Immunology/Pathology Flashcards
What is a primary follicle of the lymph node? Secondary follicle?
Primary follicles are dense and dormant. Secondary have pale central germinal centers and are active.
What is within the paracortex of the lymph node?
T cells
HLA A3 is associated with what disease(s)?
Hemochromatosis
HLA B27 is associated with what disease(s)?
Psoriatic arthritis, akylosing spondylitis, arthritis of inflammatory bowel disease, reactive arthritis (formerly Reiter syndrome)
HLA DQ2/DQ8 is associated with what disease(s)?
Celiac
HLA DR2 is associated with what disease(s)?
Multiple sclerosis, hay fever, SLE, Goodpasture
HLA DR3 is associated with what disease(s)?
DM type 1, SLE, Graves disease
HLA DR4 is associated with what disease(s)?
Rheumatoid arthritis, DM type 1
HLA DR5 is associated with what disease(s)?
Pernicious anemia –> VitB12 deficiency, Hashimoto thyroiditis
What secretes IL-1 and what is its function?
Macrophage; Aka osteoclast-activating factor, an endogenous pyrogen that causes fever and acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes.
What secretes IL-6 and what is its function?
Macrophage and Th2 cells; Endogenous pyrogen. Causes fever and stimulates production of acute-phase proteins.
What secretes IL-8 and what is its function?
Macrophage; Major chemotactic factor for neutrophils
What secretes IL-12 and what is its function?
Macrophage and B cell; Induces differentiation of T cells into Th1 cells. Activates NK cells.
What secretes TNF-alpha and what is its function?
Macrophage; Mediates septic shock. Activates endothelium. Causes leukocyte recruitment, vascular leak.
What secretes IL-2 and what is its function?
All T cells; Stimulates growth of helper, cytotoxic, and regulatory T cells
What secretes IL-3 and what is its function?
All T cells; Supports the growth and differentiation of bone marrow stem cells. Functions like GM-CSF.
What secretes interferon-gamma and what is its function?
Th1 cells; Has antiviral and antitumor properties Activates NK cells to kill virus-infected cells. Increases MHC expression and antigen presentation in all cells.
What secretes IL-4 and what is its function?
Th2 cells; Induces differentiation into Th2 cells. Inhibit Th1 cells. Promotes growth of B cells. Enhances class switching to IgE and igG.
What secretes IL-5 and what is its function?
Th2 cells; Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differentiation of eosinophils.
What secretes IL-10 and what is its function?
Th2, regulatory T cells, and macrophages; Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Macrophages secrete it to inhibit inflammatory response.
What are the cell surface proteins of T cells?
MHC I, TCR (binds antigen-MHC complex), CD3 (associated with TCR for signal transduction), CD28 (binds B7 on APC)
What are the cell surface proteins of Helper T cells?
CD4, CD40 ligand
What are the cell surface proteins of Cytotoxic T cells?
CD8
What are the cell surface proteins of B cells?
Ig (binds antigen), CD19, CD20, CD21 (receptor on EBV), CD40, MHC II, B7
What are the cell surface proteins of macrophages?
CD14 (a TLR that recognizes LPS), CD40, MHC II, B7, Fc and C3b receptors (enhanced phagocytosis)
What are the cell surface proteins of NK cells?
CD16 (binds Fc of IgG), CD56 (unique marker for NK)
What is NF-kappaB and what does it do?
A transcription factor that is turned on as a result of TLR activation. It activates immune response genes and leads to production of multiple immune mediators.
What is the role of arachidonic acid in inflammation?
Acted on by COX of 5-lipooxygenase,
What released arachidonic acid?
Phospholipase A2
What is the role of MHC?
Present antigen fragments to T cells and bind TCRs
MHC II is expressed where?
Only on APCs
What is the specific function of MHC I?
Present endogenously synthesized antigens to CD8 cytotoxic T cells
What is the specific function of MHC II?
Present exogenously synthesized proteins to T-helper cells
What do NK cells do?
Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.
What is the role of CD4 T cells?
Help B cells make Ab and produce cytokines to activate other cells of immune system
What is the role of CD8 T cells?
Kill virus-infected cells directly
Which cells are responsible for delayed cell-mediated hypersensitivity (type IV)?
CD8 T cells
What does IFN-gamma do?
Differentiates helper T cells into Th1 cells, activates macrophages
What is the role of TGF-beta + IL-6?
Helper T cell –> Th17 cell
What is the role of TGF-beta?
Helper T cell –> Treg cell, angiogenesis, fibrosis, cell cycle arrest
What are three APCs?
