Immunology Flashcards

Question

What does 5-lipooxygenase do?

Answer 1

Acts on arachidonic acid to produce leukotrienes (LTB₄, LTC₄, LTD₄, LTE₄) which attrachts neutrophuls and causes bronchospasm and increased vascular permeability (contributes to anaphylaxis but is slower acting than histamine)

Answer 2

Mast cells

Answer 3

Pyrogenic = causes fever IL-1, IL-6

Answer 4

Any condition that prevents an adequate number of neutrophils from reaching the site of infection/injury Examples: * Neutropenia (Chediak-higashi syndrome, chemotherapy) * Failure of neutrophils to migrate to the site of infection (Leukocyte Adhesion deficiency)

Answer 5

CVID = Common variable immunodeficiency Patients typically present with present but low levels of Igs, especially IgA and IgG in later childhood/adolescence (not seen in young children) Symtoms include recurrent bacterial, enteroviral, and giardia infections in later childhood/adolescence

Answer 6

Maternal IgG | (And Maternal IgA **if** they are nursing)

Answer 7

* Kappa * Lambda

Answer 8

The goal of inflammation is to eliminate pathogens and clear debris. The process is not easy on our body, but failure to eliminate pathogens can lead to disease progression and death

Answer 9

Wound healing that occurs in parenchymal organs * Excessive deposition of collagen and other extracellular matrix components in the tissue in response to injurious stimuli

Answer 10

2 signals 1. Antigen recognition by a **surface antibody** (B-cell receptor) 2. From T cells through... a) Costimulatory molecules in T-cell **dependent** immune response b) complement in T-cell **indepenent** immune response

Answer 11

The constant region of the heavy chain IgM has a Mu heavy chain IgD has a Delta heavy chain

Answer 12

Chronic granulomatous disease * Defective NADPH oxidase * -\> Failure to produce hydrogen peroxide * -\> Cannot make hypochlorite ion * Cannot kill bacteria effectively

Answer 13

C5a peptidase destroys C5a, which is a chemokine for neutrophils Without C5a, neutrophils chemotaxis will be decreased; they won't be able to effectively move toward the site of inflammation

Answer 14

1. A foreign molecule cross-links or modifies a host cell * The host cell recognizes these "new" epitopes as foreign and mounts an immune response 2. Molecular mimicry * An antibody specific for a foreign antigen binds to similar-lookig self-antigens inside fo the host

Answer 15

Mediate cell-mediated immunity * Directly kill virus-infected cells

Answer 16

* Chronic granulomatous disease * Leukocyte adhesion deficiency * Complement defects * Defects in TLRs

Answer 17

Toll-Like Receptors (TLRs) Mannose Receptors

Answer 18

C5a, C6, C7, C8, C9 -\> Direct microbe killing

Answer 19

B cell receptor associated proteins (Ig-alpha, Ig-beta) involved in signal transduction after antigen crosslinking Their activation leads to phosphorylation of ITAMs to trigger downstream signaling pathways

Answer 20

**SCID and LAD** Bone marrow transplant is starting to be used as treatmetn for Wiskott-Aldrich syndrome **(WAS)** and **Hyper-IgM**

Answer 21

* Antigen presenting cells * Macrophages * Dendritic cells * Sometimes B-cells * Th1 CD4+ helper T-cells * CD8+ cytotoxic T-cells * NK cells

Answer 22

Part of the **innate** immune response * Mucus is produced by goblet cells * It contains... * Glycocalyx * Mucins + glycolypids * A dense layer that prevents pathogens from contacting the intestinal epithelium * Defensins * Defend against luminal bacteria * Kills microbes by disrupting their glycolipid membrane

Answer 23

Surface IgM or IgD

Answer 24

Acut inflammation is predominantly an innate immune response mediated by fluid in the tissues and neutrophil migration into tissues Macrophages arrive after neutrophils and release further cytokines Can resolve or progress to chronic inflammation

Answer 25

A form of SCID - Severe Combined Immunodeficiency **No B-cells or T-cells**; VDJ recombination cannot occur without RAG1/RAG2 gene expression Normal NK cells (Boy in a bubble)

Answer 26

Neutrophils have Fc receptors for the Fc region of IgG (constant region) and complement receptors for C3b This allows them to recognize and attach to the bacteria to initiat phagocytosis

Answer 27

1. Cells of the innate immune system recognize pathogens through PAMPs 2. These cells release pro-inflammatory cytokines 3. Cytokines acute phase response and releazse of numerous mediators of inflammation

Answer 28

Heavy chain Light chain

Answer 29

* Neutrophils and monocytes first * Then monocytes, lymphocytes, and plasma cells

Answer 30

* CD4+ helper T-cells respond to gliadin (a component of gluten * The body forms IgA, IgG, specific for gluten and transglutaminase 2A * This leads to chronic inflammation * Atrophy of the intestinal villi * Malabsorption * Nutritional deficiency * Extra-intestinal manifestation * Rash * Myalgia * Diarrhea/bloating * Fatigue

Answer 31

Intracellular pathogens Often triggers granulomatous response mediated by macrophages, CD4+ (helper) T cells

Answer 32

CD38, CD138, and cytoplasmic immunoglobulins

Answer 33

Antigen presenting cells (Usually macrophages) Th1 CD4+ Helper T-cells Sometimes CD8+ Cytotoxic T-cells

Answer 34

High numbers of viral mucosal infections might indicate **IgA deficiencey** It is possible that patients with IgA deficiency have antibodies against IgA, which would put them at a **high risk of blood transfusion reaction** If unsure about the possility of a reaction, it is recommended that this patient recieves blood from another person wtih IgA deficiency

Answer 35

Oxygen-dependent

Answer 36

ITAM = Immunoreceptor Tyrosine-based Activating Motif Transmits signal from TCR to the rest of the cell * When the TCR recognizes antigen in the context of MHC, ITAMS are phosphorylated * Recrutment and activation of ZAP70 tyrosine kinase * Signaling cascade * Increased expression of cytokines, cytokine receptors, cell proliferation genes * T-cell immune response activation * **Note: costimulatory signal is required for T-cell activaiton**

Answer 37

Severe bacterial and fungal infections Organisms that are typically not harmful or have low virulence can be fatal (opportunistic infections) The bacterial infections include a wide range of bacteria (such as coagulase negative staph, other Gram positive, and Gram negative bacteria) Sepsis is a major concern Fungal infections can be invasive (Candida and Aspergillus) and can also involve the blood

Answer 38

Mediate humoral immunity * Neutralize toxins and viruses * Opsonize pathogens * Makes them tastier to macrophages :)

Answer 39

* Fixes complement; activates the classic pathway * Opsonizes bacteria * The most effective opsonizer! * Neutralizes bacterial toxins and viruses * Most abundant antibody in the secondary immune response * Can cross the placenta * Most abundant circulating antibody * Most effective antibody in many infections

Answer 40

Celiac disease Confirm with colonoscopy of small bowel mucosa * Look for atrophy (blunting) of intestinal villi following an episode

Answer 41

* Immune complexes (aka antibody-antigen complexes) have harmful effects on our bodies * Continuous activation of complement via classical pathway * Inflammation * Immune complex formation is prevented by feedback inhibition * Fc(g)RIIB receptors on the surface of B-cells binds the Fc portion of IgG * Binding activates downstream signaling through ITIM * This terminates the BCR response to the antigen

Answer 42

(Basically the same function as IL-6) * Pro-inflammatory cytokine * Endogenous pyrogen (Causes fever) * Induces acute phase response

Answer 43

IL-5 IL-5 secreted by Th2 CD4+ helper T-cells promotes class switching to IgA

Answer 44

Thymic aplasia due to a developmental defect in the 3rd and 4th pharyngeal pouches * T-cells do not develop properly, leading to T-cell deficiency

Answer 45

* Outer epithelial layer * Interfaces with the outside world * Part of the innate immune system * **Goal = prevent infasion of pathogens** * Underlying connective tissue * Contains lymphcytes, denderitic cells, macrophages, mast cells * Mediates innate immune response * Contains effectors of adaptive immune response * MALT * Contains effetors of adaptive immune response * Specialized for each particular mucosa * Draining lymph nodes * Adaptive immune responses may also be initiatied here

Answer 46

Antibodies are highly specific for an antigen This makes sense, because these plasma cells came from the B-cells with the highest affinity for a specific antigen (they were selected in affinity maturation)

Answer 47

**2 signals are required** (this provides a "safety" against an immune response to self-antigen) 1. Antigen recognition in the context of MHC * ITAMS are phosphorylated 2. Recognition of a costimulatory molecule * CD28 recognizes B7 or * Complement receptors recognize complement

Answer 48

* Rapidly divide * Interaction with antigen-specific T cells, APCs, and follicular dendritic cells * Undergo isotype switching, somatic hypermutation, and affinity maturation

Answer 49

* Mu heavy chain in **cytoplasm** (not as a surface receptor) * No rearranged light chain

Answer 50

Mast cells * **Present** throughout connective tissue * **Activated** by.. * Trauma * Complement proteins (C3a and CD5a) * Cross-linking of IgE (which is bound by IgE Fc freceptor) * Binding of their toll-like receptors to PAMPS on bacteria and viruses * **Release** histamine and other mediators of inflammation

Answer 51

Chronic rhinosinusitis = no fever Sinus infections may have fever

Answer 52

Graft vs. host disease * The T-cells in the donor thymus are trained to not attack the self-antigen of the donor * As a result, they may attack the cells of the new host (Additionally, they may not recognize the MHC of their new host, resulting in decreased immunity; this danger is less immediate)

Answer 53

Histology * Abnormal platelets and leukocytes * Small * Do not migrate normally Disease * Eczema * Thrombocytopenia

Answer 54

Drug allergies (some) Blood transfusion response due to ABO mismatch Rh hemolytic disease of newborn Good pasture syndrome (body forms antibodies against basement membrane or Type IV collagen)

Answer 55

Chediak-Higashi syndrome

Answer 56

Hyper IgM syndrome is a condition characterized by **high levels of IgM and low levels of all other Igs** This is caused by loss of CD40L -\> Can't forma a germinal center -\> Can't class switch Patients typically suffer from **recurrent, severe, pyogenic infections**

Answer 57

An X-linked mutation in the gene that encodes WASP, a protein that binds to adaptor molecules and cytoskeletal components in hematopoietic cells

Answer 58

* Present at birth * Rapid * Relies on pattern recognition * Not specific * No memory * Primarily mediated by neutrophils

Answer 59

Boys Inheritance is X-linked

Answer 60

1. Early hematopoietic stem cell 2. Lymphocyte progenitor 3. Pro B-Cell 4. Pre B-Cell 5. Immature B-Cell 6. Naïve B-Cell

Answer 61

Small cationic peptides that bind to and create pores in microbes Alpha definsins are in the GI tract Beta defensins are in the respiratory tract

Answer 62

**Pyogenic (pus-forming) infections** * B-cell abnormalities * Chediak-Higashi syndrome (innate) * Defect in TLRs (innate) **Failure to form pus** * Leukocyte adhesion defect (LAD)

Answer 63

Antigen and antibody (typically IgG) complexes Neutrophils

Answer 64

2 signals 1. TCR and co-receptor CD4 recognize and bind the peptide bound to MHC II on the APC 2. The APC also expresses B7, a protein that binds to CD28 on the T-cell Activation -\> Cytokine production

Answer 65

No, if there is no protein present, there will not be a T cell-mediated immune response There could be a T cell independent immune response driven by B cells

Answer 66

Active HIV infection leads to decreased CD4+ T-cells * CD4 = a coreceptor for HIV * The virus specifically infects and kills CD4+ helper T-cells * This results in **decreased cell-mediated immunity**

Answer 67

Not always Type 2 hypersensitivity reactions can be mediated by naturally occuring IgG or IgM that exists prior exposure However, IgG and IgM can also increase due to prior sensitization

Answer 68

An antibody (IgM and IgD in naive B cells) on the surface of B cells that has a transmembrane domain and is associated with Ig-alpha (CD79a) and Ig-beta (CD79b) Also has CD19

Answer 69

* Activated T-cells * Express chemokine receptors and adhesion molecules * Home to CLA (Cutaneous lymphocyte-associated antigen) * CD4+ helper T-cells * Th1: fight intracellular pathogens * Th2: fight extracellular pathogens * Secrete IL-4, IL-13 * B-cell differentation * IL-13 inhibits production of defensins and cathelicidins by keratinocytes * This causes infections in Th2-driven skin diseases * Th17: Fight extracellular pathogens * Secrete IL-17, IL-22 * Increase epithelial barrer function via production of defensins, cathelicidins, keratinocytes * Induce epidermal cell proliferation * CD8+ cytotoxic T-cells

Answer 70

TLRs are used to recognize patterns of invader cells; pattern recognition is the driver of the innate immune system Macrophages are the mediators of the **adaptive** immune response, but they are also important for **connecting the innate and adaptive immune systems** They use TLRs to recognize patterns of invader pathogens so they can initate the adaptive immune response

Answer 71

* Chronic inflammation * Episodic * Vomiting/diarrhea * Urgency to defecate * Weight loss

Answer 72

* Takes 5-10 days * IgM is the first secreted antibody * B-cells specific for this antigen proliferate and differentiate * Class switching, sompatic hypermutation occurs in the germinal center * IgG is the second secreted antibody * May have higher affinity for antigen than previously secreted antibodies

Answer 73

SCID (The x-linked version) T cell and NK cells are defective (B-cells are normal)

Answer 74

* IL-4 * Class switch to IgG and IgE * IL-5 * Class switch to IgA * IL-13 * Activation of eosinophils * Promotes B cell differentiation * IL-10 * Anti-inflammatory (turns off immune system)

Answer 75

* B cells switch the heavy chain constant region from the IgM constant region to a downstream isotype (IgG -\> IgA -\> IgE) * The result is different host response to antigen binding * Antigen specificity (VJD) is **not** altered by isotype switching

Answer 76

ITIM = immunomodulatory Tyrosine-based inhibition motif * ITIM is important in feedback inhibition of the humoral immune response * **Activation**: Fc(g)RIIB on surface of B-cells binds Fc portion of IgG * **Result**: termination of the BCR response to the antigen

Answer 77

* Persistent infection * Prolonged exposure to a toxic agent * Autoimmunity

Answer 78

* Antibodies that are present in the body prior to exposure to an antigen * Typically IgM * Arise from B1 B-cells in a T-cell independent B-cell response

