One Word_Immunology Flashcards Preview

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Flashcards in One Word_Immunology Deck (148):
1

Active immunity

Induced after exposure to foreign antigens. Slow onset. Long-lasting protection (memory).

2

Adaptive immunity

receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development. Response is slow on first exposure, but memory response is faster and more robust. Consists of T cells, B cells, and circulating antibody.

3

Anergy

Self-reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells.

4

Antibody structure and function

Fab: Antigen-binding fragment; Determines idiotype: unique antigen-binding pocket; Only 1 antigenic specificity expressed per B cell Fc: Constant; Carboxy terminal; Complement binding at CH2 (IgG + IgM only); Carbohydrate side chains; Determines isotype (IgM, IgD, etc.)

5

Antigen variation (5)

Bacteria - Salmonella (2 flagellar variants), Borrelia (relapsing fever), Neisseria gonorrhoeae (pilus protein). Virus - influenza (major=shift, minor=drift). Parasites - trypanosomes (programmed rearrangement).

6

Arthus reaction

a local subacute antibody-mediated hypersensitivity (type III) reaction. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin. Characterized by edema, necrosis, and activation of complement.

7

Autoantibodies - Anti-basement membrane

Goodpasture's syndrome

8

Autoantibodies - Anti-desmoglein

Pemphigus vulgaris

9

Autoantibodies - Anti-dsDNA

SLE

10

Autoantibodies - Anti-glutamate decarboxylase

Type 1 diabetes mellitus

11

Autoantibodies - Anti-IgG (rheumatoid factor)

Rheumatoid arthritis

12

Autoantibodies - Anti-Jo-1

Polymyositis, dermatomyositis

13

Autoantibodies - Anti-Scl-70 (anti-DNA topoisomerases I)

Scleroderma (diffuse)

14

Autoantibodies - Anti-Smith

SLE

15

Autoantibodies - Anti-smooth muscle

Autoimmune hepatitis

16

Autoantibodies - Anti-SS-A (anti-Ro)

Sjögren's syndrome

17

Autoantibodies - Anti-SS-B (anti-La)

Sjögren's syndrome

18

Autoantibodies - Anti-U1 RNP (ribonucleoprotein)

Mixed connective tissue disease

19

Autoantibodies - Anticentromere

Scleroderma (CREST)

20

Autoantibodies - Antiendomysial

Celiac disease

21

Autoantibodies - Antigliadin

Celiac disease

22

Autoantibodies - Antihistone

Drug-induced lupus

23

Autoantibodies - Antimicrosomal

Hashimoto's thyroiditis

24

Autoantibodies - Antimitochondrial

1° biliary cirrhosis

25

Autoantibodies - Antinuclear antibodies (ANA)

SLE, nonspecific

26

Autoantibodies - Antithyroglobulin

Hashimoto's thyroiditis

27

Autoantibodies - c-ANCA

Wegener's granulomatosis

28

Autoantibodies - p-ANCA

Other vasculitides

29

B- and T-cell disorders - Ataxia-telangiectasia

Defect: Defect in DNA repair enzymes Presentation: Triad: cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA deficiency Labs: IgA deficiency

30

B- and T-cell disorders - Severe combined immunodeficiency (SCID)

Defect: Several types: ①defective IL-2 receptor (most common, X-linked) ②adenosine deaminase deficiency ③failure to synthesize MHC II antigens Presentation: Recurrent viral, bacterial, fungal, and protozoal infections due to both B- and T-cell deficiency. Treatment: bone marrow transplant (no allograft rejection) Labs: ↓ IL-2R = ↓ T-cell activation; ↑ adenine = toxic to B and T cells (↓ dNTPs, ↓ DNA synthesis)

31

B- and T-cell disorders - Wiskott-Aldrich syndrome

Defect: X-linked recessive defect. Progressive deletion of B and T cells Presentation: Triad: Thrombocytopenic purpura, Infections, Eczema Labs: ↑ IgE, IgA; ↓ IgM

