A/26-33 IMMUNPATHOLOGY (Tamer) COPY Flashcards
how fast does type 1 hypersensitivity reaction occur?
occurs rapidly -within minutes
may be local and appear as an annoying response to hay fever (allergic rhinitis) or severly weakening the individual during asthma /in a fatal systemic disorder (anaphylaxis)
give the sequence of events during first exposure to allergen
- APC takes up the allergen and presents it via MHC 2 to CD4 + TH2
- When CD4+ TH2 cells are active they secrete cytokines and immunoglobulins. e.g. IL-4,IgE,IL-5,IL-13
- mast cells bind Fc portion of IgE
list the cytokines and immunoglobulins secreted during the first exposure to an allergen
CD4+ TH2 cells secrete :
IL-4 –> Specific B-cells –>IgE
IL-5-->Activates eosinophils
IL-13 –> Epithelial cells –> mucus secretion
what happens in the 2nd exposure to the SAME allergen ?
- allergen binds IgE on mast cells –>biochemical signals –>mast cells secrete the following :
- *Vasoactive amines :**
- Histamine
- Adenosine
- Proteases
- Kinins
LIpid mediators:
Primary:
- prostaglandins
- leukotrienes
*Secondary (late-phase reaction ,2-8 hrs later) :
-*
Neutrophils
-Lymphocytes
-Leukotrienes B4
-Eosinophils –>Release toxins to epithel–>necrosis
what are the two types of anaphylaxis ?
- systemic anaphylaxis
- local anaphylaxis
describe Systemic anaphylaxis
-due to protein antigen (bee sting) /drug (penicillin)
symptoms : itching , hives , skin erythema, respiratory difficulty , vomiting , diahrrea, abdominal crumps
-ARDS in the lung
practically we observe Laryngeal , ARDS, General **edemas
anaphylactic shock without intervention**
describe Local anaphylaxis and give at least 3 examples
- when antigen is limited within a particular site
e. g. - allergic rhinitis (Hay fever , home dust , animal hair)
- itching skin
- food allergy
- asthma bronchiale
Give the clinical picture of Asthma
chronic inflammatory disorder of the airways .
the asthma triad
1) reversible airway obstruction
2) airway inflmmation (bronchial)
3) bronchial smooth muscle hypertrophy, hyperressponsiveness
symptoms include : wheezing ,coughing,dyspnea,chest tightness
how do the pathology cock-sucking bitches classify Asthma?
The classification of Asthma is as follows :
1) extrinsic/atopic -70% of cases
type 1 hypersensitivity
2) intrinsic/non-atopic- 30% of cases
triggered by non-immune stimuli
e.g. aspirin, cold,psychological stress
pathogenesis of Asthma
-begins in childhood
1) first exposure to an allergen :
APC takes up allergen –> CD4+ TH2 cells secrete:
IL-4 –> Specific B-cells –>IgE
IL-5
IL-13
-IgE binds mast cells
——————————————————————————–
2) 2nd exposure to an allergen (allergen triggered asthma)
A) Acute immediate response
allergen binds IgE on mast cells –>biochemical signals –>mast cells secrete the following :
- *-Leukotrienes** C,D,E
- *-Prostaglandins** D2
- *-Histamine**
- Ach
- PAF
- these mediators open intercellular junctions–> more antigens enter airways and bind mast cells
- antigen directly causes vagal stimulation that leads to bronchoconstriction
- edema and mucus secretion are present
B) Secondary (late-phase reaction ,2-8 hrs later) :
mast cells release additional cytokines –> influx of other leukocytes , mainly eosinophils which then release protein toxins that amplify the response
asthmatic attacks are preceded by what ?
- allergic rhinitis
- urticartia /eczema
what are the most common antigens that cause Asthma ?
