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Basic immunology

IMMUNITY

The term Immunity is derived from the Latin word Immunitae, which referred to the protection from the legal prosecution offered to Roman Senators during their tenure in office. Refers to the resistance exhibited by the host towards injury caused by microorganisms and their products.

Protection against infectious diseases
Distinguishes self from non-self
Eliminate potentially destructive foreign substances from body


INNATE IMMUNITY
Resistance to infection which individual possesses by virtue of his genetic and constitutional make up Early defense response against microbes Immune response Non specific Innate response do not alter on repeated exposure Memory effect absent Not affected by immunisation or prior contact

ACQUIRED IMMUNITY
The resistance that an individual acquires during life Later defense response Immune response is highly specific Adaptive response improves with each successive encounter with same pathogen Memory effect present Is improved by immunisation

Species immunity
 Refers to the total or relative refractoriness to a pathogen, shown by all members of species.
 Person obtains by virtue of being a part of the human species.  Determines whether or not a pathogen can multiply in them. For e.g.  All human beings are totally unsusceptible to plant pathogens and to, many animal pathogens, such as render pest or distemper.
Pasteur’s experiments on anthrax in frogs, which are naturally resistant to the disease but become susceptible when their body temperature is raised from 25° to 35°C.

Racial immunity
 Racial differences are known to be genetic in origin For e.g.
 People of Negroid origin in USA are more susceptible than the Caucasians to tuberculosis.
 Genetic resistance to Plasmodium falciparum Malaria seen in some parts of Africa and Mediterranean coast. A hereditary abnormality of red cells (sickling) prevalent in the area, confer immunity to infections by malarial parasite.

Individual immunity
 The difference in innate immunity exhibited by different individuals in a race
 The genetic basis of individual immunity is seen in twins. For e.g. Homozygous twins exhibit similar degrees of resistance or susceptibility to Lepromatous leprosy and Tuberculosis.

Innate immunity does not recognize every possible antigen instead it recognizes pathogen-associated molecular patterns. Receptors enable the phagocyte to attach to these patterns so it can be engulfed and destroyed by lysosomes.
Pathogen-Associated Molecular Patterns Binding to Endocytic PatternRecognition Receptors on Phagocytes

Determinants of innate immunity
I. Species and strains
II. Age
III. Hormonal Influences
IV. Nutrition

MECHANISMS OF INNATE IMMUNITY
I. Epithelial surfaces Skin Mucosa of the respiratory tract Human eye. Flushing action of urine
II. Antibacterial substances in Blood and tissues
III. Inflammation
IV. Fever
V. Cellular factors

ACQUIRED IMMUNITY
 A person is said to be immune when he possesses specific protective antibodies or cellular immunity as a result of previous infection or immunization or is so conditioned by such previous experience as to respond adequately to prevent infection Because this form of immunity develops as a response to infection and is adaptive to the infection, it is called adaptive immunity.
The characteristics of adaptive immunity are
 Specificity for distinct molecules.
 An ability to remember and respond more vigorously to repeated exposure to the same microbe. Hence it is also called as specific immunity.

ACTIVE IMMUNITY
1. Produced actively by host’s immune system
2. Induced by infection or by contact with immunogens (vaccines, allergens etc).
3. Affords desirable and effective protection
4. Immunity effective only after a lag period (time required for generation of antibodies).
5. Immunological memory present; subsequent challenge more effective (booster effect)
6. Negative phase may occur
7. Not applicable in immunodeficient hosts

PASSIVE IMMUNITY
1. Received passively by the host
2. No participation by the host’s immune system
3. Conferred by introduction of readymade antibodies
4. Protection transient and less effective Immunity effective immediately
5. No immunological memory subsequent administration of antibodies less effective due to immune elimination
6. No negative phase
7. Applicable in immunodeficient hosts

Natural Active immunity
 This results from either a clinical or inapparent infection.
 Immunity following chicken pox and measles infection is usually life long Artificial Active Immunity
This is the resistance induced by vaccines.
Vaccines are preparations of live or killed microorganisms or their products used for immunization.

