IMMUNODEFICIENCY Lecture Outlines Define immunodeficiency

Slides:



Advertisements
Similar presentations
The lymphatic system and immunity
Advertisements

Immunodeficiency K.J. Goodrum Origins of Immunodeficiency Primary or Congenital –Inherited genetic defects in immune cell development or function,
Background on Zap70 SCID Slides from Arthur Weiss GEMS Journal Club August 2012.
Immunology Dr. Hal Sternberg MCB 135E Lecture
Lectures 1 & 2 The immune system Overview
Final Case Study: Case #3 Rabin Anouseyan Alex Huynh Kimberly Rampasan California State University, Los Angeles Department of Biological Sciences.
Non-specific defense mechanisms 1st line- skin and mucous –Cilia lined trachea, hairs in pathways 2nd line- –phagocytic WBC –antimicrobial proteins (compliment.
Immunodeficiency Paula O’Leary CP4004 Lecture Nov 2010.
Defenses Against Infection 1. Innate responses (humoral and cellular) 2. Immunity to intracellular pathogens NK cells, control of Th1/Th2 responses 3.
Immune cells, Receptors, and Markers: White blood cells or leukocytes serve as defenders against infection. They move around the body via the lymphatic.
Immunodeficiency K.J. Goodrum Origins of Immunodeficiency Primary or Congenital –Inherited genetic defects in immune cell development or function,
Microbiology 204: Cellular and Molecular Immunology Class meets MWF 11-12:30 Lectures are open to auditors Discussions are restricted to those enrolled.
MICR 304 Immunology & Serology
Principles of Immunology Immunodeficiency 4/20/06 ”Wise people talk because they have something to say; fools, because they have to say something” Plato.
MCB 135E: Discussion November 15-19, Immunology Development Function Important Aspects Bacterial Infection Complement Viral Infection Classes of.
General Microbiology (Micr300)
DEVELOPMENT OF IMMUNE SYSTEM - GESTATIONAL TOLERANCE (PREVENTING REJECTION - FETAL/NEONATAL PROTECTION - VACCINATION/IMMUNIZATION.
Immune Cells , Receptors, and Markers. Lymphoid Tissues and Organs.
Immunity : The Immune system plays a role in combating infection, creating inflammation (& consequently heart disease), controlling (or not) cancer and.
Cells of inflammation and Immunity G. Wharfe 2005.
Primary Immunodeficiency Conleth Feighery Dept. of Immunology MSc in Molecular Medicine 2009.
Unit 1 Nature of the Immune System Part 7 Immunodeficiency Diseases
Immunodeficiencies Board Review December 17, 2007.
Immunodeficiency disease
Immunodeficiency: Primary immune deficiency: -Caused by intrinsic or congenital defects. -Over 100 diseases of this type are known in humans, and for many.
The Wiskott-Aldrich Syndrome: An X-linked Primary Immunodeficiency
Pathophysiology of Immunodeficiency Diseases
Immunodeficiency diseases. Prof. Mohamed Osman GadElRab. College of Medicine & KKUH.
Disorders of Immunity Immunodeficiency Diseases
T cell and B cell activation For Ab production against Antigens.
Indication for an assessment of immune status. 1. Detailed examination of the human health. 2. Genetic defects of the immune system (primary immunodeficiency).
Podcasting is functional Extra slides Larger format slides.
Phagocytosis endocytosis defense role profesional phagocytes.
White Blood Cells Prepared by Dr. Hamad ALAssaf
Disorders Associated with the Immune System
Humoral and Cellular Immunity
IMMUNE SYSTEM Dr. Yıldıran different intracellular signaling pathways Dr. Yıldıran2.
This will be covered later in the course and is presented here to provide context to understanding isotype switching. It will not to be tested in Exam.
Immunology Chapter 21 Richard L. Myers, Ph.D. Department of Biology Southwest Missouri State Temple Hall 227 Springfield, MO
Chapter 18 AIDS and other Immunodeficiences Dr. Capers
Immunodeficiency.
IMMUNODEFICIENCIES AND TUMOR IMMUNOLOGY
Immunodeficiency diseases. Prof. Mohamed Osman GadElRab. College of Medicine & KKUH.
___________DEFENSES of the HOST: THE IMMUNE RESPONSE
The Immune System Dr. Jena Hamra.
IMMUNE COMPROMISED HOST
The Study Of Frequency Of Primary ImmunoDeficiency Disorders In Iran And Constructing A Database For Registering The Patients.
NAJRAN UNIVERSITY College of Medicine NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 15 Microbiology &Immunology Course.
Immune deficiency disorders Dr. Hend Alotaibi Assistant professor & Consultant College of Medicine, King Saud University Dermatology Department /KKUH.
White blood cells and their disorders Dr K Hampton Haematologist Royal Hallamshire Hospital.
INNATE IMMUNE RESPONSES
Cytokines To highlight the major cytokines that are mediators of: (i) natural immunity, (ii) adaptive immunity and (iii) hematopoesis.
IMMUNODEFICIENCY DIASEASES Tang Yongmin, MD Department of Hematology-oncology Children’s Hospital Zhejiang University School of Medicine.
Hypersensitivity, Autoimmunity and Immunodeficiency Part III Nancy L Jones, MD August 29, 2011.
Humoral immunity Antibody structure Antibody diversity
Lecture 7 Immunology Cells of adaptive immunity
Immune deficiency disorders
Immunodeficiency diseases
Summary. The main function of the immune system Defense Autotolerance Immune supervision Antigens Exoantigeny (allergens, superantigeny...) autoantigens.
M1 – Immunology CYTOKINES AND CHEMOKINES March 26, 2009 Ronald B
Effector Mechanisms of Humoral Immunity
Immunodeficiency Results from the absence, or failure of normal function of one or more elements of immune system. involve abnormalities of T or B cells,
Immunodeficiency disorders
Summary J.Ochotná.
Primary Immunodeficiency Disorders
Immunodeficiency: Primary immune deficiency:
Immunodeficiencies.
Immunodeficiency disorders
Immunodeficiency Disorders
The Lymphatic System and Immunity
Presentation transcript:

