Disorders Associated with the

Immune System

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

• Response to antigens (allergens) leading to damage

• Require sensitizing dose(s)

Hypersensitivity Reactions

• Involve IgE antibodies

• Localized: Hives or asthma from contact or inhaled antigens

• Systemic: Shock from ingested or injected antigens

Type I (Anaphylactic) Reactions

Figure 19.1a

• Skin testing• Desensitization

Type I (Anaphylactic) Reactions

Figure 19.3

• Involve IgG or IgM antibodies and complement

• Complement activation causes cell lysis or damage by macrophages

Type II (Cytotoxic) Reactions

ABO Blood Group System

Table 19.2

Hemolytic Disease of the Newborn

Figure 19.4

Drug-induced Thrombocytopenic Purpura

Figure 19.5

• IgG antibodies and antigens form complexes that lodge in basement membranes.

Type III (Immune Complex) Reactions

Figure 19.6

• Delayed-type hypersensitivities due to TD cells

• Cytokines attract macrophages and initiate tissue damage

Type IV (Cell-Mediated) Reactions

Figure 19.8

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 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

histology basophils and eosinophil antibody and

complement

complement and neutrophils

monocytes and lymphocytes

transferred with antibody antibody antibody T-cells

examplesallergic

asthma, hay fever

Erythroblastosis fetalis, Goodpasture's nephritis

SLE, farmer's lung disease

tuberculin test, poison ivy, granuloma

Comparison of Different Types of hypersensitivity

characteristics type-I (anaphylactic)

type-II (cytotoxic)

type-III(immune complex)

type-IV(delayed type)

• 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

Hypothesis of Autoimmune Diseases

• Clonal deletion during fetal development ensures self-tolerance

• Autoimmunity is loss of self-tolerance

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

Autoimmune Diseases

• Histocompatibility antigens: Self antigens on cell surfaces

• Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens

• Human leukocyte antigen (HLA) complex: MHC genes in humans

Reactions Related to the Human Leukocyte Antigen

(HLA) Complex

Diseases Related to Specific HLAs

Table 19.3

HLA Typing

Figure 19.1

Spectrum of autoimmune diseases, target organs and diagnostic tests

Disease Organ Antibody to Diagnostic Test

Hashimoto's thyroiditis

Thyroid Thyroglobulin, thyroid peroxidase (microsomal)

RIA, Passive, CF, hemagglutination

Primary Myxedema

Thyroid Cytoplasmic TSH receptor

Immunofluorescence (IF)

Graves' disease Thyroid   Bioassay, Competition for TSH receptor

Pernicious anemia Red cells Intrinsic factor (IF), Gastric parietal cell

B-12 binding to IF immunofluorescence

Addison's disease

Adrenal Adrenal cells Immunofluorescence

Premature onset menopause

Ovary Steroid producing cells

Immunofluorescence

Male infertility Sperm Spermatozoa Agglutination, Immunofluorescence

Insulin dependent juvenile diabetes

Pancreas Pancreatic islet beta cells

 

Disease Organ Antibody to Diagnostic Test

Insulin resistant diabetic

Systemic Insulin receptor Competition for receptor

Atopic allergy Systemic beta-adrenergic receptor

Competition for receptor

Myasthenia graves

Muscle Muscle, acetyl choline receptor

Immunofluorescence, competition for receptor

Goodpasture's syndrome

Kidney, lung Renal and lung basement membrane

Immunofluorescence (linear staining)

Rheumatoid arthritis

Skin, kidney, joints etc

IgG IgG-latex agglutination

Systemic lupus erythematosus

joints, etc. 

DNA, RNA, nucleoproteins

RNA-, DNA-latex agglutination, IF (granular in kidney)

• 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

Immune Deficiencies

Treatment

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

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.

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

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

• 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)

I. Disorders of T cells

• C) Bare leukocyte syndrome • MHC deficiency• these patients have fewer CD4 cells

and are infection prone

I. Disorders of T cells

II. Disorders of B lymphocytes

• x-linked infantile hypogammaglobulinemia • Transient hypogammaglobulinemia • IgA deficiency • Selective IgG deficiency • These patients are susceptible to pyogenic

infections. 

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

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.

SCONDRY IMMUNODEFICIENCIES 

Acquired Immunodeficiency Syndrome (AIDS)

Figure 19.12a

HIV Infection

Figure 19.12b