A/26-33 IMMUNPATHOLOGY (Tamer) COPY Flashcards
1
Q
how fast does type 1 hypersensitivity reaction occur?
A
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)
2
Q
give the sequence of events during first exposure to allergen
A
- 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
3
Q
list the cytokines and immunoglobulins secreted during the first exposure to an allergen
A
CD4+ TH2 cells secrete :
IL-4 –> Specific B-cells –>IgE
IL-5-->Activates eosinophils
IL-13 –> Epithelial cells –> mucus secretion
4
Q
what happens in the 2nd exposure to the SAME allergen ?
A
- 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
5
Q
what are the two types of anaphylaxis ?
A
- systemic anaphylaxis
- local anaphylaxis
6
Q
describe Systemic anaphylaxis
A
-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**
7
Q
describe Local anaphylaxis and give at least 3 examples
A
- when antigen is limited within a particular site
e. g. - allergic rhinitis (Hay fever , home dust , animal hair)
- itching skin
- food allergy
- asthma bronchiale
8
Q
Give the clinical picture of Asthma
A
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
9
Q
how do the pathology cock-sucking bitches classify Asthma?
A
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
10
Q
pathogenesis of Asthma
A
-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
11
Q
asthmatic attacks are preceded by what ?
A
- allergic rhinitis
- urticartia /eczema
12
Q
what are the most common antigens that cause Asthma ?
A
-dust
-pollen
-animal dander
(tiny particles of skin that had been shed from animals)
13
Q
describe the micro-morphology of Asthma
A
“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
14
Q
clinical course of Asthma
A
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**
15
Q
type 2 hypersensitivity - basic definition
A
caused by antibodies generated against endogenous/exogenous antigens
16
Q
what are the consequences of type 2 hypersensitivity reaction
A
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
17
Q
type 3 hypersensitivity reaction what means dat?
A
“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
18
Q
Pathogenesis of type 3 hypersensitivity reaction
A
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
19
Q
Name at least 3 diseases associated with type 3 hypersensitivity reaction
A
- reactive arthritis
- post strep. glomerulonephritis
- Systemic lupus erythematosus
- vasculitis
- Polyarteritis nodosa
20
Q
descrive the micro-morphology of type 3 hypersensitivity reaction
A
- fibrinoid necrosis (protein deposition)
- microthrombi , ischemic necrosis
- acute inflammation
- fibrosis
21
Q
Give and example of local immune complex disease
A
Arthus reaction -
results from acute immune complex vasculitis
inflammation and histologic appearance same as the systemic diseases but localized to one tissue/organ
22
Q
How does a penguin build it’s house?
A
Igloos it together.
23
Q
type 4 hypersensitivity reaction whats mean dat ?
A
T-Cell Mediated -Delayed Type Hyp.Sens
24
Q
to which disease is the type 4 hypersensitivity reaction related to ?
A
Tuberculosis
25
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**
26
is the **D**elayed **T**ype **H**ypersensitivity reaction acute or chronic ?
**Chronic -**due to the _amplification loop_
(chronic unless the toxic agent is eliminated)
27
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
28
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
29
I thought about going on an **all-almond diet**
But that's just nuts
30
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
31
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)**D**elayed **T**ype **H**ypersensitivity Rejection :_
APC's of **Donor** have **MHC2** on them--\>reconized by **CD4+ T**-cells --\> differ. into **TH1** --\>release **TNF**, **IFNγ**
--\>**DTH reaction** proceeds
32
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**
**B)** *Acute Humoral -related with **vasculitis*** caused by **antidonor Ab's**
--------------------------------------------------------------------------------
_3) Chronic rejection_
-develops within **years
-**
doesn't respond to **immunosuppression**
-charecterized by **vascular changes(fibrosis)** that lead to general **ischemia** in the organ
33
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
34
What is the **downside** of Immunosupression?
increase the risk for **viral infection**
e. g.
* EBV,HPV,Herpes
35
what are the two types of transplantation
- **organ** transplantation
- **Bone marrow** transplantation
36
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
37
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
38
what is immunologic tolerance ?
ITS MEANENN -
**a state of unresponsivness to an antigen that is induced by exposure of specific lymphocytes to that antigen**
39
Self Tolerance what means dat ?
**lack of immune responsiveness** to one's own tissue **antigens**
40
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
41
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
42
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.
43
Give a general description of **S**ystemic **L**upus **E**rythematosus (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)
44
which autoantibodies are produced in SLE ?
