UNIT X: IMMUNOLOGICAL DISORDERS 1
Objectives: Review the following concepts of immune response Components of immune response Humoral versus cell mediated immunity Antigen processing, presentation and recognition. Immediate and delayed hypersensitivity Discuss the disorder of immune response including. AIDS (Acquired Immunodeficiency syndrome) & Hypersensitivity (allergies.) Discuss the epidemiology, pathogenesis & clinical manifestation of HIV infection. Discuss the pathophysiology of different types of hypersensitivity (Type I, Type II, Type III & Type IV) 2
Immunity The defense mechanisms of the body against microorganisms, toxins and other foreign particle which are harmful for the body. Resistance to disease by means of antibodies. The human body capacity to resist almost all type of organism and toxins which tend to damage tissue or organs. 3
Components of immune system 1. Lymphocytes 2. Lymphoid tissues ( thymus, spleen, bone marrow, tonsils ) 3. Immunoglobulin's (antibodies) 4
T-lymphocytes Processed by the thymus gland, Hormone thymosin, Which leads to the formation of fully mature, functional T-lymphocytes. T-lymphocyte has been programmed to recognize only one type of antigen T-lymphocytes provide cell-mediated immunity
Types of T lymphocytes Cytotoxic or killer T cells (releases toxins, which cause foreign cell destruction) Helper T cells (Directing the immune response) Suppressor T cells (Inhibit the production of cytotoxic T cells once they are unneeded) Memory T cells (Recognize and respond to a pathogen once it has invaded and been repelled) 6
B-lymphocytes These are processed in the bone marrow. Role is in production of antibodies (immunoglobulins), which are proteins designed to bind to, and cause the destruction of, an antigen. B-lymphocytes provide antibody mediated immunity (humoral), There is therefore a vast number of different T- and B- lymphocytes in the body, each capable of responding to only one antigen.
8
9
Antibodies: Antibodies belong to a class of proteins called immunoglobulins. The antibody rich serum component is called gamma globulin. These proteins can recognize, bind to, and help cause the destruction of antigens. Antibodies can only interact with one antigenic determinant on an antigen (specific region of antigen molecule) 11
Immunoglobulin A protein produced by lymphocytes in response to the entry of an antigen into the body. Or Protein produced by the body in response to foreign antigens 12
IgG Placental Transfer Location: distributed in intra vascular and extra vascular areas Functions: weakens the bacteria Enhances phagocytosis Neutralizes bacterial toxins and viruses. enhance bacteria killing. 13
IgM Location: restricted to blood because of large molecular weight and size More effective then IgG Can t Transfer Placenta Functions: First antibodies produced during an infection. Produce in primary response to an antigen. Fixes the balance. 14
IgA Location: Secretions (tears, saliva, intestine, milk), blood and lymph. Can t Transfer Placenta Functions: Localized protection of mucosal surfaces. It prevents the attachment of bacteria and viruses on the mucous membrane 15
IgD Location: B-cell surface Can t Transfer Placental Known Functions: In serum function is unknown. 16
IgE Location: Bound to mast cells (connective tissue) and basophils throughout body. Can t Transfer Placental Functions: Mediate immediate hypersensitivity by causing release of chemical mediators from mast cells and basophils upon exposure to an Allergens. 17
Stages of immune response 1. Recognition stage (foreign body recognition) 2. Proliferation stage (differentiate into cytotoxins T or B cells) 3. Response stage (T and B performs cellular or humoral functions) 4. Effector stage (antigen destroyed or neutralized) 18
AIDS Acquired immuno deficiency syndrome HIV Human immuno deficiency virus 19
AIDS/HIV Collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV) in humans. HIV attacks the body's immune system by weakening the body's defense against disease; HIV makes the body vulnerable to a number of potentially life-threatening infections and cancers. 20
HIV Transmission HIV is transmitted in body fluids containing HIV, these fluids include Blood, Seminal fluid, Vaginal secretions, Amniotic fluid, Breast milk. Sexual route Perinatal route Parenteral Route 21
22
23
Stages of HIV/AIDS Acute HIV infection: (usually a few weeks to months), (CD4 T-cell count greater then 500 cells/mm3 ). viral replication + killing of CD4 receptors = Last for years. Asymptomatic HIV infection (no symptoms) (CD4 T-cell count b/w 200 to 499 cells/mm3 ). Symptomatic HIV infection (symptom appears) It progresses to AIDS (advanced HIV infection with CD4 T- cell count below 200 cells/mm3 ). 24
Clinical manifestations AIDS are widespread and may affect any organ system. AIDS results infections, malignancies. The followings are the common clinical manifestations and effects of severe HIV infection. 1. Respiratory manifestations Pneumocystis carinii Pneumonia (PCP): PCP is the initial manifestation of AIDS in 60% of patient. Clinical feature include fever, chills, non productive cough, shortness of breath, chest pain. Tuberculosis: Tuberculosis infection is more common in injecting drug users. Tuberculosis responds well to antituberculosis therapy. 25
