Immunology

Important cytokines

Cytokine	Secreted by	Causes
IL-1	Macrophages	Acute inflammation, endogenous pyrogen, activates endothelium to express adhesion molecules, induces chemokine production to recruit leukocytes
IL-2	Th cells	Stimulates growth of both helper and cytotoxic T cells
IL-3	Activated Th cells	Supports growth and differentiation of bone marrow stem cells. Similar function to GM-CSF
IL-4	Th2 cells	Promotes growth of B cells. Class switching to IgE and IgG
IL-5	Th2 cells	Promotes differentiation of B-cells. Class switching to IgA. Stimulates production and activation of eosinophils
IL-6	Th cells and macrophages	Stimulates production of acute-phase reactants and immunoglobulins
IL-8	Macrophages	Chemotatic factor for neutrophils
IL-10	Regulatory T cells	Inhibits actions of activated T cells. Activates Th2, inhibits Th1
IL-12	B cells and macrophages	Activates NK and Th1 cells
gamma-interferon	Th1 cells	Stimulates macrophages. Activates Th1, inhibits Th2
TNF	Macrophages	Mediates septic shock. Leukocyte recruitment, vascular leak.
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T and B cell activation

Question	Answer	Column 3
Cell activated	Signal 1	Signal 2
Th	Antigen presented on MHC II, recognized by TCR	Interaction b/w B7 and CD28
Tc	Antigen presented on MHC I, recognized by TCR	IL-2 from Th cell activates
B-cell (Class switching)	IL-4, IL5, IL-6 from Th2 cell	CD40R-CD40L binding (with Th cell)
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HLA subtypes

HLA	Disease
A3	Hemochromatosis
B27	Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome (PAIR)
B8	Grave's disease
DR2	Multiple sclerosis, hay fever, SLD, Goodpasture's
DR3	Diabetes mellitus type 1
DR4	Rheumatoid arthritis, diabetes mellitus type 1
DR5	Pernicious anemia, Hashimoto's thyroiditis
DR7	Steroid responsive nephrotic syndrome
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Lymphatic drainage

Area of body	Primary lymph node drainage site
Upper limb, lateral breast	Axillary
Stomach	Celiac
Duodenum, Jejunum	Superior mesenteric
Sigmoid colon	Colic --> inferior mesenteric
Rectum (lower part), anal canal above pectinate line	Internal iliac
Anal canal below pectinate lie	Superficial inguinal
Testes	Superficial and deep plexuses --> para-aortic
Scrotum	Superficial inguinal
Thigh (superficial)	Superficial inguinal
Lateral side of dorsum of foot	Popliteal
Right arm/right half of head	Right lymphatic duct
"Everything else"	Thoracic duct
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Immune deficiencies

B cell disorders

Disease	Defect	Presentation	Labs
Bruton's agammaglobinemia	XR defect in BTK, blocks B-cell differentiation	Recurrent bacterial infections after 6 months, opsonization defect	Normal pro-B, decreased maturation, number of B-cells, immunoglobulins of all classes
Hyper IgM syndrome	Defective CD40L on helper T cells --> inability to class switch	Severe pyogenic infections early in life	Increased IgM, decreased IgG, IgA, IgE
Selective Ig deficiency	Defect in isotype switching	Sinus and lung infections, milk allergies, and diarrhea, anaphylaxis on exposure to blood products with IgA: IgA deficiency. Failure to mature into plasma cells.	-
Common variable immunodeficiency (CVID)	Defect in B-cell maturation, many causes	Can be acquired (20s-30s), Increased risk of autoimmune diseases, lymphoma, sinopulmonary infxns	Normal numbers of B cells, decreased plasma cells and immunoglobulins
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T cell disorders

Disease	Defect	Presentation	Labs
Thymic aplasia (DiGeorge)	22q11 deletion, failure to develop 3rd and 4th pharyngeal pouches	Tetany, recurrent viral/fungal infections, congenital heart and great vessel defects	Thymus and parathyroid fail to develop, decreased T cells, Decreased PTH, Decreased calcium, absent thymic shadow on CXR
IL-12 receptor deficiency	Decreased Th1 response	Disseminated mycobacterial infections	Decreased IFN-gamma
Hyper-IgE syndrome (Job's syndrome)	Th cells fail to produce IFN-gamma, inability of neutrophils to respond	Course Facies, cold staph Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (FATED)	increased IgE
Chronic mucocutaneous candidasis	T-cell dysfunction	Candida albicans infections of skin and mucous membranes	-
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B and T cell disorders

Disease	Defect	Presentation	Labs
Severe Combined immunodeficiency (SCID)	Several types. Defective IL-2 receptor (XR), adenosine deaminase deficiency, failure to synthesize MHC II	Recurrent viral, bacterial, fungal, and protozoal infections. Treat with bone marrow transplant	decreased IL-2R, increased adenine, (decreased dNTPs and decreased DNA synthesis)
Ataxia-telangiectasia	Defect in DNA repair enzymes	Cerebellar defects, spider angiomas/telangiectasias, IgA deficiency	IgA deficiency
Wiskott-Aldrich Syndrome	XR Progressive deletion of B and T cells	Thrombocytopenic purpura, Infections, Eczema (TIE)	Increased IgE, IgA, decreased IgM
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Phagocyte dysfunction

Disease	Defect	Presentation	Labs
Leukocyte adhesion deficiency (type 1)	Defect in LFA-1 integrin (CD18) on phagocytes	Recurrent bacterial infections, absent pus formation, delayed separation of umbilicus	Neutrophilia
Chediak-Higashi syndrome	AR, defect in microtubular function	Recurrent pyogenic infections by staph and strep; partial albinism and peripheral neuropathy	N/A
Chronic granulomatous disease	Lack of NADPH oxidase	Increased susceptibility to catalase-positive organisms (staph, E. Coli, Aspergillus)	Negative Nitroblue tetraxolium dye reduction test
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