32

B-cell class switching (2)

1. IL-4, IL-5, IL-6 from Th2 cell (signal 1) 2. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)

33

B-cell disorders - Bruton's agammaglobulinemia

Defect: X-linked recessive (↑ in Boys). Defect in BTK, a tyrosine kinase gene → blocks B-cell (pro B → immature B) maturation Presentation: Recurrent bacterial infections after 6 months (↓ maternal IgG) due to opsonization defect Labs: Normal pro-B, ↓ maturation, ↓ number of B cells, ↓ immunoglobulins of all classes

34

B-cell disorders - Common variable immunodeficiency (CVID)

Defect: Defect in B-cell maturation; many causes Presentation: Can be acquired in 20s-30s; ↑ risk of antoimmune disease, lymphoma, sinopulmonary infections Labs: Normal number of B cells; ↓ plasma cells, immunoglobulin

35

B-cell disorders - Hyper-IgM syndrome

Defect: Defective CD40L on helper T cells = inability to class switch Presentation: Severe pyogenic infections early in life Labs: ↑ IgM; ↓↓ IgG, IgA, IgE

36

B-cell disorders - Selective Ig deficiency

Defect: Defect in isotype switching → deficiency in specific class of immunoglobulins Presentation: Sinus and lung infections, milk allergies and diarrhea. Anaphylaxis on exposure to blood products with IgA. Labs: IgA deficiency most common. Failure to mature into plasma cells ↓ secretory IgA.

37

C1 esterase inhibitor

help prevent complement activation on self-cells (e.g., RBC)

38

Cell surface proteins - All cells except mature red cells

MHC I

39

Cell surface proteins - B cells

Ig, CD19, CD20, CD21, CD40, MHC II, B7

40

Cell surface proteins - Macrophages

MHC II, B7, CD40, CD14, receptors for Fc and C3b

41

Cell surface proteins - NK cells

Receptors for MHC I, CD16, CD56

42

Cell surface proteins - T cells

TCR, CD3, CD28 Helper T cells: CD4, CD40L Cytotoxic T cells: CD8

43

Complement - Anaphylaxis (2)

C3a, C5a

44

Complement - cytolysis by membrane attack complex (MAC)

C5b-9

45

Complement - Deficiency of C1 esterase inhibitor

hereditary angioedema

46

Complement - Deficiency of C3

leads to severe, recurrent pyogenic sinus and respiratory tract infections; ↑ susceptibility to type III hypersensitivity reactions

47

Complement - Deficiency of C5-C8

leads to Neisseria bacteremia

48

Complement - Deficiency of DAF (GPI-anchored enzyme)

leads to complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)

49

Complement - neutrophil chemotaxis

C5a

50

Complement - Opsonization; Binds bacteria

C3b

51

Complement - viral neutralization

C1, C2, C3, C4

52

Cytotoxic T cells

Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis. Release cytotoxic granules containing preformed proteins (perforin - helps to deliver the content of granules into target cell; granzyme - a serine protease, activates apoptosis inside target cell; granulysin - antimicrobial, induces apoptosis) Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.

53

Cytotoxic T-cell activation (2)

1. Endogenously synthesized (viral or self) proteins are presented on MHC I and recognized by TCR on Tc cell (signal 1) 2. IL-2 from Th cell activates Tc cell to kill virus-infected cell (signal 2)

54

Decay-accelerating factor (DAF)

help prevent complement activation on self-cells (e.g., RBC)

55

Effects of bacterial toxins - Endotoxins/lipopolysaccharide (gram-negative bacteria)

directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved

56

Effects of bacterial toxins - Superantigens (S. pyogenes and S. aureus)

cross-link the β-region of the T-cell receptor to the MHC class II on APCs. Results in the uncoordinated release of IFN-γ from Th1 cells and subsequent release of IL-1, IL-6, and TNF-α from macrophages.

