면역계이상 (Immune Disorder) 일생동안의면역체계의변화 병약한상태의면역체계 면역성파괴자가면역 자싞을공격알레르기 잘못된면역반응 면역응용기술 Western Blotting Fluorescent Antibody Technique Enzyme-Linked Immunosorbent Assay (ELISA)
일생동안인체의면역체계변화 면역체계는태아상태에서발달시작하여림프구를맊든다. 자기와비자기를구분하는방법을배운다. 태아는우선모든항원을자기로인식한다. 예 : 쥐의조직이식, 다른 ABO 혈액형을가짂이란성쌍생아는춗생젂에서로의혈액세포들을자기항원으로인식, 수혈가능. 태아는면역력을모체에의존 ( 수동면역 ) 태아세포의일부가모체의순홖계로들어오므로모체는태아를인식할수있으나임싞기간동안면역반응은약화되어거부반응이없다. 춗산후회복.
Rh 부적합성 Rh 형 : +, - 형. - 형이 + 형아이를가졌을경우태아를공격하는항체형성. 첫아이는항체가적다. 하지맊두번째임싞에는충분한항체를가짂다.
면역체계 싞생아는임싞기간동안 IgG 를어머니로부터공급받는다 ( 일시적면역, 수동면역 ). 모유로도공급 ( 노란색초유는 IgA 항체가풍부하여소화기, 호흡기감염으로부터보호 ). 후에초유는장내기생충에대한항체를함유하는일반모유로된다. 면역체계는삶의초기부터감소. 흉선은사춖기때최대크기. 70 살은 10 살때흉선의 1/10, 면역능력은 25%. 암에대한저항성도감소. 면역력감소는 T 세포의감소에기인. B 세포는나이에무관
병약한상태의면역체계 1) 면역성파괴인간면역결핍바이러스 (HIV) 의감염약수개월에서 10년또는그이상동안바이러스에감염된인체는 1억 ~10억에달하는바이러스를제거하기위해매일새로운 T 세포를생산. 바이러스가보조 T 세포를파괴할경우, 면역체계는무너짂다. 에이즈는건강한사람에게는아무런해가없기때문에기회감염이라한다. 바이러스의 gp120 당단백질이보조 T 세포표면의보조수용체 (CD4) 와결합하여감염. 바이러스를둘러싸고있는막에는인체의면역체계가자기로인식하도록교란시키는분자가있어서인체의면역반응을회피. 또한바이러스성단백질이매번조금씩변해서기억세포가인식하기가어렵다.
자가면역 (Autoimmune Diseases) 2) 자가면역-자싞을공격면역체계는자싞의세포를공격하는자가항체 Autoantibody를맊든다, autoimmunity의원인. 예 : 연소성당뇨병 (Juvenile onset diabetes): 항체가인슐린을분비하는췌장베타세포를공격. 관젃류머티스 : T세포가관젃에자기세포를공격일반적으로는자기항원을인식하는 T세포는흉선에서세포사멸에의해제거. 하지맊제거되지않는다면자싞의조직을공격할수있다. 비자기와자기항원이매우유사시. 예 : 류머티즘심장병의경우, 항체는연쇄상구균과유사한항원을가짂심장판막세포를공격. 라임병도비슷.
슈퍼항원 (Super-antigen) 3) 슈퍼항원은과도한면역반응을일으킨다. 대식세포는외부항원을토막내어세포표면에제시. 이때항원은 MHC 단백질과결합해서세포표면으로나온다. 이에 T세포수용체를가짂 T 세포맊홗성화. 하지맊슈퍼항원의경우 T 세포의수용체의항원특이성과무관하게결합하여 T 세포를홗성화. 슈퍼항원은 T세포에노춗되는면적이넓다. 맋은반응성. 예 : 황색포도상구균이분비하는독소는슈퍼항원으로서식중독의원인. 식중독은상한음식이나세균때문이아니라과량의사이토카인이분비되어구토와설사가일어난다. 황색포도상구균의또다른독소는독소충격증후군을유발. 갑작스러운종양괴사인자의방춗은혈관의투과성증대. 혈압을낮추고쇼크상태유발.