IMMUNODEFICIENCY Lecture Outlines Define immunodeficiency Classification Specific non specific Primary and secondary B cell deficiency & Examples T Cell deficiency & Examples SCID Drug induced immunodeficiency

It is the absence or failure of normal function of one or more elements of the immune system Results in immunodeficiency disease Can be specific or non specific Specific = Abnormalities of B & T cells Non specefic = Abnormalities of non specific components PRIMARY OR SECONDARY

PRIMARY IMMUNODEFICIENCIES Primary immunodeficiencies are inherited defects of the immune system These defects may be in the specific or nonspecific immune mechanisms They are classified on the basis of the site of lesion in the developmental or differentiation pathway of the immune system

B CELL DEFICIENCY X liked a gammaglobuinemia IgA deficiency IgG subclass deficiency Immunodeficiency with increased Igm Common variable immundeficiency Transient hypogammaglobulinaemia of infancy

1- X-linked a gammaglobulinaemia In X-LA early maturation of B cells fails Affect males Few or no B cells in blood Very small lymph nodes and tonsils No Ig Small amount of Ig G in early age Recurrent pyogenic infection

2- IgA and IgG subclass defeciency IgA deficiency is most common Patients tend to develop immune complex disease About 20% lack IgG2and IgG4 Susceptible to pyogenic infection Result from failure in terminal differentiation of B cells

3- Immunodfeiciency with increased IgM (HIgM) Results in patients with IgA and IgG deficiency Production of large amount of IgM >200mg/dl of polyclonal IgM Susceptible to pyogenic infection Treatment by iv gamma globulin Formation of IgM to neutrophils, platelets and other blood components Due to inability of B cells to isotype switching

4- Common Variable Immunodeficiency (CVID) There are defect in T cell signaling to B cells Acquired a gammaglobulinemia in the 2nd or 3rd decade of life May follow viral infection Pyogenic infection 80% of patients have B cells that are not functioning B cells are not defective. They fail to receive signaling from T lymphocytes Unknown

5- Hypogamaglobulinaemia of infancy Due to delay in in IgG synthesis approximately up to 36 months In normal infants synthesis begins at 3 months Normal B lymphocytes Probably lack help of T lymphocytes

DISORDERS of T CELLS DiGeorge's syndrome: It the most understood T-cell immunodeficienc Also known as congenital thymic aplasia/hypoplasia Associated with hypoparathyroidism, congenital heart disease, fish shaped mouth. Defects results from abnormal development of fetus during 6th-10th week of gestation when parathyroid, thymus, lips, ears and aortic arch are being formed

T cell deficiencies with variable degrees of B cell deficiency 1- Ataxia-telangiectasia: Associated with a lack of coordination of movement (ataxis) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are reduced to various degrees. B cell numbers and IgM concentrations are normal to low.