-dust
-pollen
-animal dander
(tiny particles of skin that had been shed from animals)
describe the micro-morphology of Asthma
“Always On TIME”
- Atelectasis (collapsed pulmn. parenchyma)
- Overdistention due to overinflation
-Thickening of the basement membrane
–Increases size of Mucus glands
-Mucus plugs in bronchi
(Cruschmann spirals /Charcot-Leyden crystals )
-Edema and inflammatory infiltration
clinical course of Asthma
air struggles to get out –> destruction of septa–> emphysema--> capillary diameter decrease–> more effort to pump blood out –> **cor pulmonale
more frequent attacks -higher risk for emphysema and cor pulmonale . aim is to prevent frequent attacks**
type 2 hypersensitivity - basic definition
caused by antibodies generated against endogenous/exogenous antigens
what are the consequences of type 2 hypersensitivity reaction
1) opsonization - cells are tagged with antibodies and are phagocytosed (IgG, c3b)
2) complement activation : via the classical pathway and formation of MAC
3) Antibody mediated cellular dysfunction :
*no cell injury/inflammation*
- Myasthenia Gravis - antibodies against Ach receptors –>muscle weakness
- Graves Disease- antibodies againsy TSH receptors–>hyperthyroidism
- RH-incompatibility -
Mom RH+ Fetus RH-
Blood Mix –>Antibodies Generated–> 2nd Child Screwed–> EDEMA, HYPOXIA , JAUNDICE ,ICTERUS
type 3 hypersensitivity reaction what means dat?
“systemic immune complexes disease”
include formation of antigen-antibody complexes and
their deposition in blood vessels and several organs (systemic) or in a particular organs (localized)
anitgens can be endogenous/exogenous
Pathogenesis of type 3 hypersensitivity reaction
ag-ab complexes formation in circulation –>
deposition in various tissues –>
inflammatory reactions and complement activation (c3a,c4a,c5a)
- complexes also cause platelet aggregation and activation of factor 12 (hageman) –> microthrombi
- ->ischemia
Name at least 3 diseases associated with type 3 hypersensitivity reaction
- reactive arthritis
- post strep. glomerulonephritis
- Systemic lupus erythematosus
- vasculitis
- Polyarteritis nodosa
descrive the micro-morphology of type 3 hypersensitivity reaction
- fibrinoid necrosis (protein deposition)
- microthrombi , ischemic necrosis
- acute inflammation
- fibrosis
Give and example of local immune complex disease
Arthus reaction -
results from acute immune complex vasculitis
inflammation and histologic appearance same as the systemic diseases but localized to one tissue/organ
How does a penguin build it’s house?
Igloos it together.
type 4 hypersensitivity reaction whats mean dat ?
T-Cell Mediated -Delayed Type Hyp.Sens
to which disease is the type 4 hypersensitivity reaction related to ?
Tuberculosis
pathogenesis of type 4 hypersensitivity reaction
1st exposure to bacteria
- APC presents bacteria via MHC 2 –> IL-12
- generation of TH1 and memory cells
2nd exposure
- recruitment of TH1 and memory cells –>secretion of IFN-γ
- macrophages secrete –> PDGF, TGFβ , IL-12 which further enhance the reaction causing Amplification Loop
is the Delayed Type Hypersensitivity reaction acute or chronic ?
Chronic -due to the amplification loop
(chronic unless the toxic agent is eliminated)
what can a prolonged DTH (type 4) reaction result in ? and why ?
Granuloma Formation
activated macrophages –> become epitheloid cells
–>fuse and form giant cells –>surrounded by lymphocytes–>Granuloma surrounded by fibroblasts and CT
describe the T-cell mediated response that occurs during type 4 hypersensitivity reaction
-APC present via MHC 1 to CD8+ T-cells –>become cytotoxic T-cells –> releases of Granzymes and Perforins–> apoptosis of target cell
I thought about going on an all-almond diet
But that’s just nuts
there are 2 facts regarding organ transplantation what are they ?