Answer 79

Surface * CD4+, CD25+ Inside of cell * FoxP: Regulates gene transcription * CTLA-4: Binds B7 on APCs * This prevents B7:CD28 costimulatory interaction needed to activate T-cell

Answer 80

Leukocyte adhesion deficiency (LAD) Neutrophils cannot reach their destinations at the site of infection

Answer 81

Stagnant fluid allows for infection by bacteria (normally, fluid flow prevents colonization and infection)

Answer 82

Diapedesis = neutrophil migrates through endothelium to escape from the blood vessel Chemotaxis = neutrophil migrates through tissue toward chemokines IL-8 and C5a

Answer 83

Humoral response = antibodies * Protection from infection; prevents virus particles from invading cells * Antibodies can bind directly to the virus * Prevents binding to cell surface receptors * Opsonizes the virus * Antibodies can bind to new antigens on the surface of infected cells * Activate complement * Promote killing of the virus-infected cell via MAC * ADCC can kill virus-infected cells * Targets infected cells for killing by macrophages, neutrophils, or NK cells But viruses can evade humoral immunity via antigen variability! * This is why cell-mediated immunity is needed to kill infected cells

Answer 84

1. RIG-1 helicase is a pattern recognition protein that recognizes intracellular pathogens 2. RIG-1 helicase is found in cytoplasm of immune-competent cells 3. RIG-1 helicase recognizes nucleic acids of viruses

Answer 85

GI tract M cells participate in the GI tract regional immune system; they sample antigen and present it to B and T cells

Answer 86

HIV/AIDS Immunosuppression (ie: transplant, chemotherapy) Inherited T-cell deficiencies (SCID, DiGeorge) Viral infections (Measles, CMV)

Answer 87

Maternal IgA, acquired through breast milk Acquired via passive immunity

Answer 88

* H. pylori infection leads to an inflammaory reaction * Malignant transformation of B-cells in the lymphoid follicles in the gastric lamina propria * Gets progressively worse over time (without treatment)

Answer 89

None Pro B-cells do not express heavy chains, light chains, or surface antibodies

Answer 90

An exaggerated or inappropriate immune response to an external or self antigen Can cause harm to the host

Answer 91

NK cells = innate immunity * Not specific * Involved in the early antiviral immune response * NK cells recognize virus infected cells due to both... * The absence of an inhibitory ligand (MHC I) * The presense of an activating ligand (ADCC) * NK cells have an IgG Fc receptor, which binds to the IgG laid down on a virus-infected cell during ADCC

Answer 92

* Mu heavy chain and light chain = a fully formed IgM BCR

Answer 93

The thymus When a T-cell leaves the thymus, its antigen specificity does not change

Answer 94

* A specialized cell recognizes and binds an antigen * Dendritic cells * M cells in gut * Langerhans cells in cutaneous * The cell delivers the antigen to the MALT or draining lymph nodes associated with that immune system * There will either be no response (tolerance) or a response if effectory lymphocytes are activated by the antigen

Answer 95

* Drives AND is secreted by Th1 CD4+ helper T-cells * Positive feedback loop * Promotes and activates macrophages * Stimulates IgG production * Leads to more effective killing of **intracellular** pathogens

Answer 96

A defect in **Bruton Tyrosine Kinase** * Prevents maturation of B-cells (arrested as pro B cells, cannot become pre B cells) * Presentation is the same as Antibody Deficiency Syndrome * Infections by encapsulated bacteria * Otitis media * Sinusitis * Pneumonia * Enteroviral infections * Meningoencephalitis * Vaccine-associated poliomyelitis * Infection by mycoplasma (may caus arthritis)

Answer 97

* Neutrophils * Monocytes/macrophages * Basophils * Mast cells * NK cells

Answer 98

Macrophages

Answer 99

* Intact mucosal epithelium * Mucous * pH * Microbial molecules such as defensins * Macrophages * Dendritic cells

Answer 100

Mediate direct cellular killing in cell-mediated immunity

Answer 101

Location (both are forms of IBD) * Crohns: any part of GI tract, usually terminal ilium * Ulcerative colitis: Colonic mucosa

Answer 102

IgG This is important in the maternal immune response to fetal red blood cells

Answer 103

Chronic rhinosinusitis No fever = not a sinus infection Presentation in the nasal/respiratory airway and mucosa

Answer 104

Different antibody isotypes are specialized for different protective responses Note: isotype switching does **not** alter antigen binding specificity

Answer 105

The **Lamina propria is** made up of dendritic cells and macrophages * Dendritic cells and macrophages inhibit inflammation and maintain homeostasis * Innate lymphoid cells (NK cells) secrete IL-17, IL-22 * Immune defense against some bacteria * Promotes epithelial barrier function * Innate lymphoid cells (NK cells) secrete TGF-beta, IL-10, IL-2 * Maintain immune homeostasis in baowel walls * Anti-inflammatory and/or regulatory function

Answer 106

T-cell cytokine production in the context of CD40:CD40L induces the formation of a germinal center Somatic hypermutation, isotype switching, and affinity maturation of B-cell antibodies occurs in the germinal center * Isotype switching * Modification of the heavy chain constant region leads to different Ig molecules, resulting in different protective responses * Somatic hypermutation * Antibody variable regions are subject to random point mutations (by activation-induced cytidine deaminase [AID]) * Some of the mutations give rise to higher affinity/avidity antibodies which are selected for by FDCs and T cell interactions

Answer 107

Patients with IgA deficiency are at an increased risk for mucosal infections, especially viral

Answer 108

C3 convertase

Answer 109

Wiskott-Aldrich Syndrome

Answer 110

* Fight **extracellular** pathogens * Support humoral immunity * Secrete cytokines in the context of CD40:CD40L that promote the formation of a germinal center * Class switching and affinity maturation of B-cells

Answer 111

B-cell anergy = peripheral tolerance Anergy occurs when a B-cell cirulating in the periphery becomes self-reactive * Self-reactive B-cell encounters self antigen in the **absence of co-stimulation** * The B-cell becomes anergic; it does not repsond to the antigen This prevents autoimmune responses

Answer 112

* **Present** throughout connective tissue * **Activated** by.. * Trauma * Complement proteins (C3a and CD5a) * Cross-linking of IgE (which is bound by IgE Fc freceptor) * Binding of their toll-like receptors to PAMPS on bacteria and viruses * **Release** histamine and other mediators of inflammation

Answer 113

* IgA secretion by plasma cells (humoral) * Antibodies neutralize pathogens * Dimierized IgA can cross the epithelium and be released into the lumen * Th17 CD4+ helper T-cells * Secrete IL-17, IL-22 * Enhance epithelial barrier function * Th2 CD4+ helper T-cells * Defend against parasites, extracellular pathogens * Secrete IL-4, IL-13 * B cell differentiation * Promote fluid and mucus secretion * TRegs * Suppress immune response to food antigens and commensals * Prevent inflamatory reactions

Answer 114

* Bacterial, viral or fungal pathogen infections * Diarrhea/IBD-like symptoms * Failure to thrive * *Pneumocystis jiroveci* pneumonia * Adenovirus * RSV * CMV * Parainfluenza virus * Rash (Basically, lots of viruses

Answer 115

* Double negative thymocyte * Just arrived from bone marrow * CD3-, CD4-, CD8- * Double positive thymocyte * CD3+, CD4+, CD8+ * Single-positive thymocytes * CD3+, CD4+ **OR** CD3+, CD8+ * These are bout to migrate to the medulla to undergo negative selection

Answer 116

IgM -\> IgG -\> IgA -\> IgE The order can never change; in order to switch isotypes, DNA is deleted (this is irreversible)

Answer 117

1. Recognition and attachment 2. Engulfment 3. Destruction 4. Resolution

Answer 118

Type IV: delayed type hypersensitivy reaction * Poison Ivy chemical modify self-antigen * T-cells recognize chemically modified self-proteins as foreign and mount an immune response * Cytokine release * Macrophage activation

Answer 119

B-cell co-stimulation * Cd3 on antigen binds CR2 (aka CD21) on B-cell * -\> Enhancement of B-cell activation * PAMP on antigen binds TLR on B-cell * -\> Enhancement of activaton If there is no co-stimulation... * It is likely that the BCR has bound a self-antigen * Self molecules don't have complement depositions or PAMPs * To prevent an autoimmune response, the B-cell becomes anergic

Answer 120

Decreased IL-7 might cause... * Decreased lympoid progenitor cell formation (from early hematopoietic stem cells) * Decreased B-cell and T-cell formation from lymphoid progenitor cels * May eventually lead to impaired adaptive immune response

Answer 121

IgA IgA antibodies are the only ones that can dimerize and cross the mucosal epithelium They are important in mucosal immunity, which prevents pathogens from entering our cells

Answer 122

Chronic granulomatous disease (CGD)

Answer 123

* Chronic inflammatory response * Nasal obstruction * Smell loss * Drainage * Facial pain/pressure * May or pay not have polyp overgrowth * (No fever)

Answer 124

Triggers mast cells to degranulate and release histamine (anaphylatoxins)

Answer 125

Neutrophils undergo rapid apoptosis after the inflammatory stimulus is removed

Answer 126

**Yes, you should suspect an immune disorder** * *P**neumocystis jiroveci* is not usually seen in patients with super healthy immune systems * It is an opportunistic fungus * Also commonly seen in HIV patients Infection with viruses, fungi, and coxiella brunetti (cause of Q fever, obligate intracellular) point to a **T-cell deficiency** * SCID * DiGeorge syndrome

Answer 127

Pattern recognition receptors (PRRs) such as TLRs on monocytes/macrophages, mast cells, and other cells of the immune system recognize the pathogen-associated molecular patterns (PAMPs) The signal leads the cell to release pro-inflammatory cytokines

Answer 128

A defect in the pre B cell receptor or associated proteins causes an arrest of B-cell development (from pro to pre B-cells) * Defect in bruton tyrosine kinase (BTK) * Causes X-linked agammaglobulinemia (XLA) * Defect in B cell linker protein (BLNK)

Answer 129

CD21 interacts with the C3d complement component bound to antigen (alternative complement pathway) Enhances B cell activation ~1000 fold

Answer 130

Neutrophils (granulocytes, PMNs) * First responders * Rapidly migrate from bone marrow to blood to tissue (peripheral blood neutrophilia) * Engulf/kill pathogens * Release additional pro-inflammatory cytokines * Major cell of acute inflammatory response * Do not present antigen on MHC class II

Answer 131

Predispose to infections with Neisseria

Answer 132

* Tolerance of food antigens * Tolerance of commensal microbiota * \>500 types * Outnumber human cells in the whole body * Must repond to pathogens that are relatively rare * Large surface area

Answer 133

CD4+ helper T-cells * Th1: fight intracellular pathogens * Th2: fight extracellular pathogens * Secrete IL-4, IL-13 * B-cell differentation * IL-13 inhibits production of defensins and cathelicidins by keratinocytes * This causes infections in Th2-driven skin diseases * Th17: fight extracellular pathogens * Secrete IL-17, IL-22 * Increase epithelial barrer function via production of defensins, cathelicidins, keratinocytes * Induce epidermal cell proliferation

Answer 134

Too few neutrophils Often caused by chemotherapy Leads to significantly increased susceptibility to infection

Answer 135

* An antigen is any molecule that reacts with an antibody * Almost anything can react with an antibody * An immunogen is any molecule that **induces an immune response** * Not all antigens are immunogens

Answer 136

Alcohol, cigarettes, viral infections

Answer 137

Granulomatous response Macrophages, CD4+ T cells

Answer 138

An immune privileged tissue is one that is protected from/not affected by systemic immune responses This is important in order to prevent damage to these tissues * Eye, brain, testes * Damage would compromise the ability of the organism to survive and reproduce

Answer 139

Langerhan's cells express CCR7, a chemokine receptor that targets them to where T-cells are (in the lymph node)

Answer 140

TLR4 = Toll-like receptor 4 Recognizes LPS on the surface of gram negative bacteria (Works together with CD14 expressed by monocytes and macrophages to recognize LPS)

Answer 141

TH17 CD4+ Helper T-cells and innate lymphoid cells Enhance epithelial barrier function

Answer 142

A **caseating granuloma** has central necrosis (Ex: TB, fungal infection) A **non-caseating granulom**a lacks central necrosis (Ex: foreign material reaction, sarcoidosis, cat scratch disease)

Answer 143

Interferons Interferons are produced by the infected cell when intracellular PRRs bind viral nucleic acids

Answer 144

The APC ingests an extracellular pathogen, digests it, and presents it on MHC class II 1. The TCR (CD3) and coreceptor CD4 bind the peptide that is on MHC II 2. CD28 on the T-cell binds B7 on the APC **and/o****r** cytokine recepotors on the T-cell bind cytokines If signal #2 is not present, the T-cell becomes anergic to this antigen

Answer 145

CD8+ Cytotoxic T-cells NK cells B-cells

Answer 146

Anything that can bind to an anitobdy We can form antibodies to almost anything

Answer 147

Expresses only on naive B-cells Not secreted Honestly, not much is known about their function

Answer 148

To prevent errant tissue damage and inflamation

Answer 149

CCD40 is a co-stimulatory molecule expressed on B cell surface. It binds to CD40L on helper T cells to provide a second signal to B cells. * Critical for creation of a germinal center * Class switching, affinity maturation, somatic hypermutation occur here

Answer 150

SCID = severe combined immunodeficiency Presents very early in life: the patient has very low levels of all immunoglobulins, putting them at extremely high risk of life-threatening infection Permanent treatment = bone marrow transplant Temporary treatment = give immunoglobulins intravenously

Answer 151

Common Variable immunodeficiency (CVID) Caused by a defect in B-cells or helper T-cells that results in decreased numbers of memory B-cells and impaired humoral immunity

Answer 152

**Professional antigen-presenting cells** have MHC class II. They present antigen to CD4+ Helper T-cells

Answer 153

Proliferation of the epithelial cells where the basal cells at the edge of the epidermis proliferate and migrate along the dermis The epithelial cells meet in the middle to close the wound and form and intact layer under the scab Neutrophils regress and granulation tissue invades the wound space with macrophages, fibroblasts, and new blood vessels

Answer 154

X-linked agammaglobulinemia (XLA) (the most common early-onset agammaglobulinemia)

