Immunopathology

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Immunopathology

• Su Min

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Section 1 General Features of the Immune System
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1. Cells of the immune system

• (1) T lymphocytes
• (2) B lymphocytes
• (3) Macrophages
• (4) Dendritic and Langerhans cells
• (5) Natural killer (NK) cells

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2. Cytokines

• messenger molecules of the immune system
• (1) Categories
• ? Cytokines that mediate natural immunity
• ? Cytokines that regulate lymphocyte growth,
  activation, and differentiation
• ? Cytokines that activate inflammation
• ? Cytokines that stimulate hematopoiesis

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(2) General properties of cytokines

• ? Many individual cytokines are produced by
  several different cell types.
• ? Cytokines induce their effects in three ways
• autocrine effect
• paracrine effect
• endocrine effect
• ? Cytokines mediate their effects by binding to
  specific high-affinity receptors on their target
  cells.
• ? The effects of cytokines are pleiotropic

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• 3. structure and function of histocompatibility
  antigens.
• 4. Disorders of the immune system
• Disorders of the hypersensitivity reactions
• Immune syst autoimmune diseases
• immunologic
  deficiency syndrome

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Section 2 Hypersensitivity Reactions
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Type I hypersensitivity (Anaphylactic type)

• Immediate hypersensitivity reaction, resulting
  from release of pharmacologically active
  mediators.

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(2) Tissue reactions variable in severity

• Mildest may be only edema. Reaction is triggered
  by cells, basophils. If inflammatory cells are
  present, many are eosinophils.

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(3) Diseases

• ? Urticaria and angioneurotic edema
• ? Asthma
• ? Hay fever
• ?Insect allergy serious or fatal anaphylaxis may
  follow. Edema of larynx, with airway obstruction
  may occur.

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2. Type I Hypersensitivity

• Cytolytic or cytotoxic reactions
• (1) Mechanism
• ? Complement-dependent reactions
• Transfusion reactions
• Erythroblastosis fetal
• Autoimmune hemolytic anemia
• Certain drug reactions

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• ?Antibody-dependent cell-mediated cytotoxicit
  (ADCC).
• May be relevant to
• Graft rejection
• The destruction of targets too large to be
  phagocytosed, such as parasites or tumor cells.

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• ?Antibody-mediated cellular dysfunction
• Myasthenia gravis muscle weakness
• Graves disease hyperthyroidism

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3. Type ? Hypersensitivity (Immune
complex-mediated)

• (1) Reaction types
• ? Arthus reaction
• ? serum sickness
• ? Collagen diseases

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(2) Toxic complex diseases

• ? Acute glomerulonephritis
• ? Systemic lupus erythematosus
• ? Necrotizing angiitides
• ? Rheumatoid arthritis
• ? Progressive systemic sclerosis
• ? Dermatomyositis etc.

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4. Type ? Hypersensitivity (Cell-Mediated )

• Delayed hypersensitivity reaction
• (1) Tissue reaction Consist of parenchymal
  destruction associated with perivascular
  lymphocytic and macrophage reaction.

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(2) Diseases

• ? Chronic active hepatitis
• ? Viral exanthem
• ? Contact dermatitis
• ? Graft rejection
• ? Inflammatory bowel disease.

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Section 3 Transplant Rejection
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1. Terms

• Autograft transplantation within the same
  individual
• Isograft or syngeneic graft between identical
  twins or im-bred animals
• Allograft between individuals of the same
  species but of differing genetic make-up
• Xenograft between different species.

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2. Types of rejection

• (1) Superacute rejection
• ?Time within minutes or hours after
  transplantation.
• ?Causes these are major incompatibility with
  high levels of humoral antibodies.
• ?Morphology
• a. thrombotic occlusion of the capillaries
• b. Fibrinoid necrosis occurs in arterial
  walls.
• c. Infarction
• d. Neutrophils infiltrating

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(2) Acute rejection

• ? Time
• Within days to weeks in the untreated
  recipient. Or may appear suddenly months or even
  years later, when immunosuppression has been
  employed.

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? Types

• a. Acute cellular rejection diffuse mononuclear
  cell infiltrating that may invade the tubules,
  causing focal tubular necrosis, and edema as well
  as mild interstitial hemorrhage.
• b. Acute rejection vasculits (humoral rejection)
  necrotizing vasculitis with endothelial necrosis,
  neutrophils infiltration, deposition of
  immunoglobulins, complement, and fibrin, and
  thrombosis the vascular intima is markedly
  thickened and inflamed.

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(3) Chronic rejection

• ? Time monthsyears
• ? Morphology
• Vascular changes consist of dense intimal
  fibrosis
• Interstitial fibrosis, tubular atrophy, shrinkage
  of the renal parenchyma
• Mononuclear cell infiltrates containing large
  numbers of plasma cell and numerous eosinophils.

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(4) Graft-versus-host (GVH) disease

• It occurs in any situation in which
  immunologically component cells or their
  precursors are transplanted into immunologically
  crippled recipients.