-recipient and donor have **different MHC
-**
donor cells go through Turn-Over (dying cells removed by phagocytosis) process in recipient’s body–>antigens presented as foreign
List 3 mechanisms of transplant ejection
1) T-cell mediated rejection
involves CD8+ T-cells of recipient and MHC 1 of donor
cytotoxic reaction against cell of the graft
2)Antibody mediated rejection:
dying donor cells release substances–>presented by APC’s MHC2 to CD4+ T-cells–>release of IL-4 IL-5–> Ag’s bind BCR–>B-cells become plasma cells –> Ab’s against graft cells
3)Delayed Type Hypersensitivity Rejection :
APC’s of Donor have MHC2 on them–>reconized by CD4+ T-cells –> differ. into TH1 –>release TNF, IFNγ
–>DTH reaction proceeds
List all the transplant rejection types
1) Hyperacute rejection
- *-minutes/hours**
- by pre-formed antibodies of recipient
- arteritis , arteriolitis
- thrombosis
2) Acute rejection
-weeks/months
A) Acute cellular -related with tubulitis ,CD4+,CD8+,Mononuclear cells –> all cause edema
3) Chronic rejection
-develops within **years
-**
doesn’t respond to immunosuppression
-charecterized by vascular changes(fibrosis) that lead to general ischemia in the organ
list at least 3 methods that improve graft survival
1) try to match between MHC of donor/recipient
2) immunosupression by corticosteroids/cyclosporins
3) Anti CD3 therapy - supress T-cell
4) interrupt costimulation B7-CD28 between APC and T-cell
What is the downside of Immunosupression?
increase the risk for viral infection
e. g.
* EBV,HPV,Herpes
what are the two types of transplantation
- organ transplantation
- Bone marrow transplantation
what are the two types of Bone marrow transplantation
1) Autologus:
- stem cells are from your own body
- hematopoietic disease is treated with chemo/radiation and disappears, then we take out stem cells so in case disease came back we repopulate them and transplant .
2) Allogenous - recipient recieve high doses of chemo/radiation for immunosupression since the stem cells come from a donor and might be rejected .
- rejection is mediated by T-cells and NK cells
what are the possible complications of allogenic bone marrow transplantation ?
1) GVHD (graft versus host diease)
immunosupressd patient doesnt reject graft but the organ transplanted recognizes (via T-cells of donor organ) the patient’s body as foreign -ALLAHU AKBARRRRRRR
-acute GVHD- epithelial necrosis in skin,liver,gut
- *-chronic GVHD**- Skin lesions that resemble systemic sclerosis and other changes that mimic autoimmune disorders
- *2) Immunodeficiency-** increased risk for infections
what is immunologic tolerance ?
ITS MEANENN -
a state of unresponsivness to an antigen that is induced by exposure of specific lymphocytes to that antigen
Self Tolerance what means dat ?
lack of immune responsiveness to one’s own tissue antigens
what are the two mechanisms that prevent self reactivity ?
- *1) Central Tolerance**
- deletion of self reactive T/B cells occurs
in the Thymus epithelial cells present self antigen with self MHC to T-cells
T-Cell recognized self-antigen? OK, U DIE
T-Cell bind MHC too strong ? OK, U DIE
(apoptosis)
same Process with B-cells in Bone Marrow . they can also go through receptor editing.
- *2) Peripheral Tolerance -**
to eliminate autoreactive cells that managed to escape
- Anergy: inactivation of lymphocyte by interferance in B7-CD28 costimulation
- Supression of T-cells by Treg via IL-10, TGFβ
- Activation induced cell death- T-cells that get stimulated repeatedly undergo apoptisis via
FAS-R
Mention genetic factors that may lead to autoimmune diseases
-Autoimmune diseases have a tendancy to **run in families
-**
connection between **HLA Locus/other Loci and autoimmune diseases
e.g.
