Immunopathology Immunopathology Su Min

Section 1 General Features of the Immune System

1. Cells of the immune system (1) T lymphocytes (2) B lymphocytes (3) Macrophages (4) Dendritic and Langerhans’ cells (5) Natural killer (NK) cells

2. Cytokines messenger molecules of the immune system (1) Categories ① Cytokines that mediate natural immunity ② Cytokines that regulate lymphocyte growth, activation, and differentiation ③ Cytokines that activate inflammation ④ Cytokines that stimulate hematopoiesis

(2) General properties of cytokines ① Many individual cytokines are produced by several different cell types. ② Cytokines induce their effects in three ways:  autocrine effect  paracrine effect  endocrine effect ③ Cytokines mediate their effects by binding to specific high-affinity receptors on their target cells. ④ The effects of cytokines are pleiotropic

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

Section 2 Hypersensitivity Reactions

1.Type I hypersensitivity (Anaphylactic type) Immediate hypersensitivity reaction, resulting from release of pharmacologically active mediators.

(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.

(3) Diseases ① Urticaria and angioneurotic edema ② Asthma ③ Hay fever ④ Insect allergy: serious or fatal anaphylaxis may follow. Edema of larynx, with airway obstruction may occur.

2. Type I Hypersensitivity Cytolytic or cytotoxic reactions (1) Mechanism: ① Complement-dependent reactions  Transfusion reactions  Erythroblastosis fetal  Autoimmune hemolytic anemia  Certain drug reactions

② 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.

③ Antibody-mediated cellular dysfunction  Myasthenia gravis: muscle weakness Graves’ disease:  Graves’ disease: hyperthyroidism

3. Type Ⅲ Hypersensitivity (Immune complex-mediated) (1) Reaction types ① Arthus reaction ② serum sickness ③ Collagen diseases

(2) Toxic complex diseases: (2) Toxic complex diseases: ① Acute glomerulonephritis ② Systemic lupus erythematosus ③ Necrotizing angiitides ④ Rheumatoid arthritis ⑤ Progressive systemic sclerosis ⑥ Dermatomyositis etc.

4. Type Ⅳ Hypersensitivity (Cell-Mediated ) Delayed hypersensitivity reaction Tissuereaction (1) Tissue reaction: Consist of parenchymal destruction associated with perivascular lymphocytic and macrophage reaction.

(2) Diseases: ① Chronic active hepatitis ② Viral exanthem ③ Contact dermatitis ④ Graft rejection ⑤ Inflammatory bowel disease.

Section 3 Transplant Rejection

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

2. Types of rejection (1) Superacute rejection: Time ① Time : within minutes or hours after transplantation. Causes ② Causes : these are major incompatibility with high levels of humoral antibodies. Morphology ③ Morphology : a. thrombotic occlusion of the capillaries b. Fibrinoid necrosis occurs in arterial walls. c. Infarction d. Neutrophils infiltrating

(2) Acute rejection ① Time: Within days to weeks in the untreated recipient. Or may appear suddenly months or even years later, when immunosuppression has been employed. Within days to weeks in the untreated recipient. Or may appear suddenly months or even years later, when immunosuppression has been employed.

② 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.

(3) Chronic rejection ① Time: months——years ② 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.

It occurs in any situation in which immunologically component cells or their precursors are transplanted into immunologically crippled recipients. Graft-versus-host (GVH) disease: (4) Graft-versus-host (GVH) disease:

3. Methods of increasing graft survival (1) Favourable sites for transplantation ① cornea and anterior chamber of the eye ② meninges ③ testis

(2) Accurate tissue matching (3) Immune deficiency states, pregnancy, and uraemia (4) Immunosuppression ① Corticosteroids ② Azathioprine ③ Antilymphocyte serum ④ Whole-body irradiation ⑤ Induction of immune tolerance

Section 4 Autoimmune Diseases

1. Definition: An immune reaction against “ self- antigens” is the cause of certain diseases in human. An immune reaction against “ self- antigens” is the cause of certain diseases in human.

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

(3) Cross-reactions (molecular mimicry) ① Antibodies to streptococcal antigens may react with constituents of cardiac muscle or connective tissue in rheumatic fever. ② Rabies vaccine may rise to encephalitis

(4) Breakdown of tolerance ① Bypass of helper T cell tolerance ② Imbalance of suppressor-helper T cell function ③ Geneic fators ④ Emergence of a sequestered antigen ⑤ Polyclonal lymphocyte activation

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

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

② Sjogren’s 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.

③ Systemic sclerosis ④ Rheumatoid arthritis ⑤ Polymyositis ⑥ Polyarteritis nodosa

(2) Organ-specific diseases ① Hashimoto’s disease (chronic lymphocytic thyroiditis) ② Graves’s disease ③ Goodpasture’s syndrome ④ Insulin-dependent diabetes mellitus ⑤ Primary billiary cirrhosis

⑥ Chronic ulcerative colitis ⑦ Malignant pernicious anaemia with chronic atrophic gastritis ⑧ Chronic active hepatitis ⑨ Myasthenia gravis

Section 5 Immunodeficiency

1. Primary immunodeficiency (1) Pure immunoglobulin deficiency ① Bruton-type gammaglobulinaemia ② Hypogammaglobulinaemia of late onset ③ Dysgammaglobulinaemia In these disorders these is susceptibility to bacterial and yeast infections, but viral infections are controlled normally. Cell- mediated reactions are intact.

(2) Pure T-cell deficiency ① Thymic agenesis ② Thymic alymphoplasia (dysplasia) ③ Thymic hypoplasia or aplasia Here the immunoglobulin levels are normal but there is a complete absence of cell-mediated reactions (3) Mixed deficiency

2. Secondary immunodeficiency Resulting from: (1) Excessive loss of immunoglobulins ① Protein-losing enteropathy ② Nephrotic syndrome

(2) Depression of the immune system by ① Old age ② Malnutrition ③ Viral infections such as acquired immunodeficiency syndrome. ④ Leprosy ⑤ Malaria ⑥ Sarcoidosis ⑦ Surgery ⑧ Uraemia

(3) Immunosuppression by ① X-rays ② Corticosteroids ③ Cytotoxic drugs ④ Antilymphocyte serum ⑤ Anntimetabolits

(4) Neoplasia ① Hodgkin’s disease ② Multiple myeloma ③ Waldenstrom’s macroglobulinaemia ④ Chronic lymphatic leukaemia (5) Splenectomy

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 Etiology: human immunodeficiency virus (HIV)

① A long incubation period, followed by a slowly progressive fatal outcome. ② Tropism for hematopoietic and nervous systems ③ An ability to cause immunosuppression ④ Cytopathic effects in vitro. Features Features :

Epidemiology Worldwide: about 10 million people are infected. Five groups of adults at high risk for developing AIDS: ① Homosexual or bisexual males ② Intravenous drug abusers ③ Hemophiliacs ④ Recipients of blood and blood components ⑤ Heterosexual contacts

Pathogenesis HIV→CD 4+ cell→ CD 4+ cell lysis → opportunistic infections and neoplasms

Morphology Neither specific nor diagnostic. ① Widespread opportunistic infections ② Kaposi’s sarcoma ③ Lymphoid tumors

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