Immunology Flashcards
1
Q
Lymph node
A
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
Q
Lymph drainage
A
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
Q
Sinusoids of spleen
A
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
Q
Thymus
A
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
Q
Innate immunity
A
Neutrophils, macrophages, dendritic cells, NK cells, complement
6
Q
Adaptive immunity
A
Recognize pathogen–> V(D)J recombination
- Slow response at first, memory faster
- T cells, B cells, circulating antibody
7
Q
MHC I
A
HLA-A, B, C
- Nucleated cell (any) infected with antigen
- Processed in RER (+ intracell peptides)
- Presented on MHC-I + Beta-2 microglob
- Binds TCR, CD8 T-cells
** Mediates viral immunity
8
Q
MHC II
A
HLA-DR, HLA-DP, HLA-DQ
- Antigen presenting cell infected
- Antigen processed in acidic endosome
- Presented on MHC-II (peptide binding groove)
- Binds TCR, CD4 T-cells
9
Q
HLA-A3
A
Hemochromatosis
10
Q
HLA-B27
A
Psoriasis
Ankylosing Spondylitis
Inflammatory bowel disease
Reiter’s syndrome
11
Q
HLA-DQ2/DQ8
A
Celiac disease
12
Q
HLA-DR2
A
Multiple sclerosis
Hay fever
Systemic Lupus Erythematosis
Goodpasture’s disease
13
Q
HLA-DR3
A
Diabetes Mellitus, Type 1
Grave’s disease
14
Q
HLA-DR5
A
Pernicious anemia–> B12 deficiency
Hashimoto’s thyroiditis
15
Q
Natural killer cells
A
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
Q
B-cell produced antibody functions
A
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
Q
T-cell functions
A
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
Q
Dendrite cell
A
ONLY APC that can activate naive T-cell
- Phagocytoses foreign body
- Presented on MHC II–> Th (CD4+ cell) OR Presented on MHC I–> Cytotoxic (CD8+)
- Costimulation: B7 on dendrite–> CD28 on Naive T-cell
19
Q
B cell activation/class switching
A
Th1 or Th2 (helper CD4+ T-cell) activated
- B-cell endocytosis foreign antigen
- Antigen presented on MHC II–> recognized by TCR on Th cell
- CD 40 on B-cell binds CD40Ligand on Th cell
- Th cell secretes cytokines–> Ig class switching of B cell
- 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
Q
Th1 cell
A
Helper T-cell
- Secretes IFN-gamma
- Activates macrophages
- Inhibited by IL-4, IL-10 (from Th2 cell)
21
Q
Th2 cell
A
Helper T-cell
- Secretes IL-4, IL-5, IL-10, IL-13
- Recruits eosinophils for Parasite defense, promotes B-cell production of IgE
- Inihibited by IFN-gamma (from Th1 cell)
22
Q
Antibody structure
A
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
Q
IgG
A
Secondary response (delayed) Most abundant
Roles:
- Fixes complement
- Crosses placenta
- Opsonizes bacteria
- Neutralizes toxins, viruses
24
Q
IgA
A
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
