Immunology: Cellular Components Flashcards
A patient has diffuse joint pain, rashes of unclear etiology, and negative serum studies. Which human leukocyte antigen subtype should be considered?
HLA-B27; the patient may have 1 of the seronegative arthropathies (PAIR)
What receptor do all MHC molecules bind to on T cells?
T-cell receptor (TCR) (and CD4 or CD8 depending on the MHC class)
Name the 3 antigen-presenting cells (APCs).
Macrophages, B cells, and dendritic cells (Langerhans cells are a subtype)
How do MHC I and MHC II differ from each other structurally?
MHC I has 1 long and 1 short chain; MHC II has 2 equal chains (2 α chains and 2 β chains)
After B-cell activation, what 2 events occur before antibody production?
Class switching and affinity maturation
A patient has mucosal hyperpigmentation and hypotension. Which 3 human leukocyte antigen (HLA) subtypes should be considered?
HLA-B8, HLA-DR3, and HLA-DR4 (diagnosis: Addison disease)
Which 2 cytokines induce differentiation of Th2 cells?
IL-2 and IL-4
What cytokines do Th2 cells secrete?
IL-4, IL-5, IL-6, IL-10, and IL-13
Which transcription factor involved in negative T-cell selection is deficient in a patient with autoimmune polyendocrine syndrome-1?
Autoimmune regulator (AIRE)
What cytokines do Th17 cells secrete?
IL-17, IL-21, and IL-22
What is the rule of 8 regarding T cells and major histocompatibility complex (MHC) binding?
MHC II × CD4 = 8; MHC I × CD8 = 8
Th1 and Th2 cells often act to inhibit each other. Which cytokines from Th2 cells inhibit Th1-cell action?
IL-4 and IL-10
Which types of organ graft rejections are mediated by T cells?
Acute and chronic cellular organ rejection
In the process of B-cell activation, what step occurs after receptor-mediated endocytosis of an antigen?
The antigen is presented on MHC II to the T-cell receptor of T helper cells
A man with chronic diarrhea experiences improvement after starting a gluten-free diet. Which HLA subtypes are associated with this disease?
HLA-DQ2/DQ8 (diagnosis: celiac disease; I ate [8] too [2] much gluten at Dairy Queen)
Which 2 cytokines induce differentiation of Treg cells?
TGF-β and IL-2
B cells undergo somatic hypermutation and plasma cell differentiation in response to antigen. What are the purposes of these 2 functions?
Somatic hypermutation optimizes antigen specificity; plasma cell differentiation leads to secretion of specific immunoglobulins
What are the 3 components responsible for adaptive immunity?
B cells, T cells, and circulating antibodies
How do T helper cells mediate Ig class switching of B cells?
By secreting cytokines
Which 4 autoimmune-related conditions are associated with HLA subtype B27?
Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, and Reactive arthritis (PAIR)
What transporter is involved in loading of viral antigens onto an MHC I molecule?
TAP (transporter associated with antigen processing), which delivers the antigen to the rough endoplasmic reticulum for loading onto the MHC I protein
Name the structural protein associated with MHC class I.
β2-microglobulin
Th1, Th2, and Th17 cells are specialized descendants of which type of cell?
CD4+ helper T cells
Name the receptor on the surface of natural killer cells that is involved in antibody-dependent cytotoxicity.
CD16 (which binds to the Fc region of IgG bound to the target cells, thereby activating NK cells)
Which cytokines inhibit the differentiation of Th17 cells?
IFN-γ and IL-4
What type of T cell expresses CD3, CD4, CD25, and the transcription factor FOXP3?
Regulatory T cell
What is the function of toll-like receptors (TLRs)?
As pattern recognition receptors, they recognize pathogen-associated molecular patterns (PAMPs), leading to activation of NF-κB in the innate immune response
Through which mechanism does the adaptive immune system develop a highly specific defense against pathogens?
