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Flashcards in Immunology Deck (81):
1

Lymph node

Follicle= B-cells
- Primary: dense, dormant
- Secondary: pale, active

Medulla=
- Cords: lymphocytes and plasma cells
- Sinuses: reticular cells and macrophages; communicate with efferent lymphatics

Paracortex= T cells (between follicles and medulla)
- Endothelial venules: B-cell entry from blood
** Underdeveloped in DiGeorge syndrome

2

Lymph drainage

Rectum (above pectinate line): internal iliac

Anal canal (below pectinate line): superficial inguinal

Right lymphatic duct: drains right arm, right chest, right 1/2 of face
- Thoracic duct drains everything else

3

Sinusoids of spleen

Vascular channels in red pulp
- Fenestrated; macrophages nearby

White Pulp:
- T cells= periarterial lymphatic sheath (PALS)
- B cells= follicles

Macrophages remove encapsulated bacteria (IgM--> complement--> C3b opsonization--> macrophage removal)
- Strep pnumo, H. flu, N. meningitidis, Salmonella, Klebsiella, Strep agalactaciae (group B)

Post-splenectomy:
- Howell-Jolly Bodies (nuclear remnants in RBCs)
- Target cells (excess membrane: hemeglobin ratio)
- Thrombocytosis

4

Thymus

Epithelium of 3rd branchial pouches

Cortex= dense, immature T cells
- Positive selection (MHC class restriction: T cells expressing TCRs binding self MHC)

Medulla= pale, mature T cells, Hassall's corpuscles
- Negative selection (non-reactive to self antigens: high affinity for self--> apoptosis)

5

Innate immunity

Neutrophils, macrophages, dendritic cells, NK cells, complement

6

Adaptive immunity

Recognize pathogen--> V(D)J recombination
- Slow response at first, memory faster
- T cells, B cells, circulating antibody

7

MHC I

HLA-A, B, C

1. Nucleated cell (any) infected with antigen
2. Processed in RER (+ intracell peptides)
3. Presented on MHC-I + Beta-2 microglob
4. Binds TCR, CD8 T-cells

** Mediates viral immunity

8

MHC II

HLA-DR, HLA-DP, HLA-DQ

1. Antigen presenting cell infected
2. Antigen processed in acidic endosome
3. Presented on MHC-II (peptide binding groove)
4. Binds TCR, CD4 T-cells

9

HLA-A3

Hemochromatosis

10

HLA-B27

Psoriasis
Ankylosing Spondylitis
Inflammatory bowel disease
Reiter's syndrome

11

HLA-DQ2/DQ8

Celiac disease

12

HLA-DR2

Multiple sclerosis
Hay fever
Systemic Lupus Erythematosis
Goodpasture's disease

13

HLA-DR3

Diabetes Mellitus, Type 1
Grave's disease

14

HLA-DR5

Pernicious anemia--> B12 deficiency
Hashimoto's thyroiditis

15

Natural killer cells

Induce apoptosis of virally infected + tumor cells
- Only lymphocyte in innate immune system

Enhanced by IL-2, IL-12, IFN-beta, IFN-alpha

Kills target cell with:
- Nonspecific activation signal
- Absence of class I MHC

16

B-cell produced antibody functions

Type I hypersensitvity reaction: IgE produced (Allergy)

Type II reaction: IgG, IgM (Cytotoxic)

Type III reaction: IgG (immune complex)

** Hyperacute, humorally mediated acute/chronic organ rejection

17

T-cell functions

Type IV delayed cell-mediated hypersensitivity

CD4+ T cells= help B cell antibody production, make cytokines
- IL-12--> Th1 cell
- IL-4--> Th2 cell

CD8+ T-cells= Cytotoxic t-cells: kill VIRUS infected cells, neoplastic, donor graft cells. Secretes granules that contain:
- perforin (deliver granules into target cell)
- granzyme (serine protease= activates apoptosis in target cell)
- Granulysin (antimicrobial, induces apoptosis)

Regulatory T-cell (Treg)
- Express CD3, CD4, CD25 (alpha chain of IL-2 receptor)
- Activated--> anti-inflammatory IL-10, TGF-beta

18

Dendrite cell

ONLY APC that can activate naive T-cell
1. Phagocytoses foreign body
2. Presented on MHC II--> Th (CD4+ cell) OR Presented on MHC I--> Cytotoxic (CD8+)
3. Costimulation: B7 on dendrite--> CD28 on Naive T-cell

