1. AI hemolytic anemia
   1. scattered rhonci
   2. disrupted tissue barier
   3. bug mimics host >
   4. IGM, IGG
   5. Cold Abs, agglutinins
   6. CLINICAL
      1. WBC high
      2. neutrophils in sputum
      3. STRONG AGGLUTINATION OF RBC IN FRIDGE
   7. TX
      1. Erythromycin
      2. stay out of COLD!
2. Infections that lead to AI dx
   1. s. pyogenes
      1. rheumatic fever
   2. strep.
      1. acute glomerulonephtritis
   3. mycoplasma pneumonia
      1. hemolytic anemia
         1. drop in RBC due to IgM binding to RBC > cold agglutinates below 37'C
3. Drug induced serum sickness
   1. SWELLING EVERYWHERE
   2. ENLARGED LN & SPLEEN
   3. RASH EVERYWHERE
   4. TYPE 3 rxn
      1. IgG response > comp > histamine > adhesion molecules
      2. WBCs migrate, INFLAMMATION rxn
      3. DEPOSITION ZONES
      4. LOW serum C1q, C3 >>comp consumption!!
   5. PCN, horse serum
   6. RBCs, protein in urin
   7. EKG abnormal > dec. circ to post brain
   8. EDEMA
   9. IgG, C3 in perivascular area
   10. TX
       1. benadryl
       2. naprosyn
       3. prednisone
4. Allergic Asthma
   1. each time worse
   2. TYPE 1 rxn
      1. cd4, th2 cells
      2. mast cell, eosinophils, IgE >histamine
      3. AA > leukotrienes >> BRONCHOCONSTRICTION
      4. th >il3,4,5, TNFa >>PROLONG allergin rxn
      5. eosinophils >>OVERPRODUCTION OF MUCUS
      6. NKT
   3. air gets trapped in lungs > hyperinflation
   4. wheezing all over lung fields
   5. HIGH eosinophils, IgE ABs
   6. TX
      1. broncodilator = theophylline
      2. albuterol
      3. Intal = dec. mast cell granule release
      4. immunotherapy
5. Acute infectious MONO
   1. difficulty swallowing, loss of apetite
   2. EBV
      1. infects B cells
      2. 30-50d latency period
      3. latent for long time and reactivated periodically
      4. spreads thru kissing; as virus is shed in oral secretions
      5. HETEROPHILIC IGM = diagnostic
      6. binds to RBCs and agglutinates them
      7. REQ. bcrf1
   3. Foamy basophils
   4. CD8 T cells
   5. dry mouth, red and large tonsisl, PALATAL PETECHIAE
   6. soft abdomen, LIVER & SPLEEN ENLARGED
   7. HIGH WBC, w/ atypical monocytes
   8. TX
      1. hospital
      2. salive
      3. steroids
      4. poss. tonsillectomy
      5. acyclovir
      6. antiCD20 rituximab
6. Contact Hypersensitivity to Poison Ivy
   1. TH1; IFNgamma
   2. DTH 4 rxn
   3. rxn on 2nd encounter, not 1st
   4. rash after 2 d
   5. swollen eyelids, penis
   6. TX
      1. topical steroids
      2. benadryl
      3. anti-histamines
      4. protective clothes; cut nails short
7. AIDS
   1. opp. infections
   2. wt. loss
   3. CD4 = receptor for HIV
   4. TNFalpha released during inf > anorexia & rapid wt loss
   5. ELISA & Western Blot; gp 120
   6. TX
      1. anti retrovirals
      2. anti reverse transcriptase
8. Rheumatoid Arthritis (RA)
   1. stiffness in morning, goes away during day
   2. spongy swelling of joints
   3. dec. ROM
   4. autoreactive CD4 T cells
      1. help B cells make arthritogenic ABs
   5. HLADRB1
   6. C5a
      1. via ALTERNATE comp. path
   7. CD11:CD18 (LFA1)
      1. TNFalpha & IL1 > integrin
      2. infiltration of lymphocytes
   8. RF factor (IgG)
   9. high sed rate
   10. TX
       1. antimalarial = hydroxychloroquone
       2. methotrexate
       3. NSAID
       4. TNF a inhibitor - inflixamib
       5. sx for bone deformities
9. Multiple Sclerosis (MS)
   1. urinary incontinence
   2. blindness
   3. ataxia
   4. muscle weakness > paralysis
   5. nystagmus
   6. HLADR2
   7. TH1, CNS antigens, mast cell activation, complement, AB, cytokines
      1. DEMYELINATION
   8. anti-myelin
   9. more in WOMEN
   10. Major basic protein & Proteolipid FOUND IN CSF
   11. TX
       1. steroids & IFNbeta
       2. cyclophosphamide injections
          1. inhibits T cell proliferation
10. Common Variable ID (CVID)
    1. FREQUENT INFECTIONS
       1. seen in 15-35 y/o males and females
    2. mutation in TAC1 > which mediates ISOTYPE SWITCHING
       1. cant isotype switch
       2. no IgA, IgG, IgE
       3. unable to respond to vaccine
       4. cant make AB against polysacc.
