Dr ROOPAPremed 2

Pathophysiology

IMMUNITYThe term immunity refers to the resistance

exhibited by the host towards injury caused by microorganisms and their products..

Natural or Non-specific ImmunityRespone 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 memoryExposure 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.

Normal Immune SystemPrimary Lymphoid organsSecondary Lymphoid organsCellsCytokinesComplement systemHLA 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),

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) .

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.

 

HypersensitivitiesType I : immediate, anaphylactic1st exposure to an antigen: stimulates IgE to

bind to mast cells, basophils2nd exposure: IgE causes lysis of the cells,

release of histamineAllergic asthma, atopic dermatitis, seasonal

rhinitis, systemic anaphylaxis

Type II: antibody-mediated or cytotoxicAntigens are bounded to human basement

membranes in tissuesOr to blood cell membranesAntibodies, COMPLEMENT react to the

antigens, NK cells may add on to the injury

Type II hypersensitivityHemolytic disease of the newbornBlood transfusion reactionsGoodpastures syndrome: kidney and lung

abnormalities

Type III: immune complex mediated Antigen is NOT part of the cell, or basement

membraneImmune complex: antigen+ antibodyVery insoluble, not removed by macrophagesDeposited on vessel walls, extravascular sites

Type IIISystemic lupus erythematosus (SLE)Serum sicknessArthus reactionPoststreptococcal glomerulonephritis

Type IV: delayed hypersensitivity, cell-mediated

CD4 cells react to MHC Class IIMemory cells2nd exposure to antigen: stronger reactionCD cells may also be involved

Type IVTuberculin testContact dermatitis

Transplant reactionsMatching ABO blood groupMatching HLA antigensOrgans that can be transplanted:

liverkidney lungsbone marrowskin

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 rejectionHyperacute: 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.

Graft-versus-host diseaseCommon in bone marrow transplantImmunocompetent cells in the transplant

(graft)Host cells are damaged by:

CD8+ cellscytokinesmacrophages

Organs damaged: liver, skin, GITFever, rash, large liver, jaundice

Primary Immunodeficiency diseasesX-linked agammaglobulinemiaOr Bruton’s agammaglobulinemiaMale babies, more than 6 months oldAbsent plasma cells

absent germinal centersabsent IG

Prone to bacterial infections

IgA deficiencyMost common B cell defect1 in 700 persons, CaucasiansMay be with no symptoms (asymptomatic)Recurrent Upper respiratory tract infection

(URTI) and frequent diarrhea

Severe Combined Immunodeficiency Disease (SCID)Low B cells and T cellsAbsence of ADA (adenosine deaminase) or

PNP ( purine nucleotide phosphorylase): enzymes which remove metabolites in lymphocytes

Severe infectionsTreatment: gene therapy

Systemic Lupus Erythematosus (SLE)Antibodies against nucleic acids in the

connective tissues (antinuclear antibodies or ANA)

Women Immune complex deposits:

kidneys jointsskinlungsserous membranes

SLEWire-loop lesions in the kidneys

(subendothelial layer)Eye lesionsFever, body pains, joint painsPericarditis/pleuritisRaynaud phenomenonEndocarditisLibman-Sacks vegetations on mitral valve