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GER Unit 6 > Immuno > Flashcards

Immuno Flashcards

1
Q

antibody

A

also known as an immunoglobulin; large Y-shape proteins produced by plasma cells used by the immune system to identify and neutralize foreign objects (i.e., bacteria and viruses)

  • has high affinity binding sites for specific foreign structure (antigens), at other end are Fc regions (sites for effector cells or proteins to bind)
  • involved in neutralization, opsonization, help fix complement on surface (acts as better opsonist)
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2
Q

gamma globulin

A

substance made from donated human blood plasma that contains antibodies that protect the body against diseases

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3
Q

IgG

A
  • most common immunoglobulin type with widest range of dunction
  • toxin neutralizing, opsonizing, bacteriolytic with aid of complement system
  • subclasses with distinct functions; intrachain disulfide bonds between same residues
  • ability to be transported across placenta and diffuse extravascularly
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4
Q

IgM

A
  • most primitive immunoglobulin type and is most potent at complement fixation but can’t directly mediate many fuctions (e.g., ADCC or opsonization)
  • heavy, usually found in a pentamer with J chain
  • found earliest in immune response
  • antigen receptor on B cell and agglutinating, cannot aid in opsonization without complement (immune cells don’t have IgM receptors)
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5
Q

IgA

A
  • 2 forms, one of which is secreted through epithelial cells where it picks up a secretory piece (T piece) that inhibits degradation by acid hydrolysis, passes through breastmilk
  • forms dimer with J chain
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6
Q

IgD

A

coexpressed with IgM on surface of B-cells, may function as antigen receptor

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7
Q

IgE

A
  • associated with immune response to parasites
  • immediate hypersensitivity (allergies): fixes to mast cells to active them, causing release of granule contents
  • hardly any in circulation because it sticks to cells quickly
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8
Q

proteolytic cleavage of immunoglobulin

A

enzyme cleaves disulfide bonds→2 distinct fragments

  • **antigen binding fragment (Fab): **heavy and light chain variable regions contain *3 hypervariable regions each *which come together to form antigen binding pocket, framework residues orient
  • Crystallizable (repeating) Fc: contains most of the specific antigenic determinants; receptor on cells for binding immunoglobulin is called Fc receptor
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9
Q

how can antibodies be so specific to such a variety of antigen?

A
  • pieces of DNA (V, D, and J) signaled by RSS motifs are randomly chosen and brought together by recombinases (RAG1 and RAG2) to form array of antibody molecules
  • as cell develops, germline is edited
  • joining is imprecise
  • most rearranged genes won’t function, leads to loss of many T/B precursors; can try again with further editing
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10
Q

polyclonal antibodies

A

collection of immunoglobulin molecules secreted by different B cell lineages within the body that react against a specific antigen, each identifying a different epitope

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11
Q

affinity purification

A

bind the specificity you want to the antibody and wash away the rest; can also use to concentrate a weak antibody into a stronger one

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12
Q

adsorb non-specific antisera

A

opposite of affinity purification, remove the activity you don’t want by binding it up and then washing it away

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13
Q

monoclonal antibody

A

made from a single cloned B-cell with one specificity that can last forever, huge amounts can be produced

  • Fuse myeloma cells with B cells from mouse immunized with antigen, grow in drug-containing medium to kill off unattached/fused myeloma (B cells die in time), select for antigen specific hybridoma
  • Less cross reactivity but has lower affinity and very little avidity (artificial measure of affinity based on having lots of different sites binding at once, higher chance of antibody falling off)
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14
Q

what is serum sickness and how can it be avoided?

A

type of hypersensitivity that is an immune reaction to injected proteins used to treat immune conditions or antiserum; avoid by using human or partially human antibodies

  • Chimeric: variable region from mouse
  • Humanized: hypervariable region from mouse
  • Human
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15
Q

why use secondary antibodies instead of just primary antibodies?