B cells, macrophages, dendritic cells
The interaction between a naive T cell and an APC involves which receptors?
MHC I/II with presenting antigen bind to TCR on CD8/4 T cells. There is a costimulatory interaction of B7 (APC) and CD28 (T cell)
Describe how B cells are activated?
Helper T cells are first activated. B cell (APC) endocytoses antigen and presents it on MHC II which is recognized by TCR on Th cell. CD40 receptor on B cells binds to CD40 ligand on Th cell (costimulatory). Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.
What does the Th1 cell secrete and what does it do?
IFN-gamma; activates macrophages and cytotoxic T lymphocytes
What is the Th1 cell inhibited by?
IL-4 and IL-10 from Th2 cell
What does the Th2 cell secrete and what does it do?
IL-4, IL-5, IL-6, IL-13; recruits eosinophils for parasite defense and promotes IgE production by B cells
What is the Th2 cell inhibited by?
IFN-gamma from Th1 cell
What are the cell surface markers of regulatory T cells?
CD3, CD4, CD25, and transcription factor FOXP3
What do activated regulatory T cells produce?
Anti-inflammatory cytokines like IL-10 and TGF-beta
What is a thymus-independent antigen?
Antigen lacking a peptide component; cannot be presented by MHC to T cells. Weakly or nonimmunogenic.
What is a thymus-dependent antigen?
Antigen containing a protein component. Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligant interaction)
What are acute-phase reactants?
Factors whose serum concentrations change significantly in response to inflammation; produced by the liver in both acute and chronic inflammatory states.
What induces acute-phase reactants?
IL-6, IL-1, TNF-alpha, and IFN-gamma
What does hepcidin do?
Prevents release of iron bound by ferritin –> anemia of chronic disease
Is albumin upregulated or downregulated in inflammation? Why?
Downregulated - to conserve amino acids for production of positive reactants
What is the classic pathway of complement activation?
IgG or IgM mediated
What is the alternative pathway of complement activation?
Microbe surface molecule mediated
What is the lectin pathway of complement activation?
Mannose or other sugars on microbe surface responsible for activation
What is the function of C3b?
Opsonization
What is the function of C3a, C4a, and C5a?
Anaphylaxis
What is the function of C5a?
Neutrophil chemotaxis
What is the function of C5b-C9?
Cytolysis by membrane attack complex (MAC) - responsible for defense against gram neg bacteria
What are the two primary opsonins in bacterial defense?
C3b and IgG
What helps prevent complement activation of self cells?
Decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor
C1 esterase inhibitor deficiency causes what?
Hereditary angioedema
C3 deficiency causes what?
Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increased susceptibility to type III hypersensitivity reactions
DAF (GPI anchored enzyme) deficiency causes what?
Complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
What is the role of IF-alpha and beta?
Innate host defense against RNA and DNA viruses; Synthesized by viral-infected cells that act locally on uninfected cells, priming them for viral defense. “Warning and suicide”
What do superantigens do to the immune system?
Cross-link the beta region of the T cell R to the MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines.
How do endotoxins (LPS) interact with the immune system?
Directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells not involved
Does a live attenuated vaccine usually induce a cellular or humoral response?
Cellular
Does an inactivated or killed vaccine usually induce a cellular or humoral response?
Humoral
An anti-ACh receptor autoantibody is associated with what disorder?
Myasthenia gravis
An anti-basement membrane autoantibody is associated with what disorder?
Goodpasture
An anti-cardiolipin, lupus anticoagulant autoantibody is associated with what disorder?
SLE, antiphospholipid syndrome
An anticentromere autoantibody is associated with what disorder?
Limited scleroderma (CREST syndrome)
An anti-desmoglein autoantibody is associated with what disorder?
Pemphigus vulgaris
An anti-dsDNA, anti-Smith autoantibody is associated with what disorder?
SLE
An anti-glutamate decarboxylase autoantibody is associated with what disorder?
Type 1 DM
An anti-hemidesmosome autoantibody is associated with what disorder?
Bullous pemphigoid
An antihistone autoantibody is associated with what disorder?
Drug-induced lupus
An anti-Jo-1, anti-SRP, anti-Mi-2 autoantibody is associated with what disorder?
Polymyositis, dermatomyositis
An antimicrosomal, antithyroglobulin autoantibody is associated with what disorder?
Hashimoto thyroiditis
An antimitochondrial autoantibody is associated with what disorder?
Primary biliary cirrhosis
An antinuclear antibody autoantibody is associated with what disorder?
SLE, nonspecific
An anti-Scl-70 (anti-DNA topoisomerase I) autoantibody is associated with what disorder?