19

B cell activation/class switching

Th1 or Th2 (helper CD4+ T-cell) activated
1. B-cell endocytosis foreign antigen
2. Antigen presented on MHC II--> recognized by TCR on Th cell
3. CD 40 on B-cell binds CD40Ligand on Th cell
4. Th cell secretes cytokines--> Ig class switching of B cell
5. B cell matures, produces antibodies

** Mature B cells= IgM and IgD on surface
- Differentiate into plasma cells secreting IgA, IgE, IgG

B-cell receptors:
- Ig (duh)
- CD19, CD20, CD21 (EBV receptor), CD40, MHC II, B7

20

Th1 cell

Helper T-cell
1. Secretes IFN-gamma
2. Activates macrophages
3. Inhibited by IL-4, IL-10 (from Th2 cell)

21

Th2 cell

Helper T-cell
1. Secretes IL-4, IL-5, IL-10, IL-13
2. Recruits eosinophils for **Parasite defense**, promotes B-cell production of IgE
3. Inihibited by IFN-gamma (from Th1 cell)

22

Antibody structure

Fab= Antigen binding fragment
- Only 1 antigenic specificity per B cell

Fc=
- Constant
- Carboxy terminal
- Complement binding at CH2
- Carbohydrate side chains
- (Macrophage binds at CH3)

Diversity: Random, or somatic hypermutation after antigen stimulation

Role of Abs:
- Opsonization
- Neutralization: prevent bacterial adherence
- Complement activation: enhanced opsonization

23

IgG

Secondary response (delayed)
Most abundant

Roles:
- Fixes complement
- Crosses placenta
- Opsonizes bacteria
- Neutralizes toxins, viruses

24

IgA

Prevents bacterial/viral attachment to mucous membranes

Roles:
- Does NOT fix complement
- Does NOT cross placenta
- Circulation= monomer
- Secretion= dimer; crosses epithelial cells via trancystosis, picks up secretory component in epithelial cells

25

IgM

Primary response (immediate)

Roles:
- Fixes complement
- Does NOT cross placenta
- Monomer (on B cell) or Pentamer

26

IgE

Type I hypersensitivity reaction

Roles:
- Binds Mast cells/basophils
- Cross-links when exposed to allergen
- Releases histamine from mast cells
- Activates eosinophil reaction to worms

27

Antigen type and memory (thymus dependent vs independent)

Independent: antigen LACKS peptide component
- Cannot be presented by MHC (no peptide to present to T-cells)
- Ex: LPS from gram-neg bacteria, polysaccharide capsule
- NO immunologic memory

Dependent:
- Antigens contain protein component
- Ex: Diphtheria toxoid vaccine
- Class switching and memory due to B-cell Th cell CD40-CD40L interaction

28

Complement pathway

Leads to formation of MAC (membrane attack complex) to defend against gram NEGATIVE bateria

Activation:
1. Classic= IgG/IgM mediated
2. Alternative= microbe surface molecules (attract C3b)
3. Lectin= mannose/sugars on microbe

C3b= opsonization, clears immune complexes
C3a, C5a= anaphylaxis
C5a= neutrophil chemotaxis
C5b-C9= MAC formation--> cytolysis

** Pathway inhibited (from attacking self) by Decay-accelerating factor (DAF) and C1 esterase inhibitor

29

C1 esterase inhibitor deficiency

Hereditary angioedema
- ACE-I contraindicated

30

C3 deficiency

Recurrent pyogenic sinus, resp tract infections
- Increased susceptibility to Type-III hypersensitvity reactions (immune complex)

31

C5-C9 deficiencies

Recurrent Neisseria bacteremia

32

DAF deficiency

Complement-mediated lysis of RBCs
- Paroxysmal nocturnal hemoglobinuria

33

Macrophage cytokines

IL-1: fever, inflammation, recruit leukocytes
IL-6: fever, acute phase proteins
IL-8: Chemotactic factor for neutrophils
"Clean up on IL-8": neutrophils clean up infection

IL-12: differentiate Th1--> activate NK cells
TNF-alpha: Septic shock, endothelial leak

34

TH1 cell cytokines

IL-2: growth of helper, cytotoxic, Treg
IL-3: promotes bone marrow SC (GM-CSF)
IFN-gamma: activates macrophages, Th1, suppresses Th2; antiviral, antitumor