HLA-B27–>**
Ankylosing spondylitis
NOD2-crohn’s disease
mention at least 3 principals that demonstrate the role of infection/tissue injury in autoimmune diseases
1) “molecular mimicry”
when foreign epitope resembels epitope of
self-antigen the immune system attacks its own cells .
e. g. in post strep. Rheumatic Fever antibodies produced against the bacteria act also on Heart antigens
2) infections that cause necrosis and inflammation increase the number of Co.Stim. molecules on APC’S(e.g.B7) –> anergy breakdown and T-cell activation
3) local injury -causes release of self antigens
4)“epitope spreading”-
each antigen has several epitopes that are presented in the thymus during selection. BUT some aren’t presented so the T-cells that recognize them didn’t undergo apoptosis . if injury happens and this epitope is released autoreactive T-cell might recognize it and get activated.
Give a general description of Systemic Lupus Erythematosus (SLE)
-failure to maintain self tolerance followed by generation of autoantibodies
-Systemic disease that involves several organ systems.
(skin , kidney,serous membranes ,joints, heart)
-more common in women than men (9:1)
which autoantibodies are produced in SLE ?
- AntiNuclearAntibodies (DNA,Histones,Nucleolar….etc)
- Antibodies against RBC’S , WBC’S ,Platelets
- Antiphospholipid antibodies (e.g. anticardiolipin)-lead to arterial / venous thrombosis !
pathogenesis of SLE
-genetic variables-Susceptibility genes
code for T/B cells specific for self nuclear antigens and do not tolerate them bitches.
- non-genetic variables -External triggers
(e. g. UV-radiation) which interferes with clearance of self nuclear antigens thus they increase. T/B Cells fail to tolerate them - formation of autoantibodies against RBC’s , WBC’S, platelets -Type 2 hypersensitivity
- formation of Ab (ANA)-Ag complexes - type 3 hypersensitvity
mention at least 5 morphological charechteristics of SLE
1) Kidney-Most important feature of SLE
immune complexes deposition and development of glomerulonephritis . there are 5 classes of patterns.
2)Joints- mononuclear infiltration of synovial membranes ,shance for cartilage destruction, joints swell
3)Skin-erythromatous rash with butterfly pattern worsens under exposure of UV-light
4)Heart- Endo,Myo,Peri-carditis, “Libman-Sacks” mitral valve
5) reaction in vessels - Acute necrotizing Vasculitis ,fibrinoid necrosis , narrowing lumen
(acute+chronic stages)
6)CNS- ischemia may cause neuropsychiatric manifestations
7)Serous membranes- inflammation of pleura,pericardium
8)Spleen- splenomegaly , follicular hyperplasia,
in histo onion skin lesions !
what are the 5 patterns of glomerular diseases in SLE ?
CLASS 1 - normal (rare)
CLASS 2 - Mesangial lupus glomerulonephritis
CLASS 3 - Focal proliferative glomerulonephritis
- *CLASS 4-Diffuse Proliferative** glomerulonephritis
- *most serious** , most common ,effects all the glomerulus hemat+protein URIA ,hypertension , renal insuffieciency
CLASS 5- Membranous glomerulonephritis
mention few clinical findings of patients with SLE
- young women with Butterfly rash on face
- ANA in 100% of patient (not specific for SLE)
-Renal involvement , nephrotic syndrome,hemturia ,renal failure
- fever (uncertain cause)
- neuropsychiatric manifestations
dogs can’t operate an MRI machine
but CATscan
is Rheumatoid Arthritis more common in men or women ?
more common in women (5:1)
in Rheumatoid arthritis which joints are affected the most ?
- principally affects the small joints and mostly the
- *P**roximal Inter Phalangeal joints (PIP)
e.g. HANDS , WRISTS, ANKLE,FEET
Rheumatoid arthritis is a … ?
“SSS”
- Systemic , chronic , inflammatory disease
- Symmetric type of arthritis
- Suppurative proliferative synovitis
Chronic synovitis occurs in RA and is charechterized by what ?