Scleroderma (diffuse)
An anti-smooth muscle autoantibody is associated with what disorder?
Autoimmune hepatitis
An anti-SSA, anti-SSB (anti-Ro, anti-La) autoantibody is associated with what disorder?
Sjogren syndrome
An anti-TSH autoantibody is associated with what disorder?
Graves disease
An anti-U1 RNP (ribonucleoprotein) autoantibody is associated with what disorder?
Mixed connective tissue disease
A c-ANCA autoantibody is associated with what disorder?
Granulomatosis with polyangiitis (Wegener)
An IgA antiendomysial, IgA anti-tissue transglutaminase autoantibody is associated with what disorder?
Celiac disease
A p-ANCA autoantibody is associated with what disorder?
Microscopic polyangiitis, Churg-Strauss syndrome
An rheumatoid factor, anti-CCP autoantibody is associated with what disorder?
Rheumatoid arthritis
An immunocompromised patient with no T cell function will get what kind of bacterial infection(s)?
Sepsis
An immunocompromised patient with no B cell function will get what kind of bacterial infection(s)?
Encapsulated bacteria
An immunocompromised patient with no granulocyte function will get what kind of bacterial infection(s)?
Staph, Serratia, Nocardia
An immunocompromised patient with no complement function will get what kind of bacterial infection(s)?
Neisseria
An immunocompromised patient with no T cell function will get what kind of viral infection(s)?
CMV, EBV, JCV, VZV chronic infection with respiratory/GI viruses
An immunocompromised patient with no B cell function will get what kind of viral infection(s)?
Enteroviral encephalitis, poliovirus
An immunocompromised patient with no T cell function will get what kind of fungal/parasitic infection(s)?
Candida, PCP
An immunocompromised patient with no B cell function will get what kind of fungal/parasitic infection(s)?
GI giardiasis (no IgA)
An immunocompromised patient with no granulocyte function will get what kind of fungal/parasitic infection(s)?
Candida, Aspergillus
Describe a Type I hypersensitivity reaction
Anaphylactic and atopic - Free antigen cross links IgE on presensitized mast cells and basophils. Triggers immediate release of vasoactive amines that act at postcapillary venules.
Describe a Type II hypersensitivity reaction
Cytotoxic (antibody-mediated) - IgM and IgG bind to fixed antigen on “enemy” cell, leading to cellular destruction.
Describe a Type III hypersensitivity reaction
Antigen-antibody complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes
Describe a Type IV hypersensitivity reaction
Delayed (T-cell mediated) type - sensitized T cells encounter antigen and then release lymphokines (leads to macrophage activation; no Ab involved)
What is a direct Coombs’ test?
Detects Abs that have adhered to patient’s RBCs
What is an indirect Coombs’ test?
Detects Abs that can adhere to other RBCs
What are the three mechanisms of Type II hypersensitivity reaction?
- Opsonization leading to phagocytosis or complement activation
- Complement-mediated lysis
- Antibody-dependent cell-mediated cytotoxicity, usu due to NK cells or macrophages
What type of hypersensitivity reaction is “serum sickness?” And describe what serum sickness is.
An immune-complex disease (Type III) in which Abs to foreign proteins are produced (takes 5 days). Complexes form and are deposited in membranes, where they fix complement. Mostly caused by drugs.
What type of hypersensitivity reaction is “arthus reaction?” And describe what arthus reaction is.
A local subacute Ab-mediated hypersensitivity (Type III) reaction. Intradermal injection of antigen induces Abs, whcih form Ag-Ab complexes in the skin. Characterized by edema, necrosis, and activation of complement.
What type of hypersensitivity reaction is Guillain-Barre?
IV
What type of hypersensitivity reaction is Pemphigus vulgaris and bullous pemphigoid?
II
What type of hypersensitivity reaction is Polyarteritis nodosa?
III
What type of hypersensitivity reaction is Idiopathic thrombocytopenic purpura?
II
What type of hypersensitivity reaction is Multiple sclerosis?
IV
What type of hypersensitivity reaction is Erythroblastosis fetalis?
II
What type of hypersensitivity reaction is SLE?
III
What type of hypersensitivity reaction is Contact dermatits?
IV
What type of hypersensitivity reaction is acute hemolytic transfusion reaction?
II
Describe X-linked (Bruton) agammaglobulinemia
Defect in BTK, a tyrosine kinase gene –> no B cell maturation
What is the clinical presentation of Bruton agammaglobulinemia?
