1. Diseases of the Immune System (Ch 6)

Question 1

What is protection from infectious pathogens and the normal immune reponse?

Answer 1

immunity

Question 2

Innate immunity are mechanisms that are ready to react to infections before they occur. Adaptive immunity are mechanisms that are stimulated by microbes. What term referes to adaptive immunity?

Answer 2

immune response

Question 3

Innate immunity is always present and ready to provide defense against microbes/ to eliminate damage cells. What are the major components of innate immunity? 5

Answer 3

epithelial barriers
neutrophils
dendritic cells
Natural killer cells
Complement

Question 4

What cells are specialized cell population in the epithelia that capture protein antigens and displat peptides for recognition by T cells? Also initiate innate immune responses

Answer 4

Dendritic Cells

Question 5

Natural killer cells are early protection against viruses and intracellular bacteria. What protein in the plasma plays an important role?

Answer 5

Complement system

mannose binding lectin and C reactive protein coat microbes to make them tasty- opsins

Question 6

Innate immunity can recognize PAMPs and DAMPs which collectively are recognized by patterna reconition receptors PRRs. Where are PRRs located mainly?

Answer 6

cellular compartments where microbes may be present: plasma membran receptors detect extracellular microbes, endosomal receptors detect ingested microbes and cytosolic receptors detect mircobes in the cytoplasm

Question 7

What are the three major classes of innate immune receptors?

Answer 7

TLRs
NOD like receptors
C-type lectin receptors

Question 8

TLRs recognize microbial products which activate 2 transcription factors in a common pathway once bound, known as?

Answer 8

NF-kB which stimulates synthesis and secretion of cytokines and adhesion molecules **for recruitment of leukocytes
Interferon regulatory factors (IRFs) which stimulate production of antiviral cytokines (type 1 IFN)

Question 9

NOD-like receptors NLRs, are cytosolic receptors which recognize necrotic cell product like uric acid and ATP. NLRs signal the inflammosome which does what?

Answer 9

activates caspase1 which cleaves precursor form of IL1 into its biologicall active form.
(GOF mutation can cause auntoinflammatory syndrome)

Question 10

What are some examples of endogenous product that bind NLRs and cause inflammation? 3

Answer 10

Gout, lipids, cholesterol crystals

Question 11

What is the following pathway?

1. NLR creates inflammosome which activates caspase 1
2. Inflammasome = NLRP3 sensory protein, adaptor protein — activated caspase 1
3. Caspase 1 cleaves proIL1B into IL1B

Answer 11

Inflammasome pathway

Question 12

What type of receptors are expressed on the plasma embrane of Mø and dendritic cells and detect fungal glycans and elicit inflammatory reactions to fungi?

Answer 12

C-type Lectin receptors CLRs

Question 13

What are the two main reactions that the innate immune system provides host defense?

Answer 13

Inflammation
Antiviral defense via IFN1 (antiviral state)
*also stimulates adaptive response

Question 14

The adaptive immune system consists of lymphocytes and their products including antibodies. What is the difference between humoral immunity and cell mediated immunity?

Answer 14

Humoral: protects against extracellular microbes and their toxins (B cells and Ab mediated)
Cell mediated/ cellular: responsible for defense against intracellular microbes (T cell mediated)

Question 15

Match the lymphocyte with its corresponding function….
B, T helper, Cytotoxic T, T Reg, NK
-Neutralization of microbe, phagocytosis and complement activation
-killing of infected cell
-activation of macrophages, inflammation, activation of T and B cells
- Killing of infected cell
-suppression of immune response

Answer 15

B Cell/Abs-Neutralization of microbe, phagocytosis and complement activation
CTL -killing of infected cell
T helper-activation of macrophages, inflammation, activation of T and B cells
Natural Killer- Killing of infected cell
T regulatory cell-suppression of immune response

Question 16

Lymphocytes specific for a large number of antigens exist before exposure to antigen and when an antigens enteres, it selectively activates the antigen specific cell. This is known as?

Answer 16

clonal selection

Question 17

What is generated by somatic recombination of the genes that encode the receptor proteins?

Answer 17

antigen receptor diversity

Question 18

Gene segments recombine randomly as mediated by RAG1 and RAG2, there are no mature lymphocytets if RAG is mutated. What receptor will be generated for T/B cells?

Answer 18

T cell is the TCR
B cell is the BCR
*Occurs in thymus

Question 19

Because each T or B cell and its clonal progeny have a unique DNA rearrangement (and hence a unique antigen receptor), it is possible to distinguish polyclonal (non-neoplastic) lymphocyte proliferations from monoclonal (neoplastic) lymphoid tumors. Thus, analysis of antigen receptor gene rearrangements is?

Answer 19

a valuable assay for detecting tumors derived from lymphocytes (lymphoma) PCR!

Question 20

What stimulates B lymphocytes to make antibodies and activate other leukocytes to destroy microbes?

Answer 20

Helper T cells

Question 21

T cells mature in the thymus and are found in the blood constituting 60-70% of blood lymphocytes. The TCR of T cells consist of a disulfide linked heterodimer made up of an alpha and beta polypeptide chaine which variable regions. What does the AB TCR recognize?

Answer 21

antigens presented by major histocompatilbility MHC molescules on professional APCs

Question 22

By limiting specificity of T cells for peptides displayed by cell surgace MHC molecules,- MHC restriction ensures what?

Answer 22

T cells see only cell-associated antigens

Question 23

Each TCR has CD3 and Zeta chain that are invariable, involved in signal transduction. A small population of mature T cells express gama sigma polypeptide chains, which recognize?

Answer 23

peptides, lipids, and small molecules without assistance from MHC proteins @ epithelial surfaces

Question 24

What type of T cell does the following? Cytokine-secreting helper cells that assist macrophages and B lymphocytes.Bind to class II MHC molecules (coreceptor) .

Answer 24

CD4+

Question 25

What type of T cell does the following? T cells - cytotoxic (killer) T lymphocytes (CTLs) that destroy host cells harboring microbes. Bind to class I MHC molecules (coreceptor).

Answer 25

CD8+

Question 26

What is the T cell coactivator location on the T cell which interacts with CD80/86 (B7.1/7.2) to provide furth signals for T cell activation?

Answer 26

CD28

Question 27

B cells are 10-20% circulating lymphocytes found in LN, spleen and MALT. They recognize natigens via B cell receptor antigen complex which are IgM or IgD. Once activated B cells turn into plasma cells. What are the co-receptors?

Answer 27

IgA and IgB which are essential for signal transduction through the antigen receptor

Question 28

T cells activate B cells which is relevant with regard to Hyper IgM syndrome. B cells also have a type 2 complement receptor known as CR2 or CD21 which is useful for?

Answer 28

recognizing complement proteins and CR2 is used by EBV to infect B cells - signaling

Question 29

What cells are the most important antigen presenting cells for initiating T cell response against protein antigens?

Answer 29

Dendritic Cells (interdigiting dendritic cells)

Question 30

DCs are commonly seen in the epithelia, immature DCs wihtin the epidermis are called langerhans cells. Why is this location great for immune defense?

Answer 30

this is the most common area where microbes and foreign antigens enter

Question 31

What type of cell is present in germinal centers of lymphoid follicles in the spleen and LNs, which bear Fc receptors for IgG and C3b receptors to trap antigen bound to Abs or complement proteins?

Answer 31

Follicular dendritic cells (presents Ags to B cell to improve quality of Abs)

Question 32

What are mononuclear phagocytes which process antigens from microbes and proteins to present to T cells, which can inhance the cells response. They phagocytose cells that are opsonized by IGg or C3b?

Answer 32

Macrophages

Question 33

What cells function to destroy irreversibly stressed and abnormal cells such as virus infected and tumor cells? They contain azurophilic granules and can kill without prior exposure to microbes. have CD16 = Fc receptor for IgG and lyse IgG coated target cells called antibody-dependent cell-mediated cytotoxicity

Answer 33

Natural Killer cells CD16!!

Question 34

NK cell function is regulated by a balance between signals from activating and inhibitory. What activating receptors are best characterized and recognize surgace molecules that are induced by various kinds of stress?

Answer 34

NKG2D | NK inhibitory cells recognized MHC1 molecules on all healthy cells

Question 35

What occurs when the healthy inhibitor receptors on a healthy cell is no longer presented to the NK cells?

Answer 35

The NK cell will no longer receive inhibitory signals and will signal to kill due to inhibition of MHC 1, killing infected cell

Question 36

IL2 and IL15 stimulate proliferation of NK cells which release IL12 which produces Th1 which does what?

Answer 36

Releases IFNY to macrophages for activation | IL12 more for killing and secretion of IFNY

Question 37

What cells lack TCRs but produce cytokines similar to T cells, producing IFNY, IL5, IL17, IL22, and functions in early defense against infections, recognize and eliminate stressed cells, and provide cytokines that influence the differentiation of T cells?

Answer 37

Innate Lymphoid Cells ILCs

Question 38

Immune system tissues consist of generative or primary/central lymphoid organs and peripheral or secondary lymphoid organs. What are examples of each and what the produce?

Answer 38

Generative Thymus : Tcells develop/mature Bone Marrow: Blood cells and B cells Peripheral LNs: lymphocytes interact with APCs/Ags in circulating lymph Spleen: lymphocytes can interact w blood borne antigens MALT: (tonsils/adenoids/peyerspatches)- lymphocytes and plasma cells to be in vicinity of antigens within the mouth and intestinal tract

Question 39

What are organized to concentrate antigens, antigen presenting cells and lymphocytes and the development of adaptive immune reponses?

Answer 39

Peripheral lymphoid organs

Question 40

Within the peripheral lymphoid organs, T and B cells are segregated into separate areas. Where are they located?

Answer 40

B cells in follicles around the periphery and/or within the cortex T cells located in the paracortex region, in the middle of the B cell follicles

Question 41

Lymphocyte recirculation is important for T cells because naive T cells remaiin in the peripheral lymphoid organs while effector T cells travel to the site of damage. What about B cells?

Answer 41

Plasma cells remain in lymphoid organs and noe marrow and do not need to migrate to sites of infection because they secrete antibodies that are carried to distant tissues

Question 42

What is the primary site of hematopoesis, and origin of stem lymphocytes and B cell maturation?

Answer 42

Bone marrow (generative organ)

Question 43

Immature T cells arrive from bone marrow and as they mature they migrate from the peripheral cortex to the central medulla of what? The medulla contains mature T cells, dentritic APCs w high levels of MHC I and II and Hassall corpuscles which are?