35

Th2 cells cytokines

IL-2: growth of helper, cytotoxic, Treg
IL-3: promotes bone marrow SC (GM-CSF)
IL-4: differentiate Th2 cells, B-cell growth, class switching IgE, IgG
IL-5: Differentiate B cells, enhance IgA class switching, eosinophils
IL-10: inhibits actions of activated T cells and Th1

36

Hot T-Bone stEAk

IL-1: fever (hot)
IL-2: stimulates T cells
IL-3: stimulates Bone marrow
IL-4: stimulates IgE production
IL-5: stimulates IgA production

37

Interferons

Place uninfected cells in antiviral state
"Interfere with viruses": induce production of ribonuclease against viral mRNA

- alpha, beta interferons= inhibit viral protein synthesis
- gamma interferons= upregulate MHC I and MHC II expression, antigen presentation
- activate NK cells to kill virus-infected cells

38

Macrophage markers

CD14 (binds endotoxins/LPS from gram-negative bacteria)
CD40 (binds CD40L on helper T-cell)
MHC II + B7 (binds CD28 on T-cell)
Fc, C3b receptors (enhanced phagocytosis)

39

NK cell markers

CD16: binds Fc of IgG
CD56: unique to NK cells**

40

Live attenuated vaccine

Microorganism with capacity for growth and NO pathogenicity--> induces cellular response

Pro: life-long, strong immunity
Con: may revert to virulent form

Ex:
- Measles, mumps, rubella, polio (Sabin), varicella, yellow fever, Nasal flu (flumist)

41

Inactivated (killed) vaccine

Pathogen inactivated by heat, chemicals
- Epitope structure of surface antigens maintained--> induces humoral immunity

Pro: stable, safer
Con: weaker immune response, need booster

Ex:
- Cholera, hep A, polio (salk), rabies

42

Type I hypersensitivity reaction

Allergy (anaphylaxis, atopic):
- rapid: free antigen cross-links IgE on mast cells/basohils
- Test: skin test for specific IgE

Disorders:
- Anaphylaxis
- Allergic/atopic disorders

43

Type II hypersensitivity reaction

Cytotoxic: IgM, IgG antibody mediated
- Bind to antigen on foreign cell--> destruction via:
1. Opsonization--> phaocytosis, complement
2. Complement-mediated Lysis
3. Antibody-dependent cell-mediated cytotoxicity (NK cells)

Test: direct, indirect Coomb's

Disorders:
- Autoimmune hemolytic anemia (AIHA)
- Pernicious anemia
- Idiopathic thrombocytopenic purpura
- Erythroblastosis fetalis
- Acute hemolytic transfusion reactions
- Rheumatic fever
- Goodpasture's syndrome
- Bullous pemphigoid (dermis, epidermis)
- Pemphigus vulgaris (keratinocyte adhesion)

44

Type III hypersensitivity reaction

Immune-complex mediated
- Antigen-Antibody (IgG) complexes activate complement--> neutrophils attracted--> release lysosomal enzymes
Types:
- Serum sickness
- Arthus reaction

Disorders:
- SLE
- Polyarteritis nodosa
- Post-strep glomerulonephritis
- Serum sickness
- Arthus reaction

45

Serum sickness

Type III hypersensitivity reaction
- Antibodies to foreign protein produced (after ~5 days)
- Immune complex formation--> membrane deposition--> tissue damage

** Now mostly caused by drugs acting as haptens

46

Arthus reaction

Type III hypersensitivity reaction
- Intradermal injection of antigen--> antibodies fromation--> complex
- Edema, necrosis, complement activation

Test: Immunofluorescent staining

47

Type IV hypersensitivity reaction

Delayed (T-cell mediated) type:
- Sensitized T-cells encounter antigen--> release lymphokines--> macrophage activation

**4th, last
- Cell mediated (not transferrable in serum)
4 Ts: T-lymph, transplant rejections, TB skin test, Touching (contact dermatitis)

Test: patch test, PPD

Disorders:
- MS
- GBS
- GVHD
- PPD
- Contact dermatitis

48

Febrile nonhemolytic transfusion reaction (FNHTR)

Type II hypersensitivity reaction
- Host antibodies against donor HLA antigens and leukocytes
- Plasma spun to remove leukocytes