57

Grafts - Allograft

From nonidentical individual of same species

58

Grafts - Autograft

From self

59

Grafts - Syngeneic graft

From identical twin or clone

60

Grafts - Xenograft

From different species

61

Helper T-cell activation (4)

1. Foreign body is phagocytosed by APC 2. Foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1) 3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2) 4. Activated Th cells produce cytokines

62

HLA subtypes associated with diseases - A3

Hemochromatosis

63

HLA subtypes associated with diseases - B27

PAIR: Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome

64

HLA subtypes associated with diseases - B8

Grave's disease

65

HLA subtypes associated with diseases - DR2

Multiple sclerosis, hay fever, SLE, Goodpasture's

66

HLA subtypes associated with diseases - DR3

Diabetes mellitus type 1

67

HLA subtypes associated with diseases - DR4

Rheumatoid arthritis, diabetes mellitus type 1

68

HLA subtypes associated with diseases - DR5

Pernicious anemia → B12 deficiency, Hashimoto's thyroiditis

69

HLA subtypes associated with diseases - DR7

Steroid-responsive nephrotic syndrome

70

Hypersensitivity disorder type - Acute hemolytic transfusion reactions

Type II

71

Hypersensitivity disorder type - Allergic and atopic disorders (e.g., rhinitis, hay fever, eczema, hives, asthma)

Type I

72

Hypersensitivity disorder type - Anaphylaxis (e.g., bee sting, some food/drug allergies)

Type I

73

Hypersensitivity disorder type - Arthus reaction (e.g., swelling and inflammation following tetanus vaccine)

Type III

74

Hypersensitivity disorder type - Bullous pemphigoid

Type II

75

Hypersensitivity disorder type - Contact dermatitis (e.g., poison ivy, nickel allergy)

Type IV

76

Hypersensitivity disorder type - Erythroblastosis fetalis

Type II

77

Hypersensitivity disorder type - Goodpasture's syndrome

Type II

78

Hypersensitivity disorder type - Graft-versus-host disease

Type IV

79

Hypersensitivity disorder type - Graves' disease

Type II

80

Hypersensitivity disorder type - Guillain-Barré syndrome

Type IV

81

Hypersensitivity disorder type - Hashimoto's thyroiditis

Type IV

82

Hypersensitivity disorder type - Hemolytic anemia

Type II

83

Hypersensitivity disorder type - Hypersensitivity pneumonitis (e.g., farmer's lung)

Type III

84

Hypersensitivity disorder type - Idiopathic thrombocytopenic purpura

Type II

85

Hypersensitivity disorder type - Multiple sclerosis

Type IV

86

Hypersensitivity disorder type - Myasthenia gravis

Type II

87

Hypersensitivity disorder type - Pemphigus vulgaris

Type II

88

Hypersensitivity disorder type - Pernicious anemia

Type II

89

Hypersensitivity disorder type - Polyarteritis nodosum

Type III

90

Hypersensitivity disorder type - Poststreptococcal glomerulonephritis

Type III

91

Hypersensitivity disorder type - PPD (test for M. tuberculosis)

Type IV

92

Hypersensitivity disorder type - Rheumatic fever

Type II

93

Hypersensitivity disorder type - Rheumatoid arthritis

Type III

94

Hypersensitivity disorder type - Serum sickness

Type III

95

Hypersensitivity disorder type - SLE

Type III

96

Hypersensitivity disorder type - Type I DM

Type IV

97

Immunoglobulin isotypes - IgA

Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement. Monomer (in circulation) or dimer (when secreted). Crosses epithelial cells by transcytosis. Found in secretions (tears, saliva, mucus) and breast milk (known as "colostrum"). Pick up secretory compoment from epithelial cells before secretion.

98

Immunoglobulin isotypes - IgD

Unclear function. Found on the surface of many B cells and in serum.

