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Flashcards in immuno post midterm Deck (54):
1

SLE

Systemic and multiorgan. IC are formed in serum and trapped in BM of glomeruli, skin/endothelium, synovia of joints, kidney. Unknown etiology

Immune-complex-mediated.
Ag/Ab - anti-ds-DNA, anti-phospholipids (can lead to spont abortion d/t increased coagulation), anti-leukocytes.
F/M - 10:1

2

RA

Excessive Type 1 cytokines. Rheumatoid factors IgM (or IgG/IgA) to the Fc of IgG. These are not essential for dz, may enhance IC. Both IL-! and TNFa are elevated in RA -> targets for therapy. Use anti-IL-1 and anti-TNFa (monoclonal Abs - eg adalimumab and fusion protein Enbrel/Enteracept). HLA DR1/DR4

Immune-complex and cell-mediated.
Ag/Ab - Fc of IgG/Ab is called rheumatoid factor
F/M - 3:1

3

Hashimoto's thyroiditis

Thyroid. Goiter and/or hypothyroidism. (Hyperthyroidism first d/t dmg causing release of thyroid contents, then hypothyroidism) Peaks in ages 30s or 40s

Cell-mediated.
Ag/Ab - Ab released after gland destruction. Anti-thyroglobulin, anti-microsomal (proteins). Use Abs for dx.
F/M - 50:1

4

MS

Brain and spinal cord. Abs to MBP after cell death. Oligoclonal Ig bands in CSF (dx feature)

Cell-mediated. Delayed-type hypersensitivity (T cell mediated)
Ag/Ab - myelin basic protein (released after death)/anti-MBP and CNS oligoclonal Abs
F/M - 2:1

5

Goodpasture's syndrome

Lungs and kidneys. Shared Ags between lung (alveolar) and GBM. Linear deposition of IgG and complement aids dx. HLA allele associated with HLA DR2

Abs to cell surface Ags
Ag/Ab - GBM/anti-GBM
F/M - 1:4, peaks in young and elderly

6

Pernicious anemia

Cell-specific - defective RBCs d/t malabsorption of vit B12. Abs bind cell surface Ags and destroy parietal gastric cells that secrete IF or Abs bind to IF and prevent binding of vit B12. Leads to megaloblastic anemia

Blocking Ab. Abs bind and destroy parietal cells
Ag/Ab - IF or surface antigens on parietal cells/anti-IF, anti-parietal cell

7

Graves' dz

Thyroid. Stimulatory Abs mimic actions of ligand (thyroxin-stimulating hormone). Get unregulated secretion of thyroxin leading to hyperthyroidism

Stimulating Ab
Ag/Ab - TSHR/anti-TSHR
F/M - 8:1

8

MG

Neuromuscular transmission d/o. Abs are inhibitory and block ACh binding

Blocking Ab
Ag/Ab - ACH-R/anti-ACHR
F/M - 4:1

9

Cold agglutinin dz

Only manifests at temps below 37C. Occurs only at extremities (nose, fingers, toes) when pt is exposed to cold temps. Tx - keep patient warm and extremities well protected

Abs to cell surface Ags
Ag/Ab - glycophorin (Ii)/anti-Ii

10

Ankylosing spondylitis

Tissue specific w/systemic SE's. HLA allele -> HLA B27. Joints - loss of lateral flexion of lumbar spine d/t stiffening if SI and spinal facet joints. Some evidence for prior infxn w/Klebsiella pneumoniae. NO rheumatoid factor!

F/M - 1:9, younger males more often affected

11

Wegener's granulomatosis and Churg Strauss vasculitis

Similarities: anti-cANCA (against serum protease) and anti-PANCA Abs.

IgG and IgM Abs (IC formation, complement activation, phagocytosis)

12

Reticular dysgenesis

Defect: hematopoietic stem cells, autosomal recessive

Deficiencies/dysfxn: T cells, B cells, phagocytes. Anemic. Increased susceptibility to all infectious agents.