- synovial hyperplasia
- inflammatory infiltration–>form lymphoid nodules
- angiogenesis
- neutrophils on synovial surface and **fluid - important lab finding
-**
increased osteoclastic activity (RANKL)
name the striking feature caused by chronic synvoitis
PANNUS - abnormal layer of fibrovascular tissue or granulation tissue (due to inflammatory cells and others)
upon CD4+ T-Cells activation In RheumArth. Cytokines are released leading to …?
1) Macrophage activation -inflammation
2) B-cell activation
antibodies, Rheumatoid Factor (IgM/IgG , Fc portion)
3) release of RANKL (osteoclast)
what type of hypersensitivity reaction occurs in Rheumatoid arthritis ?
Type 3 hypersensitivity reaction
immune complexes formed from 2 antibodies (ab-ab)
describe the pathological changes that occur during the course of progressive Rheumatoid arthritis
- Erosion of articular cartilage and bone (Osteopenia)
- Narrowing of joint space
- permanent ankylsosis
- destruction of tendons ,ligaments,capsule
- radial deviation - wrist
- ulnar deviation -fingers
-rheumatoid subcutaneous nodules
- firm rounded masses on extensor forearm
- Histo: Central area of fibrinoid necrosis surrounded by macrophages and granulation tissue
Patients with erosive disease , rheumatoid nodules and high RF may exhibit …
- Vasculitis , Pleuritis , Pericarditis
- Interstitial fibrosis in lung
- Ocular changes
Descrive the clinical course of Rheumatoid Arthritis
1) Arthritis start with aching pain and morning stifness of joints (improves with physical activity) and as the joints gets bigger complete ankylosis develops
2) Vasculitis can lead to Raynaud Phenomenon- spasm of arteries cause episodes of reduced blood flow to the fingers.
3) Might lead to (secondary) Reactive Amyloidosis (SAA–>AA)
Juvenile Rheumatoid arthritis usually occurs in …
Chronic idiopathic arthritis that usually occurs in children
mention 2 differences between Adult Rheumatoid arthritis and Juvenile Rheumatoid arthritis
-in Juvenile Rheumatoid arthritis
- RF is absent
- Rheumatoid Nodules are absent
- Larger joints can be involved
There’s a connection between Juvenile Rheumatoid arthritis and … ?
HLA-B27
there is a link between Rheumatoid arthritis and …
HLA -DR4
I HATE JOKES ABOUT GERMAN SAUSAGES
THEY’RE THE WURST !
Sjögren syndrome is an autoimmune disease charechterised by destruction of ….
-Lacrimal and Salivary glands
if a 35-45 y.o. female patient with Sjögren syndrome comes to you and complains about not being able to “chew a cracker” and that she has “dirt in the eye” what would you tell her ?
well, DUH!
your eyes are dry (keratoconjunctivits sicca) and your mouth is dry (xerostomia)
describe the pathogenesis in Sjögren syndrome
The pathogenesis of Sjögren syndrome remains obscure
it is beleived that the disease is initiated by loss of tolerance of autoreactive CD4+ T-cells
- ANA
- Anti-RNP Ab’s (Antibodies against ribunucleoprotein antigens)
- Anti SSA
- Anti SSB
- RF
- antibody reactive with self IgG
what is the primary target of autoantibodies in Sjögren syndrome?
ductal epithelial cells of exocrine glands
25% of patient with Sjögren syndrome develope…?
Extraglandular disease
(CNS, SKIN, KIDNEY, MUSCLES)
extraglandular manifestations include :
synovitis , pulmonary fibrosis , peripheral neuropathy
presence of Sjögren syndrome increases X40 the risk for what disease ?
non-hodgkin B-cell lymphoma
in Sjögren syndrome we observe enlargement or shrinkage of salivary glands ?
there’s Enlargement of salivary glands and particularly Unilateral enlargement of the parotid gland is seen
due to lymphatic infiltration
what predisposes the development Anti-RNP Ab’s present in Sjögren syndrome?
inheritance of certain MHC 2 alleles
Sjögren syndrome can be related with which other autoimmune disease ?