    3. impaired somatic hypermutation
    4. hypogammaglobulinemic
    5. low affinity of few enzymes
    6. frequent & UNUSAL infections
    7. Deficiency of ICOs, mutation in CD19, BAffR
    8. TX
       1. IV Ig q 2 wks
11. X-linked Agammaglobulinemia
    1. chrnoic infections since infancy
    2. collapse of part of lung
    3. chronic cough
    4. NO TONSILS, BUT NO TONSILLECTOMY!
    5. pyogenic bacteria
       1. common extracellular pathogens
    6. damage airways
    7. Xq22 >BtK mutation
    8. TX
       1. IV IgG q/wkend
12. Wiskott-Alderich syndrome
    1. eczema w/ PETECHIA
    2. asthma
    3. bloody diarrhea
    4. autoimmune hemolytic anemia
       1. + coombs test
       2. RBCs coated w/ IgG***
    5. DARK URINE
    6. ABNORMAL T CELL FX
       1. abnormal protein
       2. platelets and T cells are defective in # and Fx, cell div
       3. cytoskeleton fx imparied ****
       4. monocytes and phagocytes also impaired
       5. NK cells and B cells also abnormal
       6. T cells lose surface microvilli = BALD T CELLS***
    7. SPLEEN LACKS MARGINAL ZONE = lack of IgM
    8. no blood type antigens either!
    9. normal # of B and T cells BUT mitogen response diminished & no repsonse to antiCD3
    10. Flow cytometry test & Western blot
        1. Lack Of WASP protein
        2. premature stop codon
        3. ameoboid cytoskleton messed up
    11. +EBV
    12. TX
        1. platelet transfusion
        2. steroids
        3. IV IgGs + trimethoprim/sulfa
        4. bone marrow transplant
           1. cyclosporin for GVHD ; got it > tx w/ methylprednisone
13. Kidney Graft Complications
    1. many lymphocytes in kidney
       1. = rejection
    2. fever, severe cough w/ thick yellow sputum
    3. crackles and wheezes in lungs
    4. fungus A fumigatus cultured from sputum > tx w/ fungoside
    5. TX
       1. methylprednisone
       2. anti-ICAM monoclonal AB
       3. cyclsoporin
       4. azathioprine
       5. monoclonal AB to CD3
       6. low doses for rest of life
14. Graft vs Host disease
    1. rash
    2. diarrhea
       1. bleeding from colon and diffuse GVHD in LI
    3. pneumonitis
    4. liver damage
    5. RASH ON PALMS & SOLES, scalp and neck
    6. donor attacks host
       1. occurs w/ mismatch of MCH and other..