Somatic hypermutation and affinity maturation (variable region); isotype switching (constant region)
Th1 and Th2 cells often act to inhibit each other. Which cytokine from Th1 cells inhibits Th2-cell action?
IFN-γ
Are natural killer cells a member of the innate or adaptive immune system?
Innate immune system
Which cytokine functions to inhibit the differentiation of helper T cells into Th2 cells?
IFN-γ
What is the syndrome associated with genetic deficiency of FOXP3?
Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome
Which 2 cytokines function to inhibit the differentiation of helper T cells into Th1 cells?
IL-4 and IL-10
Which cytokine functions to drive differentiation of helper T cells into T regulatory cells?
TGF-β and IL-2
Which cytokines function to drive differentiation of helper T cells into Th2 cells?
IL-2 and IL-4
A man who had childhood measles develops no disease despite repeat exposure. How does this response work?
Memory B and T cells are activated in the adaptive immune response during 1st exposure and release immunoglobulins targeting the measles virus in subsequent exposures
Name the 2 cytokines secreted by Th1 cells.
IFN-γ and IL-2
T-cell precursors are produced in the bone marrow. In which organ do they differentiate and mature?
Thymus
What is the benefit of germline-encoded target antigen recognition in the innate immune response?
It allows innate immunity to be both fast and nonspecific; however, resistance is heritable
What are the primary functions of helper T cells (CD4+ T cells)?
Assist B cells in forming antibodies and producing cytokines to recruit phagocytes and activate other leukocytes
Which cytokines function to drive the differentiation of helper T cells into Th1 cells?
IL-12, IFN-γ
What is the secondary or co-stimulatory signal in the process of B-cell activation?
Binding of CD40 receptor on the B cell to CD40L on the Th cell
A woman has a malar rash, joint pain, proteinuria, and anemia. Which HLA subtypes are associated wth her autoimmune disease?
HLA-DR2, HLA-DR3; diagnosis: systemic lupus erythematosis (SLE: 2-3, S-L-E)
Name the antigen-presenting cell responsible for sampling and presenting antigens to activate naive T cells.
Dendritic cell
What is the function of MHC receptors?
To present antigens to T cells for recognition of foreign particles and initiation of the immune response
Which MHC class is involved in mediating the T-cell response in a patient with Streptococcal pneumonia?
MHC II (presents exogenously synthesized antigens [eg, bacterial proteins] to CD4+ helper T cells)
Toll-like receptor (TLR) activation via pathogen-associated molecular patterns (PAMPs) leads to activation of what cellular protein complex?
NF-κB, which functions as a transcription factor
A woman has tachycardia, irritability, and exophthalmos. Which 2 human leukocyte antigen (HLA) subtypes are associated with her disease?
HLA-B8 and HLA-DR3 (diagnosis: Graves disease)
What is the purpose of each of the 2 signals in T-cell activation?
Signal 1 (MHC I/II to TCR) presents antigen for T-cell activation; signal 2 (B7 to CD28) induces proliferation and survival
B cells and T cells mediate different aspects of the immune response. What do we call these 2 general aspects of immunity?
Humoral immunity (B cells) and cell-mediated immunity (T cells)
Which cells express major histocompatibility complex (MHC) I on their surface?
All nucleated cells, antigen-presenting cells, and platelets (but not RBCs)
A patient has elevated lysozymes, complement, CRP, and defensins. Which arm of the immune system (innate or adaptive) is probably involved?
Innate immunity
Certain vaccines involve memory B cells. What is the purpose of memory B cells?
To accelerate the future immune response to antigens
How are bacterial antigens loaded onto an MHC II molecule?
They are loaded after the release of an invariant chain in an acidified endosome
Give an example of a pathogen-associated molecular pattern (PAMP) in viruses and bacteria.
Viruses: nucleic acids
Bacteria: lipopolysaccharides and flagellin
Which 3 cytokines enhance the activity of natural killer cells?
IL-2, IL-12, IFN (α, β, γ)
MHC receptors are encoded by what genes?