A

saves work and has a more consistant antibody that just using primary antibody and washing the rest away

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16
Q

Enzyme Linked Immuno Sorbant Assay (ELISA)

A
  • antigen stuck to bottom of well/tube, antibody added, unbound antibody washed away, second antibody with enzyme bound binds to first antibody, unbound second antibody washed away
  • amount of second antibody is detected by adding chemical reagent that turns color in presence of enzyme bound to second antibody
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17
Q

immunoflourescence

A

similar to ELISA except second antibody specific to first antibody has fluorescent molecule that emits visible light when exposed to UV light

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18
Q

Western Immunoblot

A
  • separated proteins are bound to nitrocellulose, antibody to protein of interest is reacted to nitrocellulose and specific antiserum binds, unbound antibodies washed away and specific antibodies are detected like ELISA
  • results are quantitative and qualitative: amount, molecular weight, and different forms of antigen
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19
Q

FACS/Flow Cytommetry

A
  • scan large numbers of cells for fluorescence and cell size using highly focused lasers
  • flow cytometers are only capable of analyzing cells
  • cell sorters can analyze and sort cells by the amount of fluorescence
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20
Q

phases of primary immune response

A
  1. Lag/inductive/latent phase: after initial exposure there is a period of time before antibody can be detected
  2. Logarithmic/exponential increase in antibody concentration
  3. Steady state at peak antibody concentration
  4. Decay/decline followed by an extended period of time when a small amount of antibody can be detected
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21
Q

how does the secondary immune response differ from the primary immune response?

A

after initial exposure to antigen (and resulting immune response) immune system remains primed to respond to that antigen

  • Shorter lag time
  • Higher rates of antibody synthesis
  • Higher peak of antibody titer
  • Longer persistence of antibody (e.g., need tetanus booster every 10 yrs)
  • Immediate production and predominance of IgG; IgM response remains the same
  • Higher affinity of antibody
  • Requires less antigen to mount response
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22
Q

toxin vs. toxoid

A
  • Toxin: protein that will kill you, will not necessarily induce immune response
  • Toxoid: same protein that has been modified to induce an immune response (antigenically the same) but it will not kill you
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23
Q

clonal selection theory

A
  • accounts for shorter lag time in secondary response
  • B cells develop specificities and when they respond to antigen it is activated to begin clonal expansion, the next time antigen comes along there are multiples of that B cell to respond
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24
Q

class switch

A

Over time, B cells undergo class switch from IgM expression to IgG expression

  • these memory B cells persist longer
  • this account for the higher rates of antibody synthesis and immediate production and predomindance of IgG class during secondary response
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25
Q

affinity maturation

A

immune system selectes for higher affinity antibodies: the higher affinity the B cell is to the antigen, the longer the B cells are stimulated and can clone

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26
Q

how do T cells assist B cells in the immune response?

A

T helper cells react with antigen on surface of antigen presenting cells via MHCII and co-stimulatory molecules, proliferate and produce factors that stimulate B cells to produce the same antigens that act as co-stimulators (which they can then present to T cells to continue response)

  • recognizes self vs. foreign proteins
  • makes cytokine
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27
Q

innate immune response

A

rapid, constant fixed response involving:

  • barriers i.g, skin
  • phagocytes: recognition, engulfment, degradation of bacteria
  • complement: group of serum proteims that recognize bacterial and help clear them
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28
Q

adaptive immune response

A

takes days and involves antibodies, T-cell recognition, cell mediated activation of innate immune system

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29
Q

B cell

A

small lymphocyte that expresses immunoglobulin on its surface

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30
Q

monocyte

A

circulating precursor cell to macrophage

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31
Q

PMN/Neutrophil

A

phagocytose and kil microorganisms

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32
Q

eosinophil

A

kill antibody-coated parasites through release of granule contents

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33
Q

mast cell

A

involved in expulsion of parasites from body through release of granules containing histamine and other active agents

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34
Q

dendritic cell

A

activate T cells and initiate adaptive immune response

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35
Q

cytokines

A

proteins that alter response of immune system

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36
Q

hapten-carrier effect

A

hapten is seen by B cells and carrier is seen by T cells; proved that something had to be seen by T cells in order to get the B cells to work in both primary and secondary immune responses

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37
Q

antigen presenting cells

A

(e.g., macrophages and dendritic cells) take up antigen, chop it up, and present it on the surface as small peptides on MHCII molecules

  • T cells see the whole antigen in the context of MHCII
  • APC must provide a second or co-stimulatory signal in order for T cell to divide and start producing cytokine
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38
Q

adjuvant

A

compound that increases the immunogenicity of an antigen by subverting the immune response to particular cell types (e.g., by activating T cells instead of B cells)

  • most common in vaccines in aluminum salt
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39
Q

V region

A

variable region, considerable distance away on same chromosome as J and D segments

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40
Q

J region

A

variable region in CDR3 region (site nearest constant region); doesn’t change relative position in genome in IgM/IgD producing B cells compared to the rest of the body but it changes in all other Ig producing B cells; implies rearrangement of DNA

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41
Q

D region

A

diversity region in CDR3 region; segment has different configuration in all B cells compared to its germ line position