Rheumatoid arthritis
Systemic Sclerosis(scleroderma) is an immunologic disorder charechterized by excessive …
**FIBROSIS in multiple organs
e.g.-**
skin, GI, kidney , heart , lung, skeletal muscle
Systemic Sclerosis can be divided into …
2 types :
1) Diffuse Scleromderma
progressive,entire skin,early visceral involvement
2) Limited Scleroderma
slow progression, only skin of face & fingers , late visceral involvment,better prognosis
Limited Scleroderma is Also Known AS…
the “CREST” syndrome
- *C**alcinosis/anti Centromere antibodies
- *R**aynaud phenomenon(vaso-spasm)
- *E**sophageal dismotility
- *S**clerodactyly (fibrosis in skin of fingers makes it tight ,shiny non-mimc face)
- *T**elangiectasia (small dilated vessels in skin)
during pathogenesis of systemic scleroderma , activation of mast cells and macrophages leads to …
release of (cytokines) IL-1, PDGF, TGFβ ,FGF that will activate fibroblasts and lead to excessive fibrosis
The pathogenesis of Systemic sclerosis involves activation of B cells that leads to the generation of …
ANA - Anti Nuclear Antibodies against :
1) DNA Topoisomerase 1 in Diffused type
2) Anti Centromere Antibodies in Limited type
ischemic injury is seen in systemic sclerosis. how cum dis ?
in Systemic Sclerosis there’s Microvascular disease in which endothelial damage and dysfunciton causes
Platelet aggregation–>PDGF–>Fibrosis–>narrowing of VASCULATUUUUUURE –>ischemia
Which part of the GI is most affected in Systemic Sclerosis ?
the Esophagus is affected the most. due to dismotility and L.E.S dysfunction reflux occurs and Barret metaplasia can develope
the microvascular disease present in systemic sclerosis is particulary dangerous in regarding of the lungs because …
pulmonary endothel dysfunction leads to hypertension and furthermore Cor Pulmonale Chronicum
which arteries in the kidney thicken and cause hypertension in systemic sclerosis ?
Interlobular arteries
whats the percentage of patients of systemic sclerosis that develope hypertension ?
30% of patients. out of which 20% develop malignant hypertension and die due to Renal failure
what are the pathological manifestation that occur in the heart of patients with systemic scleroderma
Cardiac raynaud - endothel injury leads to fibrosis that causes thickening of the intramyocardial arterioles
systemic sclerosis is more common in …
women ages of 50-60
how can we differintiate Systemic Sclerosis from Rheumatoid arthritis and SLE ?
in Systemic sclerosis there’s diffused cutaneous involvement
in ALL patients with Systemic Sclerosis we see …
Raynaud’s disease - causes areas such as fingers and toes to feel numb and cold in response to cold/stress.
In Raynaud’s disease, smaller arteries that supply blood to your skin narrow, limiting blood circulation to affected areas (vasospasm)
Polyarteritis Nodosa belongs to which group of disorders ?
- belongs to group of disorder characterized by necrotizing inflammation of the walls of any type of blood vessels
- Not related to infections ,has Immunologic pathogenesis
mention the 4 types of hypersensitivity reactions
“ACID”
type 1 - Allergic /IgE mediated, quick onset
type 2 - Cytotoxic
type 3 - Immune complex deposition/IgM,IgG mediated
type 4 - Delayed/cell mediated
which type of hypersensitivty reaction is resembeled in sjorgen syndrome ?
type 4 , delayed , cell-mediated hypersensitivity reaction
Primary immunodeficiencies what means dat ?
inherited genetic disorders that impair innate and humoral/cellular arms of the adaptive immunity
name few primary immunodeficiencies
- Severe Combined Immunodeficiency (SCID)
- X-linked Agammaglobulinemia
- common variable immunodeficiency
- isolated IgA deficiency
- Hyper IgM Syndrome
- thymic hypoplasia(Di-george syndrome)
- Wiskott aldrich syndrome
- complement proteins deficiency
describe X-linked Agammaglobulinemia
failure of pre-B cell to mature into B-cells due to a mutation in tyrosine kinase involved in the signal transduction of the process .