Tx: bone marrow transplant

13

Severe combined immunodeficiency disorder (SCID)

Defect: ADA deaminase (purine metabolism) deficiency, JAK-3 deficiency, CD132 defect, T-B SCID (Rag1, Rag2 defects)

Deficiencies/dysfxn: lymphocytes primarily. ADA - highest activity in lymphocytes, increased metabolites (deoxyATP and deoxyadenosine). These metabolites inhib RN reductase. CD132 is signaling molecule for cytokine recs (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R)

Tx: ADA - polyethylene glycol-ADA (PEG-ADA), gene therapy for pts for whom PEG-ADA is ineffective and no bone marrow transplant is available

14

DiGeorge's syndrome

Defect: Thymus. Most improve with age (may have activation of extrathymic maturation site)

Deficiencies/dysfxn: T cells (all phenotypes)

Tx: transplantation of fxn'l component of fetal thymus (in renal capsule), abx for milder cases

15

X-linked (Bruton's) agammaglobulinemia (hypogammaglobulinemia)

Defect: developmental block in B cell differentiation from pro-B cell to pre-B cell due to signaling defect in btk. Manifests at 5-6 months (most of maternally-derived Abs degraded). Live vaccines contraindicated in pts w/this immunodeficiency. PE can reveal absent or hypoplastic tonsils in toddlers. More susceptible to autoimmune dz's: inflammatory bowel disease, juvenile RA

Deficiencies/dysfxn: marked decrease in B cells and ALL antibody isotypes -> recurrent bacterial infxns, esp encapsulated pyogenic bacteria (Haemophilus influenzae, S. pneumoniae), and certain viral infxns (enterovirus, coxsackie virus)

Dx: serum protein electrophoresis, quantitative Igs, PHA stimulation test/candida hypersensitivity test

Tx: Igs (regular txt's), abx, nutritional supplementation for pts w/recurrent abdominal infxns and subsequent malabsorption

16

Chronic mucocutaneous candidiasis

Defect: Hole in the T cell repertoire to Candida albicans. Nml B cell immunity to C. albicans

Deficiencies/dysfxn: CD4+ cells (especially)

17

Chediak Higashi syndrome

Defect: Abnormal fusion of cytoplasmic granules w/lysosomes (phagocytes and NK cells), LYST gene mutation

Deficiencies/dysfxn: phagocytes, CTL, NK cells

Tx: short-term: anti-fungal and anti-bacterial agents. Long-term: bone marrow transplant

18

Chronic granulomatous disease

Defect: NADPH oxidase

Deficiencies/dysfxn: phagocytosis -> recurrent and uncontrolled bacterial and fungal infections

Tx: short-term - anti-fungal and anti-bacterial agents; IFNy enhances production of ROIs. Long-term: bone marrow transplant

19

Paroxysmal nocturnal hemoglobinuria (PNH)

Defect: glycosylphosphatidylinositol (GPI) linkage for DAF (CD55) w/decreased protectin (CD59) in RBCs -> causes stabilized C3 convertase and activation of terminal pathway and formation of MAC -> lysis

Deficiencies/dysfxn: RBCs lysed by complement

20

Hereditary angio(neurotic)edema (HANE or HAE)

Defect: C1 esterase inhibitor protein

Deficiencies/dysfxn: uncontrolled activation of C1 -> proteolysis of C2/C4, enhanced production of C2b (vasoactive kinin), increased C4 (anaphylatoxin -> increased vascular permeability). CI inhibitor protein also inactivates kallikrein (that cleaves kininogen -> bradykinin, which increases vascular permeability). Life-threatening acute, intermittent attacks of skin and mucosal edema

Tx: infusion of C1 esterase inhibitor

21

Leukocyte adhesion deficiency

Defect: CD18 adhesion molecule (B2 integrin) - LAD 1. Defect in counter molecule for E selection - LAD2

Deficiencies/dysfxn: impaired trafficking of leukocytes to sites of infection, defective adhesion and margination. Increased susceptibility to fungal and bacteria infxns

Tx: bone marrow transplantation

22

Recurrent Neisseria infections

Defect: C5-C9

Deficiencies/dysfxn: no effective MAC

Tx: abx

23

Multiple myeloma

Defect: Plasma cell

Deficiencies/dysfxn: Plasma cell neoplasm

24

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)

Defect: FOXP3 mutation -> autoimmune rxns

Deficiencies/dysfxn: defective development of nTregs, links immunodeficiency with autoimmunity

25

Transient hypogammaglobulinemia of infancy

Defect: lack of Th cells help (cytokines). Manifests at 5-6 months, normal number of B cells in blood. NOT X-linked. Recurrent infxn w/pyogenic bacteria.

