L9 - Immune Diseases Pathology Flashcards
Purpose of immune system
• Evolved to defend against foreign attach
– External (infections)
– Internal (cancer)
• When immune system goes wrong it results in disease
– Inadequate response
– Excessive response
– Inappropriate response
Inadequate immune response
• Primary immunodeficiency
– Present at birth (genetic disorder)
• Secondary immunodeficiency
– Acquired (drug or infection
Primary Immune Deficiency
Genetic disorders including:
• Innate disorders
– Chronic granulomatous disease
– NK cell deficiency
• Adaptive disorders
– X-linked agammaglobulinaemia (Burton’s)
– Primary IgA deficiency
– DiGeorge Syndrome
– Severe Combined Immune Deficiency (SCID)
SCID
– Failure to develop B and T cells
• Sometimes a failure of T cells
• TH required for B cells to make antibodies
• B cells OK but don’t receive TH
– Both humoral and CMI affected
– In some forms thymus and lymphoid tissue reduced
Clinical manifestations of SCID
– Early in life the child has many recurrent infections
• Bacteria (pneumonia, meningitis)
• Fungal (Pneumocystis jiroveci – pneumonia)
• Viral (Chicken pox – skin, mucous progressing to lungs and brain)
– Chronic skin rash (GVHD from mothers T cells)
– Death in 2 to 3 years without treatment
Genetic mutations in SCID
• Mutations of genes involved in lymphocyte development
– Many genes
– 50% autosomal, 50% X-linked (XSCID)
• Most common mutation – Autosomal (Adenosine deaminase deficiency leads to accumulation of toxic waste in lymphocytes)
– X-linked (Cytokine receptor common gamma chain)
Secondary Immune Deficiency
- Severe malnutrition
- Infants first 6 months only maternal Ig
• Drug therapy
– Immunosuppressant drugs to prevent transplant rejection
• HIV/AIDS
HIV/AIDS
- Acquired Immune Deficiency Syndrome (AIDS)
- Human Immunodeficiency Virus (HIV)
- T help cells (CD4) destroyed by HIV (mostly indirectly)
- T help cells help B cells and Cytotoxic T cells
- Loss of T help cells leads to severe immunosuppression
- Death due to infection or cancer
AIDS
- Human Immunodeficiency Virus causes a progressive disease called Acquired ImmunoDeficiency Syndrome (AIDS)
- First case described in 1981
• Currently ~ 50 million people infected with HIV worldwide
– ~67% cases are in Africa, Asia and South and Central America
– Becoming an infection of poor nations, peoples and classes
Opportunistic infections of HIV/AIDs
– Pneumocystis Jiroveci (formally carinii)
• Most common lung infection
– Cytomegalovirus
• Most common systemic infection
– Mycobacterium tuberculosis
– Fungal infections
• Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum
– Protozoan infection
• Toxoplasma gondii
– Viruses
• Herpes virus 1
Cancers of HIV/AIDS
– Kaposi’s sarcoma (Cancer from the lymphatic epithelium forming vascular channels filled with RBCs)
– Carcinomas of the mouth and rectum
– B-cell lymphomas or lymphoproliferative disorders
Excessive Immune Response (Hypersensitvity)
• Over reaction of immune system leads to disease states
• Four types: – Type I – Type II – Type III – Type IV
• Can be a mixture of these
Type I hypersensitivity
- immediate hypersensitivity
- IgE antibody
- involved mast cells and their mediators (cytokines, lipid mediats, vasoactive lipids)
- involved in allergic reactions
Type II hypersensitivity
- antibody mediated hypersensitivity
- IgM and IgG antibodies against cell surface or extracellular matrix antigens
- involves opsonisation and phagoocytosis of cells, complement, activation of leucocytes and when there is abnormalities in cell functions
- involved in Goodpasture’s Syndrome
Type III hypersensitivity
- immune complex mediated hypersensitivity
- involves immune complexes of circulating antigens and IgM or IgG antibodies
- involves complement and Fc receptor recruitment and activation of leucocytes
- involved in SLE