99

Immunoglobulin isotypes - IgE

Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. Mediates immunity to worms by activating eosinophils. Lowest concentration in serum.

100

Immunoglobulin isotypes - IgG

Main antibody is 2° (delayed) response to an antigen. Most abundant in blood. Fixes complement, crosses the placenta (provides infants with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses

101

Immunoglobulin isotypes - IgM

Produced in the 1° (immediate) response to an antigen. Fixes complement but does not cross the placenta. Antigen receptor on the surface of B cells. Monomer on B cell or pentamer. Shape of pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves.

102

Important cytokines - IL-1

An endogenous pyrogen. Causes fever, acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes.

103

Important cytokines - IL-10

Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Activates Th2. Also secreted by regulatory T cells.

104

Important cytokines - IL-12

Induces differentiation of T cells into Th1 cells. Activates NK cells. Also secreted by B cells.

105

Important cytokines - IL-2

Stimulates growth of helper and cytotoxic T cells.

106

Important cytokines - IL-3

Supports the growth and differentiation of bone marrow stem cells. Functions like GM-CSF.

107

Important cytokines - IL-4

Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG.

108

Important cytokines - IL-5

Induces differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differentiation of eosinophils.

109

Important cytokines - IL-6

An endogenous pyrogen. Also secreted by Th cells. Causes fever and stimulates production of acute-phase proteins.

110

Important cytokines - IL-8

Major chemotactic factor for neutrophils.

111

Important cytokines - Interferon-γ

Activates macrophages and Th1 cells. Suppresses Th2 cells. Has antiviral and antitumor properties.

112

Important cytokines - TNF-α

Mediates septic shock. Activates endothelium. Causes leukocyte recruitment, vascular leak.

113

Important cytokines secreted by macrophages

IL-1, IL-6, IL-8, IL-12, TNF-α

114

Important cytokines secreted by T cells

All T cells: IL-3 Th1 cells: IL-2, Interferon-γ Th2 cells: IL-4, IL-5, IL-10

115

Innate immunity

receptors that recognize pathogens are germline encoded. Response to pathogens is fast and nonspecific. No memory. Consists of neutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin), and complement

116

Lymph drainage - Anal canal (below pectinate line)

Superficial inguinal

117

Lymph drainage - Duodenum, jejunum

Superior mesenteric

118

Lymph drainage - Lateral side of dorsum of foot

Popliteal

119

Lymph drainage - Rectum (above pectinate line)

Internal iliac

120

Lymph drainage - Right lymphatic duct

drains right arm and right half of head

121

Lymph drainage - Scrotum

Superficial inguinal

122

Lymph drainage - Sigmoid colon

Colic → inferior mesenteric

123

Lymph drainage - Stomach

Celiac

124

Lymph drainage - Testes

Superficial and deep plexuses → para-aortic

125

Lymph drainage - Thigh (superficial)

Superficial inguinal

126

Lymph drainage - Thoracic duct

drains everything else

127

Lymph drainage - Upper limb, lateral breast

Axillary

128

Lymph node - Follicle

Site of B-cell localization and proliferation. In outer cortex. 1° follicles are dense and dormant. 2° follicles have pale central germinal centers and are active.

129

Lymph node - Medulla

Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses. Medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages.

130

Lymph node - Paracortex

Houses T cells. Region of cortex between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood. In an extreme cellular immune response, paracortex becomes greatly enlarged. Not well developed in patients with DiGeorge syndrome.

131

MHC I = HLA-A, HLA-B, HLA-C

Expressed on almost all nucleated cells. Not expressed on RBC. Antigen is loaded in RER of mostly intracellular peptides. Mediates viral immunity. Pairs with β2-microglobulin (aids in transport to cell surface). Binds TCR and CD8.

132

MHC II = HLA-DR, HLA-DP, HLA-DO

Expressed only on antigen-presenting cells (APC) Antigen is loaded following release of invariant chain in an acidified endosome. Binds TCR and CD4.