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42
Q

junctional diversity

A

novel genetic sequences replace germline sequences in heavy and light chains

  • P nucleotides are found in all joining junctions
  • N nucleotides added by Tdt enzyme found only in developing B cells in the proB stages after birth; add random nucleotides to V-D and D-J joins
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43
Q

class switching

A

Selective splicing of primary RNA transcripts is a mechanism to switch from IgM to IgD

  • T cell help must first signal for activation-induced cytidine deaminase
  • ·when transcript of Ig with M on surface is made, same transcript has coding part for IgD
  • edit to create different heavy chains: IgM secreted, IgM transmembrane or IgD transmembrane
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44
Q

somatic hypermutations

A

when a cell is stimulated during an immune response (particularly with T cell help→AID) AID enzyme attacks certain regions of DNA, allows for another editing (irreversible)

  • Induces mutations which allows variable region to be joined to a new constant region; section of DNA is looped and cut out to allow VDJ to combine with γ chain (makes IgG)
  • Responsible for affinity maturation: seen where antigen and antibody are in contact; improve affinity in places where antigen contacts the antibody
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45
Q

describe the course of immigration/emigration to the thymus

A
  1. Thymic anlage makes chemotactic factors that attract prothymocytes derived from fetal liver and bone marrow
  2. cells enter thymus at cortico-medullary junction via blood vessels
  3. mature T cells leave via venules in medulla→secondary lymphoid organ where they complete maturation​
    • ​​migration controlled by chemokines and sphingosine 1-phosphate receptors
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46
Q

what is the function of the thymus

A

identified as important by immunodeficiencies that cause loss of T cell function

  • T cells become MHC restricted, lineage committed, and tolerized to self-antigens
  • function declines with age (T cells last)
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47
Q

what are the major T cell subsets in the thymus?

A
  • CD34: uncommitted progenitor
  • CD2: committed double negative progenitor
  • CD4, CD8
  • CD8/CD4: uncommitted double positive thymocyte with TCR (majority)
48
Q

what are the two checkpoints in T cell development?

A
  1. ß chain gene rearranges→checkpoint for pre-TCR: analogous to a chain, allows ß to surface and signal that a productive ß chain has been made, stops rearrangement
  2. a gene rearranges→checkpoint for TCR
49
Q

what are the stages of T cell development and the location where they take place in the thymus?

A
  • medulla: Progenitor→proliferation→cortex
  • cortex: double negative T cells commit to lineage→rearrange ß genes→checkpoint for pre-TCR→proliferating double-negative pre-T cells→immature double positive cells→rearrange a genes→checkpoint for TCR→mature double positive cells (have fully functional T cell receptors on them)
50
Q

positive selection

A

selects the useful; double positive thymocytes are recognized by cortical epithelial cells (occurs in cortex)

  • If no contact or weak/no binding→apoptosis
  • If have moderate/strong binding→further development
    • Ex. If receptor binds MHC Class 1→CD8 T cell
  • Ensures that repertoire of TCR only recognizes self MHC molecules
51
Q

negative selection

A

destroys the harmful; double positive thymocytes are recognized by dendritic cells, macrophages, and other cells (occurs in medulla)

  • If tight binding to self peptide/MHC→dies
  • If moderate binding to self peptide/MHC→lives
  • Aire TF regulates expression of tissue specific antigens in medullary epithelial cells for the sole purpose of developing ligands that will negatively select
52
Q

avidity model of positive and negative selection

A
  • affinity of the TCR for the MHC:peptide complex and the density of the complex provide different signal strengths upon binding, which in turn dictates the outcome
    • during positive selection, a strong signal leads to deletion while a weak signal leads to survival
53
Q

T cell repertoire

A

sum of all specificities of mature T cells; shaped by thymic selection and modified in periphery through encounters with antigens

54
Q

how to T cell gene rearrangements generate different TCRs?

A
  • Double negative T cells rearrange ß γ and δ loci
    • Lineage commitment: a/ß vs. γ/δ
  • γ:δ T cell matures→periphery
  • ß chain gene rearranges, pre-TCR assembles (first checkpoint)
    • pre-TCR receptor: analogous to a chain, allows ß chain to surface and signal that a productive ß chain has been made, stops rearrangement
    • Induces proliferation and expression of CD4 and CD8; pre-T cell resumes rearrangement of a, γ and δ genes
    • Multiple rearrangements can be made to produce productive ß-chain locus
55
Q

what are the mechanisms by which immune cells innately recognize pathogens?

