1
Q
HLA associated with diseases:
HLA-A3
A
Hemochromatosis
2
Q
HLA associated with diseases:
HLA-B27
A
PAIR
- Psoriasis
- Ankylosing spondylitis
- Inflammatory bowel disease
- Reactive arthritis (Reiter’s)
3
Q
HLA associated with diseases:
HLA-DR3
A
DM1
4
Q
HLA associated with diseases:
HLA-DR4
A
Rheumatoid arthritis
DM1
5
Q
Follicular Dendritic cells
A
- not from bone marrow
- No MHC II and not APC
- only in lymph follicle
- help mature B cells
6
Q
Characteristic finding on electron microscopy of a dendritic cell with Langerhans cell histiocytosis
A
- Birbeck granules (Tennis rackets), immature dendritic cells from monocyte lineage;
- do not stimulate T lymphocytes via antigen presentation.
- Express S-100 and CD1a
7
Q
Site of negative selection for T-lymphocytes
A
- Corticomedullary junction of the thymus
- T-cells expressing TCR’s with high affinity for self undergo apoptosis
- Cells become either CD4 or CD8 T-cells
8
Q
IL-12
A
- Induces helper T cell to become Th1 cell
- Virally infected cells secrete IL-12.
- More Th1 secrete IL-2 which stimulates cytotoxic T cells to kill virally infected cells
- IL-2 is the most important cytokine in activating antigen primed helper T cells
9
Q
How do interferons work?
A
- induce production of ribonucleus that degrades viral mRNA (alpha and beta)
- Increase expression of MHC I and MCH II (gamma interferon) and antigen presentation
- Activate NK cells to kill virally infected cells
10
Q
Macrophages of bone?
A
osteoclasts
11
Q
gene complex RAG 1 and RAG 2
A
- gives rise to a protein that initiates VDJ recombination in B and T cell development
- Recognize Recombination Signal Sequences that flank VDJ sequences
- Rearrangement begins at breaks in the dsDNA located at the RSS
- Mutations in RAG genes lead to inability for VDJ recombination and arrest B and T cell development
12
Q
When is passive immunity necessary?
A
To Be Healed Rapidly
- Tetanus toxoid
- Botulinum toxin
- HBV
- Rabies, (RSV for babies, once a month vaccine)
13
Q
Screening for SLE?
A
Antinuclear antibodies (ANA)
nonspecific
14
Q
Anti-dsDNA, anti-smith
A
More specific for SLE + Renal disease
15
Q
Antihistone autoantibody
A
90% Drug induced lupus
Hydralazine
Seen in 50% of patients with SLE
16
Q
Given the following features, what type of graft rejection is occuring?
Obliterative vascular damage
(Fibrosis of the graft tissue and blood vessels)
A
- Chronic rejection
- Months-years
- Class I MHCnon-self perceived by CTLs as class I MHCself presenting non-self antigens
- Irreversible
- T-cell and antibody mediated damage
17
Q
Given the following features, what type of graft rejection is occuring?
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
A
- Acute rejection
- Weeks
- Cell mediated due to CTLs reacting against foreign MHCs
- Reversible with immunosuppresants
18
Q
Given the following features, what type of graft rejection is occuring?
Macupapular rash, jaundice, diarrhea, hepatosplenomegaly
A
- GVHD
- Timeframe Varies
- Grafted immunocompetent T cells proliferate in the irradiated immunocompromised host and reject cells with “foreign” proteins resulting in severe organ dysfunction
- Usually occurs when organs rich in lymphocytes are donated: Bone and liver
19
Q
Given the following features, what type of graft rejection is occuring?
Occlusion of graft vessels causing ischemia and necrosis
A
- Hyperacute rejection
- Within minutes!
- Antibody mediated (type II) due to presence of preformed anti-donor antibodies in transplant recipient
20
Q
$ Types of Hypersensitivities
A
ACID
- Anphylactic and Atopic (type I) - free antigen cross links IgE on presensitized mas cells and basophils, releasing vasoactive amines acting on postcapillary venules.