Answer 43

Thymus- T cell maturation Hassall corpuscles are squamous cell nests

Question 44

What region does the following occur? APCs interact with lymphocytes, T and B cell clonal expansion, B cell differentiation into plasma cells, and migration oF T cells and plasma cells out of them into circulation... (T cells in paracortex and B cells in germinal centers in cortex)

Answer 44

Lymph Nodes

Question 45

The main role of MHC (major histocompatibility complex) is to display peptide fragments of protein antigens for recognition by antigen specific T cells. What are the two types of MHCS?

Answer 45

MHC I MHC II Note MHC=HLA in human

Question 46

What is the following characteristic of? All nucleated cells Typically recognize intracellular Ags (virus/tumor) Ags are processed into peptides by proteasomes Peptides transport to ER, load into groove of MHC and entire complex migrates to surface Presentation of entire complex to CD8+ T cell

Answer 46

MHC Class I

Question 47

What is the following characteristic of? Antigen presenting cells (mø, B cells, DCs) Typically recognize extracellular Ags (microbes/allergens) Antigens are processed into peptides by endolysosomal enzymes Vesicles form with processed peptides and MHC complex Presentation of entire complex to CD4+ Helper T cells

Answer 47

MHC Class II

Question 48

What are the differences between the MHC I and MHC II subregions?

Answer 48

MHCI: HLA-A/B/C MHCII: HLA-DP/DQ/DR

Question 49

The combination of HLA alleles in each individual is called the HLA haplotype. You receive one HLA from mom and one from dad resulting in?

Answer 49

Polymorphism that means that no two individuals besides identical twins express the same MHC molecules.

Question 50

Since every has different HLA haplotypes, that means there is extensive heterogeneity leading to differences in fighting off illness and in allergic sensitivities. What is the clinical importance?

Answer 50

transplated organs -HLAs need to match | associated autoimmune diseases

Question 51

What chromosome encodes the HLA molecular structure for a given individual?

Answer 51

Chr 6

Question 52

What is the difference between MHC and HLA?

Answer 52

HLA are the MHC molecules present in humans

Question 53

Cytokines are messenger molecules of the immune system and mediate many cellular interactions and functions of leukocytes. In innate immune responses, what produces cytokines, which ones, and what do they do?

Answer 53

Mø, DCs, NK cells TNF, IL1, IL2, Type 1/2 IFN and chemokines Induce inflammation and inhibit virus replication

Question 54

In adaptive immune responses, what produces the cytokines, which cytokines and what is the main function?

Answer 54

CD4+ T cells IL2, IL4, IL5, IL17, IFNY Promotes lymphocyte proliferation and differentiation & to activate effector cells

Question 55

Cytokines that stimulate hematopoiesis are called colony stimulating factors. What is their function, what cells produce them, and what are some cytokines?

Answer 55

Produced by marrow stromal cells, T cells, Mø Function to increase leukocyte numbers GM-CSF and IL7

Question 56

In the case of immunization with a protein antigen, microbial mimics called ______, are given with the antigen and these stimulate the innate immune response.

Answer 56

Adjuvants

Question 57

What are the three main steps of adaptive immune reponse?

Answer 57

Antigen recognition/display Cell-mediated immune reponse Humoral immune response

Question 58

In cell mediate immunity, APCs bring back intracellular pathogens while expressing MHC-associated peptide antigens, leading to?

Answer 58

Recognition by T cells--- proliferation, differentiation, migration and killing

Question 59

When an antigen is presented to a lymphoid organ, CD4+ helper T cells secrete IL2 and express high affinity IL2 receptors. IL2 is a growth factor that acts on these T lymphocytes and stimulates their proliferation, leading to?

Answer 59

an increase in the number of antigen specific lymphocytes.

Question 60

CD4+ T helper cells have CD40Ligand, CD40L which is expressed when B cells or macrophages present recognizable antigens. Leading to?

Answer 60

CD40L binding CD40 on the B cell or Mø, activating the cells

Question 61

Some CD4+ cells differentiate into effector cells that secretes different cytokines. What are the 3 major types of T cells?

Answer 61

Th1 IFN Y Th2 IL4 IL5 IL13 Th17 - IL17

Question 62

Upon activation, B cells proliferate and differentiate into plasma cells that secrete different classes of antibodies. What are the two types of B cell activation?

Answer 62

T dependent*** and independent activation

Question 63

In T cell dependent humoral immunity, B cells ingest protein antigens, digest and display them via MHCII to CD4+ Helper cells. What happens next?

Answer 63

T cell is activated and expressed CD40L (**important for isotype switching and affinity maturation) which stimulate B cell

Question 64

Many polysaccharide and lipid antigens cannot be recognized by T cells but have multiple identical antigenic determinants (epitopes) that are able to engage many antigen receptor molecules on each B cell and initiate process of B cell activation, this process is known as?

Answer 64

T independent humoral immunity (nonprotein antigens)

Question 65

What is require for immunoglobulin isotype switching and affinity maturation, so this does not occur in T independent B cell activation?

Answer 65

NEED T cells --- so T independent is mainly IgM Ab

Question 66

T dependent activation allows B cells to make IgA, IgG, and IgE. Isotype switching is induced by what two things?

Answer 66

IFN-Y and IL4

Question 67

Helper T cells stimulate the production of Abs with high affinites for the antigen, known as _________, improves the quality of the humoral immune response.

Answer 67

affinity matuartion

Question 68

What are the major sites of isotype switching and affinity maturation in which B cells are directed to via follicular helper T cells?

Answer 68

migrate to follicles and form germinal centers

Question 69

Match the antibody with its function and features.... IgA/E/M/G - mucosal epithelia defense, present in high levels in colostrum - transported across the placenta and provides immunity for newborn, longest 1/2 life** - against parasites, shortest half life, highest affinity binding to FC receptor on mast cells and eosinophils - First Ig produced, pentamer = really big

Answer 69

IgA-mucosal epithelia defense, present in high levels in colostrum IgG-transported across the placenta and provides immunity for newborn, longest 1/2 life** IgE-against parasites, shortest half life, highest affinity binding to FC receptor on mast cells and eosinophils IgM-First Ig produced, pentamer = really big

Question 70

Injurious immune reactions called hypersensitivity, are the basis of the pathology associated with immunologic disease. What does it mean to be sensitized to something?

Answer 70

Meaning individuals that have been previously exposed to that antigen react upon second encounter.

Question 71

Hypersensitivity reactions can be elicited by exogenous environmental antigens or endogenous self antigens, they usually result from an imbalance between effector mechanisms of immune responses and the control mechanisms that serve to normally limit such responses. What are two other important general features?

Answer 71

1. The development of hypersensitivity diseases is often associated with inheritance of particular susceptibility genes 2. The mechanisms of tissue injury in hypersensitivity are the same as the effector mechanisms of defense against infectious pathogens

Question 72

Match the type of hypersensitivity with the thing that causes injury... - Th2 cells, IgE antibodies and mast cells - IgG and IgM antibodies bind antigens usually in the circulation and the antigen-ab complexes deposit in tissues and induce inflam - secreted IgG and IgM abs injure cells by promoting their phagocytosis or lysis and injure tissues via inflammation - sensitized T lymphocytes cause injury

Answer 72

Type 1-Th2 cells, IgE antibodies and mast cells Type 3-IgG and IgM antibodies bind antigens usually in the circulation and the antigen-ab complexes deposit in tissues and induce inflam Type 2- secreted IgG and IgM abs injure cells by promoting their phagocytosis or lysis and injure tissues via inflammation Type 4- sensitized T lymphocytes cause injury

Question 73

Type 1 hypersensitivity is a rapid immunologic reaction occurring in a previously sensitized individual that is triggered by the binding of an antigen to IgE ab on the surface of mast cells. What are the two well defined phases?

Answer 73

immediate reaction and late phase reaction

Question 74

The immediate reaction of type 1 HS occurs minutes after exposure and subsides in a few hours, epinephrine is used to treat anaphylaxis. What are the 3 characteristics of the immediate reaction?

Answer 74

vasodilation congestion edema

Question 75

the late phase reaction of type 1 HS occurs 2-24 hours later without additional exposure to the antigen and may last for several days. What are the main characteristics of late phase?

Answer 75

infiltration of tissues with EOSINOPHILS (N,B,Monocytes) and CD4+ T cells with concomitant tissue destructions in the form o mucosal epithelial cell damage

Question 76

Most immediate hypersensitivity (HS) disorders are caused by excessive Th2 responses and these cells play a central role by stimulating?

Answer 76

IgE production and promoting inflammation

Question 77

When an allergen is presented via APC to a CD4+ cell, making a Th2 T cell. The Th2 T cell will release cytokines such as IL4 IL5 and IL13, which do what?

Answer 77

IL4: class switch to IgE = more Th2 IL5: develop/activate eosinophils IL13: enhances IgE production and stimulates mucus secretion

Question 78

Mast cells are tissue cells while basophils are the circulating counterpart. Mast cells are mainly activated by what three things? Also can be triggered by chemokines, drugs, adenosine, etc.

Answer 78

activated by crosslinking of high affinity IgE FceR1 receptors along with C3a and C5a

Question 79

Mast and basophils have FceRI receptor for the Fc portion of IgE antibodies. IgE coated mast cells are said to be?

Answer 79

sensitized, because they contain the antibodie and once the allergen binds again, a reaction (type I HS) will occur (via crosslinking of antigen to IgE = mast cell degranulation)

Question 80

mast cell activation leads to degranulation, releasing primary mediators, what are the 3 preformed mediators and their actions?

Answer 80

Histamine- vasoactive amine causing SM contraction, increased vasc permeability Enzymes- neutral proteases chymase /tryptase lead to tissue damage and kinin production/ complement activation Proteoglycans- package and store amines in granules (heparin)

Question 81

Lipid mediators are also released from mast cells upon activation and degranulation, which are derived from arachidonic acids via phospholipase A2. What are the three main lipid mediators and what do they do?

Answer 81

Leukotrienes- C4/D4 vasoactive and spasmogenic agents known Prostaglandin D2- intense bronchospasm and increase mucus secretion Platele-activating factor PAF- platelet aggregation, histamine release, bronchospasm

Question 82

Mast cells also release cytokines upon degraulation, including TNF/IL1 for leukocyte recruitment, IL4 for Th2 response amplification. In all, what mediatiors are responsible for the manifestation of immediate hypersensitivity reactions?

Answer 82

Preformed mediators Lipid mediators (LKT/PGD2/PAF) Cytokines-TNF, IL1, IL4, Chemokines

Question 83

Cytokines are the main mediators that set the stage for what, by recruiting additional leukocytes?

Answer 83

late phase response.

Question 84

Late phase response is when leukocytes- mainly eosinophils are recruited which amplify and sustain the inflammatory response without doing what?