Symptoms:
- Fever, H/A, chills, flushing

49

Acute hemolytic transfusion reaction (HTR)

Type II hypersensitivity reaction
- ABO blood group incompatability--> intravascular hemolysis
- Host antibody reaction against foreign antigen on donor RBCs--> extravascular hemolysis

Symptoms:
- Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular)

50

T-cell deficiency

Think AIDS
Bacterial sepsis

Viral infections: CMV, EBC, VZV, chronic infection with respiratory/GI viruses

Fungi/parasites: Candida, PCP

51

B-cell deficiency

No antibodies, deficient complement-mediated processes
Bacteria: encapsulated (SHiN SKiS); recurrent bacterial infections

Viral: enteroviral encephalitis, poliovirus (live vaccine contraindicated)

Fungi/parasites: GI giardiasis (no IgA)

52

Granulocyte deficiency

Staph aureus, burkholderia cepacia, serratia, nocardia

Fungi/parasites: candida, aspergillus

53

Complement deficiency

Neisseria infections (no MAC)

54

X-linked (Bruton's) agammaglobulinemia

B-cell deficiency

Defect:
- X-linked recessive
- Defect in BTK (tyrosine kinase)
- No B-cell maturation

Symptoms:
- Recurrent bacterial infections starting at 6 months

Finding:
- Normal pro-B
- Decreased B cells, maturation, Ig

55

Selective IgA deficiency

B-cell deficiency

Defect: Unknown (most common primary immunodeficiency)

Symptoms:
- Majority asymptomatic
- Increased sinopulmonary infections
- GI infections
- Autoimmune disease
- Anaphylaxis to IgA-containing blood products

Labs:
- IgA < 7 mg/dL
- Normal IgG, IgM, IgG
- False positive beta-HCG due to heterophile antibody

56

Common variable immunodeficiency (CVID)

B-cell deficiency

Defect in B-cell maturation

Symptoms:
- 20s-30s,
- Increased risk of autoimmune disease, lymphoma, sinopulmonary infections

Labs:
- Normal B cell number
- Decreased plasma, immunoglobulins

57

Thymic aplasia (DiGeorge syndrome)

T-cell disorder

Defect: 22q11 deletion--> fail to develop 3rd, 4th pharyngeal pouches (thymus)

Symptoms:
- Tetany (hypocalcemia due to no parathyroid glands)
- Recurrent viral/fungal infections
- Congenital heart, great vessel defects

Labs:
- No thymus, parathyroids--> decreased T cells, PTH, Ca+2

58

IL-12 receptor deficiency

T-cell disorder

Defect: decreased Th1 response

Symptoms:
- Disseminated mycobacterial infections

Labs:
- Decreased IFN-gamma (secreted by Th1 cells--> suppresses Th2 cells; antiviral/antitumor)

59

Hyper-IgE syndrome (Job's syndrome)

T-cell disorder

Defect: Th1 cells fail to produce IFN-gamma--> neutrophils can't respond to chemotactic stimuli

Presentation: FATED
- coarse Faces
- cold staph Abscesses
- retained primary Teeth
- increased IgE
- Dermatologic problems (eczema)

Labs:
- Increased IgE

60

Chronic mucocutaneous candidiasis

T-cell dysfunction

Symptoms:
- Candida infections of skin, mucous membranes

61

Severe combined immunodeficiency (SCID)

B and T cell disorder

Defect:
- Defective IL-2 receptor (most common, X-linked)
- Adenosine deaminase deficiency

Presentation:
- Failure to thrive
- Chronic diarrhea
- Thrush
- recurrent viral, protazoal, bacterial, fungal infections
- No thymus, germinal centers, B-cells

Labs:
- decreased T-cell recombination excision circles

Treatment:
- Bone marrow transplant (no allograft rejection)

** Vs Bruton's= this has every type of infection (Bruton's= bacterial), and B and T cells missing

62

Ataxia-Telangiectasia

B and T cell defect

Defect:
- ATM gene= codes for DNA repair enzymes (can't re-seal broken dsDNA- nonhomologous end-joining broken)

Symptoms:
- Cerebellar defects (ataxia)
- Spider angiomas (telangiectasia)
- IgA deficiency

