Dr ROOPA Premed 2 Pathophysiology

IMMUNITY The term immunity refers to the resistance exhibited by the host towards injury caused by microorganisms and their products..

Natural or Non-specific Immunity Respone is antigen-independent There is immediate maximal response Not antigen-specific Exposure results in no immunologic memory

Acquired or Specific Immunity Response is antigen-dependent There is a lag time between exposure and maximal response Antigen-specific Exposure results in no immunologic memory Exposure results in immunologic memory

The key primary lymphoid organs of the immune system are thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin.thymusbone marrowspleentonsilslymph vesselslymph nodesadenoidsskin

Normal Immune System Primary Lymphoid organs Secondary Lymphoid organs Cells Cytokines Complement system HLA system

The complement system is a biochemical cascade that helps clear pathogens from an organism.

The diseases caused by disorders of the immune system fall into two broad categories: immunodefeciency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease),chronic granulomatous disease and autoimmunity, in which the immune system attacks its own host's body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and other allergies).autoimmunitysystemic lupus erythematosusrheumatoid arthritisHashimoto's diseasemyasthenia gravishypersensitivitiesasthmaallergies

Hypersensitivity refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre- sensitized (immune) state of the host. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction.

Hypersensitivities Type I : immediate, anaphylactic 1 st exposure to an antigen: stimulates IgE to bind to mast cells, basophils 2 nd exposure: IgE causes lysis of the cells, release of histamine Allergic asthma, atopic dermatitis, seasonal rhinitis, systemic anaphylaxis

Type II: antibody-mediated or cytotoxic Antigens are bounded to human basement membranes in tissues Or to blood cell membranes Antibodies, COMPLEMENT react to the antigens, NK cells may add on to the injury

Type II hypersensitivity Hemolytic disease of the newborn Blood transfusion reactions Goodpastures syndrome: kidney and lung abnormalities

Type III: immune complex mediated Antigen is NOT part of the cell, or basement membrane Immune complex: antigen+ antibody Very insoluble, not removed by macrophages Deposited on vessel walls, extravascular sites

Type III Systemic lupus erythematosus (SLE) Serum sickness Arthus reaction Poststreptococcal glomerulonephritis

Type IV: delayed hypersensitivity, cell-mediated CD4 cells react to MHC Class II Memory cells 2 nd exposure to antigen: stronger reaction CD cells may also be involved

Type IV Tuberculin test Contact dermatitis

Transplant reactions Matching ABO blood group Matching HLA antigens Organs that can be transplanted: liver kidney lungs bone marrow skin

Histocompatibility antigen test histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.

Types of transplant rejection Hyperacute: OCCURS IN MINUTES -due to preexisting antibodies to donor antigens Acute: OCCURS DAYS TO WEEKS -due to T cells Chronic: OCCURS MONTHS TO YEARS - antibodies will form to the antigens in the donor cells

Graft-versus-host disease (GVHD) is a complication that can occur after a bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body.bone marrow transplant

Graft-versus-host disease Common in bone marrow transplant Immunocompetent cells in the transplant (graft) Host cells are damaged by: CD8+ cells cytokines macrophages Organs damaged: liver, skin, GIT Fever, rash, large liver, jaundice

Primary Immunodeficiency diseases X-linked agammaglobulinemia Or Bruton’s agammaglobulinemia Male babies, more than 6 months old Absent plasma cells absent germinal centers absent IG Prone to bacterial infections

IgA deficiency Most common B cell defect 1 in 700 persons, Caucasians May be with no symptoms (asymptomatic) Recurrent Upper respiratory tract infection (URTI) and frequent diarrhea

Severe Combined Immunodeficiency Disease (SCID) Low B cells and T cells Absence of ADA (adenosine deaminase) or PNP ( purine nucleotide phosphorylase): enzymes which remove metabolites in lymphocytes Severe infections Treatment: gene therapy

Systemic Lupus Erythematosus (SLE) Antibodies against nucleic acids in the connective tissues (antinuclear antibodies or ANA) Women Immune complex deposits: kidneys joints skin lungs serous membranes

SLE Wire-loop lesions in the kidneys (subendothelial layer) Eye lesions Fever, body pains, joint pains Pericarditis/pleuritis Raynaud phenomenon Endocarditis Libman-Sacks vegetations on mitral valve