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97 Cards in this Set

  • Front
  • Back
cold agglutinin
- aka cryoagglutinin
- an IgM antibody
- produced by 60% of patients infected with Mycoplasma pneumoniae
- reversibly agglutinates human erythrocyte antigen I positive RBCs at low temperatures
- cause of cold agglutinin disease (autoimmune hemolytic anemia)
DiGeorge syndrome
- impaired thymic development (affects T-cells)
- small deletions in chromosome 22
- also spontaneous
Chronic granulomatous disease
- X-linked ressive or
- autosomal recessive
- NADPH oxidase defficiency in neutrophils
Follicle of Lymph Node
- Site of B-cell localization and proliferation.
- located in outer cortex of node
- primary follicles are dense/dormant
- secondary follicles have pale central germinal centers, active.
Medulla of Lymph node
- cords -> closely packed lomphocytes and plasma cells
- sinuses -> reticular cells and macrophages
- communicate with efferent lymphatics
Paracortex
- Houses T cells.
- between follicles and medulla
- contains high endothelial venules -> allow T and B cells to enter from blood
- enlarged in extreme cellular immune response
- undeveloped in DiGeorge syndrome
Location of T-cells in Spleen
- Periarterial lymphatic sheath
- red pulp
Location of B-cells in spleen
- follicles within the white pulp
Sinusoids of spleen
- long vascular channels in red pulp
- fenestrated "barrel hoop" basement membrane
- Machrophages found nearby
Thymus develops from what?
- 3rd Branchial pouches
- Lymphocytes originate from mesenchyme
Hassall's corpuscles
- found in medulla of thymus
- formed from type VI epithelial reticular cells
- source of cytokine TSLP (unknown function)
Components of innate immunity
- neutrophils
- macrophages
- dendritic cells
- complement
Components of Adaptive immunity
- T cells
- B cells
- circulating antibody
Differentiation of T cells
- T cell precursor from bone marrow
- in thymus, aquires T cell receptor, CD8 and CD4 (becomes CD4+ and CD8+)
- One cluster of differentiation becomes dominant
- in lymph node, CD4+ become cytotoxic T cells
- CD8+ become T helper cells (1 and 2)
Th1 cells
- produce IL-2 and IFN-gamma
- activate macrophages and cytotoxic CD8+ T cells.
Th2 cells
- produce IL-2, IL4 and IL-5
- help B cells make antibody
MHC I
- encoded by Human Leukocyte Antigen (HLA) A, B and C
- expressed on almost all nucleated cells
- antigen loaded in RER
- mediates viral immunity
- pairs with beta 2- microglobulin
MHC II
- encoded by Human Leukocyte Antigen (HLA) DR, DP and DQ
- expressed only on antigen presenting cells (APCs)
- antigen loaded in an acidified endosome
- main determinants of organ rejection
B cells
- make antibody
- IgG antibodies opsonize bacteria and viruses
- IgE responsible for Allergy from type I hypersensitivity
- Antibodies cause organ rejection (fast)
T cells
- CD4+ T cells help B cells make antibody and produce gamma-interferon that activates macrophages
- kills virus-infected cells directly (CD8+ T cells)
- produces allergy through type IV hypersensitivity
- organ rejection (slow)
Antigen-presenting cells
- Macrophages
- B cells
- Dendritic cells
Th activation
- Foreign body is phagocytosed by APC
- Foreign antigen is presented on MHC II and recognized by TCR on Th cell (first signal)
- Costimulatory signal given by B7 of APC binding with CD28 of Th
- Th cell activated -> produces cytokines
Tc activation
- Endogenously synthesized (viral or self) proteins presented on MHC I
- recognized by TCR on Tc cell (signal one)
- IL-2 from Th cell activates Tc cell to kill virus-infected cell (signal 2)
Antibody structure
- VL and VH chains recognize antigens
- CH of IgM and IgG fixes complement
- Heavy chain contributes to Fc and Fab fractions
- Light chain contributes only to Fab fraction
Antibody diversity generaged by:
- random recombination of VJ (light chain) and VDJ (heavy-chain) genes
- random combination of heavy chains with light chains
- somatic hypermutation
- Addition of nucleotides to DNA during genetic recombination by terminal deoxynucleotidyl transferase
Mature B lymphocytes express what?
- IgM and IgD
Isotype switching
- mediated by cytokines and CD40 ligand
- causes mature B lymphocytes to differentiate into plasma cells that secrete IgA, IgE or IgG
IgG
- Main antibody in secondary response
- most abundant
- fixes complement
- crosses the placenta
- opsonizes bacteria
- neutralizes bacterial toxins and viruses
IgA
- Prevents attachment of bacteria and viruses to mucous membranes
- does not fix complement
- monomer or dimer
- found in secretions
- picks up secretory component from epithelial cells before secretion
IgM
- Produced in the primary response to antigen
- fixes complement
- does not cross the placenta
- antigen receptor on the surface of B cells
- monomer or pentamer
IgD
- Unclear function
- found on surface of B cells and in serum
IgE
- Mediates immediate (type I) hypersensitivity by inducing the release of mediators from mast cells and basophils when exposed to allergen
- mediates immunity to worms
- lowest concentration in serum
Ig allotype
- Ig epitope that differs among members of same species
- on light or heavy chain
Ig Isotype
- Ig epitope common to a single class of Ig
- determined by heavy chain (IgG, IgA, etc.)