Recurrent bacterial and enteroviral infections after 6 months (when maternal IgG wears off), and giardia
What are the findings of Bruton agammaglobulinemia?
Normal CD19 B cell count, decreased pro-B, decreased IgG of all classes. Absent/scanty lymph nodes and tonsils.
Describe Selective IgA deficiency
Uknown etiology. Most common primary immunodeficiency. Forms anti-IgA IgGs - autoimmune. Anaphylactic reactions.
What is the clinical presentation of IgA deficiency?
Usu asymptomatic. Can see airway and GI infections.
What are the findings of IgA deficiency?
IgA
Describe common variable immunodeficiency
Defect in B-cell differentiation. Many causes.
What is the clinical presentation of common variable immunodeficiency?
Can be acquired in 20s-30s. Increased risk of autoimmune disease. Bronchiectasis, lymphoma, sinopulmonary infections.
What are the findings of common variable immunodeficiency?
Low plasma cells and low immunoglobulins
Describe Thymic aplasia (DiGeorge syndrome)
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches. Absent thymus and parathyroids.
What is the clinical presentation of Thymic aplasia (DiGeorge syndrome)?
Tetany (hypocalcemia), recurrent viral/fungal infections, conotruncal abnormalities
What are the findings of Thymic aplasia (DiGeorge syndrome)?
Low T cells, low PTH, hypocalcemia, absent thymus, 22q11 deletion detected by FISH
Describe IL-12 receptor deficiency
Decreased Th1 response. Aut rec.
What is the clinical presentation of IL-12 receptor deficiency?
Disseminated mycobacterial and fungal infections; may present after admin of BCG vaccine
What are the findings of IL-12 receptor deficiency?
Decreased IFN-gamma
Describe Autosomal dominant hyper-IgE syndrome (Job syndrome)
Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to sites of infection
What is the clinical presentation of Autosomal dominant hyper-IgE syndrome (Job syndrome)?
“FATED” - course Facies, cold (non-inflamed) staph Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema)
What are the findings of Autosomal dominant hyper-IgE syndrome (Job syndrome)?
High IgE, low IFN-gamma
Describe Chronic mucocutaneous candidiasis
T cell dysfunction. Many causes.
What is the clinical presentation of mucocutaneous candidiasis?
Noninvasive Candida albicans infections of skin and mucous membranes
What are the findings of mucocutaneous candidiasis?
Absent in vitro T cell proliferation in response to Candida antigens. Absent cutaneous reaction to Candida antigens.
Describe SCID
Several types including defective IL-2R gamma chain (most common, X linked), adenosine deaminase deficiency (aut rec)
What is the clinical presentation of SCID?
Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections.
What are the findings of SCID?
Low T cell receptor excision circles. Absent thymic shadow, germinal centers, and T cells.
Describe Ataxia-telangiectasia
Defects in ATM gene –> DNA ds breaks –> cell cycle arrest
What is the clinical presentation of Ataxia-telangiectasia?
Triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia), IgA deficiency
What are the findings of Ataxia-telangiectasia?
Increased AFP, decreased IgA IgG and IgE. Lymphopenia, cerebellar atrophy.
Describe Hyper-IgM syndrome
Most commonly due to defective CD40L on Th cells = class switching defect; X linked recessive
What is the clinical presentation of Hyper-IgM syndrome?
Severe pyogenic infections early in life; opportunistic infection with PCP and CMV.
What are the findings of Hyper-IgM syndrome?
Increased IgM, and decreased IgG IgA and IgE
Describe Wiskott-Aldrich syndrome
Mutation in WAS gene (X recessive); T cells unable to reorganize actin cytoskeleton
What are the findings of Wiskott-Aldrich syndrome?
Decreased to normal IgG and IgM. Increased IgE and IgA. Fewer and smaller platelets.
What is the clinical presentation of Wiskott-Aldrich syndrome?
“WATER” - Wiskott-Aldrich: Thrombocytopenia purpura, Eczema, Recurrent infections. Increased risk of autoimmune disease and malignancy.
Describe Leukocyte adhesion deficiency (type 1)
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; aut rec.
What is the clinical presentation of Leukocyte adhesion deficiency (type 1)?
Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord (>30days)
What are the findings of Leukocyte adhesion deficiency (type 1)?
Increased neutrophils. Absence of neutrophils at infection sites.
Describe Chediak-Higashi syndrome
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; aut rec.
What is the clinical presentation of Chediak-Higashi syndrome?
Recurrent pyogenic infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration infiltrative lymphohistiocytosis
What are the findings of Chediak-Higashi syndrome?
