Immunogenetics Flashcards
• Have Lymphoid Progenitor for Lymphocytes
- Becomes T cell in……..
• Important in
- Becomes B cell in ……………
Thymus
Cellular Immunity
• Develop into CD4, CD8 or other cells
- Secretes cytokines, interleukins, etc.
- Assists B cells in making immunoglobulins
Bone Marrow
• Begins with IgM
• Matures to form other immunoglobulins
- IgA, IgE, or IgG (with subelasses IgG1-4)
• Mature cell is Plasma cell
• Immunoglobulins used to surround antigens for phagocytosis
• Responsible for Specific immunity (and memory)
• Papaine splits the immunoglobulin molecule into three fragments?
- Two similar, each containing an
antibody site capable of combining with a specific antigen antigen-binding fragment or Fab - The Crystallizable fragment Fc
Second line of defense
• Phagocytic white
blood cells
• Antimicrobial proteins
• The inflammatory
response
The immunoglobulin molecule is made up of four polypeptide chains:
………..
……….
Each Fab fragment is composed ………..
Fc fragment is composed………
•Two light(L) 220 AA
•Two heavy (H) 440 AA
of L chains linked to the amino-terminal portion of the H chains,
only of the carboxy-terminal portion of the H chain
How do we acquire so many different types of antibodies?
• Somatic recombination
• Junctional diversity
• hypermutations
What is Immunoglobulin
Responsible for allergic symptoms in immediate hypersensitivity reactions
IgE
Main antibody type in external secretions such as saliva and mother’s milk
IgA
Main form of antibodies in circulation production increased after immunization; secreted during secondary response
IgG
Function as antigen receptors on lymphocyte surface prior to
immunization; secreted during primary response
IgM
Function as antigen receptors on lymphocyte surface prior to
immunization; other functions unknown
IgD
The major histocompatibility
complex is a large group of genes on chromosome
short arm
6
MHC Class I
Type
Found on
Recognized by
Function
HLA-A, HLA-B, HLA-C
All nucleated somatic cells
CD8/ TC cells
Presentation of Ag to TC cells leading to elimination of tumor or infected host cell
MHC Class II
Type
Found on
Recognized by
Function
HLA-DP, HLA-DO, HLA-DR
Macrophages, B-cells,
Dentritic cells, langerhans cells of skin and activated T cells
CD4 TH cells
Presentation of Ag to TH cells which secrete cytokines
Immunogenetic disorders
treated with
hematopoietic
Stem cell!transplantation.
Severe combined immunodeficiency (SCID):
Affect …..
Onset age …….
the most severe forms of T cell disorders. SCID can result from
genetic mutations that affect lymphocyte production, and
development.
• Onset age at early infants(4 - 5 months)
• Recurrent infection
with fungi, virus, bacteria,
mycobacterium, protozoa
• Opportunistic infections
• Poor prognosis, early infant deaths
• Severe infection after live
virus vaccine and BCG
• GVHD after blood transfusion
High risk of malignancy
X-linked hyper IgM syndrome:
occurs almost exclusively in
……
Patients with this disorder have
Male
Patients with this disorder have abnormal high levels of immunoglobulin M (IgM), and low levels of three other classes of antibodies: immunoglobulin G (IgG),immunoglobulin A (IgA), and immunoglobulin E (IgE).
X-linked agammaglobulinemia (XLA):
due to mutation in…….
the molecular basis for XLA is a disruption in B cell development
Mutation in in Bruton’s tyrosine kinase (Btk) present on X
chromosome.
liable to invasive infections from
encapsulated bacteria, ,enterovirus infections
DiGeorge Syndrome
• Deletion of chromosome
22q11.2
- Defective development of 3rd and 4th pharyngeal pouches
• Absence of Thymus
- Therefore low or absent T cells
- No B cell abnormalities except in more severe forms.
• Associated Anomalies
- Conotruncal Cardiac Defects
•VSD
• Tetralogy of Fallot
• Interrupted Aortic Arch
- Parathyroid Hypoplasia
• Low Calcium
•Tetany
Chronic Granulomatous Disease
• Genetics
- 70 % X-linked recessive
- Defect in NADPH oxidase
- Can’t form reactive oxygen species to destroy micro-organisms
• Symptoms
- Pneumonia, Abscesses, Adenitis, Osteomyelitis
- Uniquely susceptible to Aspergillosis
• Associated Symptoms
- Severe Acne
- Excessive Granulomata - often in GI tract
- Lupus
- Chorioretinitis
• Diagnosis - Nitroblue Tetrazolium Test (NBT)
• Treatment
- Antibacterial and antifungal prophylaxis
- Interferon Gamma
- Stem cell or Bone Marrow Transplant
Wiskott-Aldrich syndrome:
X-linked Recessive
• Gene defect of WAS protein
•B and T cells dysfunction
• Triad of
- Thrombocytopenia
- Eczema
- Recurrent Pyogentic infections
• Treatment - Stem cell or Bone Marrow transplant
• Prognosis - Average life expectancy 11years
