to study immune deficiencies Disease XLA Transmission X-linked Defect No mature B cells. no Ig Clinical stuff Infant with recurrent bacterial infections CVID IgA deficiency Hyper-IgM DiGeorge SCID 11/23/2011 79 .

 Death. HIV-RNA (Viral Load) 80 11/23/2011 .  Progressive T-Cell loss  Morphology: MANY  Clinical Expressions:  Infections.  Neoplasms.  Latency.  Progressive Immune Failure.AIDS(SECONDARY IDS)  Etiology: HIV  Pathogenesis:  Infection.  HIV+.

and declining)  Intravenous drug usage  (25%) Heterosexual sex (10% and rising) 81 11/23/2011 .Epidemiology  Homosexual: (40%.

providing a DNA double helix capable of integration into host cell chromosomes. 82 11/23/2011 .Reverse transcriptase  The enzyme reverse transcriptase (RT) is used by retroviruses to transcribe their single-stranded RNA genome into single-stranded DNA and to subsequently construct a complementary strand of DNA.

Pathogenesis Attaching 83 Budding 11/23/2011 .

Pathogenesis Early budding Late budding Mature new virions 84 11/23/2011 .

polyclonal  Altered monocyte/macrophage function 85 11/23/2011 .General immune abnormalities  Lymphopenia  Decreased t-cell function  B-cell activation.

 Toxoplasmosis  Fungal:  Candida.  Nocardia.AIDS related Infections  Protozoal/Helminthic:  Cryptosporidium.  Salmonella 86  Viral: CMV. HSV.  PCP (Pneumocystis Carinii Pneumonia). VZ (Herpes Family) 11/23/2011 . and the usual 3  Bacterial:  TB.

87 PCP 11/23/2011 .

88 CRYPTOSPORIDIUM 11/23/2011 .

89 Caseating granuloma 11/23/2011 .

squamous cell 90 11/23/2011 .Cancers related to AIDS  Kaposi sarcoma  B-cell lymphomas  CNS lymphomas  Cervix cancer.

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