- **A**nti**N**uclear**A**ntibodies (DNA,Histones,Nucleolar....etc)
- Antibodies against RBC'S , WBC'S ,Platelets
- Anti**phospholipid** antibodies (e.g. anticardiolipin)-lead to **arterial / venous thrombosis !**
45
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**
46
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 !_
47
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
48
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
49
dogs can't operate an MRI machine
but CATscan
50
is Rheumatoid Arthritis more common in men or women ?
more common in women (5:1)
51
in Rheumatoid arthritis which joints are affected the most ?
- principally affects the **small joints** and mostly the
* *P**roximal **I**nter **P**halangeal joints (PIP)
e.g. HANDS , WRISTS, ANKLE,FEET
52
Rheumatoid arthritis is a ... ?
"SSS"
- **S**ystemic , chronic , **inflammatory** disease
- **S**ymmetric type of arthritis
- **S**uppurative proliferative **_synovitis_**
53
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)
54
name the striking feature caused by chronic synvoitis
**PANNUS -** abnormal layer of **fibrovascular tissue** or **granulation** tissue (due to inflammatory cells and others)
55
upon CD4+ T-Cells activation In RheumArth. Cytokines are released leading to ...?
1) **Macrophage** activation -inflammation
2) **B-cel**l activation
antibodies, **Rheumatoid Factor** (IgM/IgG , Fc portion)
3) release of **RANKL (osteoclast)**
56
what type of hypersensitivity reaction occurs in Rheumatoid arthritis ?
**Type 3** hypersensitivity reaction
immune complexes formed from 2 antibodies (ab-ab)
57
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
58
Patients with erosive disease , rheumatoid nodules and high RF may exhibit ...
- Vasculitis , Pleuritis , Pericarditis
- Interstitial fibrosis in lung
- Ocular changes
59
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)
60
Juvenile Rheumatoid arthritis usually occurs in ...
Chronic idiopathic arthritis that usually occurs **in children**
61
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
62
There's a connection between Juvenile Rheumatoid arthritis and ... ?
**HLA-B27**
63
there is a link between Rheumatoid arthritis and ...
**HLA -DR4**
64
I HATE JOKES ABOUT GERMAN SAUSAGES
THEY'RE THE WURST !
65
Sjögren syndrome is an autoimmune disease charechterised by destruction of ....
-**Lacrimal** and **Salivary** glands
66
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)
67
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**
68
what is the primary target of autoantibodies in Sjögren syndrome?
**ductal epithelial cells** of exocrine glands
69
25% of patient with Sjögren syndrome develope...?
**Extraglandular disease**
(CNS, SKIN, KIDNEY, MUSCLES)
extraglandular manifestations include :
synovitis , pulmonary fibrosis , peripheral neuropathy
70
presence of Sjögren syndrome increases X40 the risk for what disease ?
**non-hodgkin B-cell lymphoma**
71
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
72
what predisposes the development **Anti-RNP Ab's** present in Sjögren syndrome?
inheritance of certain **MHC 2 alleles**
73
Sjögren syndrome can be related with which other autoimmune disease ?
Rheumatoid arthritis
74
Systemic Sclerosis(scleroderma) is an immunologic disorder charechterized by excessive ...
**FIBROSIS in multiple organs
e.g.-**
skin, GI, kidney , heart , lung, skeletal muscle
75
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
76
Limited Scleroderma is Also Known AS...
the **"CREST"** syndrome
* *C**alcinosis/anti **C**entromere 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)
77
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**
78
The pathogenesis of Systemic sclerosis involves activation of B cells that leads to the generation of ...
**ANA -** Anti Nuclear Antibodies against :
1) **D**NA Topoisomerase 1 in _**D**iffused type_
2) **Anti Centromere** Antibodies in _Limited type_
79
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
80
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
81
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**
82
which arteries in the kidney thicken and cause hypertension in systemic sclerosis ?
**Interlobular** arteries
83
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
84
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**
85
systemic sclerosis is more common in ...
**women** ages of 50-60
86
how can we differintiate Systemic Sclerosis from Rheumatoid arthritis and SLE ?
in Systemic sclerosis there's **diffused cutaneous involvement**
87
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)**
88
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**
89
mention the 4 types of hypersensitivity reactions
"ACID"
type 1 - **A**llergic /IgE mediated, quick onset
type 2 - **C**ytotoxic
type 3 **- I**mmune complex deposition/IgM,IgG mediated
type 4 - **D**elayed/cell mediated
90
which type of hypersensitivty reaction is resembeled in sjorgen syndrome ?
**type 4** , delayed , cell-mediated hypersensitivity reaction
91
Primary immunodeficiencies what means dat ?
**inherited** genetic disorders that impair **innate** and humoral/cellular arms of the **adaptive** immunity
92
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
93
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
94
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)
95
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
96
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)
97
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**
98
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)
99
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
100
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)
101
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*
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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
103
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
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