A
  • surface barriers
  • inflammation
  • complement
  • cellular barriers
  • NK cells
56
Q

endotoxin (LPS)

A

membrane component of gram-negative cell wall that is not directly toxic but induces body to produce toxic molecules

  • leads to gram-negative sepsis (usually from contaminated IV)
  • heat stable, goes through filters, use LAL assay to see if pyrogen free
  • **recognized by TLR4 **
57
Q

role of toll receptors in pathogen recognition

A
  • macrophage/phagocyte respond to LPS and secret inflammatory cytokines
  • TLR4 recognizes LPS→cascade of phosphorylations to break up complex→NPkB TF regulates production of inflammatory cytokines
58
Q

inflammasome

A

produces IL-8; requires caspase to cleave/activated pro-IL1ß

59
Q

role of different cytokines in innate immunity

A
  • IL1ß and TNFa: increase blood vessels permeability, enable effector cells and fluid containing soluble effector molecules to enter infected tissues
    • TNF has overlapping function with IL-1ß e.g., stimulates T and B cell and induces fever
  • IL-6: induces fat and muscle to metabolize→heat→raises temp in infected tissue
  • CXCL8: recruits neutrophils from blood and guides them to infected tissue
  • IL-12: recruits and activates NK cells which secrete cytokines that strengthen macrophage response to infection
60
Q

complement system

A

small proteins normally circulating as inactive precursors; trigger→proteases cleave specific proteins to release cytokines→cascade of cleavages→massive amplification of the response and activation of cell-killing membrane attack complex

  • activated by classical, alternative, and lectin pathways
61
Q

classical complement pathway

A
  • 3rd to act
  • antigen bound antibodies (or sometimes C1 or C-reactive protein) bind Fc region to the C1 component initiating complement
    • C1 complex: binds single IgM (pentamer) or 2+ IgG
    • C1r enzyme activates C1s via cleavage which cleaves C4 to become C4a and C4b→ultimately C3b is deposited on surface of pathogen
62
Q

alternative complement pathway

A
  • 1st to act
  • spontaneous hydrolysis of C3 (abundant in blood plasma) interacts with factor B and ultimately C3bBb is deposited on surface of pathogen
63
Q

important complement molecules

A
  • C5a: critical chemotactic factor, attracts polys and macrophages; anaphylatoxin
  • C3a: anaphylatoxin→histamine release from mast cells and increased vascular permeability where complement is being fixed draws monocytes and neutrophils
  • C3b: opsonization
  • C5-C9: terminal lytic pathway; only absolutely important in killing Neisseria
64
Q

humoral vs. cellular immunity

A
  • similarities: structure, organization of genes/generation of diversity
  • differences: assembly and expression, nature of antigen and antigen recognition
    • T cells use distinct receptors for antigen
    • TCR/CD3 complex escorts a/ß chains to cell surface; signal transduction
    • you can generate more diversity in TCR vs. BCR
65
Q

what are the differences in antigen recognized by T cell vs. B cells?

A

T cells recognize peptide fragments from antigenic proteins presented by MHC molecules

  • TCR must have simultaneous recognition of MHC and peptide
  • affinity for peptide and MHC is weak relative to antibodies (unable to under go somatic mutation)
  • single MHC molecule can bind multiple peptides with similar sequences/motifs
66
Q

major histocompatibility complex (MHC)

A
  • co-dominant expression
  • MHC diversity is important to survival (high polymorphism at MHC class I extends time until HIV→AIDS)
  • maybe the basis of alloreactivity
  • some diseases may be associated with specific MHC type
  • MHC I: cytosolic pathogens; presented to CD8
  • MHCII: extracellular pathogens/toxins and intravesicular pathogens; presented to CD4
67
Q

superantigens

A
  • bridge between TCR and MHC leading to a much high frequency of responsive T cells compared to conventional antigens
  • e.g., bacterial enterotoxins, TSS, unidentified endogenous antigens
  • overlapping set of symptoms as toxic shock because INF and IL-1ß are made
68
Q

MHC Class I Receptors

A
  • expressed on all nucleated cells
  • cytosolic pathogens degraded in cytosol→peptides attach to TAP protein in ER membrane→ER lumen→peptide placed in binding groove of MHC I→MHC:peptide surfaces→presented to CD8 T cells→cell death (important for viral defense)
69
Q