Answer 84

additional exposure to the triggering antigen | ***eosinophils have major basic protein that cause tissue damage (IL5 recruits)

Question 85

An increase in propensity to develop immediate HS reactions is called atopy. Atpoic individuals have higher serum IgE levels and more IL4 producing Th2 cells than general population. What is found in 50% of atopic individuals?

Answer 85

50% have a positive family history for allergies

Question 86

What is an idea that early childhood and even prenatal exposure to microbial antigens educates the immune system in such a way that subsequent pathologic responses against environmental allergens are prevented?

Answer 86

Hygeine Hypothesis

Question 87

Systemic anaphylaxis occurs within minutes after exposure: itching, hives, and skin erythema appear followed by a striking contraction of respiratoru bronchioles and respiratory distress. What are the 3 things it is characterized by?

Answer 87

vascular shock widespread edema difficulty in breathing

Question 88

What is a food antigen-driven disease of childhood that causes recurrent dysphagia and weight loss because the patient is not able to swallow effectively and because it hurts?

Answer 88

Eosinophilic Esophagitis

Question 89

Antibodies that react with antigens present on cell surfaces or in the extracellular matrix causes disease by destroying these cells, triggereing inflammation or interfering with normal functions in what HS reaction?

Answer 89

Antibody mediated type II HS (IgG/IgM)

Question 90

IgG and IgM antibodies injure cells by promoting phagocytosis and injure tissues by inducing inflammation. What is the main way they do this?

Answer 90

IgG/M activate the classical complement pathway, activating complement, allowing lysis and inflammation

Question 91

Cells coated with IgG antibodies are killed by a variety of effort cells, mainly NK cells and mø and cell lysis occurs without phagocytosis in what pathway?

Answer 91

antibody-dependent cellular cytotoxicity (ADCC)

Question 92

In ADCC, MOA- When antibody is directed at a parasitic infection, there if Fc receptor-mediated inflammation and phagocytosis, characteristic of ADCC. IgG and IgE antibodies bearing Fc receptors coat the parasite. Macrophages, natural killer cells, and neutrophils can then recognize the Fc receptor and destroy the antibody-coated target cells. What is the contribution to HS reactions?

Answer 92

Unknown

Question 93

Transfusion reactions, hemolytic disease of the newborn, autoimmune hemolyic anemia and drug reactions such as drugs that act as haptens are all examples of what?

Answer 93

antibody mediated cell destruction in disease

Question 94

When antibodies are deposited in fixed tissue, injury is due to inflammation. The depositive Abs activate complement which leads to C3a/5a. What are 2 things that can happen due to this?

Answer 94

glomerulonephritis | vascular rejection in organ grafts

Question 95

Sometimes, antibodies directed against cell surface receptors impair or dysregulation function without causing cell injury or inflammation, occuring in what two dieseases?

Answer 95

Myasthenia gravis: abs antagonize NM transmission = muscle weakness Graves: abs against TSH receptor acts as agonist and stimulates cells (anti-receptor)

Question 96

Type II hypersensitivity reactions are where antibodies directly react with antigens present on the cel surface/extracellular matrix, including what two things?

Answer 96

autoantibodies | exogenous antigens that are bound to cell surfaces

Question 97

One mechanism of Type II HS is opsonization leading to phagocytosis or direct lysis in the case of antibody-dependent cellular cytotoxicity. What two diseases use this?

Answer 97

anemia thrombocytopenia (basic mech is no cells)

Question 98

the second mechanism of Type II HS is complement and Fc receptor mediated inflammation on damaged tissues such as basement membrane proteins or streptococcal proteins that cross react with myocardium. What are three examples where this mechanism is used?

Answer 98

Vasculitis Goodpasture syndrome Acute rheumatic fever

Question 99

The third mechanism of Type II HS is antibody mediated cellular dysfunction with a basic mechanism of dysfunction due to receptor blockade. What are three examples of this?

Answer 99

Myasthenia gravis (ab blocks binding at receptor) Graves (ab activates binding at receptor) Insulin resistant diabetes (ab inhibits insulin binding at receptor)

Question 100

Type III HS occurs when antigen-ab complexes deposit in tissue and cause damage by eliciting inflammation at the sites of deposition. What is the most common area where this occurs?

Answer 100

In the vessel walls - circulation

Question 101

Antigens in type III HS can be exogenous or endogenous. besides for the blood vessels (vasculitis) what are the other two regions of the body typically involved?

Answer 101

kidney- glomerulonephritis | joints- arthritis

Question 102

What is the prototype of a systemic immune complex disease, which was once sequela to the administration of large amount of foreign serum?

Answer 102

acute serum sickness

Question 103

What are the 3 phases of pathogenensis of type IIIHS?

Answer 103

formation of immmune complexes (1 week) deposition of immune complexes (chose areas of high filtration of blood) inflammation and tissue injury (10 days post antigen)

Question 104

In what disease is there repeated or prolonged exposure to antigen- called chronic serum sickness, associated with persistent antibody reponses to autoantigens?

Answer 104

Systemic lupus Erythematosus SLE - lupus ***Fibrinoid necrosis & bumpy lumps upon immunofluorescence

Question 105

What is a local immune complex disease where a localized area of tissue necrosis forms resulting from acute immune complex vasculitis in the skin? As antigen diffuses into the vascular wall, it binds preformed antibody and LARGE immune complexes are formed locally.

Answer 105

Arthus reaction

Question 106

When performing immunofluorescence on kidney biopsies, how are you able to tell the difference between a type II and type III HS reaction?

Answer 106

Type II: will have smooth linear lines and will look clear- uniformly attached TypeIII: will have grainy/granular lines because there are deposited complexes, which do not line the tissue perfectly like type 2 HS

Question 107

Are the following type 2 or 3 HS reactions? 1. in the kidney, post-streptococcal cross-reactive antibodies are forming immune complexes that deposit in the glomeruli 2. In the heart, post-streptococcal cross reactive antibodies directly act on the myocardium

Answer 107

1. Type 3 | 2. Type 2

Question 108

Type IV HS reaction causes inflammation by either cytokines released from CD4+ T cells or by killing done by CD8+ T cells. The cytokines released may be chronic and destructive. The prototype of T cell mediated inflammation is ______, a tissue reaction to antigens given to immune individuals.

Answer 108

delayed type hypersensitivity DTH

Question 109

Activation of the T cell occurs when Naive T cells recognize antigens displayed APCs. Whether the T cell becomes Th1 or Th17 T cell depends on the cytokines the APC releases, which are?

Answer 109

APC releases IL12 = Th1 = IFNy = more Th1 | APC releases IL6, IL23, IL1 = Th17

Question 110

IFN-Y secreted by Th1 cells are mainly responsible for many of the manifestations of DTH. IFN-Y classically activates M1 macrophages leading to what outcome?

Answer 110

* Enhanced ability to phagocytose and kill microorganisms * Express more class II MHC molecules on the surface * Secrete pro-inflammatory TNF, IL-1, and chemokines * Produce more IL-12 which causes an amplified TH1 response *Activated macrophages eliminate the offending antigen, but if activation is sustained, continued inflammation leads to tissue injury

Question 111

What is tissue injury from DTH reactions, which is thought to occur by environmental chemical agents bind to and structurally modify self proteins and peptides and elicit a CD4+T cell response to the 'foreign' antigens? This same process is thought to occur in drug reactions.

Answer 111

Contact dermatitis - poison ivy | also rheumatoid arthiritis, MS and IBD are CD4+ mediated

Question 112

CD8+ T cell mediated cytotoxicity- CTLs kill antigen expressing target cells leading to tissue damage. What are two good examples of this?

Answer 112

Type I DM | Graft rejection after organ transplantation

Question 113

CD8+T cells produce IFNY and are involved in inflammatory reactions resembling DTH, especially following what infections?

Answer 113

Virus infections or exposure to some contact senitizing agent

Question 114

What is the one hallmark histologically of some type IV reactions?

Answer 114

Granulomas with macrophages, epithelioid cells, giant langhan cells, and CD4+T cells

Question 115

What are the following? 1. presence of an immune reaction that is specific for some selft antigen or self tissue 2. The reaction is not secondary to tissue damage, but rather it is the thing that is causing the tissue damage 3. absence of another well-defined cause of disease

Answer 115

Three requires that pathologic autoimmune disease must meet to be confirmed as an autoimmune dz

Question 116

Immunologic tolerance is the phenomenon of unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen. What is self tolerance?

Answer 116

refers to lack of responsiveness to an individuals OWN antigens - which is monitored by central and peripheral tolerance

Question 117

Central tolerance is learned prior to release from generative lymphoid organs while peripheral tolerance is?

Answer 117

ongoing regulation in peripheral tissues

Question 118

In T cell development, random somatic gene rearrangements generate diverse TCRs. When self reactive T cells come in contact with self ags, they are set to die via apoptosis in the thymus. This process is known as?

Answer 118

negative selection or deletion *some may become Tregs

Question 119

What protein stimulates expression of some peripheral tissue restricted self antigens in the thymus and is thus critical for deletion of immature T cells specific for these antigens?

Answer 119

AIRE -autoimmune regulator

Question 120

When B cells are developing in the bone marrow, if they strongly recognized self ags, many of the cells reactivate the machinery of antigen receptor gene rearrangment and begin to express new antigen receptors, not specific for those antigens. What is this process called?

Answer 120

receptor editing *if the editing does not help, the B cell undergoes apoptosis

Question 121

What are the two main mechanisms focused on for peripheral tolerance?

Answer 121

anergy | suppression by Tred cells

Question 122

In peripheral tolerance lymphocyte that recognize self antigens may be rendered unresponsive- anergy. Anergy may occur when both signals (MHC and costim) are not availible. What is the costimulation needed?

Answer 122

CD28 on T cell binds B7.1/7.2 on APC

Question 123

When T cells are self reactive in the periphery, they receive inhibitory signals from structures that are homologous to CD28. What are the two?

Answer 123

CTLA4 and PD1 | when tested in mice without these, mice had autoimmune diseases

Question 124

Tumors and viruses actually use PD1 and CTLA4 to inhibit T cell death, leading to tumor/virus growth. This has lead to what?

Answer 124

antibodies against CTLA4/PD1 have been made for tumor immunotherapy by removing the breaks on the immune reponse

Question 125

Treg cells (induced by TGFB) also prevent immune reactions against self antigens. The best Treg cells are CD4+ that express CD25, the alpha chain of the IL2 receptor and a transcription factor known as?

Answer 125

FOXP3 (required for development and maintence of Treg cells)

Question 126

When there are mutations in FOXP3, it results in severe autoimmune diseases known as?

Answer 126

IPEX | immune dysregulation, polyendocrinopathy, enteropathy, Xlinked

Question 127

Treg cells supress the immune system due to secretion of IL10 and TGFB, and they also express what, which may bind to B7 molecules on APCs and reduce their ability to activate T cells via CD28?