Answer 155

NOD receptors RIG-1 helicase

Answer 156

Promotes T cell growth and activation

Answer 157

* Tonsils * Adenoids * Ciliated respiratory epithelial cells (respiratory elevator) * Secretory IgA, IgM, IgG

Answer 158

AIRE = Autoimmune regualtor * A transcription factor expressed in T-cell maturation during positive selection * Induces the synthesis of an array of self-peptides that are presented on MHC I and II by medullary thymic epithelial cells * If a TCR binds too tightly, the thymocyte undergoes apoptosis or becomes a regulatory T-cells

Answer 159

* Capture complement/antigen complexes on the cell surface * Present antigen complexes to B cells and allow selection for B cells with higher affinity/avidity antibodies

Answer 160

Successful rearrangement of the light-chain (kappa or lambda) Together, the light chain and heavy chain combine to express IgM in the BCR

Answer 161

The endoplasmic reticulum

Answer 162

Clonal deletion * Immature B-cells with IgM that **does not bind** to self-antigen begin expressing IgD with the same light chain specificity as IgM, and they are released from the bone marrow * Immature B-cells with IgM that **does bind** to self-antigen have two fates... * 1) undergo apoptosis * 2) undergo receptor editing; VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a second type of **light chain,** which combines with the original heavy chain. If this second type of receptor **does not bind to self** it begins expressing IgD and is released from the bone marrow

Answer 163

B-cell surface

Answer 164

Type IV: Delayed type/cell mediated

Answer 165

Regulatory T-cells

Answer 166

A superantigen is a **protein** that can directly bind to **MHC class II** and subsequently a TCR without internal processing by the APC. * The superantigen can activate multiple T-cells at a time, regardless of TCR antigen specificity * -\> uncontrolled cytokine release by the T-cell and APC * -\> Increased IL-2, IL-1, TNF * Can contribute to illness and death (ex: toxic shock syndrome)

Answer 167

Hereditary angiodema Uncontrolled generation of bradykinins Persistent swelling in extremities, face, lips, genitals, and GI tract

Answer 168

Use PCR to amplify T-cell recelptr excision circles (TRECs) * TRECs are formed when the T-cell rearranges the variable region of its receptor * TRECs serve as a surrogate for newly-synthesized naive T-cells * There should be many in newborns! * **Too few = SCID**

Answer 169

Sialyl Lewis X on neutrophils binds to P-selectin and E-selectin. This causes the neutrophil to roll slowly along the endothelium Sialyl Lewis X is expressed constituitively on neutrophils P-selectin and E selectin are induced by histamine, IL-1, and TNF-alpha

Answer 170

**T cells are deficient** DiGeorge is caused by a **21q11 deletion** that causes **developmental defects** (partial or complete) in the **thymus** There is a **spectrum** of deficiency, depending on the fraction of the thymus that is nonfunctional Note: patients with partial DiGeorge syndrome improve with age as their cell-mediated immunity catches up

Answer 171

Nomenclature system for the proteins used to identify cells Ex: B-cells are CD19+

Answer 172

SCID Decreased T-cells Abnormal CD4+ CD8+ ratio Defective cell-mediated immunity

Answer 173

Conjugation with proteins allows T-cells to recognize the polysaccharide comonents and mount an immune response. Children under the age of 2 have impaired T-cell independent B-cell immune responses; they are relying on a T-cell dependent response for protection, and protein conjugation is required for T-cells to recognize and respond

Answer 174

1. In the respiratory burst, NADPH oxidase forms the superoxide radical 2. Superoxide dismutase turns the superoxide radical into hydrogen peroxide 3. Myeloperoxidase turns hydrogen peroxide into a hypochlorite ion 4. The hypochlorite ion is the most effective killer of pathogens

Answer 175

Organization of the wound occurs over weeks to months and involves collagen accumulation and fibroblast proliferation with decreased inflammation and regression of the vessels

Answer 176

Sensitization occurs the first time the immune system sees the antigen (primary exposure) * Antibodies form and/or memory T-cells form * This primes the immune repsponse for a stronger reaction upon any subsequent exposure

Answer 177

* IgG produced in an immune response provides negative feedback * B-cells have receptor for Fc portion of IgG (Fc(g)RIIB) * Binding activates signaling through immunomodulary Tyrosine-based inhibition motif (ITAMs) * Terminates BCR response to the antigen

Answer 178

An antigen that induces and immune response Can be a * Protein * Large multivalent non-protein * Immunogenicity depends on size, repetition

Answer 179

Inflammation causes loss of epithelial integrity * Cells ceparate * Tight junctions open up

Answer 180

* B7 on the APC, which binds to CD28 on the T-cell * Cytokines that bind to cytokine receptors on the T-cell * Usually IL-2

Answer 181

Affinity maturation increases a the specificity of antibodies produced by B-cells for a specific antigen The more tightly antibodies can bind to an antigen, the stronger and more targeted the immune response is

Answer 182

(Endothelial cell contraction -\> Increased vascular permeability) * Prostaglandins * Leukotrienes * Bradykinins * Histamines * Others

Answer 183

Prostaglandins Leukotreines Bradykinins Histamines

Answer 184

Antibodies and complement They opsonize bacteria so that neutrophils and macrophages can recognize and phagocytose them

Answer 185

1. **T-cell precursor** develops in the **bone marrow** and migrates to the **thymus** * CD3-, CD4-, CD8- (on surface) * CD3 is expressed in the cytoplasm, not on the surface 2. **Double-negative stage** occurs in the **cortex of the thymus****** * CD3-, CD4-, CD8- 3. **Double-positive stage** occurs in the **cortex of the thymus** * ****CD3+, CD4+, CD8+ * Double-positive thymocytes undergo positive selection 4. **Single-positive stage** begins in the cortex and ends in the **medulla of the thymus** * ****CD3+, CD4+ **OR** CD3+, CD8+ * Single-positive thymocytes undergo negative selection

Answer 186

Type I (immediate/anaphylactic)

Answer 187

* Proinflammatory cytokines * Arachidonic acid products * Bradykinins * Histamines

Answer 188

Lymphoid tissues

Answer 189

1. Antibody variable region of the IgM component of the BCR recognizes and binds a specific antigen 2. Binding leads to receptor cross-linking in association with Ig-alpha/Ig-beta (CD79a/CD79b) and phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) 3. ITAM phosphorylation triggers downstream signaling pathways

Answer 190

2 signals 1. TCR and coreceptor CD8 recognize and bind to the peptide bound to MHC I, presented by an APC 2. Cytokines secreted from CD4+ cells

Answer 191

IL-17, IL-22 Secreted by Th17 CD4+ helper T-cells in cutaneous and GI-tract immune systems

Answer 192

Margination includes... * Vasodilation * Increased vascular permeability * Slowing of blood flow * White blood cells moving to the periphery of flow

Answer 193

Neutropenia = fewer neutrophils than normal. The body is misisng the "first responders" to infection, which can result in more innocuous organisms taking hold and causing disease * Infection by opportunistic pathogens * Bacterial and fungal infections * Even organisms with typically low virulence can cause disease * Example: catalase (-) organisms * Fungal infections may be invasive * Increased risk for sepsis

Answer 194

IL-5 is secreted by Th2 CD4+ Helper T-cells * Enhance eosinophil release of mediators to destroy helminths * Promote class switching to IgA

Answer 195

When the injury involves only the epithelial layer and the wound edges are approximated (i.e. clean surgical incision approximated by sutures)

Answer 196

C1 esterase inhibitor Decay accelarating factor (CD55)

Answer 197

Each B cell has a BCR specific for only one antigen (Or very similar antigens)

Answer 198

Activated in a cascade of cleavage reactions This allows proteins and immune complexes to be destroyed or eliminated

Answer 199

Inserts into cell membrane of pathogen and is bound by C6, C7, C8, and C9 to make the membrane attack complex

Answer 200

A T-cell inhibitory molecule * Secreted 48 to 96 after T-cell activation * Expressed by TRegs * Binds to B7 on APCs * This prevents binding of B7 to CD28, a costimulatory signal in T-cell activation * Inhibits Il-2 synthesis, leading to T-cell cycle arrest * preventsT-cell growth and differentiation

Answer 201

**Normal flora prevent pathogen invasion** Nobody really knows exactly how this works, but it it hypothesized that the normal flora occupies receptors that could be used by a pathogen to enter the body Note: Normal flora in the wrong palce can be pathogenic

Answer 202

Leukotrienes mediate bronchoconstriction This happens after minutes (not seconds) because the mast cells must synthesize leukotriens from pre-cursors before release

Answer 203

Prostaglandins Bradykinin

Answer 204

None! Effector T-cells initiate an immune response immediately after binding to antigen

Answer 205

* Type I; seconds to minutes * Type II; minutes to hours * Type III; hours to days * Type IV; days to weeks, even months * Think latent TB infection

Answer 206

Type I: Immediate/anaphylactic

Answer 207

* Mu (IgM) * Delta (IgD) * Gamma (IgG) * Alpha (IgA) * Epsilon (IgE)

Answer 208

* Chronic inflammation means chronic complement activation * This causes activated neutrophils to release free oxygen radicals in a nonspecific manner * This is great for killing bacteria, but not great for our cells * Persistent exposure to free oxygen radicals can cause **cell proliferation and DNA damage** * This increases the risk of dysplastic or neoplastic changes in tissue

Answer 209

Leukocyt adhesion deficiency (LAD) Neutrophils can't adhere to the endothelium, which means they cannot migrate to the site of inflammation

Answer 210

Histology * Very small number of B cells in peripheral blood Disease * Infections by encapsulated bacteria * Otitis media * Sinusitis * Pneumonia * Enteroviral infections * Meningoencephalitis * Vaccine-associated poliomyelitis * Mycoplasma (can lead to arthritis)

Answer 211

Neutrophils ingest bacteria by invagination of the cell membrane around the bacteria to form a vacuole (phagosome)

Answer 212

NOD receptors Listeria is an intracellular pathogen; NOD receptors in the cytoplasm of immune-competent cells can recognize the pathogen and help mount an immune response

Answer 213

Chediak-Higashi syndrome A defect in organelle trafficking that prevents the formation of phagolysosomes; this prevents the killing of pathogens, leading to recurrent infection

Answer 214

1. Hemorrhage and formation of a blood clot 2. Acute inflammation 3. Proliferation of the epithelial cells 4. Organization of the wound 5. A scar composed of connective tissue w/ scant inflammatory cells

Answer 215

* The process of selection for increased affinity/avidity in B cells in the germinal center * The B-cells whose antibodies bind most tightly to the antigen presented by FDC are selected for * They go on to become memory B-cells and plasma cells * This occurs after B cells have undergone somatic hypermutation in the germinal center

Answer 216

Somatic recombination of the V and J gene regions occurs for antibody light chain variable regions and V, D, and J antibody regions for the heavy chain variable regions Mediated by VDJ recombinase (Encoded by RAG1/RAG2)

Answer 217

* Clonal deletion is necessary to promote the apoptosis of immature B-cells with IgM that binds to self-antigen * This is important in preventing B-cells from initiating an autoimmune response * Receptor editing rearranges the light chain of a self-reactive IgM to basically give it a "second chance" to not bind to self-antigen * If successful, the immature B-cell will begin expressing IgD and continue maturation

Answer 218

* Exposure to a mix of airborne pathogens adn innocuous microbes/particles * Must differentiate and respond to pathogens while tolerating harmless particles

Answer 219

PAMPs (pathogen-associated molecular patterns)

Answer 220

A protein sythesized in the ER Binds to MHC II to prevent inappropriate binding to peptide fragments before MHC II reaches the specialized endosomal intracellular vesicle

Answer 221

1. Monocytes and macrophages express pattern recognition proteins 2. Recognize PAMPs (ex: CD14/TLR4 recognizes LPS) 3. Release pro-inflammatory cytokines/mediators and stimulate acute phase reponse Macrophages also release anti-inflammatory cytokines to control immune response

Answer 222

Proteins recognize common patterns of infectious organisms (PAMPS) Not very specific

Answer 223

Antigen presenting cells (APCs): Macrophages and dendritic cells

Answer 224

Keratinocytes Langerhans cells Dendritic cells

Answer 225

Fc portion of the antiboty (part of the heavy chain contant region)

Answer 226

Hyper IgE syndrome Also look for a mutation in STAT3, defective/absent Th17 Cd4+ helper T-cells, and high IgE

Answer 227

1. Pro-B cell has no heavy chains 2. Pre-B cell has cytoplasmic mu heavy chains and is pre-BCR, successful gene rearrangement of mu heavy chain 3. Immature B cell has IgM surface BCR, successful gene rearrangement of the light chain (kappa or lambda) 4. Naive B cell has IgM, IgD surface BCR

Answer 228

Epithelial regeneration

Answer 229

* Drawn towards inflammatory mediators from macrophages and mast cells (Chemotaxis) * Phagocytose and destroy organisms * Release further cytokines to draw additional neutrophils Note: Neutrophils have a hard time engulfing encapsulated bacteria

Answer 230

Histology * Reduced T-cell zones in lymphoid organs * Reduced delayed hypersensitivity reactions to common antigens * Defective T-cell proliferative responses to mitogens (in vitro) Disease * Infections due to **intracellular** microbes * Viruses * Intracellular bacteria * Pneumocystis jiroveci (and other fungi\_ * Non-tuberculosis mycobacteria * EBV-associated lymphomas

Answer 231

In **positive selection**: The thymocytes begin as double positive * Self MHC I and MHC II proteins are expressed by cortical epithelial cells * Only thymocytes that recognize the self MHC will survive * This step determines whether the T-cell will be CD4+ or CD8+ In **negative selection:** The thymocytes begin as single positive * Medullary thymic epithelial cells present self-antigen on MHC I and II * T-cells with TCRs that bind too tightly to the self-antigen undergo apoptosis or become TRegs * T-cells with TCRs that bind weakly or do not bind to the self-antigen survive

Answer 232

Eczema Very itchy, dry skin, patches of redness and hyperpigmentation

Answer 233

Intracellular bacteria; they infect phagocytic cells and prevent phagolysosome formation Obligate * Mycobacterium spp * M. tuberculosis * M. leprae * Legionella pneumophila * Coxiella Burnetti Facultative * Francisella tularensis * Brucella spp * Listeria monocytogenes * Salmonella spp * S. enteriditis * S. typhi

Answer 234

Caused by a defect in NAPDH oxidase and failure to produce hydrogen peroxide and kill bacteria Patients have recurrent infections from catalase-producing organisms

