Immunodeficiencies

Question 1

Lab tests for T-cell

Answer 1

Flow cytometry, functional assays (mitogen response, MLR, DTH skin test)

Question 2

B-cell lab tests

Answer 2

circulating antibodies, flow cytometry

Question 3

Macrophage lab test

Answer 3

Enumeration (=flow cytometry), nitroblue tetrazolium for function

Question 4

Complement lab test

Answer 4

direct measurement of complement components, hemolysis assay

Question 5

What does each system specialize in? What happens if it’s impaired?

1. B-cells
2. T-cells
3. Phagocytes
4. Complement

Which deficiecnies would cause cancer?

Answer 5

1. B-cells (humoral, adaptive)= pyogenic bacteria= staph, strep, hemoph. Respiratory, GI, skin infections, sepsis, meningitis
2. T-cells (cell mediated, adaptive)= Intracellular organisms= viruses and then bacteria. Viral infections. Increased risk of cancer when immunodeficient
3. Phagocytes- catalase postive bacteria (Staph, kleb, e.coli); fungi lymphadenitis, skin liver, lung abcesses
4. Complement- pyogenic bacteria, viruses systemic bacterial infections

Question 6

X-linked agammaglobulinemia

1. symptoms
2. defect
3. therapy

Answer 6

B-cell deficiency

1. recurrent bacterial infections
2. no BTK= b-cells arrested at pro-Bcell stage
   3.

Question 7

C3 Def

Answer 7

Recurrent infection with G- bacteria

Question 8

Factor I def

Answer 8

low C3= susceptibility to encapsulated bacteria

Question 9

C5-C9 def

Answer 9

No MAC complex, increased Neisseria infections

Question 10

NEMO deficiency

Answer 10

No NFkB activation= no T-cell activation

Chronic bacterial and viral infections, developmental defectc

Question 11

MBL def

Answer 11

No lectin pathway, less phagocytosis.

Infections from n. meningitidis

Question 12

Chronic Granulomatous disease

Answer 12

NOX1 gene, no NADPH oxidase= impaired neutrophil function.

No respiratory burst= no phagycytes to kill bacteria.

Chronic bacterial and viral infections.

Question 13

NK cell def

Answer 13

GATA2 gene, HSV infections

Question 14

Hyper IgM

Answer 14

Defect in AICDA (activation induced cytosine deaminase), CD40, CD40L, IKBKG.

No isotype switching or somatic hypermutation

ECF bacterial and fungal infections

Question 15

IgG2 def

Answer 15

encapsulated bacteria

Question 16

SCID

Answer 16

No B-cell and T-cell function

Caused by: ADA, PNP def, thymic aplasia

All infections

**X-linked SCid gammac chain= T-cells only, bubble boy**

Question 17

Omenn Syndrome

Answer 17

Rag1/Rag2 gene= impaired VDJ recombination.

All infections

Question 18

MHC I def

Answer 18

TAP1/TAP2 = no MHC I receptors

Respiratory viral infections

Question 19

Pre-B cell receptor def

Answer 19

No B-cells/antibodies

Persistnet bacterial infections

Question 20

DiGeorge

Answer 20

no thymus and t-cells= all infections

Question 21

APECED

Answer 21

AIRE defect, less T-cell tolerance for self-antigens

Autoimmune

Question 22

IPEX

Answer 22

FoxP3 gene; lack of Treg cells and peripheral tolerance. Autoimmune

Question 23

ZAP70 defect

Answer 23

T-cells cannot signoalr through antigen receptors

all infections

Question 24

C4a, C4b

Answer 24

Reduced clearance of immune complexes

autoimmune disease and infections

Question 25

Selective IgA def

Answer 25

MOST COMMON!! No IgA= respiratory infections

Question 26

Wiskott-Aldrich Syndrome

Answer 26

X-linked, defective WASP gene= Defective anti-polysaccharide Ab and impaired T-cell activation Susceptible to encapsulated ECF bacteria

Question 27

Leukocyte Adhesion deficiency

Answer 27

Phagocytic cell defect CR3, CR4 and LFA-1 adhesion defects= defective migration of monocytes and neutrophils==\>widespread infection from encapsulated bacteria.

Question 28

Chedlak-Higashl SYndrome

Answer 28

**Phagocyte problem** * Lysosomal traffiking regulator protein defect * Defective fusion of endosome and lysosome, defective phagocytosis * Recurrent/persistent bacterial infections, granuloma formation

Question 29

Causes of secondary immunodeficiencyes

Answer 29

* Steroids, cytotoxic drugs, chemotherapy, irradiation * AIDs (no CD4 cells) * Nutritionals (protein, calorie, biotin, B12, iron) * Post infections * Cancer metastases to bone marrow * Asplenia

Question 30

HIV--\> AIDs * when is it AIDs * How does the HIV infection happen (receptors?) * What does HIV NEED for replication?

Answer 30

\<500CD4 cells HIV gp120 binds CCR5 or CXCR4= endocytosis * **CCR5=M-tropic-Virus infects macrophages, CD and some t-cells= spread of virus to others** * **CXCR4=**t-tropic- virus infects T-cells= disease HIV replication requires T-cell activations= NFKB

Question 31

How is HIV so effective?

Answer 31

* changes viral antigens and enzumes * targes CD4 TTcells * HIV evades host immune systm (via error prone reverse transcriptase)

Question 32

Antigenic drift

Answer 32

Mutation of serotypes/antigens on outside= epidemic Pandemic=

Question 33

HSV strategies (x2, CMV does one of them too)

Answer 33

1. reduce IFN-g effect on MHC I= no recognition of APC by CD4 \*\*CMV does this too 2. Inhibition of TAP= no peptide presentation via MHC I

Question 34

How do viruses evade humoral immunity?

Answer 34

Virally encoded complement control prtoein= less complement activation. ==Vaccinia does this.

Question 35

How do viruses inhibit inflammatory response?

Answer 35

* Produce soluble cytokine receptors--cytokines bind viral receptors instead of host= no inflammation (wastes cytokines)= vaccinia * Encoding IL-10 (EBV)

Question 36

How doe these pathogens subvert the immune system? 1. M. Tb 2. Listeria 3. terponema pallidum 4. Staph 5. Mycobacteria

Answer 36

1. M. Tb= prevent phago=lysosome fusion 2. Listeria= escapes phagosome 3. terponema pallidum= coats itself with human protiens 4. Staph= makes super antigen- polyclonal t-cell activation (no specificity)- binds CD28 and TCR of t-cell, and MHCII of APC 5. Mycobacteria= induces Th2 response

Question 37

During pregnancy, immune response is? Autoimmune diseases improve/worsen?

Answer 37

Reduced- don't want to reject fetus * FActors: a-fetoprotein, IL10, TGF-beta * improved autoimmune disease states until birht, then rebounds * Lupus gets worse.