Answer 127

CTLA4

Question 128

What are two other mechanisms in which T cells and B cells in the periphery are deleted if they are self reactive?

Answer 128

Via Bim - proapopotic signal and via Fas-Fas death receptor pathway APOPTOSIS

Question 129

What arises from a combinations of the inheritance of susceptibility genes which may contribute to the breakdown of selftolerance and environmental triggers such as infections and tissue damage which promote the activation of self-reactive lymphocytes?

Answer 129

Autoimmunity

Question 130

HLA genes have the greatest contribution to autoimmunity. Ankylosing spondylitis is typically hereditary inflammatory coniditon of the joints, particularly the spine. Inflammation leads to degeneration and then fusion of the vertebrae. What HLA gene is this disease strongly associated with?

Answer 130

HLA-B27- individuals with this class 1 HLA gene have 100-200 fold greater chance of developing the disease as compared to people without it. **Male, young, severe back pain presentation

Question 131

There are some autoimmune disease that are associated with non-MHC/HLA genes such as PTPN22 and NOD2. Mutations in PTPN22 which encodes protein tyrosine phosphatase, can lead to what diseases?

Answer 131

rheumatoid arthritis, type 1 DM, and more ***PTPN22 most frequenctly implicated in autoimmunity

Question 132

Polymorhpisms in which gene renders paneth cells in intestinal epithelium ineffective at microbial killing? Defective killing and clearance allows accumulation of bacteria and an exaggerated immune response.

Answer 132

NOD2 gene polymorphism causing crohn disease No NOD-like receptor = dysbiosis d/t increase gut flora

Question 133

Autoimmune disorders may be triggered by infections, because they upregulate the expression of costimulators on APCs and they also may express antigens that have same AA sequence as self antigens. This leads to immune response against microbial antigens resulting in the activation of self reactive lymphocytes called?

Answer 133

molecular mimicry - seen in rheumatic heart disease in which antibodies against streptococcal proteins cross react with myocardial proteins and cause myocarditis

Question 134

autoimmune diseases tend to be chronic sometimes with relapses and remissions, and the damage is often progressive. What is a cause of this, in which an immune response against one self antigen causes tissue damage, releasing other antigens and resulting in activation of lymphocytes by these newly encountered epitopes?

Answer 134

epitope spreading

Question 135

What is a good example of epitope spreading?

Answer 135

Initial T cell response leads to kertotic lesions in oral and conjunctival mucosa (oral lichen planus) causing membrane disruption which exposes antigenic proteins, leading to a secondary B cell response of blistering in secondary pemphigoid

Question 136

Match the autoantibodies with their disease: 1. anti-basement membrane, anti- type IV collagen 2. anticardiolipin, anti-β2-glycoprotein "lupus anticoagulant" 3. anti-dsDNA, anti-Sm 4. anti-histone antibodies 5 anti-SS-A, anti-SS-B 6 anti-U1-ribonucleoprotein 7 anti-Jo-1 8 anticentromeric antibody == 9 anti-DNA topoisomerase

Answer 136

1. Goodpasture Syndrome == 2. Antiphospholipid Syndrome, SLE == 3. SLE == 4. drug-induced SLE == 5. Sjogren Syndrome == 6. Mixed Connective Tissue Disease (MCTD) 7. polymyositis/dermatomyositis == 8. limited scleroderma (CREST syndrome) 9. diffuse systemic scleroderma

Question 137

ANA is a sensitive test for multiple autoimmune diseases. Its presence can prompt more specific testing to confirm the diagnosis. Other tests are more SPECIFIC, such as what for SLE?

Answer 137

``` Anti DS DNA Anti Smith (Sm) ``` Use more sensitive first becuase if it is negative then we know it is not autoimmune dz

Question 138

What are the four different staining patterns for antinuclear antibodies ANA?

Answer 138

homgenous (Lupus-abs to chromatin/histones/ DS DNA) speckled (most common least sepcific, abs to non-nuclear DNA- sjogren) Nucleolar (systemic sclerosis) Centromere (systemic sclerosis with abs specific for centromeres)

Question 139

What is an autoimmune disease involving multiple organs, characterized by a vast array of autoantibodies - ANA in which injury is caused by deposition of immune complexes and binding of antibodies to various cells and tissues?

Answer 139

Systemic lupus erythematosus

Question 140

SLE is as high as 1 in 2500, affecting mainly women, 2-3 fold increase in prevalence in blacks and hispanics than in whites. What is the hallmark of SLE?

Answer 140

production of autoantibodies *****ab to DS-DNA and Smith (Sm) are diagnostic

Question 141

What is following a classic picture of? erythematous malar facial skin rash and renal failure with proteinuria and hematuria from immune complex deposition in glomeruli.

Answer 141

SLE Lupus

Question 142

ANA are directed against nuclear antigens and can be grouped into four categories; abs to DNA, abs, to histones, abs to non-histone proteins bound to RNA, and abs to?

Answer 142

nucleolar antigens (systemic sclerosis)

Question 143

The defect in SLE is failure of mechanisms that maintain self tolerance - genetic and environmental causes. Family genetic patterns including which HLA gene?

Answer 143

HLA DQ (produce the autoabs) Female Bias: Xchromosome UV light

Question 144

Some other SLE genetics could be the inherited deficiency of complement proteins leading to failure to clear immune complexes. Deficiency in which complement protein can lead to defective phagocytic clearance of apoptotic cells?

Answer 144

C1q

Question 145

There are many immunologic factors that result in self reactive lymphocytes such as failure of self toelrance in B cells and CD4+ T cells. How do TLR engagement by nuclear DNA and RNA and Type 1 interferons contribute?

Answer 145

TLR engagement provides second signal for B cell activation = increase autoabs Type 1 IFN: activates lymphocytes in SLE

Question 146

What are the main environmental factors that can lead to SLE?

Answer 146

exposure to UV light gender bias - X chromosome Drugs like hydralazine and procainamide

Question 147

Most of the tissue injury/systemic lesions are cuased by immune complexes mediated inflammation, also known as?

Answer 147

Type III HS

Question 148

``` There are 11 criterion that someone with SLE may or may not have. ANA Immunologic DOs Hematologic DO Neurologic DO Renal DO Serositis Arthritis and what other 4 things? ```

Answer 148

Malar rash discoid rash (scarring/hypopigment) photosensitivity oral ulcers

Question 149

All of the following listed are when you start to expect lupus, which is the most important / common in SLE? ``` Arthritis Skin rashes Fever Fatigue Hemolytic anemia Edema ```

Answer 149

Hemolytic Anemia is seen in 100% of lupus patients!!

Question 150

Autoantibodies specific for red, white cells and platelets opsonize these cells and promote their phagocytosis and lysis. In tissues nuclei of damaged cells react with ANAs and lose their chromatin pattern, become homogenous known as?

Answer 150

LE bodies or hematoxylin bodies **LE cell is a phagocytic leukocyte (Neutro) which has engulfed the denature nucleus of an injured cell

Question 151

There are 6 patterns/classes of glomerular disease seen in SLE. What is the first and last stage and what occurs as the end-stage process?

Answer 151

1st stage is minimal mesangial nephritis | last stage is Advanced sclerosing lupus nephritis with fibrosis as end stage process

Question 152

The most common and severe form of lupus is the 4th (IV) stage - diffuse lupus nephritis. Half or more of the glomeruli is affected. Why is this considered to be the most common?

Answer 152

Becuase this is when people start showing symptoms of lupus! Including proteinuria and hematuria

Question 153

In Diffuse lupus nephritis, the glomeruli show increased cellularity due to proliferation of endothelial, mesangial and epithleial cells with EM showing deposits in the subendothelium. What will immunoflueorescence show?

Answer 153

granular pattern of IgG antibody contain complexes

Question 154

What can be seen in skin with people with SLE? 2

Answer 154

basal layer degeneration of the epidermis (vacuolated spaces between degen skin - white) Positive immunoflueorescence for complement and Ig deposition along dermal - epidermal jxn **fibrinoid necrosis may affect vessels present

Question 155

Cardiovascular complications are also seen in SLE. Before steroids were used, Libman-Sacks (valvular) endocarditis was more common. This nonbacterial verucous endocarditis takes the form of single or multple verrucous - warty deposits, as well as what other things?

Answer 155

The warts are comprised of fibrin and not infective but can embolize (rarely) ***Coronary artery disease increases due to many factors, but may also have contributions from immune complexes and antiphospholipid abs = endo damage and atherosclerosis

Question 156

What is a a neutrophil or macrophage that ingests the nucleus of a damaged cell? This is not used for dianosis anymore but may be seen in blood or body fluids...

Answer 156

L-E Cell (hemotoxylin)

Question 157

What are the most common causes of death due to lupus?

Answer 157

renal failure and intercurrent infections and CAD

Question 158

Chronic discoid lupus erythematosus DLE is a disease in which skin looks like SLE but there are no other systemic manifestations. What are the three things seen with DLE?

Answer 158

discoid rash positive ANA positive immunoflueorescence

Question 159

Discoid lupus is characterized by the presence of skin plaques showing varying degrees of edema, redness, scaliness and skin atrophy. Commonly located on the face and scalp above the neck. They have positive ANA but? Progression?

Answer 159

negative Anti-DS DNA Progression is possible to systemic organ involvment but only in 5-10% poeple

Question 160

``` What type of lupus presents with the following? Athralgia fever positive ANA Discoid rash hematologic disease positive immunofluorescence ```

Answer 160

Drug induced lupus erythematosus | no renal involvement, no etiology known, no positive DS-DNA

Question 161

Medicine induce breakdown of self tolerance has been seen in medications like hydralazine and procainamide. Instead of the positive DS-DNA abs, what is seen which is specific to drug induced lupus?

Answer 161

Positive Anti-Histone Abs | arthralgia/fever= positive ANA

Question 162

Hydralazine confers high risk for DIL (drug induced lupus) in people with ______ HLA Procainamide confers high risk for DIL in people with the _______ allele?

Answer 162

``` Hydralazine = HLA-DR4 allele Procainamide= HLA-DR6 allele ``` take away drug = lupus goes away

Question 163

What syndrome is a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands?

Answer 163

Sjogren Syndrome

Question 164

The decrease of tears and saliva in sjogren syndrome is from lymphocytic infiltration and fibrosis of the lcarimal and salivary glands. The infiltrate is predominantly made of what?

Answer 164

activated CD4+ T cells and some B cells w plasma cells

Question 165

Sjogren 75% people have rheumatoid factor, 50-80% have positive ANAs. But the most important antibodies associated with the syndrome are?