Answer 235

All antibodies on a B cell must be either all kappa or all lambda (This concept can be used to identify clonal B cells)

Answer 236

Immunization against Hepatitis A with Ig = passive immunity (fast acting) Immunization with the inactivated virus = long-lasting immunity

Answer 237

RAG1/RAG2 genes encode VDJ recombinase, which mediates * Somatic recombination of VJ gene regions in antibody light chain variable regions * Somatic recombination of VDJ regions in antibody heavy chain variable regions * T-Cell Receptor Gene Rearrangement

Answer 238

VJ segments These can be altered during somatic hypermutation to increase binding specificity (Mediated by activation-induced citidien deaminase, AID)

Answer 239

IL-8, C5a These molecules are chemokines; they are chemotactic for neutrophils This occurs after diapedesis (neutrophil escape from the blood vessel), when the neutrophil is in the tissue

Answer 240

* Circulating IgG or IgM exists * Due to prior sensitization, cross-sensitivity, or natural occurrence * Antibodies bind to fixed cell-surface or ECM antigens * Complement activation and/or opsonization * Neutrophil activation -\> inflammatory tissue injury * Phagocytosis * ADCC (antibody-dependent cell-mediated cytotoxicity) by NK cells or CD8+ cytotoxic T-cells * Nk cells have IgG Fc receptors

Answer 241

Proteins produced by B-cells and plasma cells that are **composed of two heavy chains and two light chains** They play a major role in providing protection against infection Antibody = immunoglobulin

Answer 242

* Naive T-cells encounter antigen in the secondary lymphoid organs (the periphery) * Usually presented by dendritic cells * TCR binding antigen + costimulatory signals = T-cell activation * The T-cell can become an effector T-cell or a memory T-cell * Effector T-cells can now encounter antigen in the secondary lymphoid organ or other tissues * The T-cell can kill more readily * Antigen binding alone is enough to initiate an immune response * **Costimulation is not required**

Answer 243

* Pattern recongnition receptors for PAMPs * TLRs, NOD, RIG-I on host cells recognize PAMPS * Receptors for opsonins: * Fc receptors regognize the Fc portion of IgG and IgM * Complement recpetors recognize complement C3b

Answer 244

Mannose-binding lectin (serum protein) binds carbohydrate antigens on the surface of micro-organisms (such as encapsulated bacteria)

Answer 245

Acts on C3 to make C3a and C3b

Answer 246

Co-stimulatory protein on T cells (2nd signal) Binds to B7 on APCs

Answer 247

* Pro-inflammatory cytokine * Numerous pro-inflammatory effects * Stimulates cell growth and proliferation * Recruits neutrophils * Increases cyclooxygenase

Answer 248

* Takes 1-3 days * Driven by memory B-cells and memory T-cells * Memory B-cells recognize the antigen * Interact with antigen-specific T-cells in the germinal center * Possible class switching and somatic hypermutation occurs with each subsequent exposure * More robust response of class-switched IgG * Produced in larger amounts, secreted more quickly

Answer 249

Catalase-producing organisms (Ex: staphylococci) They break down/neutralize hydrogen peroxide

Answer 250

NK cells NK cells recognize and kill cells with missing or downregulated MHC I

Answer 251

The body's response to infection or tissue necrosis. Inflammation allows inflammatory cells, plasma proteins, and fluid to enter the interstitial space.

Answer 252

Any nucleated cell that processes intracellular proteins (such as a virus-infected cell during an infection) can present peptides on **MHC class I** 1. The TCR (CD3) and coreceptor CD8 recognize and bind the peptide on MHC I 2. CD28 on the T-cell binds B7 on the T-cell **and/or** cytokine receptors on the T-cell bind to cytokines (usually IL-2) secreted by the Th2 CD4+ helper T-cells

Answer 253

Epidermis * Multi-layered, keratinized squamous epithelium * Keratinocytes * Secrete defensis, cathelicidins, inflammatory cytokines in response to microbes * Innate immune system

Answer 254

* Vasodilation * Increased vascular permeability

Answer 255

* Chronic inflammation fo the small bowel muosa * Atrophy of the intestinal villi * Malabsorption * Nutritional deficiency * Extra-intestinal manifestation * Rash (dermatitis herpetiformis) * Myalgia * Diarrhea/bloating * Fatigue

Answer 256

Similarities * Both are involved in inflammation * Both express... * Surface Fc receptors for IgE * TLRs * Both release... * Histamines and cytokines Differences * Basophils exist in peripheral blood * Mast cells exist in tissues

Answer 257

* Intracellular bacteria * Viruses * Fungi * Parasites * Tumors

Answer 258

Infants under two cannot generate an effective T-cell independent B cell response; IgM secretion is impaired

Answer 259

* Decreased Th1 CD4+ helper T-cell response * Decreased IFN-gamma secretion * Reduced activation of CD8+ cytotoxic T-cells * Disseminated mycobacterial infection (cell-mediated immunity can't contain the infection via granulomatous response)

Answer 260

PAMP = Pathogen-associated molecular pattern **Not** present on eukaryotic cells Basically, a PAMP is the pattern that the **innate immune system** uses to recognize non-self and initiate an immune response

Answer 261

* Acute presentation * Abdominal pain * Diarrhea * May have a low grade fever * Associated with antibiotic use or spore ingestion

Answer 262

Primary immunodeficiecy Disease Specfiically, a problem with neutrophil function Most often **leukocyte adhesion defect (LAD)**

Answer 263

Gamma-delta T-cells function in the cutanous regional immune system * Secrete IL-17 in chronic inflammatory skin diseases

Answer 264

Clinical signs * Presents at infancy * Severe viral, fungal, and protozoal infections * Some may also have pyogenic infections * Hypocalcemia (due to lack of parathyroid

Answer 265

* Anti-inflammatory cytokine * Turns off immune response

Answer 266

1. Mannose receptors recognize mannose, a polysaccharide commonly found on the surface of bacterial and yeast cells 2. Mannose receptors are found on the surfaces of dendritic cells and macrophages 3. When the mannose receptor binds mannose on the bacterial cell, it **induces phagocytosis**

Answer 267

LAD is caused by a defect in the **CD18 subunit of integrin** * Integrin is required for neutrophil adhesion to the endothelium; a key step in migration to the target tissue * Without integrin, neutrophils cannot reach their destination and aid in the immune response * The result is **recurrent bacterial infections without appropriate pus formation**

Answer 268

* Chronic * Red, scaly plaques * Only mildly itchy * Usually at elbows and knees

Answer 269

Capsules decrease ability of neutrophils to phagocytose bacteria

Answer 270

1. Neutralize toxins 2. Opsonization * Via complement deposition (classic) by **IgM, IgG** * Via exposure of **IgG** Fc (Binds Fc receptors on phagocytes) 3. Antibody-dependent cellular cytotoxicity (ADCC), **IgE** 4. Activates complement cascade; **IgG and IgM**

Answer 271

Anti-inflammatory cytokines such as IL-10 and TGF-beta (However, anti-inflammatory cytokines can also contribute to tissue damage under certain circumstances)

Answer 272

M cells Dendritic cells

Answer 273

Pyogenic (pus-forming) immune responses are due to the action of **neutrophils, antibodies, and complement** during **accute inflammation**. Often triggered by **extracellular pathogens**

Answer 274

Anti-viral proteins that bind to the cell surface and induce an anti-viral state in cells Inhibit viral replication Produced by lymphocytes and macrophages

Answer 275

* IgM * Complement deposition only (classic pathway = formation of C3b) * IgG * Complement deposition (classic pathway = formation of C3b) * Phagocytes have IgG Fc receptors that bind to the Fc region of IgG, when it is attached to the pathogen

Answer 276

Associates with pathogen cell membrane and cleaves/activates other complement proteins

Answer 277

Clostridium difficile (C. diff) colitis Acute = not IBD or celiac Fever = infection Also supported by associated antibiotic use

Answer 278

Ciliated cells (The ciliary elevator) Beta-defensin

Answer 279

Acute inflamamtion occurs initially with neutrophils and then macrophages (24-48) hours The tissue is edematous with increased fluid and necrotic debris Dehydration of the external surface of the clot and the overlying necrotic material forms a scab over the wound

Answer 280

1. Margination 2. Rolling 3. Adhesion 4. Diapedesis and Chemotaxis

Answer 281

Innate * Mast cells, macrophages, dendritic cells * Respond to microbes, injury * Mediate inflammatory response (ex: sunburn) * Dendritic cells * Transport microbial and environmental agents to lymph nodes * Initiate a T-cell response * Langerhans cells (a type of dendritic cell) * TLRs are activated by PAMPs * The cell detatches from the epidermis and migrates to the lymph node (via expression of CCR7)

Answer 282

* Fix complement * Important in primary response * 1st antibody produced upon exosure * Main antibody in a T-cell independent response

Answer 283

Skin is the first line of defense against invasion by pathogens Multiple holes/defects in this defense leave the body susceptible to infection

Answer 284

* APC recognizes the bacteria when it is extracellular * Bacteria binds antigen * PAMP on bacteria binds TLR on APC * Production of IL-2, IL-2 * IL-2 promotes T-cell growth and activation * IL-12 drives the **TH1 response** by promoting the differentiation of CD4+ helper T-cells into the Th1 subset * Th1 CD4+ helper T-cells bind the antigen presented on MHCII * Co-stimulation occurs (B7:CD28, CD40:CD40L) * Th1 CD4+ helper T-cells (now effectors) will secrete INF-gamma * Activate the APC to kill the pathogen it phagocytosed * Activate effector CD8+ Cytotoxic T-cells to kill other nucleated cells that present the same antigen on MHC I * CD8+ cytotoxic T-cells secrete... * IL-12, which continues to drive the Th1 response * Hydrolytic enzymes that drive the granulomatous response

Answer 285

IgG or IgM

Answer 286

Multivalent non-proteins Example: polysaccharide capsule, other non-protein non-self molecules

Answer 287

Surface proteins (antibodies) recognize unique molecules Highly specific

Answer 288

If the peptides from the extracellular pathogen escape the endosome, they will end up in the cytosol instead of the specialized endosomal intracellular vesicle * From the cytosol, the peptides are transported to the ER, where they will interact with MHC I * They may also encounter MHC II, but invariant chains will prevent MHC II from binding to anything until it reaches the specialized endosomal intracellular vesicle

Answer 289

IL-10 and TGB-Beta

Answer 290

* Chronic inflammatory and autoimmune diseases * IBD * Psoriasis * MS

Answer 291

Th2 CD4+ helper T-cells Secrete IL-4, IL-13 -\> B-cell differentation, fluid and mucus secretion

Answer 292

All classes (IgM, IgG, IgE, IgA)

Answer 293

Part of immune response that exists at birth and is present in all multicellular organisms * Rapid * Relies on pattern recognition to identify pathogens * Not specific * No memory * No improvement in immunity with time or repeated antigen exposure

Answer 294

Histology * Absent or reduced follicles and germinal centers in lymphoid organs Disease * Pyogenic bacterial infections * Enteric bacterial infections * Viral infections

Answer 295

Th2 CD4+ helper T-cells

Answer 296

Patient may not show the same signs and symptoms of infection with pathogens as quickly as someone that has an intact immune system, masking a serious illness

Answer 297

Myeloperoxidase Lysozyme Other degradative enzymes

Answer 298

Large surface area Exposure to many things

Answer 299

The Gut-Associated Lymphoid Tissue; part of the regional immune system in the GI tract * Found in the lamina propria * Contains * **Tonsils** * **Peyer's patches** in the ilium * **M-cells** that transport antigen from the epithelial lining * **Dendritic cells** with processes that extend into the lumen * **Diffuse effector lymphocytes** that may exert effect in other places in the body, but home back to the GALT

Answer 300

Integrins expressed on neutrophils bind to ICAM and VCAM, causing firm adhesion of the neutrophil to the endothelium * Integrin expression is induced by C5a and leukotrine * ICAM and VCAM are cellular adhesion molecules induced by TNF-alpha and IL-1

Answer 301

In the cortex of the thymus

Answer 302

Chediak-higashi syndrome; a defect of organelle trafficking The patient may also have: * Neutropenia * Giant granules in neutrophils and monocytes * Albinism * Increased risk of pyogenic and opportunistic infection

Answer 303

* IFN-gamma * Promotes and activates macrophages * Stimulates IgG production * Leads to more effective killing of intracellular pathogens * Continues to drive the Th1 response * IL-2 * Promotes T-cell growth and differentiation * Can act in an autocrine fashion

Answer 304

* Alpha-beta heterodimer (except a small subset of gamma-delta) * Alpha-chain undergoes VJ gene recombination during maturation * Beta-chain undergoes VDG gene recombination during maturation * No class-switching * Antigen recognition region is variable between T-cells * But remains the same for the life of the T-cell * ITAMs mediate signaling from TCR to rest of cell * Expresses CD3

Answer 305

Gamma-delta T-cell receptors are a small subset of all T-cell receptors in our bodies * Participate in innate immune response instead of adaptive * Less variability in their antigen receptors

Answer 306

A collection of immune cells and molecules that work together to perform the specific immune functions at a particular anatomic location The regional immune systems are **adapted** to the location that they serve

Answer 307

2 signals 1. Recognition of antigen 2. Costimulatory signal

Answer 308

**Histamine, IL-1, and TNF-alpha** induce P-selectin and E-selectin expression **on the inner walls of blood vessel endothelium** They are induced in response to inflammation; they are important in the **rolling** step of phagocytic cell recruitment and migration. Without P-selectin and E-selectin, neutrophils cannot reach the site of inflammation

Answer 309

* Some tissues can regenerate * Macrophages release anti-inflammatory TGF-beta * Macrophages recruit fibroblasts and release vascularization factors (granulation tissue) * If tissue architecture is lost, fibroblasts deposit collagen and ECM to form scars

Answer 310

Failure of the adaptive immune system to tolerate food antigen * Too many Th2 CD4+ helper T-cells, not enough TRegs * Overactive Th2-dependent IgE resposne to antigen * Mast cells are activated * Potent mediators/cytokines are released * Acute inflammatory reactions (including systemic anaphylaxis)

Answer 311

* They differentiate into Antibody-producing plasma cells * Some may become long-lived memory B cells

Answer 312

Variable; depends on the component that is defective * May see a mix of pyogenic bacterial and viral infections