-light chains not produced.
-decreased B-cell number and absence of plasma cells
-reccurent bacterial infecitons
(obviously apears more in males because x-linked)
*intravenous ig’s are given
common vairable immunodeficiency is charechterized (CVID) by …
- group of disorders characterized by Low IgG due to B/Th cells defects
- increased susceptibility to infections/lymphoma and impaired response to infections.
- Same clinical features as in XLA except that sexes are equally affected and the late onset (2nd-3rd decade)
(unlike XLA normal number of B-cells BUT Absence of plasma cells)
what is the most common primary autoimmune disease ?
isolated IgA deficiency in which serum/mucosal IgA levels are low due to a block in terminal differintiation of IgA secreting B-cells to plasma cells.
- weak mucosal defenses predisposes patient to infections -especially viral.
- seen in celiac’s disease
Hyper IgM syndrome is charechterized by low IgG , IgA,IgE. why?
in normal cases IgM is produced first and then there’s “class switch” mediated by CD40L of Th cells to IgG,IgA,IgE
- in Hyper IgM syndrome there’s a defect in CD40L of Th cells and they can’t activate B cells leading to an impaired “class switching”
- less macrophage activity and less opsonization (low IgG) lead to higher risk for infections.
- note thate IgM is produced in normal levels (supranormal)
Di-george syndrome occurs due to …
-defect in 3rd/4th pharyngeal pouches
(thymus , PThy.G ,face ,Aortic arch )
-in 90% of cases- deletion of chromosome 22q11!!!
-thymus hypoplasia
leads to impaired T-cell maturaiton thus increased risk for infection by intracellular bacteria
- parathyroid gland malformation
- *hypocalcemia**
SCID (severe combined immunodeficiency is a group of genetic syndromes characterized by …
-defects in humoral and cellular component of the immune system and **impaired development of T/B cells
-**
higher risk for fungal, viral ,bacterial,opportunistic, infections
——————————————————————————-
The most common forms of SCID:
-50% x-linked**
- mutation in gene encoding common gamma chain of various cytokines especially IL-7 which is necessary for survival of immature T/B cells precursor
-40-50% autosomal recessive
- ADA (adenosine deaminase-2nd most common) mutation results in impaired purine metabolism
- impaired MHC2 expression
-
mutation in recombinase gene
(involved in ig’s production)
mention the clinical features of SCID
for both common gamma chain /// ADA mutations
- Hypoplastic thymus
- atrophic lymph nodes and lymphoid tissue
- lymphopenia of T/B cells
Wiskott-Aldrich syndrome is charechterized by a Triad of clinical features,namely ..
1) Thrombocytopenia
2) Eczema
3) Recurrent infections
- defected gene located on X chromosome codes for Wiskott-Aldrich protein .
- progressive (as you age) T cells depletion
- no antibodies against LPS so can’t fight encapsulated bacteria (e.g. pyogenic)
complement proteins deficiency is an example of genetic deficiency of …
the innate immune system .
examples :
- C1 inhibitor - leads to HANO (hereditary angioedema)
- edema especially in periorbial region
- C5-8 deficiency -recurrent infection be Neisseria
- C3 deficiency -increased risk for infection with pyogenic bacteria
- C1q ,C2, C4 - risk for immune complex mediated disease e.g. SLE
which defects in phagocytic activity can lead to deficiency of the innate immunity ?
- defects in oxidase enzyme - chronic granulomatous disease
- defect in integrins and selectin ligand- impaired adhesion of leukocyte
Secondary immune deficiencies are …
Aquired. more common than primary (inherited) immune deficiencies.
mostly commonly seen in patients with therapy induced -suppression of bone marrow and lymphocye function
also seen in patients with -cancer,diabetes ,infection ,malnutrition,renal disease ,sarcoidosis
