MCQ 1 Flashcards
What does TH1 cell secrete?
IFN-gamma
What does TH2 cell secrete?
IL-4, IL-5, IL-10, IL-13
What does TH17 cell secrete?
IL-17, IL-21, IL-22
What does Treg cell secrete?
TGF-ß, IL-10, IL-35
Function of Th1 cell?
Activates macrophages
and cytotoxic T cells
to kill phagocytosed
microbes
What is Th1 induced by?
IFN-gamma, IL-12
What is Th1 inhibited by?
IL-4, IL-10 (from Th2
cell)
What immunodeficiency will be seen with Th1 deficiency?
Mendelian
susceptibility to
mycobacterial disease
What is the function of Th2?
Activate eosinophils
and promote
production of IgE for
parasite defense
What is Th2 induced by?
IL-2, IL-4
What is Th2 inhibited by?
IFN-gamma (from Th1 cell)
What is the function of Th17 cell?
Immunity against
extracellular
microbes, through
induction of
neutrophilic
inflammation
What is Th17 induced by?
TGF-beta, IL-1, IL-6
What is Th17 inhibited by?
IFN-gamma, IL-4
How does immunodeficiency of Th17 present?
Hyper-IgE syndrome
What is the function of Treg?
Prevent autoimmunity
by maintaining
tolerance to self-antigens
What is Treg induced by?
TGF-gamma, IL-2
What is Treg inhibited by?
IL-6
How will immunodeficiency of Treg present?
IPEX
What is the function of IFN-gamma?
Th1 cells secrete IFN-gamma, which enhances the ability of monocytes and macrophages to kill microbes they ingest. This function is also enhanced by interaction of T cell CD40L with CD40 on macrophages.
Cytotoxic T cells
Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis.
Release cytotoxic granules containing preformed proteins (eg, perforin, granzyme B).
Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.
Regulatory T cells
Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.
Identified by expression of CD3, CD4, CD25, and FOXP3.
Activated regulatory T cells (Tregs) produce anti-inflammatory cytokines (eg, IL-10, TGF-beta).
What are the APCs?
B cells, dendritic cells, Langerhans cells, macrophages
Describe T-cell activation
- ) Dendritic cell (specialized APC) samples antigen, processes antigen, and migrates to the draining lymph node.
- ) T-cell activation (signal 1): Exogenous antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell.
Endogenous or
cross-presented antigen is presented on MHC I to Tc (CD8+) cell.
3.) Proliferation and survival (signal 2): costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell and
CD28 on naïve T cell.
4.) Th cell activates and produces cytokines. Tc
cell activates and is able to recognize and kill
virus-infected cell.
B-cell activation and class switching
1.) Th-cell activation as mentioned in T-cell activation
2.) B-cell receptor–mediated endocytosis; foreign antigen is presented on MHC II and
recognized by TCR on Th cell.
3.) CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.
4.) Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.
Antibody structure and function: describe fab
Fab (containing the variable/hypervariable regions) consisting of light (L) and heavy (H) chains recognizes antigens
Fab: Fragment, antigen binding
Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell
Antibody structure and function: describe Fc
Fc region of IgM and IgG fixes complement. Heavy chain contributes to Fc and Fab regions. Light chain contributes only to Fab region
Fc:
Constant
Carboxy terminal
Complement binding
Carbohydrate side chains
Determines isotype (IgM, IgD, etc)
Antibody structure
Generation of antibody diversity (antigen independent)
- Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes
- Random addition of nucleotides to DNA during recombination by terminal
deoxynucleotidyl transferase (TdT)
- Random combination of heavy chains with light chains
Generation of antibody specificity (antigen dependent)
- Somatic hypermutation and affinity maturation (variable region)
- Isotype switching (constant region)
Describe three functions of antobodies:
- opsonization
- neutralization
- complement activation
What do naive B cells express prior to activation?
naive B cells prior to activation express IgM and IgD on their surfaces
What type of cells will naive B cells differentiate into by isotype switching?
They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; induced by cytokines and CD40L) into plasma cells that secrete IgA, IgE, or IgG.
Describe IgG
Main antibody in 2 degree response to an antigen. Most abundant isotype in serum. Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses. Only isotype that crosses the placenta (provides infants with passive immunity).