Deficiencies/dysfxn: IgG, IgA, IgE.

Tx: pts usually recover w/abx, but use IgG for particular infxns in severe cases. Improves w/age

26

Common variable hypogammaglobulinemia

Defect: immature B cells or lack of Ag-induced differentiation. Normal numbers of peripheral blood B cells. Increased susceptibility to viral and fungal infxns. In males and females of all ages

Deficiencies/dysfxn: all Igs -> defective Ab production following infxn.

Tx: injection of Ig

27

Selective IgA deficiency

Defect: Unknown. Common in Caucasians. Increased incidence of recurrent sinopulmonary infxn

Deficiencies/dysfxn: IgA

Tx: abx (not passive Ig, bc there are only low levels of IgA in serum -> it does not get to target sites, and recipients quickly form Abs to donor IgA)

28

Ig Deficiency w/increased IgM/hyper IgM syndrome

Defect: Isotype switching d/t lack of CD40/CD40L interaction. X-linked disorder. Many IgM Abs are autoAbs

Deficiencies/dysfxn: IgG, IgA, IgE

29

C3 deficiency

Enhanced susceptibility to ALL bacterial infxns. Chronic nephritis (d/t complement activation and deposition of C3 nephritic factor, an autoAb that binds C3 and stabilizes alternative pathway C3 convertase to prevent its degradation) -> accumulate complement debris in the glomeruli. C3 defect predisposes to failure to activate alternate or classical pathways

Tx: abx

30

Cytokine rec defects

Mutations or defects in recs for cytokines that are needed for differentiation of Th0 to Th1 cells -> similar to having deficiency of Th1 cells

31

Waldenstrom's macroglobulinemia

Monoclonal gammopathy

32

Type I hypersensitivity

Immediate. Occurs when Ag crosslinks IgE on mast cells/basophils -> release histamine. Local effects - asthma or allergic rhinitis, systemic effects - anaphylaxis for acute. Require pre-existing Abs (primary exposure can't trigger this response)

Late response - sustained inflammation, involves Th2 cells (secrete IL-5), eosinophils, and basophils.

Dx: RAST (measures amt of allergen-specific IgE in serum, false negative because IgE bound to mast cells is not estimated or IgG may compete for allergen)

Tx: antihistamine (H1 and H2-histamine rec antagonist), sodium cromoglycate -> stabilize mast cell and basophil mems, epi (30-90 minutes), steroids (4-8 hours), allergy shots, antileukotrienes, anti-IgE

33

Type II hypersensitivity

Ab-mediated. Production of IgG and IgM Abs for cell surface Ag, destroy Ag-expressing cells via classical complement -> osmotic lysis or opsonin-mediated phagocytosis; OR ADCC when NK cells expressing FcyR bind IgG

Manifestations - transfusion rxns, hemolytic dz of the newborn (prevent with RhoGam), Goodpasture's syndrome, autologous cell death, chronic idiopathic urticaria

34

Type III hypersensitivity

Immune complexes d/t persistent immune challenge (autoimmune dz or chronic Ag exposure).

