Immunology- FirstAID

Defect- X-linked recessive. Defect in BTK (Tyrosine kinase gene) that blocks B-cell differentiation.
Presentation- Recurrent bacterial infections after 6 months due to opsonization defect
Lab- Normal pro-B, decreased maturation/number of B cells/all Ig classes

Defect- Defective CD40L on Th cells so B cells cannot class switch.
Presentation- Severe pyogenic infections early in life
Lab- Increased IgM, markedly decreased IgG, IgA, IgE

Defect- Defect in isotype switching resulting in deficiency in a specific class of Igs
Presentaiton- Sinus and lung infections, milk allergies, associated with asthma and atopy, diarrhea, Anaphylaxis on exposure to blood products with IgA (form IgG against IgA). Giardia infection
Lab- IgA deficiency most common, decreased secretory IgA

Defect- Defect in B-cell maturation
Presentation- Can be acquired in 20s-30s; increased risk of autoimmune disease, lymphoma, sinopulmonary infections.
Lab- Normal number of B cells; Decreased plasma cells and Ig

Defect- 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches
Presentation- Tetany (hypocalcemia) seen by Chovstek and Trousseau's signs, recurrent viral/fungal/protozoan/intracellular infections (T-cell deficiency), congenital heart and great vessel defects
Lab- Thymus and parathyroids fail to develop so Decreased T cells, Decreased PTH, decreased Ca, absent thymic shadow on CXR

Defect- Decreased Th1 response
Presentation- Disseminated mycobacterial infection
Lab- Decreased INF-G

Defect- Th cells fail to produce IFN-G so neutrophils cannot respond to chemotactic stimuli (C5a, LTB4)
Presentation- Course facies (broad nose, frontal bossing, deep set eyes, doughy/thick skin), cold straph abscesses, retained primary teeth (2 rows), increased IgE, Eczema
Lab- Increased IgE

Defect- T cell dysfunction
Presentation- Candida albicans infections of skin and mucous membranes

Defect- Several types including defective IL-2 receptor (most common, X-linked), adenosine deaminase deficiency, failure to synthesize MHC II antigens. Need to use NK cells
Presentation- viral (RSV, VZV, HSV, measles, PCP!!), bacterial, funal, and protozoan infections due to both B- and T-cell deficiency. Thymic hypoplasia, FTT, chronic diarrhea. NEED BM transplant!
Lab- Decreased IL-2R, increased adenine, decreased dNTPs and DNA synthesis also

Defect- Defect in DNA repair enzymes
Presentation- Triad of cerebellar defects (ataxia) and poor smooth pursuit of moving objects with eyes, spider angiomas (telangectasia), IgA deficiency. Increased risk for acute lymphoma and leukemias
Lab- IgA deficiency, Increased AFP

Defect- X linked recessive defect resulting in progressive deletion of B and T cells
Presentation- Triad of thrombocytopenic purpura, infections (encapsulated Nesseria, H. flu, S. pneumo), and eczema
Labs- Increased IgE, IgA, decreased IgM!!!

Defect- LFA-1 integrin (CD18) protein on phagocytes. Phagocytes cannot exit into the circulation.
Presentation- Recurrent bacterial infections, absent pus formation, delayed separation of the umbilicus
Labs- Neutrophilia

Defect- AR defect in microtubular function with decreased phagocytosis. Cannot get degradative enzymes in lysosomes because of a LYST gene mutation.
Presentation- Recurrent pyogenic infections by Staph, Strep, partial albinism, peripheral neuropathy (seizures)
Lab- Neutrophils have large granules.

Defect- Lack of NAPDH oxidase leads to increased reactive oxygen species and absent respiratory burst in neutrophils.
Presentation- Increased susceptibility to catalase positive (S. aureus, E. coli, Aspergillus, candida) organisms
Lab- Negative Nitroblue tetrazolium dye reduction test (does not make the yellow to blue-black color change)

Massive enlargement of the paracortex of lymph nodes during an extreme cellular response. Not well developed in DiGeorge Syndrome.

Axillary

Celiac

Superior mesenteric

Colic to the inferior mesenteric

Internal iliac, anal canal

Superficial and deep plexuses ---> para-aortic!!!!

Superficial inguinal

Popliteal

Right lymphatic duct

Salmonella
S. pneumoniae
H. influenzae
N. meningitidis

(encapsulated)

At the corticomedullary junction- the medulla has mature T cells and is pale (negative). The cortex has immature T cells, epithelial reticular cells, and Hassall's corpuscles, and is dense (positive).

Viral immunity; Antigen is loaded in the RER of intracellular peptides. It pairs with beta2-microglobin. Single heavy-chain and highly polymorphic.

Pathogens in endosomal compartments of APCs (phagocytosed bacteria). The antigen is loaded following release of invariant chain in acidified endosme.

IL-12, IFN-beta, IFN-alpha

Signal 1: Foreign Ag present on MHC II
Signal 2: B7 on MHC II with CD28 on TH cell

Signal 1: Endogenously synthesized or viral Ag presented on MHC I
Signal 2: IL-2 from Th cell activates Tc to kill the virus-infected cell

Signal 1: IL-4/5/6 from Th2 cell
Signal 2: CD40L on Th cell binds CD40 on B cell

They release granules containing perforin (helps deliver granules to into target cells), granzyme (serine protease, activates apoptosis- via the extrinsic pathway), and granulysin (antimicrobial, induces apoptosis)

Antigen-binding fragment: consists of 2LC + 2HC
Determines the idiotype (unique antigen binding pocket)

2 HC
Constant, carboxy terminal (binds FcR) complement binding site at CH2 (for IgG and IgM), carbohydrate side chains, determines isotype