2. Gastrointestinal manifestations. Wasting syndrome: Diagnostic criteria include profound involuntary weight loss, weakness, intermittent or constant fever. Anorexia, diarrhea, GI mal-absorption and lack of nutrition in chronic disease all contribute to wasting syndrome. Oral Candidiasis: A fungal infections occur in nearly all patients with AIDS. It is characterized by creamy white patches in oral cavity. If untreated then oral candidiasis will progress to involve the esophagus and stomach. 26
3. Oncologic manifestations Kaposi s sarcoma (KS): KS is the most common HIVrelated malignancy, is involving the endothelial layer of blood vessels and lymphatic system. KS was first noticed in 1872 by Dr. Moritiz Kaposi. KS is most often seen in homosexuals and bisexuals. Cutaneous lesions (Usually brownish pink to deep purple) appears on whole body. Diagnosis of KS is conformed by biopsy of suspected lesions. 27
4. Neurological Manifestation HIV encephalopathy: It is also referred as the AIDS dementia complex (ADC). This condition occurs in two thirds of patients with AIDS. It is clinical syndrome characterized by a progressive decline in cognitive, behavioral and motor functions. HIV has been found in the brain and cerebrospinal fluid (CSF) of the patient s with ADC. HIV release the toxins or lymphokinnes that cause the cellular dysfunction or interference the functions of neurotransmitters rather than cell damage. 28
5. Depressive manifestations Irrigational guilt and shame Loss of self esteem Helplessness feelings Suicidal idiatation. 6. Specific manifestations in women Vaginal candidiasis 29
Investigation ELISA TEST (enzyme-linked immuno sorbent assay) Polymerase Chain Reaction (PCR) Viral load Western blot CD4 ratio T lymphocytes 30
Treatment of HIV Infection: Treatment decisions for an individual patient are based on three factors: Nucleoside analog reverse transcriptase inhibitors (NRTIs) Zidovudine Lamivudin 31
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) These drugs bind to and block HIV reverse transcriptase (an HIV enzyme). HIV uses reverse transcriptase to convert its RNA into DNA (reverse transcription). Blocking reverse transcriptase and reverse transcription prevents HIV from replicating. Drugs are: Nevirapine (Viramune) Delavirdine (Rescriptor) Efavirenz (Sustiva) Tenofovir (Viread) 32
Hypersensitivity (Allergy) Allergy is powerful immune response to an antigen (allergen). The allergen itself is usually harmless (e.g. house dust, animal dander, grass pollen). It is therefore usually the immune response that causes the damage to the body, not the allergen itself. There are four mechanisms of hypersensitivity, which are classified according to what parts of the immune system are involved.
Type I, anaphylactic hypersensitivity Inherited very high levels of a type of antibody immunoglobulin E (IgE). When exposed to an allergen, e.g. house dust, antibody activate mast cells and basophils. They released is histamine, which constricts some smooth muscle (e.g. airway smooth muscle), causes vasodilatation and increases vascular permeability Examples of type I reactions include the serious situation of anaphylaxis. There is profound bronchoconstriction and shock due to extensive vasodilatation. The condition can lead to death.
Type II, cytotoxic hypersensitivity Antibody reacts with an antigen on a cell surface, that cell is marked for destruction by a number of mechanisms, e.g. phagocytosis, or destruction by lytic enzymes. This is the usual procedure in the elimination but if the antibodies are directed against self-antigens the result is destruction of the body's own tissues (autoimmune disease). Type II mechanisms cause other conditions, e.g. haemolytic disease of the newborn and transfusion reactions.
Type III, immune-complex-mediated hypersensitivity Antibody-antigen complexes (immune complexes) are usually cleared efficiently from the blood by phagocytosis. If they are not, for example when there is phagocyte failure or an excessive production of immune complexes (e.g. in chronic infections), they can be deposited in tissues, e.g. kidneys, skin, joints and the eye, where they set up an inflammatory reaction. The kidney is a common site of deposition since it receives a large proportion of the cardiac output and filters the blood. Immune complexes collecting here lodge in and block the glomeruli, impairing kidney function (glomerulonephritis). Sensitivity to penicillin is also a type III reaction; antibodies bind to penicillin (the antigen), and the symptoms are the result of deposition of immune complexes in tissues rashes, joint pains and sometimes haematuria.
Type IV, delayed type hypersensitivity Unlike types I-III, type IV hypersensitivity does not involve antibodies, but is an overreaction of T-lymphocytes to an antigen. When an antigen is detected by memory T-lymphocytes, it provokes clonal expansion of the T-lymphocyte, and large numbers of cytotoxic T-lymphocytes are released to eliminate the antigen. Usually this system is controlled and the T-lymphocyte response is appropriate. If not, the actively aggressive cytotoxic T-lymphocytes damage normal tissues. An example of this is contact dermatitis. Graft rejection is also caused by T-lymphocytes; an incompatible skin graft, for instance, will become necrotic and slough off in the days following application of the graft.
References Porth, MC. (6th ED). Pathophysiology. (2002). Philadelphia. USA. Lippincott Willams& Willkins, A Wolters Kluwer Company McPhee, J. S., & Papadakis, A. M. (2011). Current Medical Diagnosis and Treatment. (50 th ED). Chicago. USA: Mc Graw Hill
40