Answer 313

In specialized endosomal intracellular vesicles

Answer 314

The light chain variable region

Answer 315

* Abundant antigen leads to the formation of soluble antigen-antibody immune complexes * The complexes are deposited in tissues * Complement activation may occur * Inflammation due to... * Chemotaxis of neutrophils in response to complement activation * Vessel leakage * Vessel damage

Answer 316

IgG bound to antigen

Answer 317

* Antibody deficiency syndrome * Also look for * Enteroviral infections * Common Variable immune deficiency * Also look for * Lymphoid hyperplasia * Granulomatous lesions * Lymphoma and autoimmune manifestations * Cytopenias * IBD

Answer 318

Allows fluid, proteins, and cells to reach pathogen or tissue damage

Answer 319

C5a, leukotrine Integrins are important because they bind to ICAM and VCAM in the **ahesion** step of phagocytic cell recruitment and migration. Without integrins (and C5a and leukotrine), neutrophils would not be able to reach the site of inflammation

Answer 320

If a thymocyte has a high affinity for self-antigen, it could cause an autoimmune response Fortunately, our bodies try to prevent this from happening through... * Negative selection in the thymus * Thymocytes with TCRs that bind tightly to self-antigen undergo apoptosis or become TRegs * Peripheral Tolerance * If a T-cell in the periphery binds to an antigen and there is no co-stimulatory signal, the T-cell becomes **anergic** (nonresponsive) to that antigen * This would happen if a TCR bound to self-antigen; no B7 expression or simultaneous cytokine binding

Answer 321

The membrane attack complex

Answer 322

* Mediates antibody-dependent cellular cytotoxicity (ADCC) against parasites * Binds to extracellular parasites, recruits other cells to kill them * Mediates the killing of parasites by eosinophils * Mediates allergies, anaphylaxis

Answer 323

* Dendritic cells sample airway antigen * Migrate to lymph nodes to present to naïve T-cells * Promote differentiation to Th2 CD4+ helper T-cells * Th2 cells effect response * Th2 cells return to bronchial mucosa * Here they can be re-activated by allergens presented by dendritic cells next time they appear

Answer 324

Brain Eye Testes

Answer 325

* M cells * Luminal antigen sampling * Secretory IgA, IgM * Neutralized microbes in the lumen * Dendritic cell subsets * Luminal and lamina proria antigen sampling * T-cell tolerance induction * Effector T-cell activation * Induction of B-cell IgA class switching * Imprint gut-homing phenotypes of B cells and T cells

Answer 326

Loss of organ function

Answer 327

The patient has been exposed to the virus at some point in their lives It is not likely that the first exposure was recent; IgG specific for a virus takes time to generate. The patient has likely been exposed multipel times

Answer 328

Encapsulated bacteria

Answer 329

When the defective gene is known (this method is in development) * X-linked SCID * Adenosine deaminase deficient SCID

Answer 330

Small proteins that are produced by cells and have effects on cells Include chemokines, interleukins, lymphokines, tumor necrosis factors, interferons

Answer 331

Induction of an immune response (exposure to antigen) Slow Memory (long-lived)

Answer 332

* X-linked SCID * X-linked Hyper IgM * X-linked Agammaglobulinemia * Wiskott-Aldrich Syndrome All except Wiskott-Aldrich Syndrome can also be caused by autosomal defects

Answer 333

Autoimmune disease

Answer 334

NK cells (CD56+ and CD16+) * Directly kill infected cells * Recognize virus-infected cells and tumor cells via lack of MHC class I on those cells * Binds Fc (constant region) of antibody bound to those cells * Produce and secrete cytotoxic granules such as perforin and granzyme B * Do not express specific antigen receptors

Answer 335

Prostaglandins Bradykinins Histamines

Answer 336

* CD8+ Cytotoxic T-cells are activated by Th1 CD4+ helper T-cells that secrete IFN-gamma * Activated CD8+ Cytotoxic T-cells secrete IL-12, which drives the Th1 CD4+ helper T-cell response * This continues to drive the CD8+ Cytotoxic T-cell response

Answer 337

Caused by endothelial cell contraction and damage Allows fluid and cells to reach areas of infection

Answer 338

After a B-cell presents antigen on MHC class II to a T-cell receptor... * **T-cells express CD28** that binds to B7 on the B-cell * This acts as a second signal to T-cells to produce cytokines * Induces CD40 expression on the B-cell * B7 on the B-cell induces **CD40L expression on the T-cell** * B-cell CD40 binds to T-cell CD40L * This is a "second second" signal for B-cell activation * T-cells produce cytokines that induce the formation of a germinal center * In the germinal center, B-cells undergo class switching and somatic hypermutation, leading to B-cell differentiation

Answer 339

Due to short time before her potential exposure to Hepatitis A, she should receive immune globulin (Ig), which is passive immunization, since the antibody is preformed and the protection is rapid. This protection is short-lived, so she should also receive inactive Hepatitis A vaccine, which provides longer protection. Ideally, she would also have a booster in 6 months for much longer protection.

Answer 340

Passive immunization - give pooled gamma globulin from healthy individuals intravenously (IVIG) or subcutaneously (SCIG)

Answer 341

* FDCs are present in the germinal center and trap complement/antigen complexes on their surface to present to B cells * B cells recognize and bind to the antigen on the surface of FDC * FDCs select for the B cells with antibodies on their surface (BCRs) that bind with high affinity/avidity to the antigen on the surface of the FDCs * These B-cells go on to become memory B-cells or plasma cells

Answer 342

Microbial products directly activate complement

Answer 343

Production of cytokines by the CD4+ T cells in the presence of CD40:CD40L interaction

Answer 344

Regulation prevents tisue damage Complement proteins circulate as precursors that are activated by relevant signals

Answer 345

IgM specific for that virus

Answer 346

IL-10 TGF-beta

Answer 347

No protection from infection

Answer 348

Psoriasis Red scaly plaques, itchy, on elbos and knees Not itchy enough to be eczema

Answer 349

Hyper IgM syndrome Caused by loss of CD40L on CD4+ helper T-cells * The B-cells cannot class switch because a germinal center can't form * The result is high IgM, but low levels of all other Igs

Answer 350

* The cell-mediated arm of adaptive immunity * Protects us from **intracellular** bacteria, viruses, fungi, parasites * Mediated by T-cells and macrophages

Answer 351

Fc(g)RIIB receptors on the surface of B-cells bind to the Fc portion of IgG secreted in the immune response Binding activates ITIMs to terminate the BCR response to the antigen

Answer 352

Type II: Cytotoxic/antibody mediaed

Answer 353

SCID; RAG1/RAG2 mutation prevents VDJ recombination during lymphocyte maturation T cells and B cells are absent (NK cells are normal)

Answer 354

GI Tract Respiratory Cutaneous (Genitourinary was mentioned in the learning guide briefly)

Answer 355

MHC applies to T-cells The T-cell receptor and co-receptor can **only recognize antigen in the context of a sefl-MHC molecule** (T-cells are selected ofr thwen they recognize self-MHC expressed by cortical epithelial cells during positive selection\_

Answer 356

Peripheral tolerance = the "check" to prevent B-cells and T-cells from reacting to self-antigen after they have completed maturation * If a BCR or TCR binds to self-antigen, there will be no co-stimulatory signal (at least there shouldn't be) * B-cell: TLR will not be activated, nor will Cd3 bind to CR2 * T-cell: B7 will not bind to CD28 on the T-Cell, nor will appropiate cytokines activate receptors on the T-Cell * BCR or TCR binding without a co-stimulatory signal will make the lympcyte **anergic (nonresponsive to that antigen)** * T-cells * Anergy is antigen-specific, but **clonal deletion** will occur if a T-cell repeatedly encounters and reacts to self-antigen

Answer 357

Dyseregulated innate and T-cell mediated immune responses * Overactive plasmacytoid dendritic cells * Respond to environmental stimuli * Produce IFN-alpha * T-cells circulate to the dermis * Overactive Th1, Th17 cells * Secrete too much IL-17 * Persistent keratinocyte proliferation

Answer 358

Cytotoxic T cells Binds to MHC class I

Answer 359

* Antitoxins for botulinum toxins * Antibodies to rabies virus * Maternal IgG antibodies crossing the placenta * Maternal IgA antibodies in breast milk

Answer 360

Promotes class switching to IgE

Answer 361

Modulate the immune reponse * Inhibit effector function of CD4+ helper T-cells and CD8+ cytotoxic T-cells * Loss of regulatory T-cell function -\> autoimmune problems

Answer 362

VDJ segments These can be altered durign somatic hypermutation to increase binding specificity (Mediated by activation-induced citidine deaminase, AID)

Answer 363

Attrach neutrophils, mediate bronchospasm, and increased vascular permeability

Answer 364

**Innate** * Physical barrier * Pseudostratified, ciliated, columnar epithelium * Chemical barrier * Mucins, defensins, cathelicidins trap foreign substances * Surfactant * In alveoli * Prevents spread of infection * Suppresses inflammatory allergic response in the lungs * MALT * Alveolar macrophages * Anti-inflammatory * Inhibit T-cell response **Adaptive** * Mast cells, eosinophils, dendritic cells, CD4+ helper T-cells * IgA - mosty in upper airway * IgE - mediates allergic response, asthma when bound to mast cells

Answer 365

Hypochlorite ion

Answer 366

Acute phase response Increased synthesis of plasma proteins by the liver, including C-reactive protein, mannose-binding lectin, Factor XII Contributes to sepsis

Answer 367

Inhibits the formation of C3

Answer 368

* Neutralize toxins and viruses * Opsonize bacteria (enhance phagocytosis)

Answer 369

Th1 CD4+ helper T-cells fight **intracellular pathogens** * Promotes CD8+ cytotoxic T-cells to kill pathogens * Secretes IFN-gamma and IL-2

Answer 370

Chronic granulomatous disease; A defect in NADPH oxidase results in downstream failure to produce the hypochlorite ion from hydrogen peroxide; Hydrogen peroxide alone is not effective at killing catalase (+) bacteria, because these bacteria can break down hydrogen peroxide.

Answer 371

Defects in C2 and C4 * Autoimmune disease * Ex: Systemic lupus erythematosus Defects in C2 and C3 * Infections by encapsulated bacteria Defects in any of C5-C9 * Recurrent, invasive nesseria infections

Answer 372

Hemorrhage and formation of a blood clot involving activation of the coagulation cascade, platelets, and fibrin

Answer 373

Predominantly Type I immediate/anaphylactic hypersensitivity reactions

Answer 374

Part of adaptive immunity * Antibody-mediated * Protects us from **extracellular** bacteria, viruses, toxins * Mediated by B-cells and plasma cells

Answer 375

* Imparied isotype switching * Imparied somatic hypermutaiton This can result in increased risk of infection, decrease antigen binding specificity

Answer 376

Phagolysosomes do not form; there is a defect in phagosome-lysosome fusion NK cells are also abnormal **Clinical manifestation** * Impaired killing of intracellular pathogens = recurrent **pyogenic infections** * Bacterial and viral * Other abnormalities * Partial albinism * Abnormal platelet function * Defective NK cells

Answer 377

Acts on arachidonic acid from the cell membrane to produce prostaglandins which mediate vasodilation and increased vascular permeability, pain, and fever

Answer 378

* They constituitively express receptors for the Fc portion of IgE; they can bind immediately upon IgE binding antigen * They have pre-formed effector molecules that are stored in granules and released immediately upon binding * Histamine * Kinins/kininogenase * Serotonin * TNF * Proteases

Answer 379

Antibodies against ABO glycoproteins in people with red blood cells lacking A or B antigen * Type O: Has natural antibodies to A and B antigens * Type A: Has natural antibodies to B antigen * Type B: Has natural antibodies to A antigen

Answer 380

SCID = severe combined immunodeficiency * Mutation in the x-linked gene encoding the **common gamma chain**, an important component of many IL receptors * Lack of IL-7, IL-15 signaling = defective T and NK cells * A mutation in **RAG1/RAG2 that prevents VDJ recombination** * No B or T cells * **Loss of MHC II** due to loss of transcription factors required for expression leads to **bare lymphocyte syndrome** * No T cell positive selection = **no T-cells** * Impaired CD4+ T cell activation * Defective cell-mediated immunity * Defective T-cell dependent humoral immunity * **Defective T cell signaling** due to defective TCR/CD3 complex component or T cell activation signal transduction cascade * Decreased T cells * Abnormal CD4+ : CD8+ ratio * Defective cell-mediated immunity

Answer 381

Receptor editing occurs in the bone marrow during clonal deletion. When a B-cell expresses IgM that binds to self-antigen, it must be altered to prevent that cell from being released and initiating an autoimmune response **Receptor editing:** VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a **second type of light chain**, which combines with the original heavy chain. If this second type of receptor **does not bind to self** it begins expressing IgD and is released from the bone marrow If the second type of of receptor **continues to bind to self**, the B-cell undergoes apoptosis

Answer 382

Vasodilation -\> Edema Hypotension Smooth muscle contraction -\> Bronchoconstriction

Answer 383

The B-cell will become anergic (non-reactive) * B-cell reaction to self-antigen = anergy * This is due to **reaction in the absense of co-stimulation** * Co-stimulation usually takes the from of Cd3 binding CR2 (CD21) or PAMPs binding TLRs * Only non-self antigens have complement deposition and/or PAMPs

Answer 384

Secondary lymphoid tissues To interact with T cells, antigen-presenting cells, and follicular dendritic cells

Answer 385

Medulla of the thymus

Answer 386

Histamine, prostaglandins, and leukotrienes

Answer 387

Mediate vasodilation, increased vascular permeability, pain, and fever

Answer 388

* Evade immune system * Capsules prevent phagocytosis * Internalization in cells "hides" the pathogen * Use elements of immune system for their own advantage

Answer 389

Integrin is required for adhesion of the neutrophils to the endothelium Without adhesion to endothelium, neutrophils cannot cross the endothelium to exit in peripheral blood and other tissues The number of neutrophils in peripheral blood will increase because the neutrophils cannot leave the peripheral blood

Answer 390

Somatic hypermutation Isotype/class switching

Answer 391

* Prevents complement activation * Decreases C3b binding (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae)

Answer 392

Type III: Immune complex

Answer 393

Histology * Few or defective Th17 CD 4+ helper T-cells Disease * Recurrent neonatal eczematous rash * Retention of primary teeth * High IgE