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3. Methods of increasing graft survival

• (1) Favourable sites for transplantation
• ? cornea and anterior chamber of the eye
• ? meninges
• ? testis

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• (2) Accurate tissue matching
• (3) Immune deficiency states, pregnancy, and
  uraemia
• (4) Immunosuppression
• ? Corticosteroids
• ? Azathioprine
• ? Antilymphocyte serum
• ? Whole-body irradiation
• ? Induction of immune tolerance

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Section 4 Autoimmune Diseases
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• 1. Definition
• An immune reaction against self-antigens is
  the cause of certain diseases in human.

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2. Mechanism

• (1) Alteration of self-proteins (modification of
  the molecule)
• ? Partial degradation of autoantigens.
• ? Complexing of self-antigens with drugs or
  micro-organisms.
• (2) Hidden antigens exposure

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• (3) Cross-reactions (molecular mimicry)
• ? Antibodies to streptococcal antigens may react
  with constituents of cardiac muscle or connective
  tissue in rheumatic fever.
• ? Rabies vaccine may rise to encephalitis

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• (4) Breakdown of tolerance
• ? Bypass of helper T cell tolerance
• ? Imbalance of suppressor-helper T cell function
• ? Geneic fators
• ? Emergence of a sequestered antigen
• ? Polyclonal lymphocyte activation

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3. Classification

• (1) Systemic autoimmune diseases
• ? Systemic lupus erythematosus (SLE)
• a. Definition It is the classic prototype of
  the multisystem disease of autoimmune origin.

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b. Characteristics

• (i) Immunologically, the disease involves a
  bewildering array of auto-antibodies,
  particularly antinuclear antibodies (ANAs).
• (ii) Anatomically, all sites of involment have in
  common vascular lesions with fibrinoid deposits.
• (iii) Clinically, it is an unpredictable
  remitting, relapsing disease of acute or
  insidious in the body, but principally affects
  the skin, kidneys, serosal membranes, joints and
  heart

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• ? Sjogrens syndrome
• Definition It is a clinicopathologic entity
  characterized by dry eyes and dry mouth resulting
  from immunologically mediated destruction of the
  lacrimal and salivary glands.

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• ? Systemic sclerosis
• ? Rheumatoid arthritis
• ? Polymyositis
• ? Polyarteritis nodosa

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(2) Organ-specific diseases

• ?Hashimotos disease (chronic lymphocytic
  thyroiditis)
• ? Gravess disease
• ? Goodpastures syndrome
• ? Insulin-dependent diabetes mellitus
• ? Primary billiary cirrhosis

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• ? Chronic ulcerative colitis
• ? Malignant pernicious anaemia with chronic
  atrophic gastritis
• ? Chronic active hepatitis
• ? Myasthenia gravis

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Section 5 Immunodeficiency
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1. Primary immunodeficiency

• (1) Pure immunoglobulin deficiency
• ? Bruton-type gammaglobulinaemia
• ? Hypogammaglobulinaemia of late onset
• ? Dysgammaglobulinaemia
• In these disorders these is susceptibility to
  bacterial and yeast infections, but viral
  infections are controlled normally. Cell-mediated
  reactions are intact.

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• (2) Pure T-cell deficiency
• ? Thymic agenesis
• ? Thymic alymphoplasia (dysplasia)
• ? Thymic hypoplasia or aplasia
• Here the immunoglobulin levels are normal but
  there is a complete absence of cell-mediated
  reactions
• (3) Mixed deficiency

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2. Secondary immunodeficiency

• Resulting from
• (1) Excessive loss of immunoglobulins
• ? Protein-losing enteropathy
• ? Nephrotic syndrome

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• (2) Depression of the immune system by
• ? Old age ? Malnutrition
• ?Viral infections such as acquired
• immunodeficiency syndrome.
• ? Leprosy ? Malaria
• ? Sarcoidosis ? Surgery
• ? Uraemia

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• (3) Immunosuppression by
• ? X-rays
• ? Corticosteroids
• ? Cytotoxic drugs
• ? Antilymphocyte serum
• ? Anntimetabolits

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• (4) Neoplasia
• ? Hodgkins disease
• ? Multiple myeloma
• ? Waldenstroms macroglobulinaemia
• ? Chronic lymphatic leukaemia
• (5) Splenectomy

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Acquired Immunodeficiency Syndrome (AIDS)

• In June 1981, the centers for disease control
  of the United States reported that five young
  homosexual men in the Los Angeles area had
  contracted the AIDS
• Etiology human immunodeficiency virus (HIV)

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Features

• ? A long incubation period, followed by a
  slowly progressive fatal outcome.
• ? Tropism for hematopoietic and nervous
  systems
• ? An ability to cause immunosuppression
• ? Cytopathic effects in vitro.

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• Epidemiology
• Worldwide about 10 million people are
  infected. Five groups of adults at high risk for
  developing AIDS
• ? Homosexual or bisexual males
• ? Intravenous drug abusers
• ? Hemophiliacs
• ? Recipients of blood and blood components
• ? Heterosexual contacts

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Pathogenesis

• HIV?CD4 cell? CD4 cell lysis ? opportunistic
  infections and neoplasms

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Morphology

• Neither specific nor diagnostic.
• ? Widespread opportunistic infections
• ? Kaposis sarcoma
• ? Lymphoid tumors

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• Lymph nodes
• Marked follicular hyperplasia (early stages)?
  Lymphoid cells depletion (empty-looking lymph
  nodes or spleen and thymus in later stages).
• Mortality 100

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