Types of Vaccine:
Immunizing agents that are used for immunoprophylaxis
 Bacterial vaccines: Live (BCG vaccine for T.B.).
 Killed (Cholera vaccine).
 Subunit (Typhoid Vi antigen).
 Bacterial products (Tetanus Toxoid).
 Viral Vaccine: Live (Oral polio vaccine – Sabin).
Killed (Injectable polio vaccine – Salk).
 Subunit (Hepatitis B-vaccine).
 Combinations If more than one kind of immunizing agent is included in the vaccine, it is called a mixed or combined vaccine.
DPT (Diphtheria – pertussis - tetanus)
MMR (Measles, mumps and rubella).
DPTP (DPT plus inactivated polio).

Natural Passive immunity
 This is the resistance passively transferred from the mother to the baby. In human infants, maternal antibodies are transmitted predominantly through the placenta.
 Human colustrum, which is also rich in IgA antibodies and resistant to intestinal digestion.
Synthesis of antibodies (IgM) occurs at 20th week of IUL but its immunogenic capacity is still inadequate at birth. It is only by about the age of three month that the infants acquire a satisfactory level of immunological independence.

Artificial passive immunity
This is the resistance passively transferred to a recipient by administration of antibodies.
Passive immunization is indicated for immediate and temporary protection in a non-immune host
Employed for the suppression of active immunity, when the latter may be injurious. Used as treatment of some infections.
Hyper immune sera of animal or human origin, convalescent sera and pooled human gamma globulins are used for prophylaxis and therapy. Rh immune globulin is used during delivery to prevent immune response to the Rhesus factor in Rh-negative women with Rh-positive babies.

Cells of the Innate Immune System: Phagocytes Macrophages play several roles in the immune responses:
 Phagocytosis.
 Required to process and present antigen to immunocompetent T cells for induction of CMI.
 Production of cytokines, such as IL-1 and TNFα, which are proinflammatory
 Lyses tumor cells by secreting toxic metabolites and proteolytic enzymes
 Examples of tissue macrophages are kuppfer cell of the liver, microglial cells of brain, mesangial phagocyte of the kidney, alveolar macrophages of lungs and osteoclasts of bone.


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혈액형 검사( ABO typing)

* 검사가 필요한 경우 혈액이나 성분 혈액제제를 수혈 받을때와 헌혈기관에서 헌혈을 할때, 장기이식할때 혈액형별 수혈 * 분석대상 검체 정맥혈액, 신생아의 경우 발뒤꿈치 혈액 *  ABO 혈액형 검사 원리 적혈구 표면에는 무수히 많은 항원들이 발현되어져 있습니다. 적혈구 인간 적혈구의 두가지 주요 항원 또는 표면표지자들은 A와 B항원들입니다. 혈액형은 이 항원들의 존재유무에 따라 결정됩니다. 적혈구에 A 항원을 가진 사람의 혈액형은 A형; B 항원은 B형; A와B 항원을 모두 가진 사람은 AB형이고 그 어느 표지자도 갖고 있지 않은 사람은 혈액형이 O형이 됩니다.  우리 몸은 자신의 적혈구에 표현되지 않은 A와 B 항원에 대해 자연적으로 항체를 생산합니다. 예를들어 A형 혈액형인 사람은 B형 적혈구 표면항원에 대한 항체를 가지고 B형 혈액형인 사람은 항-A 항체를 가지고 있습니다.  혈액형검사 혈구형 검사(cell typing, front typing) :적혈구에 항-A혈청, 항-B혈청과 반응시키면, 해당항원이 있을 경우 항원-항체 반응에 의해 응집을 보인다. 혈구형 검사 혈구형 검사 혈청형 검사(serum typing, back typing) : 환자의 혈청을 알고 있는 혈액형의 혈구(A cell or B cell)와 반응시키면 환자 의 혈청 내에 동종항체 (항-A 또는 항-B)가 있는지를 알 수 있다. 혈청형검사 혈청형검사 ABO 혈액형을 맞추어 수혈 (또는 장기이식)을 해야 하는 이유는 무엇일까? 앞에서 설명한 바와 같이 A형인 사람은 anti-B 항체를, B형인 사람은 anti-A 항체를, 그리고 O형인 사람은 anti-A,B 항체를 '이미' 가지고 있다. 만약 A형인 사람에게 B형 적혈구를 수혈하면 (즉 major mismatch인 경우에는) A형인 사람이 '이미' 가지고 있는 anti-B가 수혈된 B형 적혈구와 반응하여 보체계(c