HLA genes (human leukocyte antigen gene complex)
In the process of naïve T-cell activation, what serves as the primary signal for Th (CD4+) cell activation?
Binding of the MHC II–antigen complex on antigen-presenting cells to the T-cell receptor (TCR) on Th cells
Which cells express major histocompatibility complex (MHC) II?
Antigen-presenting cells
How does the adaptive immune response differ during 1st and 2nd exposures to an antigen?
Adaptive immunity is slow to develop on 1st exposure but fast on any subsequent exposures
CD8 on cytotoxic T cells binds to what on virus-infected cells?
Major histocompatibility complex I (MHC I)
What is the function of Th2 cells?
To activate eosinophils and promote IgE production for defense against parasites
Which 3 HLA loci encode for MHC class II in antigen-presenting cells such as macrophages and B cells?
HLA-DP, HLA-DQ, HLA-DR (MHC II have 2 letters)
Differentiating T cells undergo negative selection at the thymic medulla. How does this selection occur?
T cells that have TCRs with a high affinity for self-antigens will become regulatory T cells or undergo apoptosis
A deficiency in Treg cells is associated with which disease?
IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome
After sampling and processing foreign antigens in tissues, how do dendritic cells reach naïve T cells to activate them?
Via draining lymph nodes
Which 3 autoimmune-related conditions are associated with human leukocyte antigen (HLA) subtype B8?
Addison disease, myasthenia gravis, Graves disease (Don’t Be late[8] Dr. Addison, or else you’ll send my patient to the grave).
Cytotoxic T cells induce apoptosis in their targets after the release of cytotoxic granules. What do these granules contain?
Granzyme B and perforin
Cytotoxic T cells work to kill virus-infected, neoplastic, and donor graft cells. Which cell-mediated process allows them to do so?
Apoptosis
How are self-antigens expressed in the thymus for appropriate negative selection?
Autoimmune regulator (AIRE) allows self-antigens to be expressed specifically in the thymus
Name the various components of the innate immune system.
Neutrophils, monocytes, macrophages, dendritic cells, natural killer cells, complement, secreted enzymes, epithelial barriers
After T-cell activation, what is the function of Th and Tc cells, respectively?
Th cells produce cytokines, and Tc cells kill cells infected with viruses
A 7-year-old patient has polyuria, polydipsia, and high blood sugar. Which 2 HLA subtypes are associated with this patient’s disease?
HLA-DR3 and HLA-DR4 (diagnosis: type 1 diabetes mellitus)
What cytokines do T regulatory cells secrete?
TGF-β, IL-10, and IL-35
Which MHC class is primarily involved in mediating the T-cell response in a patient with measles?
MHC I; it presents endogenously synthesized antigens (eg, cytosolic or viral proteins) to CD8+ cytotoxic T cells
A deficiency in Th17 cells is associated with which disease?
Hyper-IgE syndrome
What is the primary function of CD8+ cytotoxic T cells?
Killing virus-infected cells
The ability of monocytes/macrophages to kill microbes is enhanced by the interaction between what cellular marker and cell ligand?
CD40 (on macrophages) and CD40L (on T cells)
Contrast the receptors used during presentation of an endogenous or cross-presented antigen vs an exogenous antigen.
Endogenous antigens are presented on MHC I to CD8+ T cells; exogenous antigens are presented on MHC II to CD4+ T cells
A male infant with diabetes is found to have a deficiency of FOXP3. What other conditions might be expected in this patient?
Dermatologic conditions (eg, nail dystrophy, dermatitis), enteropathy, and endocrinopathy (this is IPEX syndrome)
Name 3 functions of B cells.
Antigen recognition (via somatic hypermutation), antibody production (plasma cell differentiation, Ig secretion), maintenance of immunologic memory
Which cytokines induce differentiation of helper T cells to Th17 cells?
TGF-β and IL-6
The initial differentiation of T cells occurs in the thymus. What are the locations of positive and negative selection within the thymus?