Labs:
- Increased alpha-fetoprotein

63

Hyper-IgM syndrome

T and B cell defect

Defect:
- CD40L on helper T-cells defective: no class switching on B cells

Symptoms:
- Pyogenic infections early in life

Labs:
- Increased IgM
- Decreased IgG, IgA, IgE

64

Wiskott-Aldrich Syndrome

B and T cell defect

Defect:
- X-linked
- WAS gene on X-chrom--> T-cells can't reorganize actin cytoskeleton

Symptoms:
- Thrombocytopenic purpura
- Infections
- Eczema

Labs:
- Increased IgE, IgA
- Decreased IgM
- Thrombocytopenia

65

Leukocyte adhesion deficiency

Genetic CD18 deficiency--> no integrin formation--> leukocytes can't migrate from vasculature

Symptoms:
- No pus formation
- Late separation of umbilicus**
- Poor wound healing

Labs:
- Neutrophilia

66

Chediak-Higashi syndrome

Autosomal recessive:
1. Lysosomal trafficking defect (LYST gene)
2. Microtubule dysfunction in phagosome-lysosome fusion

Symptoms:
- Recurrent pyogenic infections (staph and strep)
- Albinisim
- Peripheral neuropathy
- nystagmus

Labs:
- Giant granules on neutrophils

67

Chronic granulomatous disease

No NADPH oxidase
- No respiratory burst in neutrophils

Symptoms:
- Susceptible to catalase-positive infections (can break down their own H2O2)= S. aureus, E. coli, aspergillus
- WBCs can utilize H2O2 generated by invading organisms and convert to ROS (reactive oxygen species) if organism can't degrade H2O2 (cat negative)

Labs:
- Abnormal dihyrorhodamine (DHR) flow cytometry test)
- Neutrophils don't turn blue on nitro blue tetrazolium test

Tx: Gamma-interferon

68

Acute transplant rejection

Weeks after transplant

Path:
- Cell-mediated: cytotoxic T-lymphocytes react to foreign MHCs
- Reversible with immunosuppression (cyclosporine, Muromonab-CD3)

Symptoms:
- Vasculitis of graft vessels, dense lymphocytic interstitial infiltrate

69

Chronic transplant rejection

Months to years post-transplant

Path:
- Class I MHC (non-self) seen by immune system as Class I MHC (self) presenting antigen--> destroy cell
- Irreversible

Symptoms:
- T-cell antibody-mediated vascular damage
- Fibrosis of graft tissue, blood vessels

70

Cyclosporine

MOA:
- Binds cyclophilins
- Inhibits calcineurin--> prevents IL-2 production--> blocks T-cells

Use: organ transplant, autoimmune disease

Tox:
- Nephro, HTN, hyperlipidemia, hyperglycemia, tremor
- Gingival hyperplasia, hirsutism

71

Tacrolimus

MOA:
- Binds FK-binding protein
- Inhibits calcineurin--> prevents IL-2 production--> blocks T-cells

Use: Organ transplant

Tox:
- Nephro, HTN, hyperlipidemia, hyperglycemia, tremor

72

Sirolimus

aka Rapamycin
MOA:
- Inhibits mTOR--> blocks IL-2 (T-cell proliferation)

Use: kidney transplant, drug-eluting stent

Tox:
- Hyperlipidemia
- Thrombocytopenia
- Leukopenia

73

Azathioprine

MOA:
- Antimetabolite precursor of 6-mercaptopurine (interferes with pyramidine synthesis by blocking PRPP amidotransferase)
- Toxic to lymphocyte proliferation

Use: kidney trans, autoimmune

Tox:
- Bone marrow suppression
- Metabolized by Xanthine Oxidase (XO)- beware with allopurinol administration

74

Muromonab-CD3 (OKT3)

Monoclonal binding to CD3 on T-cells

Use: kidney trans

Tox:
- Cytokine release syndrome, Hypersensitivity reaction

75

Filgrastim

G-CSF: granulocyte colony-stimulating factor

76

Sargramostim

GM-CSF: granulocyte-macrophage colony-stimulating factor
- Like IL-3 from T-cells

77

Alpha-IFN

Used for: Hep B, C, Kaposi's, leukemia, malignant melanoma

78

Beta-IFN

Used for MS

79

Gamma-IFN

Used for Chronic Granulomatous disease Tx

80

Infliximab, Adalimumab

TNF-alpha
- Crohn's, RA, psoriatic arthritis,
- Ankylosing spondylitis (Infliximab)

81

Herceptin (trastuzumab)

HER2-overexpressing breast cancer