Answer 394

CVID = common variable immunodeficiency * Caused by multiple etiologies; a variety of different genes may cause an **underlying defect in B cells or helper T-cells**. * Low immunoglobulins (IgG and IgA, maybe IgM) * Decreased numbers of memory B-cells * Impaired humoral immunity * Increased risk of bacterial, enteroviral, giardial infections * Presents in late childhood/adolescence * Increased risk of autoimmune disease an lymphoma

Answer 395

Bone marrow transplant Gene therapy (in development)

Answer 396

* Early B-cell activation = T-cell independent B-cell response * Antibody binds antigen * Cd3 on antigen binds CR2 (CD21) -\> enhancement * PAMP on antigen binds TLR -\> enhancement * Later B-cell activation * B-Cell or other APC presents peptides on MHC class II to the T-cell * B-cell expresses B7 and CD40 * B7 on B-cell binds CD28 on T-cell; this induces CD40L on the T-cell * CD40 on B-cell binds CD40L on T-cell * Induces T-cell cytokine release, formation of a germinal center * B-cells undergo rapid proliferation, class switching, somatic hypermutation * B-cells differentiate to plasma cells, long-lived memory B-cells

Answer 397

Mast cells (stimulated by binding of C3a and C5a complement) Leads to vasodilation, endothelial cell contraction, and increased vascular permeability

Answer 398

Intracellular antigens are presented on MHC I by any nucleated cell * Endogenously synthesized proteins (ex: viral proteins) are cleaved by a proteasome in the **cytosol** * Peptide fragments associate wtih a TAP transporter * The TAP transporter transports the fragment to the ER * Peptide fragments in the ER bind to MHC I * Binding stabilizes MHC I * The peptide/MHC I complex is transported to the surface through the golgi

Answer 399

Myeloperoxidase catalyzes formation of hypochlorite ion from hydrogen peroxide Hypochlorite ion is the most effective mediator of pathogen destruction

Answer 400

2 methods 1. Production of cytotoxic molecules like perforin or granzyme 2. Expresion of FasL (induces apoptosis when binding to the Fas protein)

Answer 401

Pyogen (pus-producing) response Neutrophils, antibodies, complement

Answer 402

Yes, but it is very limited T cells express CD40L, which binds to CD40 on B cells. This is critical in the formation of an effective germinal center response which gives rise to the majority of isotype switching and somatic hypermutation

Answer 403

* Healing by first intention (primary union) * Healing by second intention (secondary union)

Answer 404

Infants under 2 years old and the elderly

Answer 405

Promotes differentiation of B-cells Activation of eosinophils

Answer 406

Constant region of the heavy chain

Answer 407

IL-8 A pro-inflammatory cytokine

Answer 408

Catalase breaks down hydrogen peroxide This decreases the formation of hypochlorite by myeloperoxidase

Answer 409

1. TLRs = Toll Like Receptors - A family of 10 receptors 2. TLRs are found on the surfaces of macrophages, dendritic cells, mast cells, and B cells - Cells that help connect the innate and adaptive immune systems 3. TLRs recognize microbial components (like PAMPs) and initiate the synthesis of cytokines

Answer 410

Cortex of the thymus

Answer 411

After binding of antigen, B cell upregulates costimulatory molecules (B7 and CD40) CD40 on the B cell interacts with CD40L on T cell B7 on the B cell interacts with CD28 on T cell BCR takes up the antigen and presents protein antigens on MHC class II protein to T-cells

Answer 412

B-cells Only B-cells undergo somatic hypermutation to increase their antigen specificity NK cells do not have antigen specificity, and T-cells do not alter their specificity after leaving the thymus

Answer 413

Anaphylaxis Allergic rhinitis Astham attack Hives

Answer 414

Wound contraction Myofibroblasts This process basically makes scar formation more complicated and can lead to complications

Answer 415

Forms a hole in the membrane causing the pathogen to lyse Gram-negative bacteria are particularly susceptible

Answer 416

Immediate hypersensitivity reaction (Seconds) * Mast cells have effectors that are pre-formed in granules * Histamine * Kinins and Kininogenase * Serotonin * TNF * Proteases Slower hypersensitivity reactions (minutes) * Mast cells synthesize effectors * Arachidonic acid metabolites * Leukotrienes and prostaglandins * Cytokines and chemokines

Answer 417

* Nucleotides are added and removed during recombination * Occurs at the joining ends of the gene segments * Significantly increases diversity of the VDJ and VJ regions * Known as hypervariable regions

Answer 418

* **Innate defects** in the epithelial barrier, mucociliary elevator, or production of anti-microbial peptides * **Abnormal activation** of eosinophils, mast cells, innate lymphoid cells * **Th2-skewed pathway** * Direct activation of T and B cells promotes IgE and eosinophil activation

Answer 419

Antigen cross presentation occurs when peptides from extracellular pathogens are presented on MHC class I instead of MHC class II * Usually occurs on on dendritic cells * After engulfment of the pathogen and digestion to peptides, the peptides escape the endosome and end up in the **cytosol** * From the cytosol, the peptides are transported to the ER * Peptide in the ER binds MHC I * The peptide/MHC I complex is transported to the cell surface

Answer 420

TLR 4 CD14 Both are expressed by monocytes and macrophages

Answer 421

* Mucosal immunity * Prevetns the attachment of bacteria and viruses to mucosal membranes * This prevents bacteria from entering the mucosa * Passively transferred in breast milk

Answer 422

Heavy chain constant region

Answer 423

* Allergens cause crosslinking of IgE Fc receptors on mast cells * This promotes histamine release * Mediates allergies and anaphylaxis

Answer 424

All T cells

Answer 425

* Perforins * Form channels in the target cell membrane * Granzymes * Proteases that lead to apoptosis * Degrade proteins in the target cell membrane * Activate caspases * FasL * Binds to Fas proteins on the target cell * Fas:FasL binding -\> apoptosis

Answer 426

Mostly IgM | (Maybe some IgG and IgA)

Answer 427

\>20 plasma proteins that augment inflammation

Answer 428

The process by which immature B-cells become naive B-cells B-cells that bind self-antigen must be eliminated or edited so that they do not mount an autoimmune response * Immature B-cells with IgM that **does not bind to self-antigen** begin expressing IgD with the same light chain specificity as IgM, and they are released from the bone marrow * Immature B-cells with IgM that **does bind to self-antigen** have two fates... * 1) undergo apoptosis * 2) undergo receptor editing; VDJ recombinase is re-expressed via activation of Rag1/Rag2. VJ recombination is repeated to express a second type of light chain, which combines with the original heavy chain. * If this second type of receptor **does not** bind to self it begins expressing IgD and is released from the bone marrow * If this second type of receptor **does** bind to self, the B-cell undergoes apoptosis

Answer 429

* Pro-inflammatory cytokine * Recruits neutrophils (chemokine) "Clean up in aisle 8 (IL-8)"

Answer 430

IgM and IgD (Both sets of antibodies on an individual B-cell have the same antigen binding specificity)

Answer 431

**All nucleated cells** in the human body have MHC class I and can present antigen to CD8+ Cytotoxic T-Cells

Answer 432

When tissue loss is extensive and the wound edges cannot be brought together (e.g. ulcer)

Answer 433

A signal transduction protein required for pre-B cells to differentiate to B cells Mutations in Bruton's tyrosine kinase cause X-linked agammaglobulinemia

Answer 434

Single layer on a basement membrane * Dominanted by goblet cells, M cells, Paneth cells * Innate * Forms a barrier to pathogens * TLRs and NLRs recognize PAMPS and initiatie an immune response * Participates in tolerance of commensals * Limit inflammatory response * Antigen sampling happens here * Adaptive * Antigen-sampling cells may activate effector B and T cells

Answer 435

Neutrophils

Answer 436

IgA is passed from mom to baby in breast milk IgA confers mucosal immunity, preventing attachment and invasion by bacteria and viruses through mucosal membranes This can help prevent infection in infants

Answer 437

CD8+ cytotoxic T-cells recognize viral peptides presented on MHC I by virus infected cells * CD8+ cytotoxic T-cells can directly kill the virus-infected cells * This can cause tissue injury even if the virus itself is not pathogenic

Answer 438

Overactive Th2 response in genetically susceptible individuals * Susceptible due to innate barrier defect, increased antigen exposure * Leads to... * B-cell production of IgE * Mast cell activation * Acute inflammatory response due to release of cytokines/mediators

Answer 439

Involves other numerous enzymes and is not as effective as oxygen-dependent killing

Answer 440

* IL-17, IL-22 * Defense against some bacteria * Enhance epithelial barrier function * TGF-Beta, IL-10, IL-2 * Maintain immune homeostasis in the bowel * Anti-inflammatory/regulatory function

Answer 441

A mutation in STAT3 that results in abnormal Th17 CD4+ helper T cell development

Answer 442

Pyogenic infections (No antibodies -\> decreased opsonization -\> trouble w/ extracellular bacteria especially ones with capsules -\> get a neutrophil pus-producing response)

Answer 443

T-cell receptors (TCRs) will ony recognize **proteins** All T-cells require the activation of the TCR **and** co-receptor: CD4+ and CD 8+ co-receptors only recognize **linear peptides presented by MHC** * CD4+ Helper T-cells recognize peptides presented by **MHC II** * CD8+ Cytotoxic T-cells recognize peptides presented by **MHC I**

Answer 444

Extracellular pathogens

Answer 445

Defects of antibody-mediated immunity * Antibody deficiency syndrome * Including X-linked agammaglobulinemia * CVID

Answer 446

ADCC = Antibody-mediated cellular cytotoxicity * Also known as antibody-dependent cell-mediated cellular cytotoxicity * Antibody binding to antigens attached to the surface of infected cells targets these infected cells for **direct killing by macrophages, neutrophils, or NK cellss**

Answer 447

In healing by secondary intention, * The clot is larger * Inflammation is more intense * There is more granulation tissue with greater likelihood of complications * Wound contraction occurs due to myofibroblasts

Answer 448

Bradykinins are produced from the kinin system (cleavage of high molecular weight kinogen/kalikrein) Mediate vasodilation, increased vascular permeability, and pain **Hint: Tom Brady = Brady-kinin** - Dilates the defense and creates holes in it - Causes pain to opponents

Answer 449

Th17 CD4+ helper T-cells enhance mucosal immunity * Promote neutrophilic inflammation * Via seretion of IL-17 * Recrute neutrophils and monocytes to the site of infection

Answer 450

An antigen that does **not** induce an immune response on its own Ex: A small chemical

Answer 451

Opsonin for phagocytosis (iC3b and C3d are breakdown products of C3b)

Answer 452

Epithelial lining of the genitourinary system Dermis * Langerhan's cells are a type of dendritic cell; they basically sample antigens in the cutaneous and genitourinary regional immune systems * Contain TLRs that are activated by PAMPS. When activated, the cell will migrate to a lymph node to initate a T-cell response

Answer 453

Antibiotic treatment or ingestion of C. diff spores This alters the quantity and/or diversity of normal flora, reducing the ability of the GI tract regional immune system to prevent harmful/inflammatory responses

Answer 454

Wiskott-Aldrich Syndrome Results in abnormally small platelets and leukocytes that do not migrate properly

Answer 455

Recognizes antigen-antibody complexes in the classical pathway of complement activation

Answer 456

* Direct lysis of cells * Generation of mediators of inflammation * Opsonization (enhancement of phagocytosis)

Answer 457

Induration formation in a positive PPD Skin test for *M**ycobacterium tuberculosis* Contact dermatitis (ex: poison ivy) Graft vs. host disease

Answer 458

Promotes class switching to IgG and IgA

Answer 459

Th1 CD4+ helper T-cells may be involved in... * Autoimmune disorders * Chronic inflammaton * Examples: * IBD * Psoriasis * Granulomatous inflammation

Answer 460

A subset of antigen-specific T-cells that have gone through a primary immune response to an antigen, then differentiated * Memory T-cells have the **same antigen-binding specificity and affinity** as the original T-cell * Can live for years * When they recognize the same antigen again, there are already higher than baseline levels of the antigen-specific T-cell in the body * Activation with a lower required threshold of costimulation * Rapid, more robust cytokine release

Answer 461

After antigen binds We only want complement active when an immune response is necessary

Answer 462

* Production of pro-inflammatory cytokines * IL-1, IL-6, TNF-alpha, IL-12 * Increased risk of severe **pyogenic bacterial or viral infections** * Usually accompanied by significant inflammatory response

Answer 463

* Viral peptides can still be presented on MHC class II to CD4+ helper T-cells * Can be captured by B-cells before the virus has been internalized * Can be presented by dendritic cells infected with the virus (Viral peptides can also be presented on MHC class I to CD8+ cytotoxic T-cells, but this is not humoral immunity)

Answer 464

Tissue macrophages * Recognize pathogens through pattern recognition * Release cytokines to recruit neutrophils * Macrophages phagocytose organisms * Antigen-presenting cells (express MHC class II)

Answer 465

Cell mediated arm of adaptive immunity T-cells are defective or absent; this may or may not affect B-cell maturation, depending on the defect that is causing SCID

Answer 466

Typically, extracellular pathogens activate humoral immunity that involves support from Th2 CD4+ helper T-cells However cross-presentation can cause extracellular pathogens to have a CD8+ cytotoxic T-cell response * After engulfment by an APC, the extracellular pathogen peptides escape the endosome, end up in the cytosol, and are transported to the ER, where they bind MHC I * The peptide/MHC I complex is transported to the surface of the antigen-presenting cell * Binding of Th1 CD4+ helper T-cells to the peptide on MHC I will **initiate a CD8+ cytotoxic T-cell response**

Answer 467

**Antibody-driven immune response** 1. Highly specific, humoral arm of adaptive immunity 2. Mediated by CD 4+ helper T-cells and B-Cells 3. MHC II presents peptides to CD4+ helper T-cells * The helper T-cells **help out** by secreting molecules that activate B-cells to produce antibodies * The antibodies activate CD8+ cytotoxic T-cells to attack and destroy virus-infected cells

Answer 468

PD1 is an inhibitory molecule to T-cells, expressed by T-cells * Binds to PDL1 receptor, expressed by APCs * Macrophages and dendritic cells * This leads to hinibition of th eimmune response **Note**: Some cancer cells express PD1 to downregulate the immune response against the cancer cell. This is a potential target for immunotherapy in cancer treatment

Answer 469

A complement receptor expressed with CD19 on the B cell surface Bindint of CD21 to complement Cd3 on bacteria that is already bound to the BCR -\> enhancement of B-cell activation