Answer 165

two ribonucleoprotein antigens SS-A(Ro) and SS-B(La) in 90% patients ppl with SSA will have early onset and longer disease duration

Question 166

Trigger of sjogren may be viral infection of the salivary glands which causes local cell death and release of self ags. T and B cells in the area attack resulting in?

Answer 166

inflammation, tissue damage, and fibrosis eventually

Question 167

Along with lcarimal and salivary glands as targets, exocrine glands sucha as lining the respiratory and GI tracts and vagina are affected as well. What is the first histologic finding?

Answer 167

periductal and perivascular lymphatic infilitration

Question 168

What are the three most common clinical presentation of someone with sjogren syndrome?

Answer 168

``` dry eyes (due to decreased lacrim secretions evaulated with schirmers test), dry mouth- smooth tongue (papillary atrophy) with superimposed candida yeast infection due to dry mouth Root caries/cavities due to dry mouth - difficulty swallowing ```

Question 169

What is essential for the diagnosis of sjogren syndrome?

Answer 169

biopsy of the lip to examine the minor salivary glands

Question 170

there are some complications with sjogren syndrome including extraglandular disease such as pulmonary fibrosis. Over time there is persistent lymphocytic inflammation that switches over to mainly B cells due to somatic rearragment. In about 5% of patients this B cell inflammation leads to?

Answer 170

Lymphoid proliferation becoming clonal leading to marignal zone LYMPHOMA (Bcell malignancy due to chronic lymphocytic inflammation)

Question 171

What disease is characterized by 1- chronic inflammation thought to be the result of autoimmunity 2- widespread damage to small blood vessels 3- progressive interstitial and perivascular fibrosis in the skin and multiple organs?

Answer 171

Systemic Sclerosis (scleroderma old name but didnt encompass the totality of the disease)

Question 172

There are two categories of systemic sclerosis known as diffuse and limited, what are the differences?

Answer 172

Diffuse scleroderm is characterized by widespread skin involvement at onset with rapid progression and early visceral involvement Limited scleroderma: skin involvement is often confined to fingers, forearms, and face

Question 173

Systemic sclerosis is fibrosis throughout the body including skin, GI tract, kidneys, heart, lungs or can occur in a limited form. The cause is unknown but the disease likely results from three interrelated processes known as?

Answer 173

autoimmune responses, vascular drainage, collagen deposition

Question 174

Clinical features of systemic sclerosis has a female to male ratio of 3:1 with peak incidence around 50-60 years. Upon histological slides, you can see dense collagenous deposition consisten with?

Answer 174

subcutaneous fibrosis + inflammation **vascular hyalinization

Question 175

Distinctive features of systemic sclerosis are striking cutaneous changes, especially skin thickening. What is episodic vasconstriction of the arteries and arterioles of the extremities seen in virtually all patients and preceds other symptoms in 70% of the cases?

Answer 175

Raynaud phenomenon

Question 176

What in systemic sclerosis is attributable to esophageal fibrosis and its resultant hypomobility in 50% of people with the disease?

Answer 176

Dysphagia

Question 177

Sclerosis tends to be more severe in black women with pulmonary and sometimes renal disease causing the majority of deaths. What are the two ANAs strongly associated with systemic sclerosis?

Answer 177

***DNA topoisomerase I (anti-scl70) abs (highly specific) | Anticentromere Abs in 20-30% of people who tend to have CREST

Question 178

Renal disease with sclerosis is mild, with mild proteinuria but rarely severe enough to cause nephrotic syndrome. However when there is malignant hypertension, is can cause?

Answer 178

fatal renal failure

Question 179

Sclerodactyly can progress to raynauds disease, causing enough blood block to cause necrosis and ?

Answer 179

distal phalangeal bone undergoes ischemic resoprtion

Question 180

Additional manifestations of system sclerosis includes GI tract - GI reflux and esophageal ulceration (d/t no blood/ischemia), renal vascular disease, pulmonary hypertension and?

Answer 180

pulmonary fibrosis d/t sclerosis

Question 181

Upon immunoflueorescence anti scl-70 (anti DNA topoisomerase) representative of systemic sclerosis can be seen as what pattern? Anticentromere antibody which is indicative of CREST syndrome can be seen immunoflueorescently as what pattern?

Answer 181

Anti Scl-70 : Speckled Anticentromere Ab: Centromere

Question 182

What is a unique form of limited sclerosis with a better prognosis than diffuse sclerosis because it involves less of the body/organs?

Answer 182

CREST syndrome

Question 183

``` Describe each of the following clinical presentations of limited sclerosis - CREST syndrome... Calcinosis Raynaud's phenomenon Esophageal dysfunction Sclerdactyly Telangiectasis ```

Answer 183

Calcinosis: calcium deposits in the skin Raynaud's phenomenon: spasm of blood vessels in response to cold/stress Esophageal dysfunction: dysphagia d/t abnormal esophageal contraction Sclerodactyly: thickening and tightening of skin on fingers and hands Telangiectasis: dilation capillaries causing red marks on surface of skin

Question 184

What leads to the fibrosis in scleroderma?

Answer 184

fibrosis may be the result of activation of fibroblasts by cytokines produced by T-cells and alternatively activated macrophages

Question 185

What are the three hallmarks of scleroderma?

Answer 185

chronic inflammation, widespread damage to small blood vessels, progressive interstitial and perivascular fibrosis

Question 186

What is a disease with clinical features that are a mixture of the features of SLE, systemic sclerosis and polymyositis?

Answer 186

mixed connective tissue disease MCTD

Question 187

In MCTD, it is characterized by serologically high titers of antibodies to ribonucleoprotein particle containing-? What is most common present feature?

Answer 187

U1 ribonucleoprotein (anti-ribonucleoprotein RNP) Raynaud Phenomenon

Question 188

What disease is a newly recognized constellation of DOs characterized by tissue infiltrates dominated by IgG4 antibody producing plasma cells and lymphocytes, particularly T cells, storiform fibrosis, obliterative phlebitis and usually increase serum IgG4?

Answer 188

IgG4 related disease

Question 189

IgG4 disease commonly affects middle aged and older men, pathogenesis is not understood although IgG4 production in lesions is a?

Answer 189

hallmark of the disease

Question 190

Autoimmune pancreatitis, Riedel thyroiditis, Mikulicz syndrome (sjogren), idiopathic retroperitoneal fibrosis and what other two diseases are now known to be caused by IgG4 related disease?

Answer 190

inflammatory pseudotumors and inflammatory aortitis

Question 191

What is uniting pathophysiology? IgG4-producing plasma cells, T lymphocytes, and fibrosis. Eventual fibrotic scarring and?

Answer 191

irreversible damage to involved areas

Question 192

Rejection is a process in which T lymphocytes and antibodies produced against graft antigens react and destroy tissue grafts. The major antigenic differences between a donor and recipient that result in rejection of transplants are?

Answer 192

differences in HLA alleles.

Question 193

Grafts between the same species are called allografts, between different species is xenograft. There are two pathways for recognition of organ grafts including?

Answer 193

Direct- use APCs from the donor | Indirect- use recipients APCs to activate B and T cell response

Question 194

In direct allorecognition, Dentritic cells from donor meet T cells at the grafted organ or travel to lymph node near by. The donor DC via class I and II MHC will do what?

Answer 194

Activate CTLCD8 and CD4+ T helper cells causing tissue damage, inflammation, and killing graft cells

Question 195

In the indirect pathway of allorecognition, the recipients APC presents the antigen to the CD4 cell which can then activate macorphages or B cells which then leads to?

Answer 195

plasma cells to attack the blood vessels + inflammation from macrophages ** No CTL because these CTLs recognize graft antigens present by host APCs and cannot recognize graft cells directly.

Question 196

``` Which of the following is B cell or T cell mediated? Hyperacute rejection Acute rejection Acute Antibody mediated rejection Chronic Rejection Chronic Antibody mediated rejection ```

Answer 196

``` B- Hyperacute rejection T- Acute rejection B- Acute Antibody mediated rejection T- Chronic Rejection B- Chronic Antibody mediated rejection ```

Question 197

Acute cellular rejection within the initial months after transplantation presents with signs of organ failure. Cytokines secreted by activated CD4+ T cells -- inflammation results in increased vascular permeability and local accumulation of mononuclear cells leading to?

Answer 197

graft injury caused by activated macrophages

Question 198

Hyperacute rejection occurs when preformed antidonor antibodies are present in the circulation of the recipient. Possibly present due to previous transplant, prior blood transfusions. Rejection occurs within minutes to hours. What is seen morphologically in kidneys?

Answer 198

Ig/complement deposited in vessel wall causing endothelial injury and thrombi to form *marked inflammation, thrombotic microvasculopathy and fibrinoid necrosis

Question 199

Acute antibody-mediated rejection is caused by antidonor abs produced after transplantation. The abs formed by the recipient may cause injury via?

Answer 199

complement activation, inflammation and antibody dependent cell mediated cytotoxicity.

Question 200

What type of rejection usually develops insidiously without preceding acute rejection and primary affects vascular componenets? Abs are detected in the circulation but are not readily identified within the graft.

Answer 200

Chronic antibody mediated rejection

Question 201

Acute rejection occurs within days of tranplantation, months or years after immunosuppression is tapered. What are the two histological patterns seen with acute cellular (T cell mediated) rejection?

Answer 201

1. tubulointerstitial pattern - interstitial inflammation of tubules w CD4/8 T cells 2. Vascular pattern- vessel inflammation, swollen endothelial cells *endotheliitis

Question 202

Acute antibody mediated rejection is manifested mainly by damage to glomeruli and small blood vessels. Typically the lesions consist of inflammation of glomeruli and peritubular capillaries with deposition of?

Answer 202

complement breakdown product Cd4- produced during activation of complement system by ab-dependent classical pathway ****Note C4d stain will be positive = acute ab - mediated rejection

Question 203

Chronic antibody mediated rejection is becoming increasingly frequent. It is dominated by vascular changes including thickening with inflammation, glomerulopathy, and what main thing?

Answer 203

fibrosis with primary effect on the vessels

Question 204

There are many methods to improve graft survival such as HLA matching between donor and recipient for kidney transplants to match HLA-A-B-DR, but it is not matched for other transplants. What is a practical necessity in all other donor-recipient combinations?

Answer 204

Immunosuppressive drugs/therapy

Question 205

Immunosuppressive drugs in current use includ steroids (reduce inflammation), mycophenolate mofetil (inhibits lymphocyte proliferation) and tacrolimus (FK506) which does what?

Answer 205

inhibits T cell functions by inhibiting NFAT which stimulates transcription of cytookine genes (IL2)

Question 206

Another drug used to treat rejection include T cell and B cell depleting antibodies and?

