One Word_Immunology Flashcards
Active immunity
Induced after exposure to foreign antigens. Slow onset. Long-lasting protection (memory).
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.
Anergy
Self-reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells.
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.)
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).
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.
Autoantibodies - Anti-basement membrane
Goodpasture’s syndrome
Autoantibodies - Anti-desmoglein
Pemphigus vulgaris
Autoantibodies - Anti-dsDNA
SLE
Autoantibodies - Anti-glutamate decarboxylase
Type 1 diabetes mellitus
Autoantibodies - Anti-IgG (rheumatoid factor)
Rheumatoid arthritis
Autoantibodies - Anti-Jo-1
Polymyositis, dermatomyositis
Autoantibodies - Anti-Scl-70 (anti-DNA topoisomerases I)
Scleroderma (diffuse)
Autoantibodies - Anti-Smith
SLE
Autoantibodies - Anti-smooth muscle
Autoimmune hepatitis
Autoantibodies - Anti-SS-A (anti-Ro)
Sjögren’s syndrome
Autoantibodies - Anti-SS-B (anti-La)
Sjögren’s syndrome
Autoantibodies - Anti-U1 RNP (ribonucleoprotein)
Mixed connective tissue disease
Autoantibodies - Anticentromere
Scleroderma (CREST)
Autoantibodies - Antiendomysial
Celiac disease
Autoantibodies - Antigliadin
Celiac disease
Autoantibodies - Antihistone
Drug-induced lupus
Autoantibodies - Antimicrosomal
Hashimoto’s thyroiditis
Autoantibodies - Antimitochondrial
1° biliary cirrhosis
Autoantibodies - Antinuclear antibodies (ANA)
SLE, nonspecific
Autoantibodies - Antithyroglobulin
Hashimoto’s thyroiditis
Autoantibodies - c-ANCA
Wegener’s granulomatosis
Autoantibodies - p-ANCA
Other vasculitides
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
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)
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
B-cell class switching (2)
- 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)
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
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
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
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.
C1 esterase inhibitor
help prevent complement activation on self-cells (e.g., RBC)
Cell surface proteins - All cells except mature red cells
MHC I
Cell surface proteins - B cells
Ig, CD19, CD20, CD21, CD40, MHC II, B7
Cell surface proteins - Macrophages
MHC II, B7, CD40, CD14, receptors for Fc and C3b
Cell surface proteins - NK cells
Receptors for MHC I, CD16, CD56
Cell surface proteins - T cells
TCR, CD3, CD28 Helper T cells: CD4, CD40L Cytotoxic T cells: CD8
Complement - Anaphylaxis (2)
C3a, C5a
Complement - cytolysis by membrane attack complex (MAC)
C5b-9
Complement - Deficiency of C1 esterase inhibitor
hereditary angioedema
Complement - Deficiency of C3
leads to severe, recurrent pyogenic sinus and respiratory tract infections; ↑ susceptibility to type III hypersensitivity reactions
Complement - Deficiency of C5-C8
leads to Neisseria bacteremia
Complement - Deficiency of DAF (GPI-anchored enzyme)
leads to complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)
Complement - neutrophil chemotaxis
C5a
Complement - Opsonization; Binds bacteria
C3b
Complement - viral neutralization
C1, C2, C3, C4
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.
Cytotoxic T-cell activation (2)
- 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)
Decay-accelerating factor (DAF)
help prevent complement activation on self-cells (e.g., RBC)
Effects of bacterial toxins - Endotoxins/lipopolysaccharide (gram-negative bacteria)
directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved
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.