Answer 470

* Polymorphisms of genes associated with bacterial processing, sensing, and autophagy * Defective TReg function

Answer 471

Memory T-cells * After the primary response, the T-cells that responded to the antigen will proliferate, creating a larger subset of T-cells specific for that antigen * Upon repeat exposure, these cells are "ready" * Rapid, more robust cytokine production * Activation with a lower threshold of costimulation required

Answer 472

1. NOD receptors are pattern-recognition receptors that regognize pathogens within our cells 2. In the cytosol of immune-competent cells 3. NOD receptors recognize **peptidoglycan**

Answer 473

**Individuals with CGD don't have enough NADPH to kill via respiratory burst** * They cannot create O2-, which is needed to make H2O2, and subsequently the hypochlorite ion * They must kill organisms using the oxygen-independent pathway **You would expect a patient to experience...** * Recurrent infections from catalase positive organisms * Catalase interferes with the oxygen-independent pathway of killing * Granuloma formation (lungs, liver, brain) * Severe infections of skin and bone * Recurrent oral stomatitis * Infections of respiratory tract and skin * Abscess formation

Answer 474

Plasma cell surface

Answer 475

Cell-surface antigens or ECM antigens

Answer 476

Humoral * Mast cells, eosinophils, dendritic cells, CD4+ helper T-cells * IgA * IgE Cell-Mediated * Dendritic cells * Sample airway antigen, migrate to lymph node, and present to naive T-cells * T-cells are activated by dendritic cell sampling and presentation * Occurs in peri-broncial and mediastinal lymph nodes * Effect response, return to broncial mucosa *

Answer 477

Dry skin Patches of redness and hyperpigmentation Very itchy

Answer 478

Predominantly an adaptive immune response\ Mediated by lymphocytes, plasma cells, and monocytes/macrophages

Answer 479

Phagosomes containing bacteria merge with lysosomes (containing myeloperoxidase, lysozyme, and other degradative enzymes) to form phagolysosomes, where killing occurs Some bacteria are able to prevent fusion of the phagosome and the lysosome; they basically re-model the phagosome as a nice new home

Answer 480

C1 (C**1** = the **#1** antigen-antibody recognizing protein)

Answer 481

Autoimmunity

Answer 482

Helper T cells Binds to MHC class II

Answer 483

T-cells acquire their antigen specificity as they mature in the thymus * The alpha chain undergoes VJ recombination * The beta chain undergoes VDJ recombination After the T-cell leaves the thymus, its antigen specificity and that of its progeny **will not change;** The T-cell will not become more specific with repeated exposure

Answer 484

SCID; Bare Lymphocyte Syndrome * CD4+ T-cell activation is impaired * No MHC II for it to recognize * Cell-mediated immunity is defective * T-cell dependent humoral immunity is impaired * No Th2 CD4+ T-cells * No germinal center formation * No class switching or somatic hypermutation | (T-cell positive selection does not occur)

Answer 485

The balance between Th2 cells and TRegs is important * Need Th2 cells to defend against pathogens * Need TRegs to limit inflammatory/immune responses to food antigens, commensals, non-pathogenic particles

Answer 486

Macrophages Pro-inflammatory effects including increased cyclooxygenase

Answer 487

**T-Cell independent immune response** 1. Highly specific, humoral (antibody-mediated) arm of adaptive immunity 2. Mediated by B-cells 3. Produces IgM in response to multivalent non-proteins (ex: polysaccharide capsule)

Answer 488

Acts on C5 to make C5a and C5b

Answer 489

* Slow (on first exposure) * Diverse * Adapts to antigen (not pre-formed) * Highly specific * Generates memory and improved immunity w/ repeated antigen exposure

Answer 490

* Primary exposure * IgE production and sensitization to the antigen * Type 1 hypersensitivity cannot occur without this prior sensitization! * Secondary/subsequent exposure * Pre-existing IgE binds immediately to the antigen. Antibodies cross-link * Bast cells and basophils bind IgE at the Fc region * Immediate release of pre-formed... * Histamine * Kininogenase * Kinins * Serotonin * TNF * Proteases * This causes rapid, severe inflammatory effects * Vasodilation * Hypotension * Smooth muscle contraction

Answer 491

A T cell receptor excision circle * Forms when a T-cell rearranges the variable region of its receptor * Too few TRECs in newborns = worry for SCID

Answer 492

1. Skin and mucous membranes 2. Ciliated cells in the respiratory tract 3. Enzymes in saliva, other secretions 4. Low pH of skin and mucous 5. Defensins in GI tract and respiratory tract 6. Normal fluid flow 7. Normal flora

Answer 493

* Anti-inflammatory cytokine * Turns off immune response

Answer 494

Primary response * APCs create memory T-cells * Prime T-cells to respond to the antigen * Drive a Th1 CD4+ helper T-cell response Secondary response * Memory T-cells proliferate rapidly and activate a macrophage response and cytokine release * This may lead to granuloma formation

Answer 495

* Combinatorial diversity * Due to somatic recombination of VJ (light) and VDJ (heavy) regions * Junctional diversity * Addtional removal or addition of nucleotides at area of joining ends (hypervariable region)

Answer 496

IgG and IgE

Answer 497

(Basically the same function as IL-1) * Pro-inflammatory cytokine * Endogenous pyrogen (Causes fever) * Induces acute phase response

Answer 498

Splenic marginal zone (not lymph nodes) Patients without a functional spleen (ex: sickle cell) do not mount successful T-cell independent B-cell responses

Answer 499

Hypervariable regions

Answer 500

Passive immunity * **IgG** crosses the placenta to confer passive immunity * Neonates are protected for about the first 6 months of life * **IgA** is passed from mom to infant in breast milk; also passive immunity * Breastfeeding infants are protected

Answer 501

Type II Type III

Answer 502

A scar composed of connective tissue with scant inflammatory cells The epidermis is fairly normal and dermal appendeges are absent Maximum strength slowly increases but never reaches the same level as before the wound

Answer 503

* Occurs in the cortex of the thymus * Thymocytes begin positive selection as double-postive (CD4+, CD8+) * Cortical epithelial cells express self-MHC class I and self-MHC class II * If a double positive thymocyte interacts with MHC I, it will become a CD8+ T-cell * If a double positive thymocyte interacts with MHC II, it will become a CD4+ T-cell ## Footnote **The result is a single-positive T-cell that migrates to the medulla of the thymus**

Answer 504

Innate barrier defects * Filaggrin = a protien important in the keratinocyte structural barrier is compromised * Abnormal environmental or food antigen response * Increased antigen exposure

Answer 505

Successful rearrangement of the Ig Mu heavy chain

Answer 506

B-Cells; B-cell receptors can recognize and respond to almost anything, including proteins, carbohydrates, drugs, etc. (T-cells can only recognize peptides in the context of MHC)

Answer 507

Shingles is the reactivation of a latent varicella zoster virus infection. Latent infections are kept in their latent state by cell-mediated immunity Latent infections are more likely to be reactivated in elderly patients because their cell-mediated immunity is waning

Answer 508

Immunosuppression T-cells are impaired and cannot respond to the PPD antigens; no induration is formed, leading to a false-negative test result

Answer 509

Variable regions of both heavy and light chains are identical between the IgM and IgD antibody B cells only express one heavy chain variable region and one light chain variable region, even when the constant regions differ

Answer 510

No; not all B-cells will undergo somatic hypermutation and class switching * If the B-cell is in the germinal center... * It will undergo class switching, somatic hypermutation, and proliferation * The result is plasma cells and memory B-cells that make antibodies with increased affinity for the antigen * If the B-cell is **not** in the germinal center * It will **not** undergo class switching or somatic hypermutation * It will become a short lived plasma cell * It will make antibodies that have the same specificity/affinity as the original B-cell * No increased affinity

Answer 511

A subtype of chronic inflammation characterized by granuloma formation A granuloma is a collection of macrophages, sometimes with giant cells (large macrophages with multiple nuclei) and surrounding lymphocytes

Answer 512

* Susceptibility to infections * Bacteria (especially intracellular) * Viruses * Fungi * Opportunistic pathgens * Increased risk of neoplasia * Especially from virus-driven tumors (HPV) * Reactivation of latent viral or bacterial infections

Answer 513

Without a functional thymus, T-cells cannot develop * There will be a lack of CD4+ Th2 helper T-cells, resulting in lack of support for B-cell differentiation * No class switching, no affinity maturation * B-cells do not become more specific, cannot generate memory * Recurrent infections

Answer 514

Transfer of pre-formed antibody from one person or animal to another Rapid Short-lived

Answer 515

Epithelial cell junctions Cilia movement Mucous protection

Answer 516

IL-4 and IL-5 are secreted by Th2 CD4+ helper T-cells in the germinal center; they support isotype switching IL-4 -\> IgG and IgE IL-5 -\> IgA

Answer 517

Bone marrow and tissue

Answer 518

CD8+ Cytotoxic T-cells NK cells Neutrophils IgG/IgM (Naturally occuring or produced by B-cells)

Answer 519

ADCC = antibody-dependent cellular cytotoxicity * IgE binds to the helminth * An eosinophil recognizes the Fc region of IgE * The Fc(e)RI receptor on the eosinophil binds the Fc region of IgE * Pretend (e) is the little epsilon symbol * The eosinophil releases mediators to destroy the helminth * This is enhanced by IL-5 released by Th2 CD4+ helper T-cells

Answer 520

IL-2 promotes T-cell growth and differentiation Can have autocrine function (if IL-2R is expressed on the cell that secretes IL-2)

Answer 521

ICAM and VCAM are induced by **TNF-alpha and IL-1** ICAM and VCAM are c**ellular adhesion molecules** expressed on the **inner endothelium of blood vessels** ICAM and VCAM bind to integrins on neutrophils in the **adhesion** step of phagocytic cell recruitment and migration; without ICAM and VCAM, neutrophils would not reach the site of inflammation

Answer 522

* Gets progressively worse over time * Constant (not episodic) * Treatment of H. pylori can cause regression * Most common in patienst \>30 years old

Answer 523

* Staphylococcal enterotoxins * Staphylococcal Toxic Shock Syndrome Toxin (TSST) * Streptococcal SPEA, SPEC * Scarlet fever * Streptococcal toxic shock syndrome

Answer 524

Failure to form phagolysosomes due to genetic defect Leads to neutropenia, giant granules in the neutrophils and monocytes, albinism, and increased risk of pyogenic infections due to impaired killing of intracellular pathogens

Answer 525

* An **antibody** is secreted by B-cells * A **B-cell receptor** remains attached to the B-cell membrane Antibodies and B-cells have similar structures and can bind similar molecules

Answer 526

If multiple haptens are bound to a carrier protein, the hapten/protein complex can elicit a T-cell response * B-cell binds to haptens attached to carrier proteins * BCR endocytosis; the receptor bound to the haptens + protein is internalized * The protein is degraded to peptides * The B-cell presents the peptides on MHC Class II to CD4+ helper T-cells * The T-cell is activated and makes antibodies

Answer 527

C1q binds to the constant fragment of IgG or IgM (antigen-antibody complex)

Answer 528

* Occurs in the medulla of the thymus * Thymocytes begin as single-positive (CD4+ **OR** CD8+, all are CD3+) * Medullary thymic epithelial cells express autoimmune regulator (AIRE), a transcription factor * AIRE expression -\> Synthesis of an array of **self-peptides** that are expressed by medullary thymic epithelial cells in the context of **MHC I and II** * T-cells with TCRs with a **high affinity for self peptides** in the context of MHC will undergo **apoptosis** or become **regulatory T-cells** * T-cells with TCRs with a **weak or absent** **affinity for self-peptides** wil lsurvive and become mature T-cells in the periphery

Answer 529

Extracellular antigens are typically presented on MHC II by professional antigen-presenting cells * Pathogens and foreign molecules are engulfed by phagocytosis or endocytosis * Phagosomes or endomes fuse with lysosome * Proteases in the lysosome degrade the polypeptides into peptide fragments * In **specialized endosomal intracellular vesicles**, peptide fragments bind MHC II * Before binding, MHC II is bound to an **invariant chain** that prevents MHC II from binding to peptides in the ER (where it is synthesized * The MHC II/peptide complex is transported to the cell surface for presentation

Answer 530

Binding of **IgG antibody** or **C3b complement** to the bacteria improves recognition and attachment of the bacteria for engulfment by neutrophils (opsonization)

Answer 531

Turns off the immune system (anti-inflammatory)

Answer 532

Genetic diseaes such as Cystic Fibrosis and Duchenne Muscular Dystrophy

Answer 533

Acquired disesases Cancer, HIV

Answer 534

Genes are introduced directly into living tissues

Answer 535

Cells are removed from patients Genes are introduced into these cells while they are replicating *in vitro* The cells that successfully integrated the new gene are selected and then re-introduced to the patient **Note: only works in cells that divide**

Answer 536

* In vivo* therapy can be delivered into differentiated **dividing and _non-dividing_ cells** * Ex vivo* therapy can only be delivered to dividing cells

Answer 537

In *ex vivo* therapy, the new gene integrates into the host genome, making it **more stable** Also, the gene will **persist for life** (*in vivo* = unsatable because the DNA is episomal (not integrated), treatment is temporary and may need to be repeated)

Answer 538

Cell tropism = specific viruses preferentially target specific species and/or cell types within those species This is important because it **defines the ability of a viral vector to transduce (enter into) a particular cell type**

Answer 539

Altering the cell tropism of a virus/viral vector to target a specific cell type The result: you can choose which cells the viral vector will target

Answer 540

Retrovirus and Lentivirus * Both * Long-term, stable integration * Retrovirus * Can only be integrated into **dividing cells** * Lentivirus * Can be integrated into **dividing and nondividing cells**

Answer 541

All are episomal; not integrated into host genome * Herpes virus * Long-term * Adenovirus * Temporary * Adeno-associated virus * Stable * Long term Also: DNA, but not widely used because it's temporary and inefficient

Answer 542

Advantages * Large cloning capacity * Integrates into the genome of the target cell * Does not transfer virus protein coding sequences Disadvantages * Only integrates into actively dividing cells * Integration could lead to **gene inactivation** of tumor suppressor genes * Depending on the site of integration * Low titer

Answer 543

Lentiviruses are basically retrovirus vectors that can be integrated into both **dividing and non-dividing cells** by making use of the _control elements_ of HIV