Answer 206

pooled intravenous IgG (IVIG) which supresses inflammation

Question 207

Although immunsuppression prolongs graft survival it carries its own risks, for example there is an increased risk for infection and tumors. One of the most frequent infection is?

Answer 207

poyloma virus - common in the renal tubules, may cause graft rejection

Question 208

Immunosuprresion also leads to an increased chance in neoplasia/tumor growth. Viral induce tumors such as lymphomas, kaposi sarcoma, HPV, EBV as well as what on the skin?

Answer 208

squamous cell carcinomas

Question 209

Use of hematopoietic stem cells (HSC) transplants for hematologic malignancies, BM failure syndromes and disorders caused by inherited HSC defectis is increase in number each year. How are the retreived?

Answer 209

from the peripheral blood upon administration of hematopeitic GFs or from the umbilical cord blood of newborn infants.

Question 210

In most cases of BM transplant, the patients own BM is killed with high doses of chemotherapy to destroy the immune system to allow new stem cell transplant to be accepted by the body. What are the two main complications with this proceess?

Answer 210

graft versus host disease GVHD | immunodeficiencies

Question 211

What occurs when immunologically competent cells or their precurosors are transported into immunologically crippled recipients and the transffered cells recognize alloantigens in the host and attack host tissues?

Answer 211

Graft versus host disease

Question 212

GVHD is most commonly seen in HSC transplantation. Donor T cells recognize recipient HLA as foreign and react against them. To try to minimize GVHD, HSC transplants are done between donor and recipients that are?

Answer 212

HLA matched using precise DNA sequencing mehtods for molecular typing of HLA alleles

Question 213

Acute GVHD occurs within days to week after allogenic BM transplant. Any organ may be affected by most clinical presentations are of immune system and epithelia of the skin, liver and intestines. Involvement of the skin is manifested as? what other two manifestations are commonly seen

Answer 213

a generalized rash that may lead to desquamation in sever cases * also small bile duct destruction leads to jaundice, mucosal ulceration leads to bloody diarrhea

Question 214

Chronic GVHD may follow acute or occur insidiously. pt has extensive cutaneous injury with destruction of skin appendages and fibrosis of dermis, chronic liver disease presented as cholestatic jaundice. Damage to the GI tract which may cause? What other two things

Answer 214

esophageal strictures - involution of thymus/depletion of lymphocytes in LNs - life threatening infections

Question 215

GVHD is mediated by T lymphocytes contained in the transplanted donor cells, so depletion of donor T cells before transfusion virtually eliminates the disease. What does this lead to ?

Answer 215

recurrence of tumor in leukemic patients -- graft versus leukemia effect

Question 216

Immunodeficiency is common complication of HSC transplantation as well. It may be due to a prior treatment, myeloablative preparationg for the graft, a delay in repopulation of the recipients immune system and/or?

Answer 216

attack on the hosts immune cells by grafted lymphocytes

Question 217

Affected individuals of immundeficiency due to HSC transplantation are easy prey to infections. Infection with what is important and why?

Answer 217

cytomegalovirus CMV because of CMV induce pneumonitis is fatal

Question 218

What is the morphology of rejection mediated by preformed antibodies?

Answer 218

hyperacute rejection-- thrombosis, ischemic damage and rapid graft failure

Question 219

All of the following are? • arteriosclerosis • activated T-cells secrete cytokines that induce proliferation of vascular smooth muscle cells • antibodies cause endothelial injury • vascular lesions + T-cell reactions cause parenchymal fibrosis • intimal thickening and luminal narrowing

Answer 219

They are hallmarks of chronic rejection

Question 220

Immunodeficiencies can be divided into primary (congenital) and secondary (acquired) which sometimes aris due to cancers, infections, malnutrition or side effects of immunosuppression, irradiation or?

Answer 220

chemotherapy for cancer and other diseases

Question 221

Most primary immunodeficiencies are detected in infancy between 6mo to 2 years of life with the tell tale signs being?

Answer 221

susceptibility to recurrent infections

Question 222

What disease is a primary innate immunodeficiency of leukocytes, which is autosomal recessive condition characterized by defective fusion of phagosomes and lysosomes, resulting in defective phagocyte function and susceptibility to infections?

Answer 222

Chediak Higashi Syndrome

Question 223

Chediak higashi occurs when there is failure of phagolysosomal fusion, which leads to no killing of the phagocytosed bacteria within the cell. What is seen upon blood smear as well as clinically?

Answer 223

Upon blood smear you can see luekocytes with giant granules There are abnormalities in melanocytes (leading to albinism), cells of nervous system and platelets

Question 224

What is there an increased chance of infection with chediak higashi and why?

Answer 224

increase bacterial infection because neutrophils cannot kill bacteria

Question 225

What disease is an inherited defect of microbicidal activity , which is characterized by defects in bacterial killing and render patients susceptible to recurrent infection?

Answer 225

Chronic granulomatous Disease

Question 226

Chronic granulomatous Disease results from inherited defects of phagocyte oxidase (superoxide production), which leads to formation of granuloma which is?

Answer 226

accumulation of macrophages around the bacteria walls off the infection, forming center of necrosis with T cells and macrophages around the edge

Question 227

The terminal components of complement C5,6,7,8,9 are required for MAC lysis of organisms. When there is a deficiency in any of the ones listed, lysis of microbial membrane cant occur leading to what infection and disease?****

Answer 227

****Neisseria infections are extremely common which are gram negative bacteria and can lead to meningitis

Question 228

A deficiency of C1 inhibitor C1INH gives rise to hereditary angioedema. This is an AD DO more common than complement deficiency states. The C1 inhibitor's targets are proteases, specifically?

Answer 228

C1r and C1s of complement, XII of coagulation, and killakrein system

Question 229

What are 3 common clinical presentations of someone with hereditary angioedema due to C1 inhibitor deficiency?

Answer 229

face swelling hand mobility decreases + swelling intestinal swelling

Question 230

What deficiency is the most common complement protein deficiency associated with increased bacterial or viral infections?

Answer 230

C2 deficiency

Question 231

In C2 complement deficiency, most patients have no clinical manifestations, however some have SLE like autoimmune disease... Why are there no clinical manifestations?

Answer 231

because the alternative complement pathway is adequate for the control of most infections (doesnt need C2)

Question 232

What ID represents a constellation of genetically distinct syndromes, all having in common defects in both humoral and cell mediated immune responses?

Answer 232

Severe combined Immunodeficiency SCID

Question 233

SCID people are extremely susceptible to recurrent severe infections by a wide range of pathogens including candida albicans, pneumocystis jiroveci and?

Answer 233

pseudomonas **without HSC transplant death occurs in 1st year of life

Question 234

The most common form of SCID is the Xlinked, hence why SCID is more common in boys than girls, the mutation is in the common Y-chain (yc) subunit of?

Answer 234

cytokine receptors which is a signal tranducer for IL2,4,7,9,11,15,21 IL7 needed for T cell prolif, IL15 need for NK prolif (T cells are deminshed and B cells are present but cannot produce Abs without T cellS)

Question 235

The remaining 40% of SCID cases is autosomal recessive DOs, the most common being a deficiency of the enzyme?

Answer 235

adenosine deaminase ADA Lack of ADA leads to accum of deoxyadenosine which is toxic to immature lymphocytes (blocks T cells, some B cells availble but cant make Abs without T cells)

Question 236

SCID patients/infants present with prominent thrush (oral candidiasis)m extensive diaper rahs and?

Answer 236

failure to thrive , some with morbilliform rash (measels like) shortly after birth because maternal T cells are transffered across placenta and attack fetus

Question 237

What is characterized by the failure of B cell precursors (pro-B cells and pre-B cells) to develop into mature B cells?

Answer 237

X linked agammaglobulinemia (bruton)

Question 238

in X linked agammaglobulinemia B cells are absent or markedly decreased. There are CD19+ B cells in normal numbers but they dont express BCRs. it is caused by mutations in?

Answer 238

bruton tyrosine kinase BTK gene on X chromosome

Question 239

BTK protein tyrosine kinase is associated with Ig receptor complex of preB and mature B cells and is needed to transduce signals from the receptor. When it is mutated, the pre B cell receptor cannot?

Answer 239

deliver the signal, and B cell maturation stops.

Question 240

X linked agammaglobulinemia is mainly seen in males but sometimes in females. The disease usually does not present until about 6 months however, because?

Answer 240

maternal abs are provided via breast milk and IgG from placenta until they wane around 6 months, then start to show signs

Question 241

Recurrent bacterial infections of respiratory tract, sinusitis, otitis media, bronchitis and pneumonia call attention to the disease. Almost always due to what three organisms?

Answer 241

Haemophilus influenzae streptococcus pneumoniae staphylococcus aureus

Question 242

X linked agammaglobulinemia has issues with enteroviruses such as giardia lamblia an intesetinal protozoan which causes persistent infection. What are 3 other characteristics beside absent B cells seen with this dz?

Answer 242

germinal centers are underdeveloped plasma cells are absent T cell mediated reactions are NORMAL *** treat with IVIG

Question 243

What is a T cell deficiency that results from failure of development of the third and fourth pharyngeal pouches? What do 3/4 give rise to?

Answer 243

DiGeorge Syndrome (thymix hypoplasia) Gives rise to thymus, parathyroid, C cells of thyroid, and ultimobranchial body (heart/ great vessels malformed)

Question 244

Individuals with digeroge syndrome have no thymus, which means there is no maturation of T cells. This may be inherited in a sporadic or familial pattern, most involving what deletion?

Answer 244

22q11 deletions

Question 245

Digeorge also manifest with facial and palatal, cardiac abnormalities, T cell deficiency and humoral deficiency cause no CD4+ Helper cells. Why might there be tetany?

Answer 245

due to decrease or no calcium in the body cause of the hypoplastic parathyroid

Question 246

What disorder of a patient makes IgM antibodies but are deficient in their ability to produce IgG, IgA and IgE antibodies?

Answer 246

Hyper-IgM syndrome

Question 247

70% of people with Hyper-IgM syndrome have the X linked form, caused by mutations in the gene encoding CD40L. What occurs when there is a CD40L deficiency (on T cells) or lack there of?

Answer 247

When there is no CD40L on T cells to engage CD40 on B cells, there is no Ig class switching or affinity maturation of B cells **** Recurrent pyogenic infections

Question 248

Hyper-IgM syndrome again has problems with encapsulated bacterial (pyogenic) infection becuase of the lack of?

Answer 248

opsonizing antibodies (IgG)

Question 249

Hyper-IgM syndrome you will see increased IgM and decreases of all other classes. You can treat with either IVIg or?