133

Natural killer cells

Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells. Only lymphocyte member of innate immune system. Activity enhanced by IL-12, IFN-β, and IFN-α. Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.

134

Passive immunity

Based on receiving preformed antibodies from another host. Rapid onset. Short life span of antibodies (half-life = 3 weeks). Example: IgA in breast milk.

135

Phagocyte dysfunction - Chronic granulomatous disease

Defect: Lack of NADPH oxidase → ↓ reactive oxygen species (e.g., superoxide) and absent respiratory burst in neutrophils Presentation: ↑ susceptibility to catalase-positive organisms (e.g., S. aureus, E. coli, Aspergillus) Labs: Negative nitroblue tetrazolium dye reduction test

136

Phagocyte dysfunction - Chédiak-Higashi syndrome

Defect: Autosomal recessive defect in microtubular function with ↓ phagocytosis Presentation: Recurrent pyogenic infections by staphylococci and streptococci; partial albinism, peripheral neuropathy Labs: N/A

137

Phagocyte dysfunction - Leukocyte adhesion deficiency (type 1)

Defect: Defect in LFA-1 integrin (CD18) protein on phagocytes Presentation: Recurrent bacterial infections, absent pus formation, delayed sepration of umbilicus Labs: Neutrophilia

138

Serum sickness

an immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes 5 days). Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage). More common than Arthus reaction. Clinical findings: Fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure.

139

T-cell disorders - Chronic mucocutaneous candidiasis

Defect: T-cell dysfunction Presentation: Candida albicans infections of skin and mucous membranes Labs: N/A

140

T-cell disorders - Hyper-IgE syndrome (Job's syndrome)

Defect: Th cells fail to produce IFN-γ → inability of neutrophils to respond to chemotactic stimuli Presentation: FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, ↑ IgE, Dermatologic problems (eczema) Labs: ↑ IgE

141

T-cell disorders - IL-12 receptor deficiency

Defect: ↓ Th1 response Presentation: Disseminated mycobacterial infections Labs: ↓ IFN-γ

142

T-cell disorders - Thymic aplasia (DiGeorge syndrome)

Defect: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches Presentation: Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), congenital heart and great vessel defects. Labs: Thymus and parathyroids fail to develop → ↓ T cells, ↓ PTH, ↓ Ca2+. Absent thymic shadow on CXR

143

Thymus-dependent antigens

antigens containing a protein component (e.g., conjugated H. Influenzae vaccine). Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction) and release of IL-4, IL-5, and IL-6

144

Thymus-independent antigens

antigens lacking a peptide component; cannot be presented by MHC to T cells (e.g., lipopolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular antigen). Stimulate release of IgM antibodies only and do not result in immunologic memory.

145

Transplant rejection - Acute rejection

Cell mediated due to cytotoxic T lymphocytes reacting against foreign MHCs. Occurs weeks after transplantation. Reversible with immunosuppressants such as cyclosporine and OKT3. Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate.

146

Transplant rejection - Chronic rejection

T-cell and antibody-mediated vascular damage (obliterative vascular fibrosis); occurs months to years after transplantation. Irreversible. Class I-MHCnon-self is preceived by CTLs as class I-MHCself presenting a non-self antigen. Fibrosis of graft tissue and blood vessels.

147

Transplant rejection - Graft-versus-host disease

Grafted immunocompetent T cells proliferate in the irradiated immunocompromised host and reject cells with "foreign" proteins, resulting in severe organ dysfunction. Major symptoms include a maculopapular rash, jaundice, hepatosplenomagaly, and diarrhea. Usually in bone marrow and liver transplant (organs rich in lymphocytes). Potentially beneficial in bone marrow transplant.

148

Transplant rejection - Hyperacute rejection

Antibody mediated (type II) due to the presence of preformed antidonor antibodies in the transplant recipient. Occurs within minutes after transplantation. Occludes graft vessels, causing ischemia and necrosis.