-Main Ab in delayed response to an antigen (secondary)
-Most abundant in blood (half life is 23 days)
-Crosses the placenta
-Fixes complement
-Opsonizes bacteria, neutralizes bacterial toxins and viruses

-Prevents attachment of bacteria and viruses to mucous membranes
-Monomer in circulation, but dimer when secreted (picks up secretory component from epithelial cells before secretion)
-Found in secretions and breast milk

-Produced in the immediate (primary) response to an antigen
-Fixes complement
-Antigen receptor on the surface of B cells
-Monomer on B cell or pentamer

-Unclear but found on the surface of many B cells and in serum.
-Periodic fever syndromes have increased IgD

-Binds mast cells and basophils via Fc region
-Cross links when exposed to an allergen, mediating type I hypersensitivity via histamine release
-Mediates immunity to worms by activating eosinophils
-Lowest serum concentration

Antigens that lack a peptide component so they cannot be presented by MHC to T cells (ex: LPS). They stimulate the release of IgM antibodies ONLY and no memory

Antigens that contain a protein component (conjugated vaccine) are presented to Th-cells by MHC II and the Th-cell is activated. The activated Th-cell then binds B-cells that are also presenting the antigen, resulting in class switching and memory

IgG and C3b (C3b also aids in clearance of the immune system)

C3a and C5a

It causes cytolysis of plasma membrane to defend against GN bacteria.

Hereditary angioedema

Severe, recurrent pyogenic sinus and respiratory tract infections, increased susceptibility to type III hypersensitivity (esp glomerulonephritis) reactions.

Neisseria bacteremia

PNH- complement mediated lysis of RBCs

Induces differentiation of T cells into TH1 cells and activates NK cells. Patients deficient in IL-12 can receive IFN-gamma

IL-1 (pyrogen, activates endothelium to express adhesion molecules, recruits leukocytes by inducing chemokine secretion)
IL-6 (pyrogen, stimulates production of acute-phase proteins)
TNF-a (Septic shock; activates endothelium, leukocyte recruitment, vascular leak, cachexia)
IL-10 (modulates it by inhibiting action of Th1 cells)

-Activates macrophages and Th1 cells; suppresses Th2 cells; granuloma formation.
-Antiviral- increases MHC I and II expression and antigen presentation in all cells, induces production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA
-Antitumor

Induces differentiation of Th2 cells, B cell growth, class switching to IgE and IgG

Induces class switching to IgA, stimulates growth and differentiation of eosinophils.

-Induces production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA
-Activate NK cells to kill virus-infected cells

MHC II, B7, CD40, CD14 (binds LPS in a T-independent response), FcR, C3bR

Ig, CD 19, CD20, CD21 (receptor for EBV), CD40, MHC II, B7

TCR, CD3, CD40L, CD28, CD4

TCR, CD3, CD28, CD8

Receptors for MHC I, CD16 (binds Fc of IgG), CD56

RBCs

Directly bind to CD14 (T-independent)

Salmonella (2 flagellar variants)
Borrelia (relapsing fever)
N. gonorrhoeae (pilus)
Influenza
Trypanosomes (programmed rearrangement)

After exposure to tetanus toxin, botulinum toxin, HBV, rabies (in addition to vaccines)

To Be Healed Rapidly

SELF-antibodies (IgM or IgG) bind to FIXED antigens on cell surfaces.
-Opsonize cells or activate complement
-Recruit neutrophils or macrophages to cause tissue damage
-Bind to normal cell receptors and interfere with functioning

Test: Coombs

Antigen-antibody complexes are deposited in membranes, where they fix complement and incite tissue damage by attracting neutrophils (release lysosomal enzymes).

Test: Immunofluorescent staining

A type of type III hypersensitivity characterized by fever, urticaria, arthralgias, proteinuria, glomerulonephritis, vasculitis (fibrinoid necrosis), LAD 5-10 days after antigen exposure, leads to hypocomplementemia. Sulfonamides can cause this

Intradermal infection of an antigen induces IC to form in the skin, causing edema, necrosis, and complement activation.

Ex- Tetanus shot

Anaphylaxis, allergic and atopic disorders (rhinitis, hay fever, eczema, hives, asthma)

Hemolytic anemia, pernicious anemia, ITP, erythroblastosis fetalis, ACUTE hemolytic transfusion reactions (diff blood types), rheumatic fever, Goodpasture's, Bullous pemphgoid, Pemphigus vulgaris, Graves, MG

SLE, Rheumatoid arthritis, PAN, APSGN, serum sickness, arthus reaction, hypersensitivity pneumonitis, Churg-Strauss

Type I DM, MS, GBS, Hashimoto's, GVHD, PPD, contact dermatitis, sarcoidosis, candida extract skin reaction

Cytotoxic T cell mediated; reversible with immunosuppressants; There is vasculitis of graft vessels with dense interstitial lymphocyte infiltrate.

T-cell and antibody mediated vascular damage (obliterative vascular fibrosis); irreversible; bronchiolitis obliterans; fibrosis of vessels and tissue

Graft T-cells proliferate and reject host proteins- see maculopapular rash, jaundice, HSM, and diarrhea. usually occurs in BM and liver transplant.

Obturator, external iliac, and hypogastric nodes

Follicles- B cells isotype switching and proliferating
Paracortex- T cells; contains High endothelial venules
Cords- Plasma cells
Sinuses- Macrophages and reticular cells

Superficial inguinal

Hemochromatosis

Psoriasis, ankylosing spondylitis, IBD, Reiter's syndrome

Graves' disease

MS, Hay fever, SLE, Goodpasture's

DM1

RA, DM1

Pernicious anemia, Hashimoto's

Steroid-responsive nephrotic syndrome

Viral neutralization