Describe IgA
Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement. Monomer (in circulation) or dimer (with J chain when secreted). Crosses epithelial cells by transcytosis. Produced in GI tract (eg, by Peyer patches) and protects against gut infections (eg, Giardia). Most produced antibody overall, but has lower serum concentrations. Released into secretions (tears, saliva, mucus) and breast milk. Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases.
Describe IgM
Produced in the 1 degree (immediate) response to an antigen. Fixes complement. Cannot cross the placenta. Antigen receptor on the surface of B cells. Monomer on B cell, pentamer with J chain when secreted. Pentamer enables avid binding to antigen while humoral response evolves.
Describe IgD
Unclear function. Found on surface of many B cells and in serum.
Describe IgE
Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type”I) hypersensitivity through release of in#ammatory mediators such as histamine. Contributes to immunity to parasites by activating eosinophils. Lowest concentration in serum.
Thymus-independent antigens
Antigens lacking a peptide component (eg, lipopolysaccharides from gram negative bacteria); cannot be presented by MHC to T cells. Weakly immunogenic; vaccines often require boosters and adjuvants (eg, pneumococcal polysaccharide vaccine).
Thymus-dependent antigens
Antigens containing a protein component (eg, diphtheria vaccine). Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells.
Describe complement
System of hepatically synthesized plasma proteins that play a role in innate immunity and inflammation. Membrane attack complex (MAC) defends against gram negative bacteria
Describe classic complement activation pathway:
IgG or IgM mediated.
GM makes classic cars
Describe alternative complement activation pathway:
microbe surface molecules
Describe lectin complement activation pathway:
mannose or other sugars on microbe surface.
function of c3b
opsonization
c3b _b_inds bacteria
Function of C3a, C4a, C5a
C3a, C4a, C5a—_a_naphylaxis
function of c5a
anaphylaxis and neutrophil chemotaxis
function of c5b-9
cytolysis by MAC
Opsonins
C3b and IgG are the two 1 degree opsonins in bacterial defense; enhance
phagocytosis. C3b also helps clear immune complexes.
inhibitors of complement
Inhibitors—decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (eg, RBCs).
Early complement deficiencies (C1-C4)
Increased risk of severe, recurrent pyogenic sinus and respiratory tract infections. Increased risk of SLE.
Terminal complement deficiencies (C5–C9)
Increased susceptibility to recurrent Neisseria bacteremia.
C1 esterase inhibitor deficiency
Causes hereditary angioedema due to unregulated activation of kallikrein = increased bradykinin.
Characterized by decreased C4 levels. ACE inhibitors are contraindicated.
Paroxysmal nocturnal hemoglobinuria
A defect in the PIGA gene preventing the formation of anchors for complement inhibitors, such as decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59).
Causes complement-mediated lysis of RBCs.
Interleukin
What interleukins are secreted by macrophages?
IL 1
IL 6
IL 8
IL 12
TNF-alpha
Interleukin-1
Causes fever, acute in#ammation. Activates
endothelium to express adhesion molecules.
Induces chemokine secretion to recruit WBCs.
Also known as osteoclast-activating factor
Interleukin-6
Causes fever and stimulates production of acute-phase
proteins.
Interleukin-8
Major chemotactic factor for neutrophils
“Clean up on aisle 8.” Neutrophils are recruited by IL-8 to clear infections
Interleukin-12
Induces differentiation of T cells into Th1 cells.
Activates NK cells.
Tumor necrosis factor-alpha
Activates endothelium. Causes WBC
recruitment, vascular leak
Causes cachexia in malignancy.
Maintains granulomas in TB.
IL-1, IL-6, TNF-“ can mediate fever and sepsis
What interleukins are secreted by all T Cells?
What interleukin is secreted by TH1 cells?
What interleukins are secreted from TH2 cells?
respiratory burst
interferon alpha and beta
Cell surface proteins: T cells
cell surface proteins: b cells
cell surface proteins: macrophages
cell surface proteins: NK cells
CD16 and CD56 (marker for NK)
cell surface proteins: hematopoietic stem cells
CD34
anergy
State during which a cell cannot become activated by exposure to its antigen. T and B cells become anergic when exposed to their antigen without costimulatory signal (signal 2). Another mechanism of self-tolerance.
passive vs active immunity
Types of vaccination
Type 1 hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
How do Marcrophages identify what to engulf?