Thymic cortex for positive selection; thymic medulla for negative selection
In the process of naïve T-cell activation, what serves as the primary signal for Tc (CD8+) cell activation?
Binding of MHC I–antigen complex on antigen-presenting cells to T-cell receptor (TCR) on Tc cells
What 2 signals allow natural killer cells to recognize and kill target cells via cell-mediated immunity?
Presence of nonspecific activation signal and absence of MHC I on the target cell surface
A patient has weight gain, fatigue, and cold intolerance; anti-thyroid peroxidase antibodies are detected. Which HLA subtypes are associated with this disease?
HLA-DR3 and HLA-DR5 (diagnosis: Hashimoto thyroiditis; Hashimoto is an odd Dr [DR3, DR5])
What are 3 kinds of cells that cytotoxic T cells kill?
Neoplastic, virus-infected, and donor graft cells
What serves as the primary signal for B-cell activation?
Binding of activated Th cell to the antigen presented on MHC II by B cells
Which cytokine that enhances monocyte/macrophage killing of ingested microbes is secreted by Th1 cells?
IFN-γ
Name the structural protein associated with MHC II.
Invariant chain
Which 4 autoimmune-related conditions are associated with HLA subtype DR2?
DR2 is associated with multiple sclerosis, hay fever, systemic lupus erythematosus, and Goodpasture syndrome (multiple hay pastures are dirty [DR2])
How do regulatory T cells maintain specific immune tolerance?
They suppress CD4 and CD8 T-cell effector responses
What is the function of Th17 cells?
To provide immunity against extracellular microbes by potentiating neutrophilic inflammation
A deficiency in Th1 cells increases the susceptibility to which type of infections?
Mycobacterial infections
On the 1st day of a viral infection, a girl has ↑ neutrophils and fever. Is this response a result of the innate or adaptive immune system?
The innate immune system, which is responsible for the initial response to a pathogen
What is the function of T regulatory cells?
To maintain tolerance to self-antigens to prevent autoimmunity
Differentiating T cells undergo positive selection at the thymic cortex. How does this selection occur?
T cells with T-cell receptors that are able to bind self-MHC on cortical epithelial cells will survive
A woman has symmetric swollen metacarpal joints and elbow nodules. Which HLA subtype is associated with her disease?
HLA-DR4 (diagnosis: rheumatoid arthritis; there are 4 walls in a “rheum” [room])
A patient has ptosis and muscle weakness that worsens with time. Autoantibodies to acetylcholine receptors are detected. What HLA subtype do you suspect?
HLA-B8 (diagnosis: myasthenia gravis)
A patient has bronze skin, a hematocrit of 60%, diabetes, and elevated iron levels. Which HLA subtype is associated with his disease?
HLA-A3 (diagnosis: hA3mochromatosis)
In an innate immune response to a virus or bacteria, which receptors are activated?
Toll-like receptors, which recognize pathogen-associated molecular patterns (PAMPs)
Which 2 enzymes do natural killer cells use to induce apoptosis of tumor cells and virally infected cells?
Granzymes and perforin
Before the process of B-cell activation can occur, what must happen first?
Th-cell activation
A man has significant induration 2 days after an intradermal injection of tuberculin from a purified protein derivative (PPD) test. Which immune cells mediate this response?
T cells (test result is type IV delayed cell-mediated hypersensitivity)
Which receptor on T cells binds to B7 protein (CD80/86) on dendritic cells, serving as a costimulatory signal in T-cell activation?
CD28
Which cytokine inhibits the differentiation of Treg cells?
IL-6
Which cytokines work to induce differentiation of Th1 cells?
IFN-γ and IL-12
What is the function of Th1 cells?
To activate macrophages and cytotoxic T cells to kill phagocytosed microbes
Which 3 cytokines induce differentiation of Th17 cells?
TGF-β, IL-1, and IL-6
Which 3 HLA loci encode for MHC class I in all nucleated cells?
HLA-A, HLA-B, HLA-C (MHC I loci have 1 letter)