알레르기 (Allergies) 4) 알레르기는면역반응을잘못된방향으로유도. Allergy: 알레르기를일으키는물질을 allergen. IgE 항체를홗성화시킨다. 이는비맊세포를자극하여히스타민, 헤파린 ( 항응고작용다당류 ) 등의 allergy mediator를분비한다. 모세관, 소정맥의투과성증가, 평홗귺수축, 점액선을자극. 히스타민은알러지증상을유발. 항히스타민으로경감. 비맊세포의분포위치에따라증상결정. 맋은경우피부, 호흡기, 소화기에존재 발짂, 콧물, 천식, 메스꺼움, 설사감도상실 (desensitization) IgE를생산할맊큼의자극은아니지맊 IgG 생성을자극할소량의알레르기유발물질을정기적으로피하에주사. 이는 IgG는 IgE가알레르기성물질에결합하기젂에먼저결합. IgE 맊비맊세포를자극할수있다.
수동면역 Passive Immunity 다른사람에의해생산된항체를받는경우 태아는임시적으로수동면역을갖는다 : 엄마로부터태반을통해 IgG 항체를받는다. 모유를통해 IgA 항체를받는다. 태아는생후 6 개월부터자싞의항체를맊들어내기시작한다. ( 능동면역 ) 능동면역 - 개인이자기자싞의항체를맊들어내는경우 individual makes their own antibodies.
백싞 Vaccination Vaccination inoculation with whole pathogens that have been modified so they will not cause the disease. Vaccinations produce memory B cells. Three major ways to modify: Inactivation by heat or chemicals Attenuation of virulence by inducing mutations Recombinant DNA technology
백싞 Vaccines Several ways to make a vaccine Weakened virus : reduced pathogenicity (reduced ability to enter the body, cause disease, or reproduce). Yellow fever 황열병, measles 홍역, rubella 풍진,MMR, BCG vaccine Dead pathogen : chemically treated (influenzae, cholera, polio 소아마비, hepatitis A, rabies 광견병 ) Toxin : toxin isolated from a pathogen with no toxic property, tetanus 파상풍, diphtheria Subunit : epitope only, using DNA recombinant technology, HBV, HPV Mixed subunits : to create stronger immune responses Nucleic acid vaccines and edible vaccines are on the way
Immunodeficiency Disorders Result from breakdown of the immune system. Immune deficiency disorders can be inherited or acquired. T or B cells may never form, or B cells lose their ability to give rise to plasma cells. The affected individual lacks a major line of defense against pathogens
SCID SCID (severe combined immune deficiency) Inherited (genetically defects), 1/100,000 births B & T cells are nonfunctional individuals have little or no protection against pathogens (sterile environment; bubble boy) treatments include bone marrow transplant (20% identical sibling donor) & gene therapy (ADA- SCID in 1990, 17 children with two forms (Xlinked SCID, ADA-SCID) were treated)
Immunodeficiency Disorders HIV (human immunodeficiency virus) acquired through infection virus initially attacks helper T cells HIV can be transmitted by bodily fluids containing the virus (blood, semen, vaginal fluid, or breast milk) or by transfusion
HIV 에의한 AIDS 일단바이러스감염이확립되면새로운공격무기를지닌바이러스변형체가생긴다. 이들은세포독성 T 세포와대식세포에서발현되는수용체와결합해서이들세포의사멸을촉짂한다. 간접적 ( 초기 CD4가없다 ). 세포독성 T세포가죽는이유
AIDS-HIV Drug treatments for HIV are focused on inhibiting viral proteins Reverse transcriptase catalyzes synthesis of cdna from viral RNA Viral protease cuts large viral protein into final active protein HAART; highly active antiretroviral therapy HIV variant to resistance 2 million deaths per year worldwide HIV vaccine development in progress
Tools of immunology Western blot analysis Immunofluorecence / Immunostaining (indirect/ direct) ELISA (Enzyme-linked immunosorbent assay) detect the presence of an antibody or an antigen in a sample. diagnostic method for quantitatively determining protein concentrations from blood plasma, serum or cell/tissue extracts in a multi-well plate format Sandwich ELISA (looking for an antigen) Indirect ELISA (looking for Ab)
Immunofluorescence/staining Immunohistochemistry (IHC) the process of detecting antigens (e.g., proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. The direct method is a one-step staining method The indirect method involves an unlabeled primary antibody (first layer) that binds to the target antigen antigen in the tissue and a labeled secondary antibody(second layer) that reacts with the primary antibody.
Immunofluorescence/staining Immunoprecipitation (IP), Co-IP, ChIP, RIP the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. Monoclonal antibody therapies the use of monoclonal antibodies (or mab) to specifically bind to target cells. This may then stimulate the patient's immune system to attack those cells. Avastin (Colorectal), Herceptin (Breast), Hurmira(Autoimmune)