- Cytotoxic (antibody mediated) (type II) - IgM, IgG bind and fix cell leading to lysis, recruit neutrophils and macrophages do most damage.
- Immune complex (type III) - Antigen-antibody (IgG) complexes activate complement, attracts neutorphils -> release lysosomal enzymes
- Delayed (cell mediated) (type IV) - Sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody)
21
Q
4 T’s of Type IV hypersensitivity
A
- T lymphocytes
- Transplant rejections
- TB skin tests
- Touching ( contact dermatitis)
22
Q
What causes more eosinophils in circulation?
A
DNAAACP + IL-5 (snot interleukin)
- Drugs
- Neoplastic
- Asthma , Atopic, Allergic processes, Churg strauss
- Addison’s
- Acute interstitial nephritis
- Collagen vascular diseases
- Parasites (invasive)
23
Q
$$$ Bruton Agammaglobulinemia
A
- X-linked (Boys)
- B cell deficiency -> defective tyrosine kinase gene (BTK) -> low levels of all immunoglobulins
- Recurrent Bacterial infections after 6 months
- Absent thymic shadow
24
Q
$$$ Thymic plasia (DiGeorge)
A
- 3rd and 4th pouches fail to develop
- No thymus -> No T cells
- No parathyroids -> low Ca2+ -> tetany
- Congenital defects in heart/great vessels
- Recurrent viral, fungal protozoal infections
- 90% have a chrom 22q11 deletion (detect with FISH)
- Absent thymic shadow on CXR
25
**$$$ Triad seen in SCID**
**_1. Severe recurrent infections _**
* Chronic mucocutaneous Candidiasis
* Fatal or recurrent RSV, VZV, HSV, measles, flu, parainfluenza
* PCP pneumonia
**_2. Chronic diarrhea_**
**_3. Failure to thrive_**
26
**$$$ Whatis SCID?**
**_Severe Combined Immunodeficiency (SCID)_**
* Defect in **early stem cell differentiation**
* Can be caused by at least 7 different gene defects:
* **IL-2 receptor (most common, X-linked) -\> T cells don't activate**
* Adenosine deaminase deficiency - increased adenine is toxic to B and T cells
* Failure to synthesize MHC II antigens
* Last defense is cytotoxic NK cells
* TRIAD - Recurrent infection, CD, FtT
* No thymic shadow on newborn CXR
* Treatment: Bone marrow transplant
27
**$$$ Chronic Mucocutaneou Candidiasis**
* **T cell dysfunciton** v. C. albicans
* Recurent RSV, VZV, HSV
* Rx: Ketoconazole
28
**$$$ What are the X-linked Immunodeficiencies?**
*X-linked are "WBC H"*
* **W**iskott-Aldrich
* **B**ruton Agammaglobulinemia
* **C**hronic Granulomatous Disease (+/-)
* **H**yper-IgM syndrome (3 types), **all increased IgM and reduced Ig**
* X-linked -\> No CD ligand
* AR -\> no CD40
* -NEMO deficiency
29
**$$$ Wiskott Aldrich**
*"WAITER"*
* **W**iskott
* **A**ldrich
* **I**mmunodeficiency - pregressive deletion of B and T cells
* _**T**hrombocytopenia and purpura_
* _**E**czema_
* _**R**ecurrent pyogenic infections_
* **No IgM v. capsular polysacchraides of bacteria - *Strep, Staph, Haemophilus, Moraxella***
* **Low IgM, high IgA, IgE**
* **X-linked**
* *Triad = TIE: Thrombocytopenic purpura, Infections, Eczema*
30
$$$ Ataxia-Telangiectasia
Triad: AAA
**Cerebellar defects (**_A_**taxia)**
**Spider **_A_**ngiomas (telangiectasia)**
**Ig**_A_** deficiency**
* ***Defects in ATM gene - codes for _DNA repair enzymes_***
* Cerebellar ataxia, and **poor smooth pursuit of moving target w/ eyes**
