1. Diseases of the immune system
Prof.dr. Manal Fawzy Gadalla
Professor of pathology
Faculty of medicine
Ain Shams University

2. ILOs of the first lecture
-Know the types of immune responses and be able to give examples of each type .
-What is the pathogenesis of hypersensitivity reactions?
-What are the types of hypersensitivity reactions?
-What is the pathogenesis of graft rejection?
-What are the types of graft rejection?

3. Immunity refers to a state of protection against infections
Mechanisms of normal immune responses:
Innate immunity
non-specific reaction to a microbe
Adaptive immunity
specific to the microbial antigen.
Humoral immunity: It is mediated by B-lymphocytes
Cell mediated immunity: It is mediated by T lymphocytes
B cells; that differentiate into plasma cells producing specific antibodies
CD4+ helper T cells
CD8+ cytotoxic T cells

4. ???
All of the following are considered as innate ways of defense except: A- Complete integrity of the skin B- Mucous released by the respiratory airways. C- IgM against rubella virus D- Hcl content of the stomach

5. Hypersensitivity Diseases

6. hypersensitivity diseases
Immune responses
tissue injury
Causes of hypersensitivity diseases:
Self antigens
autoimmune diseases
inflammation
Microbes or any injurious agent
allergy
Environmental antigens

7. Types of hypersensitivity reactions (according to the immunological mechanisms)
Ig E
Mast cells
Localized bronchial asthma
Type 1 Hypersensitivity
Generalized anaphylaxis
Autoimmune hemolytic anemias
Type 2 Hypersensitivity
Antibody mediated
Localized Arthus reaction
Generalized serum sickness
Immune complex
complement
Type 3 Hypersensitivity
Cell mediated with T helper cytokines or T cytotoxic
TB, Graft rejection
Type 4 Hypersensitivity

8. Hypersensitivity reactions
The different mechanisms by which immune system reacts to antigen
Type I,II,II
Ab mediated
Type IV
Cell mediated

9. Type I hepersensitivity
Allergic Rhinitis
Food Allergies: peanuts, egg, fruits,
wheal and flare reaction (atopic urticaria)
Asthma: airborne pollens, dust, viral Ag

10. Mast cell degranulation mediated by antigen cross-linking of IgE bound to IgE Fc receptors (FcRI).

11. Role of mediators released by mast cells
Marked vasodilatation of blood vessels
Bronchospasm
Increased mucous secretion

12. Wheal-and-flare reaction (atopic urticaria).

13. Anaphylaxix: Laryngeal oedema

14. Type II hepersensitivity reaction (cytolytic hypersensitivity)
Antibody binds to the antigen on cell surface leads to cell lysis
E.g incompatible blood transfusion

16. Type III Hypersensitivity reaction immune complex mediated e
Type III Hypersensitivity reaction immune complex mediated e.g systemic lupus erythematosis
immunecomplex
Ag+Ab
Deposited in tissue (walls of blood vessels)
+ complement which activates inflammatory cells

17. Systemic lupus erythematosus (SLE)

18. Type IV hypersensitivity reaction delayed (cell mediated)
T lymphocytes secrete cytokines lead to macrophage activation which form granulomas e.g TB

19. ???
The pathogenesis of one of the following types of hypersensitivity reactions does not depend on antibodies: A- Type I hypersensitivity B- Type II hypersensitivity C- Type III hypersensitivity D- Type IV hypersensitivity

20. ???
A female patient 30 years old complains of lower lip swelling after eating strwberry, the most propable pathogenesis of her condition is: A- Type I hypersensitivity B- Type II hypersensitivity C- Type III hypersensitivity D- Type IV hypersensitivity

21. Transplant Rejection

22. Hypersensitivity reaction types 2 and 4 ( both delayed and cytotoxic)
Rejection of transplantation
Hypersensitivity reaction types 2 and 4 ( both delayed and cytotoxic)
Direct pathway
Antigens present on cells of the graft are recognized directly by
T helper and T cytotoxic
Indirect pathway
Antigens present on cells of the graft are presented by APC (antigen presenting cell of the host)
T helper (1 and 2)
Delayed hypersensitivity
Antibody mediated hypersensitivity(BLymphocytes)