IgM

Monomeric IgM IgM only exists as a monomer on the surface of  B cells. Monomeric IgM has a very low affinity for antigen C m 4 contains the transmembrane and cytoplasmic  regions.  These are removed by RNA splicing to produce  secreted IgM Polymeric IgM IgM forms pentamers and hexamers. C m 3 binds C1q to initiate activation of the classical  complement pathway C m 1 binds C3b  to facilitate uptake of opsonised  antigens by macrophages C m 4 mediates multimerisation   (C m 3 may also be involved)

Homocysteine 호모시스테인 과 알츠하이머병

노인들의 기억력 저하와 가장 밀접하게 관련된 질병은 알츠하이머병(Alzheimer’s disease, AD)으로 서양뿐만아니라 동양에서도치매를 일으키는 가장중요한원인 질환으로 알려져있다. 알츠하이머병의 발병에는 나이뿐만 아니라 교육경험, 생활습관, 아밀로 이드 베타 프로테인과 같은 생물학적 요인, 정신과적 문제 등 다양 한 요인들이 영향을 미치는 것으로 알려져 왔다. 최근 연구들에 의하면 고혈압, 동맥경화증, 심방세동, 당뇨, 비만, 뇌졸중과같은 혈관성 질환들이 알츠하이머병의 발생에 위험인자로서 알려져 있다. 더욱이 호모시스테인은 메티오닌의 대사물질로 혈관벽에 산화성 손상을 일으키고 혈관벽의 증식을 일으켜 혈전생성이 촉진되는 상태를 일으킬 수 있어 여러 혈관성 질환의 발생과의 연관성도 밝혀져있다. 특히 혈중 호모시스테인농도는 건강한 정상노인 보다 인지기능의저하가 있는 노인에게 더 높은것으로 여러연구에서 밝혀졌고 이는 알츠하이머병과 다른 종류의 치매에서도 비슷한 결과를 보였다 호모시스테인 농도 수준과 언어적 기억력 및 시각적 기억력 지표들 간에서는 유의한 상관이 발견 되었으나 혈중 호모시스테인농도 수준과 작업기억지표간 에서는유의한 상관이 발견되지 않았다. 혈중 호모시스테인 농도 수준은 언어적 기억력 검사의 지연회상점수와는 부적 상관을 보였으나(r = -0.28, p< 0.05) 즉각회 상점수나 재인점수와는 상관을 나타내지 않았다. 그러나 시각적 기 억력 검사에 있어서는 혈중 호모시스테인 농도 수준과 지연회상점수(r = -0.32, p< 0.05) 및 재인변별력(r = -0.28, p< 0.05)과의 부적 상관 이 관찰되었고 즉각회상은 호모시스테인 수준과 관련이 없는 것으 로 나타났다(Table 2). 상관분석 결과에서와 마찬가지로 회귀분석 결과에서도  혈중 호모시스테인 농도 수준은 언어적 기억력 검사의 지연회상(6.20%)과 시각적 기억력 검사의 지연회상(8.60%) 및 재인 수행(6.40%)에 유의한영향을미치는