Answer 249

stem cell transplantation

Question 250

In addition to pyogenic infections, people with Hyper-IgM syndrome are also susceptible to pneumonia cuased by the intracellular organism _______ because CD40L mediated macrophage activation ( a key reaction of cell mediated immunity) is also defective.

Answer 250

pneumocytis jiroveci ** will have normal amount of B and T cells

Question 251

What ID is a realtively frequent but poorly defined entity which encompasses a heterogeneous group of disorders in which the common feature is hypogammaglobulinemia, generally affecting all the antibody classes but sometimes only IgG?

Answer 251

Common variable immunideficiency CVID

Question 252

The diagnose of CVID is based on the exclusion of other causes of decreased antibody production. It is the most common significant primary immunodeficiency, however as opposed to x-linked aggamaglobulinemia...?

Answer 252

there is normal or near normal numbers of B cells, But these B cells do not differentiate into plasma cells

Question 253

The patient with CVID typically presents with recurrent sinus and pulmonary infections (pyogenic bacteria, d/t no IgA). patient are prone to development of persistent diarrhea via giardia lamblia. In contrast to agammaglob, CVID affects male and females?

Answer 253

equally and the onset of symptoms is later in childhood or adolescence

Question 254

With CVID there is also granuloma formation and autoimmune disease such as? 2

Answer 254

anemia and thrombocytopenia ( attacks self)

Question 255

Isolated IgA deficiency occurs in 1 in 600 eastern european, affected individuals have low levels of both serum and secretory IgA. This can occur in familial and acquired forms, loss of IgA means less defense against inhaled and ingested pathogens leading to what 3 things?

Answer 255

sinus and respiratory infections urinary bladder infections gastrointestinal infections (high frequency of autoimmune diseases and allergies)

Question 256

Most times people dont know they have isolated IgA deficieny until what occurs?

Answer 256

transfusion related anaphylaxis - red cells induce anaphylaxis = IgA deficiency *red cell washing can prevent these reactions to rid IgA

Question 257

What disease is characterized by an inability to eliminate epstein-Barr virus (EBV) and eventually lead to fulminant infectious mononucleosis and the development of B cell tumors?

Answer 257

X linked lymphoproliferatuve syndrome

Question 258

in X linked lymphoproliferatuve syndrome, what is the defect which causes attenuated NK and T cell activation resulting in increased susceptibility to viral infections?

Answer 258

SLAM-associated protein SAP is deficient which is involved in the activation of NK, T and B cells

Question 259

What syndrome is an X linked disease characterized by thrombocytopenia, eczema, and a marked vulnerability to reccurent infection resulting in early death?

Answer 259

Wiskott Aldrich Syndrome

Question 260

in Wiskott Aldrich Syndrome, the thymus is normal wiht loss of T cells in the blood and T cell zones of LNs.IgM levels are low but IgG are normal, IgA and IgE are elevated. What is the deficient gene and how can this be treated?

Answer 260

WASP gene mutation which is thought to be involved in linking membrane receptors to cytoskeletal elements * treat with stem cell transplant HSC

Question 261

What is an autosomal recessive disorder characterized by abnormal gait (ataxia), vascular malformations (telangiectases), nuerologic deficits, increased incidence of tumors and immunodeficiency?

Answer 261

Ataxia telangiectasia

Question 262

in Ataxia telangiectasia, there is a mutated gene known as the ATM gene, which causes defective DNA repair. What is the first presentation of the dz, and what can be seen due to being immmune deficient in IgA and IgG?

Answer 262

First presentation is neurodegenerative disease with ataxia, first vascular malformation is excessive BV around eye in sclera * respiratory infections, autoimmune dz, cancer via lymhpomas

Question 263

Secondary or acquired immunodeficiencies may be encounterd in idividuals with cancer, diabetes, malnutrition, chronic infection, and in persons receiving chemotherapy/radiation for cancer or immunsuppressive drugs to prevent graft rejection. What is the most common?

Answer 263

Acquire immunodeficiency syndrome (AIDS)

Question 264

What is a disease caused by retrovirus human immunodeficiency virus (HIV) and characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms and neurologic manifestations?

Answer 264

AIDS

Question 265

What is the main difference between HIV and AIDS?

Answer 265

AIDS is the manifestation of what occurs when HIV affects the body to a degree where immune dysfunction results in infections, neoplasms, and neurologic manifestations

Question 266

The highest groups at risk for HIV/AIDS are homosexuals or bisexual men 60%, intravenous drug abusers 20%, hemophiliacs 0.5%, recipients of blood and blood components 1%, heterosexual contacts, HIV infection of newborn. What are the three major routes of transmission?

Answer 266

sexual contact parenteral inoculation passage of virus from infected mothers to newborns

Question 267

Sexual transmission of HIV constitutes about 75% of the cases- virus within semen and enters recipients body through?

Answer 267

abrasions in rectal or oral mucosa 1- direct inoculation into blood vessels 2-infection of DC or CD4+ in mucosa

Question 268

Parenteral transmission of HIV occurs in IV drug users**, hemophiliacs and recipients of blood transfusions. How can mother to infacnt transmission of AIDS occur? 3

Answer 268

in utero by transplacental spread during delivery through infected birth canal after birth by ingestion of milk

Question 269

Does this risk of transmission of HIV/AIDs increase or decrease when you have STDs such as chlamydia and syphillis?

Answer 269

There is an increase rate of transmission

Question 270

Health care works have the risk of seroconversion (contracting a disease from a patient) after a needlestick accident varies with the type of infection. What is the chance of contracting HIV from needlesitck as compared to HepC?

Answer 270

HIV- o.3% chance | HEPC- 30%

Question 271

HIV is a nontransforming human retrovirus belonging to the lentivirus family. there is HIV1 and HIV2, what is the most common type of US/Europe and which is the most common in west africa/india?

Answer 271

Africa india is HIV 2 | US is HIV1

Question 272

HIV1 retrovirus is spherical with cone shaped core derived from host cell membrane, the virus core contains nucleocapside protein P7/p9, two copies of viral genomic RNA, three viral enzymes and?

Answer 272

major capsid protein p24 *** most relevant cause we can test for p24 antigen to determine if infected

Question 273

Most important structures of HIV are p24 capsid protein, viral enzymes such as protease, reverse trancriptase, and integrase, HIV-1 RNA genome containing gag pol and env genes which are typical of retroviruses and what glycoproteins? What are they good for?

Answer 273

gp120 and gp41 - which stud the outside of the spherial virus important for attachment and also good drug/vaccine targets

Question 274

The two major targets of HIV are the immune system and central nervous system. Immune deficiency affect cell mediated immunity is hallmark of AIDS**. This results chiefly from infection and loss of?

Answer 274

CD4+ T cells as well as impairment in the function of surviving helper T cells. Virus becomes established in lymphoid tissue where it may be latent for a while

Question 275

The life cycle of HIV consists of infection of cells, integration of the provirus into the host cell genome, activation of viral replication and?

Answer 275

production and release of infectious virus

Question 276

HIV-1 high yield genome regions to know... Match function with genome region LTR, gag, env, pol -Encodes for the surface glycoproteins - encodes for the protein inside the virus -initiates trasncription, binds transcription factors -encodes viral enzymes

Answer 276

env-Encodes for the surface glycoproteins gag- encodes for the protein inside the virus LTR-initiates trasncription, binds transcription factors pol-encodes viral enzymes (-ases)

Question 277

HIV infects cells using CD4 molecules as receptor various chemokine receptors as coreceptors. What are the chemokine coreceptors?

Answer 277

CCR5 and CXCR4 **bind of virus gp120 to CD4 is not enough for infection, needs gp120 to also bind to CCR5 and CXCR4

Question 278

Once virus gp120 binds to CD4 and to CCR5 (if R5 strain) or CXCR4 (if X4 strain) after conformational change, leads to another conformational change in gp41 resulting in exposure of the fusion peptide of GP41. This does what?

Answer 278

uses fusion peptide to drill into the host target cell membrane, and inserts the viral genome

Question 279

Note- if there is high chemokines in the area of HIV infection, they take up their receptors, which could possibly lead to?

Answer 279

lack of receptors for HIV to bind to leading less viral infection

Question 280

Once the viral genome is internalized into the T cell, the RNA genome of the virus undergoes reverse transcription. How?

Answer 280

reverse transcriptase synthesizes proviral DS DNA from the original RNA genome

Question 281

Once reverse transcriptase is complete, integrase inserts the proviral DNA sequence into the host genome. lastly, host cell activation via cyotkines occur, leading to?

Answer 281

triggering of LTR to initiate transcription of HIV viral RNA

Question 282

HIV effects memory and activated T cells but is inefficient at infecting Naive T cells because it contains an enzyme that introduces mutations in the HIV genome which inhibit further DNA replication. What is thh enzyme?

Answer 282

APOBEC3G

Question 283

Completion of viral life cycle occurs only after cell activation, most CD4T cells virus activation results in cell lysis. When an antigen stimulation occurs- it activates the CD4 cell which releases NF-kB which normally upregulates the T cell response. What does it do when the cell is infected w HIV?

Answer 283

NFkB activates the transcription of HIV proviral DNA through LTR (cause has NFkB binding sites) *NFkB is bound to inhibitor IkB until activated via cytokines/microbes

Question 284

Loss of CD4T cells with HIV is mainly due to infection of the cells and direct cytopathic effects of the replicating virus. In infected individuals, 100 billion viral particles are produced each day and 1-2 billion CD4 T cells die. What are 2 possible mechanisms for CD4T cell death?

Answer 284

increased plasma membrane permeability d/t budding of virus particles from infected cells and virus replication interfering with protein synthesis (direct killing/cytopathic effect)

Question 285

Non-cytopathic HIV infection activates the inflammasome pathway and leads to a form of cell death known as? In which inflammatory cytokines and cellular contents are released - increasing chance of infecting new cells

Answer 285

Pyroptosis

Question 286

Note: as time goes on, the body is no longer able to keep up with the decline in CD4+ T cells, so acute infection compared to AIDS 10 years later shows?

Answer 286

A huge decline in the number of CD4T cells

Question 287

There are many immune abnormalities seen due to the decrease/lack of T cells in a person with AIDS, including, decreased T cell function in vivo, altered T cell function in vitro, polyclonal B cell activation, altered monocyte/macrophage function and?

Answer 287

lymphopenia

Question 288

In addition to loss of CD4+ T cells, infection of macrophages and dendritic cells is also important in the pahtogenesis of HIV. Like T cells the number of affect macrophages is high in tissues but low in?

Answer 288

blood (monocytes low)

Question 289

HIV1 can infect and multiply in terminally differentiated macrophages because of the vpr gene. Mø have some budding of the virus but the majority is stored within. Unlike CD4T cells, mø are resistant to?