23. Effector mechanisms of graft rejection
T cell mediated Rejection
AB mediated Rejection
T helper (1)
Activate macrophages
Infammatory cytokines
Endothelial cell and parenchymal cell damage
Antibodies
Complement
(C5-9)membrane attack comlpex and leucocytes recruitment
Endothelial cell damage
T cytotoxic (CD8)
Direct toxicity
Endothelial and Parenchymal cell damage

24. Classification of Graft Rejection
Hyperacute
Antibody mediated endothelial damage
Acute vasculitis and ischemic necrosis
Acute
Cellular and antibody mediated
Parenchymal and vascular damage
Chronic
Cellular mediated
Parenchymal and vascular damage

25. ???
One of the following statements is incorrect concerning the graft rejection: A- Chronic rejection occurs within years after transplant. B- Antigen presenting cell is an important component of the direct pathway. C- Hyperacute rejection is merely antibody mediated mechanism. D- The most important target of the transplant rejection is the blood vessels.

27. ILOs of the second lecture
-What is the pathogenesis of autoimmune diseases?
-What is systemic lupus erythematosus?
-What is the clinical features of SLE?
-What are the laboratory investigations of SLE?

28. Autoimmune Diseases

29. AUTOIMMUNE DISEASES Immune reaction self antigen disease
Organ specific
Graves disease
Autoimmune hemolytic anemia
Systemic
Systemic lupus erythromatosus
Rheumatoid arthritis
Nbn

30. MECHANISMIS of AUTOIMMUNE DISEASES
Autoimmunity loss of self tolerance
Infection or injurious agent
Genetic
Mechanisms of self tolerance
Peripheral tolerance
Anergy
Regulatory T cells
Apoptosis
Central tolerance
T cell thymus
B cell bone marrow

32. SYSTEMIC LUPUS ERYTHROMATOSUS
Systemic autoimmune disease
female, remission and relapse
Any organ affection
Autoantibodies direct injury
immune complex
Break of self tolerance inherited
enviromental factors

33. Pathological features
Renal affection
Acute necrotizing vasculitis
Skin invovement (malar rash)
Joint affection
CNS involvement
splenomegaly
Serofibrinous pericarditis and pleurisy
Heart involvement

34. SLE: Malar Rash

35. SLE: vasculitis

36. Spleen: Periarteriolar fibrosis (onion skinning)

37. Clinical manifestation Laboratory investigations
Diagnosis
Clinical manifestation
Laboratory investigations
Nnnmn
+ve Serum ANA
Urine analysis
Renal biobsy
Serum complement

38. ؟؟؟
A female patient 22 years old presented to ER complaining of severe dyspnea, on examination ,she had pleural effusion. Serum ANA was positive, one of the following statements concerning her case is incorrect: A- There is a defect in her immune tolerance B- She has a decreased level of serum complement C- Malar flush is a renal complication D- She will suffer of multiple excerbations.

39. Thank You
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40. ILOs of the third lecture
-Know the types of immune dificiency diseases?.
-What is the pathogenesis of AIDS?
-What is the Route of infection of AIDS?
-What is the clinical picture of AIDS?

41. Immune Difficiency Diseases

42. IMMUNE DEFICIENCY DISEASES
Causes and types:
primary = inherited
Secondary = aquired
Infection
HIV
Malnutrition
Chemotherapy
others
Clinical effects:
Infection
cancers

43. AQURIED IMMUNODEFECIENCY SYNDROME (AIDS)
Retroviral infection (HIV1 ,HIV2) of CD4 positive cells
T helper
Profound immunosuppression
Opportunistic
Infections
Secondary Neoplasms
NEUROLOGICAL MANIFESTATION
Opportunistic infection
Secondary neoplasms
Direct viral affection through macrophages and microglia infection

44. Routes of infection NO TRANSMISSION BY USUAL PERSONAL CONTACT
Sexual transmission
Parentral transmission
Mother to infant transmission
NO TRANSMISSION BY USUAL PERSONAL CONTACT