* **Telangiectasias of face \> 5yo**
* ↑ cancer risk: **_lymphoma & acute leukemias_**
* Radiation sensitivity (avoid X-Rays)
* **±↑_A_FP in chlidren \>8m**
* Average age of death: 25 y/o
31
**$$$ Selective Immunoglobulin Deficiencies**
**IgA deficiency is most common**
* *Defect in isotype switching*
* Most appear healthy
* Sinus and lung infections
* 1/600 European descent
* Associated with atopy, asthma
* **Possible anaphylaxis to blood transfusions and blood producs with IgA**
32
**$ IL-12 receptor deficiency**
**Mycobacterial infections**
Reduced Th1 response -\> reduced IFN-gamma
33
$$$ Phagocyte Deficiencies
* **Chronic granulomatous disease**
* **Chediak-Higashi syndrome**
* **Job syndrome**
* **Leukocyte adhesion deficiency syndrome**
34
$$$ Chronic Granulomatous Disease (CGD)
* **Lack of NADPH oxidase** activity -\> impotent phagocytes
* **Susceptible to organisms with catalase *(S. aureus, E. coli, Klebsiella spp., Aspergillus spp., Candida spp.)***
* **Dx: (-) nitroblue tetrazolium (NBT) dye** - No yellow to blue-black oxidation (healthy phagocytes oxidize yellow dye to blue)
* Prophylactic **TMP-SMX**
* **INF-gamma** also helpful
35
**$$$ Chediak-Higashi Syndrome**
* **Defective LYST gene (lysosomal transport)**
* Defective phagocyte lysosome *(microtubule dysfunciton in phagosome-lysosome fusion)* -\> **giant cytoplasmic graules in PMNs are diagnostic**
* Presentation triad:
* **Partial albinism**
* **Recurrent respiratory tract and skin infections - Pyogenic infections by staph, strep**
* **Neurologic disorders - Peripheral neuropathy, seizures**
36
**$$$ Hyperimmunoglobulin E Syndrome**
**Job Syndrome - "*FATED"***
* coarse **_F_**acies
* cold (noninflamed) staphylococcal **_A_**bscesses
* retained pirmary **_T_**eeth
* ↑ Ig**_E_**
* **_D_**ermatologic problems (eczema)
* Hyperimmunoglobulin E syndrome
* **Deficient INF-gamma (T-cells don't make any)-\> PMNs fail to respond to chemotactic stimuli (C5a, LTB4)**
* High levels of IgE and Eosinophils
* Presentation triad:
* **Eczema**
* **Recurrent cold (no IL-1) *staph. aureus* abscesses** (think of bibilical Job with boils
* **Course facial features:** broad nose, prominent forehead ("frontal bossing"), deep set eyes, and "doughy" skin
* Also common to have **retained primary teeth resulting in 2 rows of teeth**
37
**$$$ Leukocyte Adhesion Deficiency Syndrome**
* **Abnormal integrins** (Defect in LFA-1 integrin (CD18) protein on phagocytes -\> Inability of phagocytes to exit circulation
* **Delayed separation of umbilicus**
* **Recurrent bacterial infections **
* **Absent pus formation**
* **Neutrophilia**
38
Child with staph abscesses, if the neutrophils fail to respond to chemotactic stimuli, what is the most likely diagnosis?
Job Syndrome (Hyperimmunoglobulin E syndrome)
39
Which embyonic germ layer is the thymus derived from?
Endoderm
40
Newborn with chronic diarrhea, failure to hrive and chronic Candida
SCID
41
Child with eczema, course facial features, cold abscesses
Hyper-IgE Syndrome (job syndrome)
42
Child with partial albinism, peripheral neuropathy, and recurrent infections
Chediak-Higashi Syndrome
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