They have a CD14 (TLR) receptor that binds to PAMPs (LPS) and DAMPS (necrotic tissue)
Explain macrophage interaction with opsonin
FC receptor binds to IgG (opsonin)
C3b receptor binds to C3b (opsonin)
Macrophage activity in ACUTE INFLAMMATION
- infiltrates tissue with 2-3 days
- phagocytosis and O2-independent killing
- Cytokine secretion
- possible abscess formation
Macrophage activity during CHRONIC INFLAMMATION
- local antigen presentation
- cytokine secretion
- possible granuloma formation
Explain Macrophage O2 independent killing
following phagocytosis, macrophages use lysozyme to hydrolyze bacterial peptidoglycan to lysis bacteria
What cytokines do macrophages and dendritic cells produce?
IL-1, TNF, IL-6, IL-8 (NEUTOPHIL CHEMOTAXIS), IL-12 (ACTIVATES NK CELLS AND Th1 cells
Macrophages form _________ during acute inflammation and __________ during chronic inflammation.
Macrophages form ABSCESS during acute inflammation and GRANULOMA during chronic inflammation.
What is the difference in dendritic and macrophage interaction with t cells?
dendritic cells activate t cells whereas macrophages restimulate activated T cells
What effect does surface protein CD40 (macrophage) and CD40L (t-cell) interaction have on macrophages?
macrophage stiumlation -> continued phagocytosis, O2 independent killing, and antigen presentation
What surface protein on macrophage is targeted by HIV?
CCR5
Describe formation of noncaseating granulomas
Th1 cells release IFN —–> macrophages become epithelioid cells —> some epitheliloid cells combine to form multi-nucleated giant cells —> epithelioid and giant cells surround infection —-> granuloma surrounded by lymphocytes (Th1 cells)
Describe caseating (necrotic) granulomas
formation: Th1 cells release IFN —–> macrophages become epithelioid cells —> some epitheliloid cells combine to form multi-nucleated giant cells —> epithelioid and giant cells surround infection —-> granuloma surrounded by lymphocytes (Th1 cells)
Describe maintenance and degradation of granulomas
maintenance: epithelioid cells (formerly macrophages) secrete TNF –> granuloma remains intact
degradation: TNF inhibitors –> granuloma breakdown –> possible disease dissemination
What kind of cells are MHC 1 receptors found on?
all nucleated cells
What are the two ways a Cytotoxic T-cell can kill infected cells?
- release perforins and granzymes –> apoptosis
- FasL binds to Fas on infected cell –> apoptosis
What are the three ways Natural Killer cells recognize what to kill?
- Lack of MHC I
- Presence of foreign surface proteins or carbohydrates
- antibody-dependent cell-mediated cytotoxicity (ADCC)
How does Natural Killer Cells kill infected cells?
- Release perforins and granzynes –> apoptosis
- FasL on NK cell binds to Fas–> apoptosis
What are Natural Killer Cells stimulated by?
IFN-alpha, IFN-beta = infected cell (saying kill me)
IL-2 (NK and Th1)
IL-12 (macrophages)
What cytokines do Natural Killer Cells secrete?
IFN-gamma
IL-2 (keeps its own activity going)
What are the surface proteins associated with Natural Killer cells?
- CD56 (helps identify NK cells)
- FasL (binds to Fas)
- CD16 (aka FC receptor) (binds to IgG)
Describe positive selection
- Occurs in the thymic cortex
- selction for T cells that bind self MHC
- Thymic epithelial cells express self MHC
- If T cells are unable to bind –> apoptosis
- If T cells successfully bind –> negative selection
- after positive selection T cells will express either CD4 or CD8
Describe negative selection
- occurs in thymic medulla
- selection against T cells that bind self sntigens with high affinity
- apoptosis or Treg development
Describe autoimmune regulator (AIRE) gene
- responsible for intrathymic expression of self antigens
- mutations –> impaired negative selection (results in abundance of self-destructive T cells)
- results in autoimmune endocrine diseases
- recurrent candida infections
- hypoparathyroidism
- adrenal failure