Ig idiotype
- Ig epitope determined by antigen-binding site
IL-1
- secreted by macrophages
- stimulates T cells, B cells, neutrophils, fibroblasts and epithelial cells to grow, differentiate or synthesize specific products
- an endogenous pyrogen
IL-2
- Secreted by Th cells.
- Stimulates growth of helper and cytotoxic T cells
IL-3
- Secreted by activated T cells
- supports the growth and differentiation of bone marrow stem cells
- similar function to GM-CSF
GM-CSF
- granulocyte macrophage colony-stimulating factor
- stimulates production of white blood cells
- located on myeloblasts and mature neutrophils, not on any erythroid or megakaryocytic lineage cells
IL-4
- Secreted by Th2 cells
- Promotes growth of B cells
- enhances class switching if IgE and IgG
IL-5
- Secreted by Th2 cells
- Promotes differentiation of B cells
- enhances class switching of IgA
- Stimulates production and activation of eosinophils
IL-6
- Secreted by Th cells and macrophages
- Stimulates production of acute-phase reactants and immunoglobulins
IL-8
- Major chemotactic factor for neutrophils
IL-10
- Secreted by Th2 cells
- Stimulates Th2 while inhibiting Th1
IL-12
- secreted by B cells and macrophages
- Activates NK and Th1 cells
gamma-interferon
- secreted by Th1 cells
- Stimulates macrophages
TNF-alpha
- Secreted by macrophages
- increases IL-2 receptor synthesis by Th cells
- increases B-cell proliferation
- Attracts and activates neutrophils
- stimulates dendritic cell migration to lymph nodes
Helper T cell surface proteins
- CD4
- TCR
- CD3
- CD28
- CD40L
Cytotoxic T cell sufrace proteins
- CD8
- TCR
- CD3
B cell surface proteins
- IgM
- B7
- CD19
- CD20
- CD40
- MHC II
Macrophage surface proteins
- MHC II
- CD14
- Receptors for Fc and C3b
NK cell surface proteins
- Receptors for MHC I
- CD 16
- CD56
Membrane attach complex
- defends against gram-negative bacteria
- activated by IgG or IgM in the classic pathway
- activated by molecules on the surface of microbes (endotoxin) in the alternate pathway
- C3b and IgG primary opsonins in bacterial defense
Complement:
C1, C2, C3, C4 function
- viral neutralizaion
C3b
opsonizaion
C3a and C5a
- anaphylaxis
C5a
- neutrophil chemotaxis
C5b-9
- cytolysis by MAC
Deficiency of C1 esterase inhibitor
- hereditary angioedema (overactive complement)
Deficiency of C3 leads to
- severe, recurrent pyogenic sinus and respiratory tract infections
Deficiency of C6-C8
- Neisseria bacteremia
Deficiency of decay accelerating factor
- paroxysmal nocturnal hemoglobinuria (PNH)
Classic complement pathway
- antigen/antibody complexes

(draw)
Lectin Complement pathway
- microbial surfaces

(draw)
Alternative complement pathway
- Microbial surfaces (nonspecific activators, endotoxin)

draw
Interferon mechanism
- alpha, beta and gamma
- proteins that place unifected cells in an antiviral state
- induce the production of a 2nd protein that inhibits viral protein synthesis by degrading viral mRNA
- activate NK cells to kill virus-infected cells
Interferon alpha and beta
- inhibit viral protein synthesis
gamma-interferons
- increase MHC I and II expression and antigen presentation in all cells
Passive immunity given for:
- preformed antibody injection
- Tetanus, botulinum, HBV or Rabies
Type I hypersensitivity
- Anaphylactic and atopic
- antigen cross-links IgE on presensitized mast cells and basophils
- triggers release of vasoactive amines (histamine)
- develops rapidly due to preformed antibody
Antibody mediated hypersensitivities
- type I, II and III
Type II hypersensitivity
- Antibody mediated (IgM, IgG
- binds to antigen on enemy cell
- lysis by complement or phagocytosis
Type III hypersensitivity
- Immune complex
- Serum sickness
- Arthus reaction
Immune complex hypersensitivity
- type III
- antigen-antibody complexes activate complement -> attracts neutrophils
- neutrophils release lyosomal enzymes
Serum sickness
- Type III hypersensitivity
- immune complex disease
- antibodies to the foreign proteins are produced over 5 days
- immune complexes formed and deposited in membranes
- fix complement -> tissue damage
Arthus reaction
- Type III hypersensitivity
- local subacute antibody-mediated hypersensitivity reaction
- intradermal injection of antigen induces antibodies
- andigen-antibody complexes form in skin
- edema, necrosis, activation of complement
common problems of serum sickness
- often caused by drugs instead of serum
- fever, urticaria, arthralgias, proteinuria, lymphadenopathy
- occurs 5-10 days after exposure
Type IV hypersensitivity
- Delayed (T-cell mediated)