Answer 544

Advantages * E1 is deleted (the gene required for viral replication) * High transduction efficiency = can get DNA into many cells * **Dividing and non-dividing cells** * Wide cell tropism (many cell and tissue types) * Large cloning capacity * Can be grown to high titer Disadvantages * Immunogenic * Transient transgene expresion (not long lasting)

Answer 545

Adenovirus vectors have a **can contain larger genes** Adeno-associated viral vectors **are less immunogenic** Both have wide cell tropism

Answer 546

Cystic fibrosis (inherited) ALS aka Lou Gehrig's Disease (acquired) Parkinson's disease (acquired)

Answer 547

Bystander effect = only a few cells need to have induced gene expression to eradicate the whole tumor Due to transfer of effector enzyme to adjacent cells through GAP junctions Example: Induced expression of Type I Thymidine kinase (TK) that render cells sensitive to non-toxic prodrugs. Phosphorylated GCV, made from the prodrug, is transferred to adjacent cells, integrates into DNA, causes apoptosis

Answer 548

Ethical and safety problems altering germline cells * Changes are heritable * Unknown long-term effects

Answer 549

1. Ability to get the transgene into the appropriate cell 2. Abiltiy to express the transgene in that cell

Answer 550

1. Need to know the gene responsible for disease 2. Need a wild type allele of the gene to express 3. Need a convenient mentod to target the functional WT gene to appropriate sites

Answer 551

A transplant between genetically identical individuals (Between identical twins)

Answer 552

Both Expression of MHC proteins is **codominant**

Answer 553

MHC I: Encoded by HLA-A, HLA-B, HLA-C MHC II: Encoded by HLA-D (DR, DP, DQ)

Answer 554

Close matching minimizes the immune response of the host to the graft HLA proteins that are closely matched can be recognized as "self" by T cells, even if they come from another individual

Answer 555

A 10/10 HLA match means that all of the major HLA antigens are matched There are still many minor antigens that could still trigger an immune response from the host Pharmacologic immunosuppression is still necessary for a transplant between any individuals that are not genetically identical

Answer 556

Organ rejection = the **host attacks the graft** Graft vs. host diseae = the **graft attacks the host** (GVHD is most commonly seen when large numbers of lymphocytes are transplanted into a new host, i.e. hematopoietic stem cell or liver)

Answer 557

* Time scale: minutes * Mediated by: Pre-formed antibodies * Ex: anti-ABO antibodies * Symptoms: * Activation of complement damages endothelium and vessels: a **Type II hypersensitivity reaction** * "White graft"

Answer 558

* Time scale: Weeks (7-10 days after transplant) * Mediated by: **CD8+ Cytotoxic T cells** * The donor MHC is recognized as "non-self" * Cytokine production by CD4+ helper T cells enhances killing of graft cells * This is a **Type IV hypersensitivity reaction** * Symptoms: * Killing of graft cells results in decreased perfusion * Necrosis of graft?

Answer 559

* Time scale: Months to years * Mediated by: **CD4+ T cell response, macrophages** * APCs present donor peptides to CD4+ T cells * T cells secrete cytokines and activate **macrophages** * ****This is a **Type IV hypersensitivity reaction** * Donor specific antibodies can deveop, can contribute to chronic rejection in a **Type II hypersensitivity reaction** * Symptoms: * Vascular injury to donor graft * Thickening/hardening of vessels * FIbrosis * Due to **chronic immune response, cytokines**

Answer 560

Direct * The **MHC I or MHC II from the donor** is recognized by the **recipient TCR** * ****This does not fit with our paradigm of MHC restriction, because the donor's MHC I and MHC II **are not presented on self-MHC** Indirect * Phagocytosis of donor cells by host APCs * Presentation of **donor MHC** peptides on **self-MHC I and self-MHC II** * Fits better with MHC restriction paradigm

Answer 561

Mixed lymphocyte reaction * Donor lymphocytes are treated so they cannot divide * Treated donor lymphocytes are mixed with recipient lymphocytes * Recipient lymphocytes that recognize T cells as foreign will proliferate * **More proliferation = more reactive to donor = less likely to have a successful transplant**

Answer 562

Killing leukemia or lymphoma in bone marrow transplants The recipeints cells **need** to be killed; this is accomplished through the action of donor lymphocytes

Answer 563

* Mediated by: **Immunocompetent donor T cells** * Mechanism: * Donor T cells expand in the immunosuppressed recipient * Recognize recipient cells as "non-self" and destory them * Usually recognize MHC antigens * **Type IV hypersensitivity reaction** * Symptoms * Severe multi-organ dysfunction (not limited to graft) * Rash, diarrhea, and jaundice * Can range from mild to life-threatening.

Answer 564

Hematopoietic stem cell (bone marrow) Liver High number of donor lymphocytes are transplanted; likely to recognize new host as foreign

Answer 565

Corticosteroids suppress the response of the **innate and adaptive immune systems** * Increase transcription of IL-10 * General suppression of inflammation * Can induce apoptosis of immune cells

Answer 566

Low-level immunosuppression is recommended initially, but can most likely be safely stopped after a little while Genetically identical individuals may have some differences in antigen presentation due to small differences in the development of their immune systems

Answer 567

Graft vs. Host Disese

Answer 568

**Positive selection:** Thymic cortical epithelial cells express MHC without any costimulatory activity - Thymocytes must recognize self MHC to continue **Negative selction:** Bone-marrow derived APCs in the thymic medulla present self antigen (generated by AIRE expression) on MHC - Tight binding -\> apoptosis or TReg - Weak binding -\> T cell maturation

Answer 569

Nowhere (B cells do not undergo positive selection)

Answer 570

Both B cells and T cells Rag1/Rag2

Answer 571

B cells only

Answer 572

Anergy is induced when a T cell sencounters an antien on self-MHC **without costimulatory molecules.** The T cell **will not produce IL-2 in response to this antigen** Anergy can be overcome **if the T cell is exposed to high levels of IL-2** (ex: during a robust inflammatory response). This can cause autoimmunity

Answer 573

1. **Clonal anergy:** Lack of costimulatory molecule on APC 2. **Clonal deletion:** FasL-mediated Activation-Induced Cell Death (AICD) 3. **Regulation/suppression:** TRegs secrete IL-10, TGF-beta

Answer 574

* T cell repeatedly encounters high levels of self-antigen in the periphery * Repeated TCR activation -\> T cell expresses FasL * FasL binds the Fas receptor expressed on B cells and T cells * FasL:Fas induces caspase cascade * Apoptosis

Answer 575

Autoimmune lymphoproliferative syndrome (ALPS) Symptoms are similar to systemic lupus T cells that react to self-antigen are not deleted

Answer 576

TRegs (especially CD4+CD25+Foxp3+) are important Direct cell-cell contact, as well as expression of IL-10, TGF-beta

Answer 577

Th1 CD4+ helper T cells secrete IFN-gamma, which inhibits the Th2 response Inhibition of Th2 response = inhibition of allergic response

Answer 578

Th2 cells secrete IL-4, which inihibts Th1 effector functions Inhibition of Th1 = inhibition of excessive inflammation

Answer 579

* Eliminate the antigen * Programmed cell death or apoptosis of responding lymphocytes * CTLA-4 and PD-1 expression * 48-96 hours after initial T cell activation * Inhibit co-stiumlation by preventing CD28 from binding to B7 (CD80/86) * Inhibit TCR signal transduction * **Note: small subset of T cells remain; they become memory T cells**

Answer 580

All autoimmune diseases reslt from a breakdown of tolerance

Answer 581

1. Inappropriate expression of costimulatory molecules 2. Infection 3. Molecular mimicry 4. Mutation or defective function of regulatory molecules

Answer 582

Damage to tissues can release self-antigen that was sequestered away (hidden from immune system) These antigens activate local APCs to phagocytose them This upregulates the expression of co-stimulatory molecules **The antigens are presented to T-cells in the presence of costimulation -\> Autoimmune disease** Note: These T-cells that react to the self antigen slipped through central tolerance mechanisms

Answer 583

Epitope spreading: When an immune response against a microbe leads to an immune response against an unrelated self-antigen Often occurs when infection -\> tissue destruction -\> exposes a typically-sequestered self-antigen to the immune system Phagocytosis and presentation by APC -\> immune response to self-antigen

Answer 584

* Tissue injury or damage due to inflammatory response -\> epitope spreading * Induction of APC maturation * Increased expression of costimulatory molecules * Infections can alter self antigen to a **neoantigen** Note: Many of these responses occure when self-reactive T-cells have slipped through central tolerance. This typically isn't a problem when antiens are sequestered away or co-stimulation is low

Answer 585

Rheumatic fever M protein of strep. pyogenes resemles cardiac myocytes -\> immune response to M protein destroys cardiac myocytes

Answer 586

Mutations in... * Fas/FasL * Downstream caspase machinery that induces apoptosis * AIRE * Problems creating central tolerance

Answer 587

Specifically target only the autoreactive T cells or B cells: ## Footnote **Induced antigen-specific tolerance**

Answer 588

Autoimmune disease Increased co-simulation = reaction to self tissues (Normally CTLA-4 and PD-1 inhibit co-stimulation) Note: Loss of CTLA-4 means that TRegs are not working (TRegs express CTLA-4, but all cells may express PD-1?)

Answer 589

* CD8+ cytoxoic T cells * Recognize foreign antigen on tumor cell's MHC I * NK Cells * If tumor cell downregulates MHC I to avoid the T cell, the NK cell **recognizes the lack of MHC I**

Answer 590

1. Direct killing of cells that lack MHC I 2. Binding to Fc portion of antibodies on the tumor cell -\> **Antibody-Dependent Cellular Cytotoxicity (ADCC)**

Answer 591

1. Downregulate expression of tumor antigen 2. Decrease expression of MHC molecules to present antigen *(but NK cells may swoop in)* 3. Suppress T cell response through **production of anti-inflammatory cytokines** 4. Suppress T cell response through **expression of cell surface molecules that interact with inhibitory proteins on T cells** * Example: Increase PDL1 expression on tumor cells -\> interact with PD on T cells -\> dampen response

Answer 592

If PDL1 on the tumor cell binds to PD1 on T-cells, it **dampens the immune response of the T cell**

Answer 593

Antibodies against PD1 or PDL1 would **prevent the PD1:PDL1 interaction** (PD1 on tumor cell, PDL1 on T cell), thus **preventing the down-regulation of T cell activation** **The result: Increased T cell activation -\> increased killing of cancer cells** (Normally, the PD1:PDL1 downregulates T cell activity)

Answer 594

Monoclonal antibodies can be targeted against tumor antigens The antibodies bind to the tumor antigens and lead to killing of tumor cells

Answer 595

anti-CD20 (rituximab) Binds CD20 on B cells (normal and malignant), leading to the killing of these cells Used to treat B cell cancers (ex: non-Hodgkin lymphoma)

Answer 596

IgE-mediated = mast cell activation Location: **Local** Reaction: **Wheal and flare (hives)** (Wheal = swelling, flare = redness)

Answer 597

Location: Mast cell activation **beneath the nasal mucous membrane** Reaction: Sneezing, runny nose (allergic rhinitis, hay fever) Loaction: Mast cell activation **in lower airway** Reaction: Bronchial constriction (allergic asthma)

Answer 598

IgE-mediated = mast cell activation Location: Mast cell activation in **GI tract** Reaction: Smooth muscle contraction -\> Vomiting, diarrhea Location: Mast cell activation in **skin** Reaction: Disseminated swelling under the skin

Answer 599

IgE-mediated = mast cell activation Location: All blood vessels Reaction: Systemic anaphylaxis (ex: bee sting)

Answer 600

Asthma * Epinephrine * Sodium cromolyn Allergies * Corticosteroids * Anti-histamine * Leukotriene receptor antagonist Anaphylaxis * Epinephrine

Answer 601

Decrease levels of IgE specific for a given antigen (IgG often rises as a result) (Suppress Th2 resposne, promote Th1, TReg)

Answer 602

IL-4 and IL-13 promote class switching to IgE Antibodies against these ILs decreases IgE response

Answer 603

Type **II** hypersensitivity = **2** words for _Ig**G** and Ig**M**_ against cell surface or ECM antigens **GArG-MAtH** * **G**oodpasture's syndrome * Antibodies specific to Type IV collagen attack basement membrane of kidney glomeruli * **A**cute **r**heumatic fever * Antibody against M protein of strep pyogenes attacs cardiac myocytes * **G**raves disease * Thyroid disease: autoantibodies bind to the TSH receptor, mimicking natural ligand -\> excess thyroid hormone production * **M**yasthenia gravis * Autoantibodies destory ACh receptors * **A**utoimmune **t**hrombocytopenic purpura * Antibodies against platelet surface antigens * **H**emolytic disease of the fetus * Maternal IgG specific for fetal blood group antigens cross placenta and destory fetal RBC * Treat wtih Rhogam during delivery

Answer 604

**Soluble IgG/IgM** immune complexes **PSAS** * **P**ost-streptococcal glomerulonephritis * Only kidney =\> antigen binds here, then antibody follows * **S**erum sickness * **A**rthus reaction * **S**ystemic lupus erythematosus (SLE)

Answer 605

**T cells** **Th1 CD4+ helper T cells** -\> Delyaed type hypersensitivity **CD8+ cytotoxic T cells** -\> Classic cytotoxic reaction against cells expressing self or foreign antigen **Examples = CTC** * Contact dermatitis * Poison ivy product modifies host self-antigen * New epitope is not recognized, presented to CD8+ cytotoxic T cells * Tuberculin test * Th1 CD4+ T cells are activated, produce cytokines, chemokines, cytotoxins * Celiac disease * Th1 CD4+ T cells respond to peptides from gluten, presented on MHC II

Answer 606

Type III = soluble immune complexes Attack kindey, glomerulus, synovium of joints, blood vessels **Why?** Immune complexes float around in the blood and are trapped or formed in the above tissues

Answer 607

Type II reactions are mediated by IgG and IgG that are membrane bound (in cells or basement membrane), resulting in a localized response

Answer 608

Atopic (hyperallergic) individuals may have genetic changes in IL-4 and/or MHC II genes They may also have had different exposures early in life, or have an altered gut microbiome

Answer 609

Acute Antigen/antibody complexes are produced as a result of IV bolus of a soluble antigen Resolves after complexes are cleared

Immunology Flashcards

Intro, innate, B-cell differentiation, humoral