1. Disorders Associated with the Immune System

3. Disorders Associated with the Immune System
Infection and immunosuppression are failures of the immune system.
Superantigens cause release of cytokines that cause adverse host responses.
Allergies and transplant rejection are harmful immune reactions

4. Hypersensitivity Reactions
Response to antigens (allergens) leading to damage
Require sensitizing dose(s)

5. Type I (Anaphylactic) Reactions
Involve IgE antibodies
Localized: Hives or asthma from contact or inhaled antigens
Systemic: Shock from ingested or injected antigens
Figure 19.1a

6. Type I (Anaphylactic) Reactions
Skin testing
Desensitization
Figure 19.3

7. Type II (Cytotoxic) Reactions
Involve IgG or IgM antibodies and complement
Complement activation causes cell lysis or damage by macrophages

8. ABO Blood Group System
Table 19.2

9. Hemolytic Disease of the Newborn
Figure 19.4

10. Drug-induced Thrombocytopenic Purpura
Figure 19.5

11. Type III (Immune Complex) Reactions
IgG antibodies and antigens form complexes that lodge in basement membranes.
Figure 19.6

12. Type IV (Cell-Mediated) Reactions
Delayed-type hypersensitivities due to TD cells
Cytokines attract macrophages and initiate tissue damage
Figure 19.8

13. Comparison of Different Types of hypersensitivity
characteristics
type-I
(anaphylactic)
type-II (cytotoxic)
type-III (immune complex)
type-IV (delayed type)
antibody
IgE
IgG, IgM
None
antigen
exogenous
cell surface
soluble
tissues & organs
response time
15-30 minutes
minutes-hours
3-8 hours
48-72 hours
appearance
weal & flare
lysis and necrosis
erythema and edema, necrosis
erythema and induration
histology
basophils and eosinophil
antibody and complement
complement and neutrophils
monocytes and lymphocytes

14. Comparison of Different Types of hypersensitivity
characteristics
type-I
(anaphylactic)
type-II (cytotoxic)
type-III (immune complex)
type-IV (delayed type)
histology
basophils and eosinophil
antibody and complement
complement and neutrophils
monocytes and lymphocytes
transferred with
antibody
T-cells
examples
allergic asthma, hay fever
Erythroblastosis fetalis, Goodpasture's nephritis
SLE, farmer's lung disease
tuberculin test, poison ivy, granuloma

15. Hypothesis of Autoimmune Diseases
Molecular Mimicry: Due to antibodies against pathogen’s epitope that is identical to a self antigen e.g Streptococcus gp A and rheumatic fever.
Modification of cell-surface antigens : eg. Thermbocytopenia (low level of platelets) and anemia (low level of RBC) due to sulfa drugs.
Availability of normally sequestered self-Ag: The emberyonic Ags are not recognized as self present in very low concn. to induce autoimmune dis. Some cases as in thyroid and testes

16. Autoimmune Diseases
Clonal deletion during fetal development ensures self-tolerance
Autoimmunity is loss of self-tolerance

17. Autoimmune Diseases Type I — Due to antibodies against pathogens
Type II — Antibodies react with cell-surface antigens
Type III (Immune Complex) — IgM, IgG, complement immune complexes deposit in tissues
Type IV — Mediated by T cells

18. Reactions Related to the Human Leukocyte Antigen (HLA) Complex
Histocompatibility antigens: Self antigens on cell surfaces
Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens
Human leukocyte antigen (HLA) complex: MHC genes in humans

19. Diseases Related to Specific HLAs
Table 19.3

20. HLA Typing
Figure 19.1

21. Spectrum of autoimmune diseases, target organs and diagnostic tests
Antibody to
Diagnostic Test
Hashimoto's thyroiditis
Thyroid
Thyroglobulin, thyroid peroxidase (microsomal)
RIA, Passive, CF, hemagglutination
Primary Myxedema
Cytoplasmic TSH receptor
Immunofluorescence (IF)
Graves' disease
Bioassay, Competition for TSH receptor
Pernicious anemia
Red cells
Intrinsic factor (IF), Gastric parietal cell
B-12 binding to IF  immunofluorescence

22. Organ Antibody to Diagnostic Test
Disease
Organ
Antibody to
Diagnostic Test
Addison's disease
Adrenal
Adrenal cells
Immunofluorescence
Premature onset menopause
Ovary
Steroid producing cells
Male infertility
Sperm
Spermatozoa
Agglutination, Immunofluorescence
Insulin dependent juvenile diabetes
Pancreas
Pancreatic islet beta cells

23. Insulin resistant diabetic 
Systemic
Insulin receptor
Competition for receptor
Myasthenia graves
Muscle
Muscle, acetyl choline receptor 
Immunofluorescence, competition for receptor
Rheumatoid arthritis
Skin, kidney, joints etc
IgG
IgG-latex agglutination

24. Rheumatoid arthritis
Skin, kidney, joints etc
IgG
IgG-latex agglutination

25. Immune Deficiencies 1ry =Congenital: Due to defective or missing genes
Selective IgA immunodeficiency
Severe combined immunodeficiency
2ry= Acquired: Develop during an individual's life, due to drugs, cancers, infections
Artificial: Immunosuppression drugs
Natural: HIV infections

26. Treatment
Anti-inflammatory (corticosteroid) and immunosuppressive (cyclosporin) drug therapy is the present method of treating autoimmune diseases.

27. PRIMARY IMMUNODEFICIENCIES
Primary immunodeficiencies are inherited defects of the immune system. These defects may be in the specific or nonspecific immune mechanisms. They are classified on the basis of the site of lesion in the developmental or differentiation pathway of the immune system.

28. Disorders of lymphoid stem cells
Severe combined Immunodeficiency: (SCID).
Patients with SCID are susceptible to a variety of bacterial, viral, mycotic and protozoan + TB infections.
Diagnosis is based on enumeration of T and B cells and immunoglobulin measurement
Severe combined immunodeficiency can be treated with bone marrow transplant

29. I. Disorders of T cells
A) DiGeorge's syndrome: This the most clearly defined T-cell immunodeficiency
Recurrent intercellular bacterial (eg. TB) and fungal infection infections

30. I. Disorders of T cells B) Wiskott-Aldrich syndrome
This syndrome is associated with normal T cell numbers with reduced functions
Boys with this syndrome develop severe eczema, petechia (Fungal Infection)

31. I. Disorders of T cells C) Bare leukocyte syndrome MHC deficiency
these patients have fewer CD4 cells and are infection prone

32. II. Disorders of B lymphocytes
x-linked infantile hypogammaglobulinemia
Transient hypogammaglobulinemia
IgA deficiency
Selective IgG deficiency
These patients are susceptible to pyogenic infections. 

33. III. Defects of the phagocytic system
A) Chronic granulomatous disease (CGD)
Leukocytes have poor intracellular killing and low respiratory burst.
B) Chediak-Higashi syndrome
inability of phagosome and lysosome fusion and proteinase deficiency

34. Acquired Immunodeficiency Syndrome (AIDS)
SCONDRY IMMUNODEFICIENCIES 
Acquired Immunodeficiency Syndrome (AIDS)
1981 In U.S., cluster of Pneumocystis and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function.
1983 Discovery of virus causing loss of immune function.

35. Acquired Immunodeficiency Syndrome (AIDS)
Figure 19.12a

36. HIV Infection
Figure 19.12b