Effector phase - xs ICs deposited in capillary walls -> neutrophils try to phagocytose, but end up secreting inflammatory mediators, dmging endothelium and exposing sub endothelium -> activation of intrinsic coagulation pathway, generating kallikrein and bradykinin

Manifestations: SLE, RA, farmer's lung, serum sickness (pts immunized w/horse serum), arthus rxn

35

Type IV hypersensitivity

Cell-mediated. Chronic - re-exposure to Ag topically or intradermally, or persistent intracellular existence of microbe, and activation of memory Th1 cells

Chronic - granulomatous inflammation - microorganisms persist in macrophage, where they have escaped intracellular enzymatic and biochemical destruction after phagocytosis (ex: M. leprae and M. tuberculosis). Infected macrophages fuse to form multinucleated giant cells, surrounded activated immune cells form granuloma (tuberculosis, sarcoidosis)

Acute: Mantoux run - intradermal PPD test for tuberculosis. PPD presented to Th1 cells by APCs after previous exposure. Memory Th1 cells secrete IFNy, TNF -> activate macrophages -> local cytokine-induced erythema (non-pitting edema) for 24-48 hours. Called delayed type hypersensitivity run

Contact - poison ivy dermatitis d/t activation of specifically sensitized memory Th1 cells in response to urshiol hapten. Effector phase after second exposure -> erythema, swelling

36

MAGE-1, MAGE-3

Melanoma, normal testicular protein

37

Surface IgG

Lymphoma, normal B cell receptor

38

NY-ESO-1

Breast cancer, normal testicular protein

39

GAGE

Melanoma

40

BAGE, PRAME, caspase-8

Squamous cancer

41

Carcinoembryonic antigen (CEA)

Oncofetal Ag. Colon, lung, breast, stomach tumors. Monitor early recurrence of treated tumors. Present in nonmalignant tissues (cigarette smokers, alcoholic cirrhosis, COPD)

42

Alpha fetoprotein Ag

Oncofetal Ag. Liver, testicular, pancreatic, gastric, lung tumors. Nmlly synthesized by fetal liver, yolk sac, and GI cells. Present in viral and alcoholic cirrhosis of the liver

43

Beta chorionic gonadotrophin

Gonadal germ cell tumors. Adenocarcinomas of the ovary, pancreas, stomach. Hepatomas. Used to monitor efficacy of therapy. Produced by trophoblast epithelium of placenta

44

HER2

Member of ErbB protein family, gene on chromosome 17. Corec of tyrosine kinase-associated growth factors, involved in signal transduction and cell growth and differentiation. Amplification seen in breast, ovarian, endometrial cancers. HER2+ breast cancer leads to marked overexpression of HER2 on the cell surface altering normal signaling fxn. Increased susceptibility for recurrence and worse prognosis

45

Bence Jones proteins

Serum free light chains with exposed hidden areas. Seen in myeloma cells

46

Prostate specific antigen (PSA)

Screen for prostate cancer and follow for treatment. May be falsely elevated in prostatitis

47

Non-specific immunosuppressants

Cyclosporin and FK506, anti-CD3 Abs, prednisone

48

Specific immunosuppresion

Block CD40-CD40 ligand interaction, CTLA4 to block CD80-CD28, CD200-CD200R

49

Live, virulent vaccine

For natural infxn (buttock exposure to Leishmania).

"Controlled" development of sterile immunity; safety a concern

50

Live, attenuated vaccine

Sabin polio virus
Mycobacterium tuberculosis (BCG)
MMR

In rare cases, attenuated organisms revert to WT

51

Inactivated/killed vaccine

Salk polio virus
Rabies virus
Influenza virus (moderately effective)
Cholera bacteria (moderately effective)

Safer, but less effective than live or attenuated organisms

Killed pertussis vaccine is toxic w/risk of dmg to CNS, contamination w/endotoxin (the vaccine itself is a bacterial product)

52

Inactivated toxin and toxoid vaccine

Bacterial vaccines for tetanus and diphtheria
Carrier molecule for vaccination w/malaria organism

Most successful vaccines yet tested

53

Recombinant vaccines

Ag peptide, eg Hep B, Salmonella proteins

Fewer SE's than other vaccines. Advantage of ability to manipulate (add/subtract) epitopes of importance

54

DNA vaccines

Plasmid-containing genes encoding pathogen

Main fxn is for immunity to pathogens that will infect cells. Used to generate Ag-specific CTLs for life-threatening pathogens that infect cells