       2. CD4
    7. TX
       1. busulfan >eradicate host lymphocytes
       2. steroids
       3. tacrolimus - immunosupportive
       4. antithymocyte serum
       5. monoclonal anti CD2 injections q 2ds
       6. LONG term steroids
15. Recurrent Herpes Simplex Encephalitis
    1. relapsing seizures
    2. lateralized seizures
    3. lateral paralysis
       1. 5yrs later remains
    4. cold sores
    5. lesions on temporal and parietal lobe****
    6. VIRAL MENINGOENCEPHALITIS
    7. HIGH WBCs
    8. TLR > IFNa/b DEFECTIVE
       1. TLR3 FAILURE
       2. DEFECT IN STAT1
    9. Genetic testing > homo deletion in exon 1 of UNC93B
    10. HSVI - db stranded DNA virus > travels in trigeminal nerves and ganglia
    11. noramlly bening, but when invades brain > HSE (via olfactory tract and trigeminal nerves > affects neurons and glia
    12. Photophobia
    13. TX
        1. acyclovir
        2. ? IFNa/b - potential
16. Lepromatous Leprosy
    1. hypopigmentation
    2. loss of sensatino
       1. permanent
    3. loss of hair
    4. deformities; nose bleeds
       1. affect nasal mucosa > congesiton and breakage of bld vessels
    5. LL VS TbL
       1. LL
          1. TH2
             1. inc. risk for asthma
          2. IL4,5,6,10
             1. promote IgE
       2. TbL
          1. TH1
    6. mycobacterium
       1. acid fast
       2. bacilli
       3. virchow's cells - foam cells
    7. DTH 4 rxn
    8. TX
       1. multiple drug regimen
       2. dapsone, clofazamine
       3. rifampine
17. Myasthenia gravis
    1. muscle weakness
       1. weakness of facial mm
       2. ptosis
       3. trouble swallowing, chewing
       4. trouble talking, breathing
       5. improves w/ rest
    2. ENGLARGEMENT OF THYMUS GLAND
       1. thymomas > IMPAIRED NEG. SELECTION
    3. humor AI
    4. AB attack ACH receptor @ NMJ
    5. AB against MUSK
    6. double vision, improves spontaneously, but also worsens
    7. TX
       1. pyridostigmine >ACHase inhbitor
       2. hospital > azatioprine
          1. inhibits dna synthesis to keep b and t cell division minimal
          2. more sus. to infections
       3. removal of thymus may help
18. Di George Syndrome - aka - Severe T cell Deficiency
    1. congenital heart defects
    2. hypoparathyroidism
    3. hypocalcemia
    4. dysmorphic facial featrues
    5. deletion or mutation of Tbxl1.> t box factors @ chromo 22q11
       1. FISH showed deltion
    6. FOXn1 mutation
    7. 2d old > feeding/ breathing problesm >> turn blue
    8. truncus arteriosus
    9. 2d/o > seizures, very low ca
    10. sx for heart, NO THYMUS
    11. no CD3 t cells
    12. TX
        1. thymic transplant + mitogens PHA & CONA
        2. ca *& vit D supplements
        3. prophylactic Abs
19. Systemic onsent Juvenile Idiopathic Arthritis (sJID, sJIA)
    1. fever wont stop
    2. rash w/ fever
    3. high WBC & inflammatory markers
    4. ENLARGED SPLEEN AND LN
    5. IL1, TNFa, IL6, Th17
       1. il6 > fever, anorexia, fatique, high acute phase reactants
    6. MUTATION in INFLAMMASOME
    7. mutation in NLRP3 > inc il1; ILIRRN mutation
    8. joint swelling; dec ROM but gets better thruout day
    9. anemia
    10. high neutrophil
    11. TX
        1. indomethacin
        2. prednisone
        3. methotrexate
        4. TNFa, IL1, IL6 inhibitors
           1. toclizumab (6)
           2. ankinara (1)