Giant granules in neutrophils and platelets. Pancytopenia. Mild coagulation defects.
Describe Chronic granulomatous disease
Defect of NADPH oxidase. Decreased ROS and absent respiratory burst in neutrophils; X linked recessive.
What is the clinical presentation of Chronic granulomatous disease?
Increased susceptibility to catalase positive organisms
What are the findings of Chronic granulomatous disease?
Abnormal dihydrorhodamine (flow cytometry) test. Nitroblue tetrazolium dye reduction test is negative.
What is the treatment of SCID?
Bone marrow transplant (no concern for rejection)
What is the pathogenesis of hyperacute transplant rejection? (within minutes)
Pre-existing recipient Abs react to donor antigen (type II reaction), activate complement. Leads to widespread thrombosis of graft vessels.
What is the pathogenesis of acute transplant rejection? (weeks to months)
Cellular: CTLs activated against donor MHCs. Humoral: Similar to hyperacute, except Abs develop after transplant. Results in vasculitis of graft vessels with dense interstitial lymphocytic infiltrate. Prevent/reverse with immunosuppressants.
What is the pathogenesis of chronic transplant rejection? (months to years)
Recipient T cells perceive donor MHC as recipient MHC and react against donor antigens presented. Both cellular and humoral.
What is the pathogenesis of graft-versus-host transplant rejection? (timeline varies)
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with “foreign” proteins –> severe organ dysfunction. Presents as maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usu in bone marrow and liver transplants.
How does chronic transplant rejection manifest in the heart?
Atherosclerosis
How does chronic transplant rejection manifest in the lungs?
Bronchiolitis obliterans
How does chronic transplant rejection manifest in the liver?
Vanishing bile ducts
How does chronic transplant rejection manifest in the kidney?
Vascular fibrosis, glomerulopathy
When may graft-vs-host be beneficial?
In bone marrow transplant for leukemia (graft-vs-tumor effect)
Which four things attract neutrophils?
C5a, IL-8, LTB4, bacterial products
What is the mechanism through which inflammation causes fever?
Macrophage releases IL-1 and TNF which travel through bloodstream to perivascular cells of hypothalamus. This activates the COX pathway to increase PGE2 which raises temperature set point in the hypothalamus.
In which vessels does leukocyte extravasation occur?
Postcapillary venules
How do CD8 T cells kill?
Release cytotoxic granules containing preformed proteins (perforin - helps to deliver content of granules into target cell; granzyme B - a serine protease that activates apoptosis in target cell; granulysin - antimicrobial, induces apoptosis)
What mediates B cell isotype switching?
IL-4 and IL-5
What is the defining cell of a granuloma?
Epithelioid histiocyte (macrophage with abundant pink cytoplasm)
What are the steps of granuloma formation?
A macrophage presents an antigen via MHC II to CD4 helper T cell. Macrophage secretes IL-12 inducing differentiation of CD4 cell to Th1 subtype. Th1 secretes IFN-gamma which causes macrophages to become epithelioid histiocytes.
What is the difference between branchial arches and pharyngeal arches?
None! The branchial apparatus is also called the pharyngeal apparatus. This was just confusing me..
A defective CD40 or CD40ligand causes what disease?
Hyper-IgM syndrome
Lynch syndrome is a defect in which genes?
MSH2, MLH1, MSH6, or PMS2
What are the associated neoplasms of Lynch syndrome?
Colorectal cancer, endometrial cancer, ovarian cancer
What is the mutated gene in Familial adenomatous polyposis?
APC
What are the associated neoplasms of familial adenomatous polyposis?
Colorectal cancer, desmoids and osteomas, brain tumors
What are the associated neoplasm of von Hippel-Lindau syndrome?
Hemangioblastomas, clear cell renal carcinoma, pheochromocytoma
What is the mutated gene in Li-Fraumeni syndrome?
TP53
What are the associated neoplasms of Li-Fraumeni syndrome?
Sarcomas, breast cancers, brain tumors, adrenocortical carcinoma, leukemia
What are the associated neoplasms of multiple endocrine neoplasia type 1?
Parathyroid adenomas, pituitary adenomas, pancreatic adenomas
What is the mutated gene is multiple endocrine neoplasia type 1?
MEN1
What is the mutated gene in multiple endocrine neoplasia type 2?
RET, MEN2A
What are the associated neoplasms of multiple endocrine neoplasia type 2?
Medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia (MEN2A)
What is the pathogenesis of multiple endocrine neoplasia type 2?
Aut dom, activating gain-of-function mutation in proto-oncogene, continuous stimulation of cell division predisposes to tumor growth