Answer 289

cytopathic effects of HIV so they are RESIVOIRS of infection

Question 290

In addition to Mø, 2 types of DCs are important targets for HIV- mucosal and follicular DCs. What is though of both of these DCs?

Answer 290

Mucosal DCs: are infected by the virus and transport it to lymph nodes Follicular DCs: are in the germinal centers of LNs and are reservoirs of HIV

Question 291

There are B cell abnormalities associated with AIDS as well, such as polyclonal acitvation of B cells resulting in B cell hyperplasia. This may be from EBV, due to lymphoma, nonspecific HYPERgammaglobulinemia, but have impaired humoral immmunity--- why?

Answer 291

because there are CD4T cells to allow isotype switching so there is a reduction in Ab production leading to inc. infection by encapsulated bacteria - pneumoniae and influenzae (need IgG for opsinization)

Question 292

The nervous system is a major target for HIV, predominantly infected cells of CNS are microglia and mø. HIV is carried into the brain by infected monocytes -> microglia. Neurologic symptoms are caused indirectly by?

Answer 292

viral products and soluble factors produced by infected microglia

Question 293

What is characterized by infection of memory CD4T cells (w CCR5) in mucosal lymphoid tissues and death of many infected cells?

Answer 293

acute/early HIV infection

Question 294

T cell's largest reservoir of memory cells is in the mucosal tissues, acute infection causes large depletion of lymphocytes. After mucosal injury and entry of the virus, what follows?

Answer 294

dissemination of the virus and development of host immune response *transported via DCs to LNs, where they present virus to CD4T cells, viral replication occurs in LNs

Question 295

The replication in the LNs lead to viremia (2-3 weeks) = high numbers of HIV particles are present in the patients blood. As HIV spreads the individual mounts what at about 3-7 weeks?

Answer 295

Individual mounts antiviral humoral and cell mediated immune response to stop viral replication (virus specific CD8CTLs which partially control infection - see drop in viremia by 12 weeks) **seroconversion where go from Ab negative to Ab positive

Question 296

What is the clinical presentation of the intial spread of HIV virus and host response. Occurs 3-6 weeks after infection, with flu like symptoms occuring in 40-90% of people. Symptoms include sore throat, myalgia, fever, weight loss, fatigue, rash, cervical adenopathy, diarrhea, vomiting

Answer 296

Acute retroviral syndrome

Question 297

The extent of viremia, measured as ______ levels in the blood, is a useful surrogate marker of HIV disease progression and is of clinical value in the management of people with HIV.

Answer 297

HIV-1 RNA

Question 298

Note: blood CD4+ counts are the most reliable short-term indicator of disease progression , instead of?

Answer 298

Viral load

Question 299

The first detectable substance of HIV is viral RNA (10days) via nucleic acid test NAT. What are the second and third substances detectable?

Answer 299

2nd is the protein antigen p24 (15 days) | 3rd is the antibody to HIV (25 days)

Question 300

Why is the window period important in regards to HIV and showing positive in blood?

Answer 300

Donated blood! entails a 7-14 days window period from exposure to positive results and is tested via NAT for HIV

Question 301

The viral set point is at the end of initial viremic spike and may predict CD4 cell loss. What is clinical latency (chronic infection)?

Answer 301

period of silent massecre of CD4 cells which may last years without symptoms, which replicatoin and destruction occurs in the LNs and spleen

Question 302

HIV escapes immune control via many mechanisms including antigenic variation, down modulation of Class I MHC (avoids CD8), evolves and switches to using both CCR5 and CXCR4 which leads to a more rapid?

Answer 302

decline in CD4T cells because of the greater infection of the T cells

Question 303

In what phase of HIV infection are patients asymptomatic or develop opportunistic infections such as oral candidiasis (trush), vaginal candidiasis, herpes zoster and possibly MTb?

Answer 303

Chronic phase of infection

Question 304

The final phase of progression to AIDs is characterized by breakdown of host defense, increase in plasma virus, and severe life threatening clinical disease. Pt presents with long lasting fever, fatigue, weight loss and diarrhea. After a variable period what else may occur? 3

Answer 304

opportunistic infections, secondary neoplasms, clinical neurologic disease

Question 305

In the united states, the typical adult patient with AIDS present with fever, weight loss, diarrhea and what else? 4

Answer 305

lymphadenopathy multiple opportunistic infections** neurologic disease secondary neoplasms

Question 306

Opportunistic infections account for the majority of deaths in untreated patients with AIDS, frequency of these infections have decreased due to?

Answer 306

highly active antiretroviral therapy HAART which relies on combination of three-four drugs that block differe steps of HIV life cycle

Question 307

A patient presents with mulptiple lesions upon brain mri and one is biopsied. It is not cancer but shows CNS toxoplasmosis... What is your dx?

Answer 307

AIDS! metastatic

Question 308

15-30% of untreated HIV infected people develop pneumonia at some time during the course of disease with what type of fungus? This used to be in 20% of AIDS patients but has dropped since HAART

Answer 308

Pneumocytis jiroveci fungus (via reactivation of a prior latent infection*) **AIDS defining illness

Question 309

What is the most common fungal infection in AIDS patients with common clinical manifestations being infection of oral cavity, vagina and esophagus? Note: oral infection is sign of immuno decompensation and heralds transition to AIDS. Invasive infection is infrequent usually due to drug-induced neutropenia/ catheters

Answer 309

Candidiasis (fungus)

Question 310

What virus more commonly affects the eye and GI tract. Chorioretinitis is seen in 25% of patients before HAART? This occurs exclusively in patients with CD4+ T cell counts less than 50/microliter

Answer 310

Cytomegalovirus (virus)

Question 311

What is a protozoa lead to 400,000 people in milwaukee being infected, which was traced back to the city's water supply. Deaths due to excessive diarrhea where more likely in HIVand elderly populations

Answer 311

Cyptosporidium (enteritis)

Question 312

AIDS patients have a high incidence of tumors including Kaposi sarcoma KS, B cell lymphoma, cervical cancer, and anal cancer. What are these caused by?

Answer 312

oncogenic DNA viruses specifically kaposi sarcoma herpesvirus, EBV, HPV

Question 313

What is a vascular tumor that are rare in the US besides AIDS patients, which it is the most common type? Which is characterized by proliferation of spindle shaped cells that express markers of bothe endothelial and smooth muscle cells?

Answer 313

Kaposi Sarcoma KS

Question 314

Kaposi Sarcoma KS is believed to be caused by what? Which establishes latent infection during which several proteins are produced with potential roles in stimulating spindle cell proliferation and preventing apoptosis.

Answer 314

Human Herpesvirus 8 or KS herpesvirus

Question 315

KSHV is not only restricted to endothelial cells but is also seen in rare B cell lymphomas (primary effusion lymphoma) and also in?

Answer 315

castleman's disease (a B cell proliferative DO)

Question 316

Lymphomas are AIDS defining condition - partially explained by T cell deficiency, there are two mechanisms that underlie the increased risk of B cell tumors in HIV, which are?

Answer 316

1. unchecked proliferation of B cells infected with oncogenic herpesviruses in the setting of profound T cell depletion (AIDS) 2. Germinal center B cell hyperplasia in the setting of early HIV infection

Question 317

Without T cells, control of B cell proliferation infected with EBV/KSHV is lost, leading to the formation of B cell lymphomas composed of tumor cells infected by (EBV). EBV is latent in memory B cells and when activated without T cell presence what occurs?

Answer 317

EBV mutates and causes EBV+ B cell lymphomas since T cells are not availble to kill the virus

Question 318

In early HIV infection, germinal center B cell hyperplasia occurs. Mutations occur during class switching and somatic hypermutation leading to B cell lymphomas with translocations where? 2

Answer 318

``` Burkitt lymphoma (MYC) Large B cell lymphoma (BCL6) ```

Question 319

Patients with AIDS have an increased occurence of carcinoma of the uterine cervix and anal cancer. This is due to the reactivation of latent HPV infection. 10 times more common in HIV patients, what is seen clinically? 3

Answer 319

squamous cell carinoma of cervix, cervical dysplasia and carcinoma in situ (precursor to cancer)

Question 320

Involvement of the NS is a common manifestation of AIDS, 90% upon autopsy demonstrate neurologic involvement. Including meningoencephalitis, aseptic meningitis, vacuolar myelopathy, peripheral neuropathy, and most commonly what?

Answer 320

progressive encephalopathy designated clincally as HIV associated neurocognitive disorder :)

Question 321

What is the most common neoplasms seen in association with AIDS?

Answer 321

B cell non-hodgkin lymphomas

Question 322

What is a condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise?

Answer 322

Amyloidosis

Question 323

In amyloidosis abnormal fibrils are produced by aggregation of misfolded proteins- insoluble B pleated sheets are formed and accumulate. Amyloid may be systemic or localized, what are the subclassifications of systemic?

Answer 323

systemic/generalized is primary amylodsis- associated with plasma cell disorder secondary amyloidosis occurs when complication of underlying chronic inflammatory or tissue destructive process.

Question 324

In systemic amyloidosis the difference between primary and secondary amyloidosis, is that primary has plasma cell proliferations and secondary is due to chronic inflammatory conditions. What is the difference in major fibril protein?

Answer 324

Primary is AL - light chain disease | Secondary is AA - amyloid associated

Question 325

If amyloidosis is systemic, you can also try to dianose it in an abdominal fat pad biopsy. Otherwise, what are the common areas to be manifested by amyloid? 4

Answer 325

kidney brain liver heart

Question 326

Histologically, amyloid deposition is always extracellular and begins between cells - close to basement memebranes. What is the most common organ for amyloidosis?

Answer 326

Kidney

Question 327

Kidneys may be normal sized grossly, histologically the amyloid is deposited primarily in the glomeruli, first appearing as subtle thickening. What can this lead to?

Answer 327

proteinuria and edema, often the initial presentation

Question 328

Amyloidosis of the heart is major organ effected in senile systemic A. Heart is enlarged and firm with deposits as focal subendocardial accumulations within the myocardium between muscle fibers. This disruption of the myocardium may result in?

Answer 328

dysrhythmias - often the initial presntation

Question 329

What causes vascular fragility that may lead to bleeding, sometimes massive that can occur spontaneuously or following seemingly trivial trauma?

Answer 329

Vascular amyloidosis

Question 330

What is the best stain for diagnosis of amyloidosis, in which the protein aggregates will turn red and then look apple green on flueoresence?

Answer 330

congo red stain for amyloid

Question 331

What is the difference between seeing bubble gum pink and apple green colors when congo red stain is introduced?

Answer 331

Bubble gum pink deposits that means there are presence of amyloid with congo red stain Apple green is seen as amyloid under polarized light