Grafts - Allograft
From nonidentical individual of same species
Grafts - Autograft
From self
Grafts - Syngeneic graft
From identical twin or clone
Grafts - Xenograft
From different species
Helper T-cell activation (4)
- 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
HLA subtypes associated with diseases - A3
Hemochromatosis
HLA subtypes associated with diseases - B27
PAIR: Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter’s syndrome
HLA subtypes associated with diseases - B8
Grave’s disease
HLA subtypes associated with diseases - DR2
Multiple sclerosis, hay fever, SLE, Goodpasture’s
HLA subtypes associated with diseases - DR3
Diabetes mellitus type 1
HLA subtypes associated with diseases - DR4
Rheumatoid arthritis, diabetes mellitus type 1
HLA subtypes associated with diseases - DR5
Pernicious anemia → B12 deficiency, Hashimoto’s thyroiditis
HLA subtypes associated with diseases - DR7
Steroid-responsive nephrotic syndrome
Hypersensitivity disorder type - Acute hemolytic transfusion reactions
Type II
Hypersensitivity disorder type - Allergic and atopic disorders (e.g., rhinitis, hay fever, eczema, hives, asthma)
Type I
Hypersensitivity disorder type - Anaphylaxis (e.g., bee sting, some food/drug allergies)
Type I
Hypersensitivity disorder type - Arthus reaction (e.g., swelling and inflammation following tetanus vaccine)
Type III
Hypersensitivity disorder type - Bullous pemphigoid
Type II
Hypersensitivity disorder type - Contact dermatitis (e.g., poison ivy, nickel allergy)
Type IV
Hypersensitivity disorder type - Erythroblastosis fetalis
Type II
Hypersensitivity disorder type - Goodpasture’s syndrome
Type II
Hypersensitivity disorder type - Graft-versus-host disease
Type IV
Hypersensitivity disorder type - Graves’ disease
Type II
Hypersensitivity disorder type - Guillain-Barré syndrome
Type IV
Hypersensitivity disorder type - Hashimoto’s thyroiditis
Type IV
Hypersensitivity disorder type - Hemolytic anemia
Type II
Hypersensitivity disorder type - Hypersensitivity pneumonitis (e.g., farmer’s lung)
Type III
Hypersensitivity disorder type - Idiopathic thrombocytopenic purpura
Type II
Hypersensitivity disorder type - Multiple sclerosis
Type IV
Hypersensitivity disorder type - Myasthenia gravis
Type II
Hypersensitivity disorder type - Pemphigus vulgaris
Type II
Hypersensitivity disorder type - Pernicious anemia
Type II
Hypersensitivity disorder type - Polyarteritis nodosum
Type III
Hypersensitivity disorder type - Poststreptococcal glomerulonephritis
Type III
Hypersensitivity disorder type - PPD (test for M. tuberculosis)
Type IV
Hypersensitivity disorder type - Rheumatic fever
Type II
Hypersensitivity disorder type - Rheumatoid arthritis
Type III
Hypersensitivity disorder type - Serum sickness
Type III
Hypersensitivity disorder type - SLE
Type III
Hypersensitivity disorder type - Type I DM
Type IV
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.
Immunoglobulin isotypes - IgD
Unclear function. Found on the surface of many B cells and in serum.
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.
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
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.
Important cytokines - IL-1
An endogenous pyrogen. Causes fever, acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes.
Important cytokines - IL-10
Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Activates Th2. Also secreted by regulatory T cells.
Important cytokines - IL-12
Induces differentiation of T cells into Th1 cells. Activates NK cells. Also secreted by B cells.
Important cytokines - IL-2
Stimulates growth of helper and cytotoxic T cells.
Important cytokines - IL-3
Supports the growth and differentiation of bone marrow stem cells. Functions like GM-CSF.
Important cytokines - IL-4
Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG.
Important cytokines - IL-5
Induces differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differentiation of eosinophils.
Important cytokines - IL-6
An endogenous pyrogen. Also secreted by Th cells. Causes fever and stimulates production of acute-phase proteins.
Important cytokines - IL-8
Major chemotactic factor for neutrophils.
Important cytokines - Interferon-γ
Activates macrophages and Th1 cells. Suppresses Th2 cells. Has antiviral and antitumor properties.
Important cytokines - TNF-α
Mediates septic shock. Activates endothelium. Causes leukocyte recruitment, vascular leak.
Important cytokines secreted by macrophages
IL-1, IL-6, IL-8, IL-12, TNF-α
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
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
Lymph drainage - Anal canal (below pectinate line)
Superficial inguinal
Lymph drainage - Duodenum, jejunum
Superior mesenteric
Lymph drainage - Lateral side of dorsum of foot
Popliteal
Lymph drainage - Rectum (above pectinate line)
Internal iliac
Lymph drainage - Right lymphatic duct
drains right arm and right half of head
Lymph drainage - Scrotum
Superficial inguinal
Lymph drainage - Sigmoid colon
Colic → inferior mesenteric
Lymph drainage - Stomach
Celiac
Lymph drainage - Testes
Superficial and deep plexuses → para-aortic
Lymph drainage - Thigh (superficial)
Superficial inguinal
Lymph drainage - Thoracic duct
drains everything else
Lymph drainage - Upper limb, lateral breast
Axillary
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.
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.
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.
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.
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.
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.
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.
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
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
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
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.
T-cell disorders - Chronic mucocutaneous candidiasis
Defect: T-cell dysfunction Presentation: Candida albicans infections of skin and mucous membranes Labs: N/A
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
T-cell disorders - IL-12 receptor deficiency
Defect: ↓ Th1 response Presentation: Disseminated mycobacterial infections Labs: ↓ IFN-γ
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
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
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.
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.
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.
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.
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.