IgG is often reduced IgA is considerably reduced (in 70% of the cases). There is a high incidence of malignancy, particularly leukemia in these patients. The defects arise from a breakage in chromosome 14 at the site of TCR and Ig heavy chain genes

2- Wiskott-Aldrich syndrome: Associated with normal T cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced but IgG levels are normal Both IgA and IgE levels are elevated. Boys with this syndrome develop severe eczema. They respond poorly to polysaccharide antigens and are prone to pyogenic infection.

MHC DEFICIENCY (Bare leukocyte syndrome): Due to defect in the MHC class II transactivator (CIITA) protein gene, which results in a lack of class-II MHC molecule on APC. Patients have fewer CD4 cells and are infection prone !. There are also individuals who have a defect in their transport associated protein (TAP) gene and hence do not express the class-I MHC molecules and consequently are deficient in CD8+ T cells.

Defects of the phagocytic system Defects of phagocytic cells (numbers and/or functions) can lead to increased susceptibility to a variety of infections. 1- Cyclic neutropenia: It is marked by low numbers of circulating neutrophil approximately every three weeks. The neutropenia lasts about a week during which the patients are susceptible to infection. The defect appears to be due to poor regulation of neutrophil production.

2- Chronic granulomatous disease (CGD): CGD is characterized by marked lymphadenopathy, hepato- splenomegaly and chronic draining lymph nodes. In majority of patients with CGD, the deficiency is due to a defect in NADPH oxidase that participate in phagocytic respiratory burst.

3- Leukocyte Adhesion Deficiency: Leukocytes lack the complement receptor CR3 due to a defect in CD11 or CD18 peptides and consequently they cannot respond to C3b opsonin. Alternatively there may a defect in integrin molecules, LFA-1 or mac-1 arising from defective CD11a or CD11b peptides, respectively. These molecules are involved in diapedesis and hence defective neutrophils cannot respond effectively to chemotactic signals. 

4- Chediak-Higashi syndrome: This syndrome is marked by reduced (slower rate) intracellular killing and chemotactic movement accompanied by inability of phagosome and lysosome fusion and proteinase deficiency. Respiratory burst is normal. Associated with NK cell defect, platelet and neurological disorders

Disorders of complement system: Complement abnormalities also lead to increased susceptibility to infections. There are genetic deficiencies of various components of complement system, which lead to increased infections. The most serious among these is the C3 deficiency which may arise from low C3 synthesis or deficiency in factor I or factor H. 

SEVERE COMBINED IMMUNODEFICENCY In about 50% of SCID patients the immunodeficiency is x-linked whereas in the other half the deficiency is autosomal. They are both characterized by an absence of T cell and B cell immunity and absence (or very low numbers) of circulating T and B lymphocytes. Patients with SCID are susceptible to a variety of bacterial, viral, mycotic and protozoan infections.

The x-linked SCID is due to a defect in gamma-chain of IL-2 also shared by IL-4, -7, -11 and 15, all involved in lymphocyte proliferation and/or differentiation. The autosomal SCIDs arise primarily from defects in adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) genes which results is accumulation of dATP or dGTP, respectively, and cause toxicity to lymphoid stem cells

Diagnosis Is based on enumeration of T and B cells and immunoglobulin measurement. Severe combined immunodeficiency can be treated with bone marrow transplant

SECONDARY IMMUBODEFICIENCY

IMMUNODEGECIENCY CAUSED BY DRUGS CORTICOSTEROIDS Cause changes in circulating leukocytes Depletion of CD4 cells Monocytopenia Decreased in circulating eosinophils and basophils Inhibition of T cell activation and B cell maturation Inhibit cytokine synthesis

METHOTREXATE Structural analogue of folic acid Blocks folic acid dependent synthetic pathways essential for DNA synthesis Prolonged use for treatment reduces immunoglobulin synthesis

CYCOLOSPORIN Have severe effects on T cell signaling and functions It binds to immunophilins which are believed to have a critical role in signal transduction Also inhibit IL 2 dependent signal transduction

OTHER CAUSES Malnutrition Minerals Vitamins Obesity