20. Crohn's Disease
    1. fever
    2. chronic ABD pain
    3. wt loss****
    4. inflammatory lesion spanning GI
    5. NOD proteins ; imparied secretion of Defensins
    6. DYSREGULATION OF COMPLEX MUCOSAL IMMUNE FX - don''t really understand yet
    7. HIGH WBC, platelet, sed rate, CRP
    8. endoscpy
       1. ulceration of esophagus & sm int
       2. perianal fistula
    9. Bx
       1. neutrophil infiltration
       2. colitis w/ crypt abscesses
    10. TX
        1. PPI - omeprazole
        2. steroids
        3. 6-mercaptopurine- chemo agent
        4. infliximab & adalimumam - anti TNFa
        5. natalizumab - anti integrin > dec. t cell homeing to gut
        6. ileum & cecum resection > drain abscesses
21. Celiac Disease
    1. diarrhea, malabsorption
    2. failure to thrive
    3. abd distension
    4. anemia
    5. irritability
    6. muslce waste
    7. nause/vomiting
    8. constipation
    9. PERMANENT SENSITIVITY TO GLUTEN***
    10. HLA2 DQA & B; Chromo 6
        1. 95% A
           1. present to TH1 >IFNg
        2. other B
    11. high IL15 > activates APCs
    12. 33a peptides > passes into int. lining bc of tissue damage > response
    13. anti-IgA ABs****
    14. edema & flattening of mucosal folds in duodenal bulb > villous atrophy***
    15. TX
        1. nutritional counseling > gluten free diet
22. Systemic Lupus Erythrematous (SLE)
    1. butterfly rash***
    2. SYMETRIC morning stiffness, swelling in fingers
    3. fever, chills, wt loss
    4. enlarged LN
    5. GLOMERULONEPHRITIS & ARTHRITIS
    6. IMMUNE COMPLEX CLEARANCE not working
       1. complexes are small and get trapped in tissue and joings
    7. Autoantibodies against DNA!!!
    8. IFNa/b > activate autoreactive T cells > inc. class switch > inc IgG + hyperplasia of of LN, inc. plasma cells in medulla of LN
    9. IRF5****
    10. sun causes rash
    11. LOW C3
        1. the lower the worse the disease
    12. High IgG
    13. TX
        1. antimalarial - plaquenil, hydroxyquinolone
        2. avoid direct sun
        3. prednisone
        4. NSAID
23. Congenital Asplenia
    1. many OPPORTUNISTIC infections
       1. more sus. to encapsulated bacteria
    2. missing spleen
    3. HIGH WBC
    4. TX
       1. vaccination against common pathogens
       2. prophylactic antibiotics
    5. autosomal recessive
24. Chediak-Higashi Syndrome
    1. recurrent infectins
       1. EBV
    2. lighter skin and hair (compared to family)
       1. partial absence of melanin
    3. parents are second cousins
    4. platelet dysfunction > tendency to bleed
    5. MASSIVE ORGAN INFILTRATION OF LYMPHOCYTES
       1. imparied lymphocyte cytotoxicity
       2. immune system can't kil virus infected cells
       3. Lymphocytes proliferate w/o restraint in attempt to control the infection
    6. microtubule polymerization defect
       1. decrease in phagocytosis
          1. recurrent PYOGENIC infections
          2. partial albinism
          3. peripheral neuropathy
          4. progressive neuro defects
             1. cerebellar ataxia
             2. CNS atrophy
             3. seizures, etc
       2. affects the normal formation and TRAFFIC of vesicles in the cells
       3. no affect on NADPH fx
       4. NBT test is thus normal
    7. TX
       1. prophylactic antibiotics
       2. aggressive mgmt of infections
25. Neutropenia
    1. block of myeloid differentiation in bone marrow
       1. due to destruction > see neutrophils in all stages of devo w/ bone marrow smear
       2. due to decreased production > see reduced myeloid cells in bone marrow
    2. large reserves of neutrophils are stored in bone marrow and released to fight infection
    3. INCREASED peripharal NEUTROPHIL destruction
       1. 8hr half/life
       2. neutrophil transplant not used unless, life-threatening infection and no other tx has worked
    4. TX
       1. Stem cell transplant
       2. chemo
26. Chronic Granulomatous Disease (CGD)
    1. vulnerable to AEROSOLIZED pathogens
       1. SUS. to pneumococcal infections
       2. bc they dont make CATALASE
    2. repeat resp infections
    3. abscesses
    4. infections that "can't be cleared"
    5. chronic inflammation > CD4+ > GRANULOMAS
    6. "MICROBICIDAL ACTIVITY OF MACROPHAGES IMPAIRED"
    7. neutrophils and macrophages can't destroy pathogens they take up
       1. phagocytes cant produce H202, superoxide
       2. defect in NADPH oxidase enzymes
    8. NBT TEST > NO REDUCTION (+)
    9. TX
       1. IFNg
27. Leukocyte Adhesion Deficiency (LAD)
    1. pyogenic infections
    2. wound healing problems
    3. severe gingivitis
    4. defect in CD18
       1. common beta chain of integrins, LAF1, Mac1, p150, 95
       2. req. for leukocyte adhesion
       3. neutrophils and monocytes can't get out of bloodstream and to site of infection to assit
       4. can't get there >> NO INFLAMMATORY LESIONS
    5. normal T cell fx
    6. HIGH WBC
    7. TX
       1. busulfan
       2. cyclophophamide
       3. anti-thymocyte serum
       4. bone marrow transplant
    8. autosomal recessive
28. Multiple Myeloma
    1. excessive fatigue
    2. malignancy of term. diff. B cells > CANCER OF PLASMA
    3. high sed rate, high IgG
    4. HOLES IN BONE/SKULL
    5. TX
       1. cyclophosphamide
       2. eoposide
       3. decadrom
       4. periodic blood transfusions
       5. chemo
29. Hemolytic disease of the newborn
    1. DROP IN FETAL HEMATOCRIT
    2. anti-rh Ab of mom attack RH+ factor of baby
    3. anti-Rh >>IgG
    4. TX
       1. Rhogam
       2. O-blood transfusion
30. Factor I deficiency
    1. REPEAT MIDDLE EAR INFECTIONS
       1. very vulnerable to NEISSERIA infections
    2. mastoiditis, pneumonia
    3. due to pus fomring neutrophils
    4. HIVES ON BODY
    5. (similar to H factor def.)