- sensitized T lymphocytes encounter antigen
- release lymphokines -> macrophage activation
complications of Type IV hypersensitivity
- Transplant rejections,
- contact dermatitis
- TB skin test uses this mechanism
Diseases of type I hypersensitivity
- anaphylaxis
- allergic rhinitis (hay fever)
Diseases of type II hypersensitivity
- Hemolytic anemia
- Idiopathic thrombocytopenic purpura
- Erythroblastosis fetalis
- Rheumatic fever
- Goodpastures's syndrome
- Bullous pemphigoid
- Graves'disease
- Myasthenia gravis
Diseases of Type III hypersensitivity
- Lupus
- Rheumatoid arthritis
- Polyarteritis nodosum
- Post-streptococcal glomerulonephritis
- Serum sickness
- Arthus reaction
- Hypersensitivity pneumonitis
Diseases of Type IV hypersensitivity
- Type I diabetes mellitus
- Multiple sclerosis
- Guillain-Barré syndrome
- Hashimoto's thyroiditis
- Graft-versus-host disease
- PPD (test for M. tuberculosis)
- Contact dermatitis
Immune deficiency causing a decrease in production of B cells
- Bruton's agammaglobulinemia
- X-linked recessive defect in a tyrosine kinase gene associated with low levels of all classes of immunoglobulins
- recurrent bacterial infections after 6 monts of age (declining maternal IgG
- occurs in boys
Immune deficiency causing a decrease in production of T cells
- Thymic aplasia (DiGeorge syndrome
- Thymus/parathroids fail to develop
- failure of development of 3rd and 4th pharyngeal pouches
- presents with Tetany owing to hypocalcemia
- recurrent viral and fungal infections from T-cell deficiency
- congenital defects of heart and great vessels
- 22q11 deletion
Immune deficiency causing a decrease in production of B and T cells
- Severe combined immunodeficiency (SCID)
- Defect in early stem-cell differentiation
- presents with recurrent viral, bacterial, fungal and protozoal infections
- can have multiple causes (failure to synthesize MHC II antigens, defective IL-2 receptors or adenosine deaminase deficiency.
Immune deficiency causing a decrease in activation of T cells
- IL-12 receptor deficiency
- Presents with disseminated mycobacterial infections
Hyper IgM syndrome
- decrease in the activation of B cells
- defect in CD40 ligand on CD4 T helper cells -> inability to class switch
- Presents early in life with severe pyogenic infections
- High levels of IgM
- Very low levels of IgG, IgA and IgE
Wiskott-Aldrich syndrome
- decrease in B cell activation
- X-linked defect in the ability to mount an IgM response to capsular polysaccharides of pacteria
- elevated IgA levels, normal IgE levels, low IgM levels
- Triad of symptoms includes recurrent pygenic infections, thrombocytopenic Purpura, Eczema
Job's syndrome
- decreased activation of Macrophages
- failure of gamma-interferon production by helper T cells
- Neutrophils fail to respond to chemotactic stimuli
- presents with recurrent "cold" (noninflamed) staphylococcal abscesses, eczema, coarse facies, retained primary teeth, high levels of IgE
Leukocyte adhesion deficiency syndrome
- Defect in LFA-1 adhesion proteins on phagocytes
- presents early with severe pyogenic and fungal infections
- delayed separation of umbilicus
Chédiak-Higashi disease
- Autosomal recessive
- defect in microtubular function and lysosomal emptying of phagocytic cells
- presents with recurrent pyogenic infections by staphylococci and streptococci
- partial albinism
- peripheral neuropathy
chronic granulomatous disease
- defect in phagocytosis of neutrophils owing to lack of NADPH oxidase activity or similar enxymes
- presents with marked susceptibility to opportunistic infections with bacteria, esp. S. aureus, E. coli and Aspergillus
- diagnosis confirmed with negative nitroblue tetrazolium dye reduction test
Chronic mucocutaneous candidiasis
- T-cell dysfunction specifically against Candida albicans
- presents with skin and mucous membrane Candida infections
Selective Immunoglobulin deficiency
- Idiopathic dysfunction of B cells
- Deficiency in a specific class of immunoglobulins (possibly due to defect in isotype switching)
- Selective IgA deficiency is most common selective immunoglobulin deficiency
- presents with sinus and lung infections, milk allergies and diarrhea common
Ataxia-telangiectasia
- Idiopathic dysfunction of B-cells
- Defect in DNA repair enzymes with associated IgA deficiency
- Presents with cerebellar problems (ataxia)
- spider angiomas (telangiectasia)
Common variable immunodeficiency
- Idiopathic dysfunction of B cells
- Normal numbers of circulating B cells
- decreased plasma cells
- decreased Ig
- can be acquired in 20's and 30's.