45. PATHOGENESIS
HIV kill T helper cells

46. Phases of HIV infection
The acute phase:
Immunity is intact
The chronic phase:
Immunity is largely intact
The crisis phase:
Catastrophic breakdown of the host defenses

47. Classification of HIV infected patients according to T helper count
More than 500 cells/uL: Asymptomatic
Between 200 and 500 cells/uL : Early symptoms
Less than 200 cells/uL : Severe immunosuppression

48. Full blown AIDS manifestations
Neoplasms
Opportunistic Infections
CNS Involvement

49. Opportunistic infections
Protozoa and Helminth
e.g: toxoplasmosis
Fungal infection
e.g: candidiasis
Bacterial infection
e,.g: mycobacteriosis
Viral
Infection
e.g: Herpes
Simplex
Pneumocystis jiroveci (fungus) Pneumonia

50. AIDS: pneumocystis carinii infection

51. AIDS: Oral candidiasis

52. Neoplasms Kaposi sarcoma
Non Hodgkin lymphomas (Burkitt’s, immunoblastic)
Primary lymphoma of the brain
Cervical carcinoma

53. CNS involvement Opportunistic infections
Neoplasms (primary CNS lymphoma)
Aseptic meningitis (viral meningitis)
AIDS dementia complex

54. ???
A male 22 years old patient presented to the clinic with high fever, dyspnea, oral thrush, diarrhea, x ray chest revealed complete opacification of the lower right lung lobe, bacteriological examination to the sputum revealed pneumocystis jiroveci: A- What is your diagnosis? B- What is the investigations you would like to do for him? C- What are the expected prognosis of this case?

55. Tank You
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56. ILOs of the fourth lecture
-What is amyloidosis?
-What is the chemical nature of amyloid protein?
-What is the physical nature of amyloid protein?
-What are the types of amyloidosis?
-What is the gross, microscopic picture of amyloidosis?
-What are the investigations of amyloidosis?

57. Amyloidosis

58. AMYLOIDOSIS Oid amyl starch Osis process similar
Protein (amyloid protein) + mucopolysaccharrhides
Interstitial tissues +wall of blood vessels
Pressure atrophy May lead to organ failure

59. Physical nature of amyloid protein

60. Chemical nature of amyloid protein
Amyloid light chain
Amyloid associated protein
Transthyretin
beta2 microglobulin
Beta amyloid protein
Others

61. Primary amyloidosis Kidney, liver, spleen Heart, skin, respiratory
Multiple myeloma
Just increase plasma cells in bone marrow
Heart, skin, respiratory
Tract, peripheral nerves, tongue
Excess kappa and lambda light chains +
Defect in enzymatic degradation
Kidney, liver, spleen

62. Secondary amyloidosis
Kidney, liver, spleen, LNs, adrenal
Tuberculosis,
Bronchiectasis,
Rheumatoid arthritis
Renal cell carcinoma
Excess amyloid associated protein+ defect enzymatic degredation

63. Gross Microscopic Electron microscope non branching fibrils Size
enlarged
Surface
flat
Colour
brown
Consistency
Firm waxy
Edge
sharp
Microscopic
Homogenous eosinophilic material in
Blood vessel wall + interstitial tissue
Special stain
Congo red +polarized light apple green
Electron microscope non branching fibrils

65. Examples of organs affection Clinical presentation
Kidney nephrotic syndrome renal failure
Liver Hepatomegaly
Spleen sago spleen or diffuse spleen
HHeart restrictive cardiomyopathy
Others , macroglssia, malabsorption, carpal tunnel syndrome

66. Generalized amyloidosis poor prognosis
Diagnosis of Amyloidosis
Clinical symptoms and signs
Microscopic
Congo red stain
Rectal and gingival biopsies
Generalized amyloidosis poor prognosis

67. ؟؟؟
A female patient 55 years old with long history of rheumatoid arthritis, complained recently of nephrotic syndrome. Renal biopsy examination revealed mesangial expansion of most of the glomeruli by pink homogenous material, which is present as well in the interstitial tissue: -What is your diagnosis? How can you be sure? -Is it a primary or secondry disease? -Describe other clinical features?

68. Thank You
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