    6. C3 depletion
       1. alternate pathway C3 convertase is UNIHIBITED >>C3 consumption is accelerated >>
       2. lack of C3 & iC3b > INEFFECTIVE OPSONIZATION
       3. C3a > hives
       4. C3 levels are normal
       5. BUT C3 broken down at 4x normal rate
31. C8 Deficiency
    1. C5-9 Deficiencies >>NEISSERIA infections
    2. fever, stiff neck,
    3. REDISH/PURPLE rash
    4. loss of complement lytic fx
    5. HIGH WBC in CSF
    6. TX
       1. lumbar puncture
       2. draw blood
       3. IV AB for infection
32. MHC I deficiency
    1. recessive
    2. midline granulomatous disease
    3. resembling WEGENER'S GRANULOMATOSIS
    4. VASCULITIS in extremities
    5. normal humoral immunity"
       1. "mhc 2 okay >> cd4 normal >>
       2. normal DTH rxn to candida & tuberculin
       3. bc depends on CD4 t cells
    6. CD8 T cells - DEFICENT
       1. most gamma/delta CD8 T cells
       2. gamma delta form INDEPENDENT OF MHC 1
       3. less alpha/beta bc DEPEND ON MHC i
    7. HIGH IgG
       1. caused by ok CD4
       2. caused by inability of CD8 to suppress
       3. leads to overproduction of AB!
    8. TAP 1 def resembles TAP 2 deficeincy
33. MHC II deficiency
    1. pneumonia
       1. OPPORTUNISTIC pathogens
    2. MILD FORM OF SCID
    3. B CELLS don't express HLA-DQ/DR
    4. T cells can't respond to nonspecific mitogen
    5. deficient in CD4
       1. so B cells can't proliferate
    6. defect in transcription factor req to regulate expression of MHC 2
    7. clinical
       1. low Ig's
       2. T cells can't respond, b/c not directed by absent Igs
       3. low CD4
       4. high WBC
       5. Subtopic 5
    8. TX
       1. maternal bone marow transfer
34. Omenn Syndrome
    1. severe OPPORTUNISTIC infections
    2. severe edema, SCID
    3. VDJ recombo defect
       1. RAG1/2 knocked out
       2. B & T cell devo abolished > SCID
       3. few T cells > IL4 > convert few Igs > IgE >
    4. High Ige
       1. rash worst on face
       2. blisters on palms and soles
       3. preponderance of eosinophils
    5. low Ig count
    6. Tx
       1. rapidly fatal unless tx w/ bone marrow transplant
    7. x-linked recessive
35. T cell Lymphoma
    1. t cell precursors in THYMUS > malignant tranformation & clonal expansion
    2. double positive T cells
    3. Cliinical
       1. low body wt
       2. BULGING L. CHEST
       3. no sound over L. chest
       4. mod. enlarged LN
       5. mediastinal shift to R
       6. L chest > abundant EOSINOPHILS
       7. high WBC
       8. growth of mediastinal tumor
          1. rise in IgE
    4. TX
       1. cytotoxic drugs
       2. anti-tumor drugs
36. Toxic Shock Syndrome
    1. superantigens
       1. excessive stimulation of T cells
       2. macrophages > bind to MHCII
       3. overstimulate CD4
       4. release high cytokines
    2. high neutrophils
    3. localized S. aureus infection OR staph poisoning
    4. TSST-1
    5. Edema, fluid loss
       1. due to TNFa
       2. may lead to multiple organ failure
    6. TX
       1. IV fluids
       2. Abs
37. Hyper IgM immunodeficiency
    1. recurrent sinus infections
    2. DEFECT IN CD40L
       1. production and isotype switching problem
       2. higher IgM , Very low all otehrs