MHC Class II Receptors

A
  • expressed on hematopoietic cells that are professional APCs and thymic stromal cells
  • intravesicular pathogens degraded in endocytic vesicles→peptides bind to MHC II→displace CLIP and surface→presented to CD4→activation to kill
  • extracellular pathogens/toxins ingested and degraded in endocytic vesicles→peptides bind to MHC II→displace CLIP and surface→ presented to CD4→activation of B cells to secrete Ig to eliminate pathogen
70
Q

alloreactivity

A
  • response in transplant rejection
  • modes of cross-reactive recognition may explain this phenomenon: MHC presented in other individuals appear as non-self, even though T cell responds to non-self, there may be differences in binding dominances (either peptide dominant or MHC dominant)
71
Q

CD4 vs CD8 T cells

A

function as co-receptors on T cels, increased aßTCR sensitivity for peptide:MHC

  • interact with nonvariable regions of MHC II and MHC I respectively
  • focused bidning of T cell to appropriate antigen
72
Q

how are naive T cells activated?

A
  • need an antigen-specific signal AND a costimulatory signal (unless there is a strong 1st signal)
  • signal 1: antigen recognition
  • signal 2: costimulatory signal: B7/CD28
    • only APCs express B7 proteins
    • B7-2 major initial ligand for CD28
    • B7-1 sustains T cell activation (expressed later in response)
  • CD8 and yd T cells are CD28 independent; effector and memory T cells do not need costimulation
73
Q

how do activated T cells proliferate and differentiate?

A
  • naive t cells express low-affinity IL-2 receptor
  • once activated, T cells express high-affinity IL-2 receptor and secrete IL-2
  • binding of IL-2 to high affinity receptor sends signal to T cell that induces proliferation
74
Q

what are the 5 functional classes of effector CD4 T cells?

A
  • TH1: induced by IL12, IFNy; macrophage activation, B cell activation and producong of opsonizing antibodies
  • TH17: IL6, IL21; enhances neutrophil response
  • TH2: induced by IL4, IL5; general activation of B cells to make antibodies
  • TFH: induced by IL16, TGFß, IL23; activates B cells, maturation of antibody responnse
  • Treg: induced by TGFß; supresses other effector T cells
75
Q

CD8 T cells (cytotoxic T lymphocytes/CTLS)

A
  • precursors: low frequency, no lytic granules, non-dividing
  • naive T cell and APC interactions→proliferation, synthesis of granzymes and perforin, and cytokine production
  • kill via 3 mechanism
    • granule exocytosis: predominant pathway, release of granzymes and perforin to induce apoptosis
    • expression of cell surface TNF-family effector molecules (TNF, lymphotoxin, Fas ligand, Trail)
    • secretion of soluble toxic cytokines (TNF, interferon-y)
      *
76
Q

what are the factors that contribute to shutting off the immune response?

A
  • T cell activation regulated by CTLA-4, inhibitory receptor for B7
    • ​has higher affinity for B7 than CD28, competes for binding
    • engagement of CTLA-4 leads to anergy, defects related to autoimmune disease
  • Elimination of antigen or other stimuli
  • Treg
  • Killing by immunoregulatory cells (Fas-FasL)
77
Q

what are the two checkpoints in B cell development

A
  • **pre-BCR **surrogate light chain that connects to heavy chain signals that functional receptor has been made
    • most cells don’t make it, multiple gene rearranges can resce developing B cell
  • B cell receptor produced and recognized​
78
Q

what is the difference between B1 and B2 cells?

A

B1: in fetus, V region repertoire is restricted, located in peritoneal and pleural cavities, self renewing (division, no need for bone marrow), most have IgM, little somatic permutation, little to no memory development

B2= B cell

79
Q

how do central and peripheral tolerance eliminate self-reactive B cells?

A

central tolerance

  • if developing B cell reacts with self-antigen they are retained in bone marrow and undergo apoptosis unless rescuable
  • receptor editing can rescue self-reactive B cell: more opportunities to make light chain through reexpression of RAG

​​peripheral tolerance

  • immature B cells to HEV→lymph node→primary follicle→interactions with follicular dendritic cells and cytokines drives maturation→mature B cells recirculate until they find an antigen, if autoreactive, cells are suppressed by Treg
80
Q

what is the basic structure of BCR and co-receptor?

A
  • cross-linking of B cell receptors by antigen
  • clustering of antigen receptors allows receptor-associated kinases to phosphorylate receptors and induce cascade
  • B cell coreceptor 1: binding to C3b on pathogen facilitates cleavage by factor 1, can then bind to C3d
  • B cell coreceptor 2: receptor and coreceptor cooperate in binding soluble antigen
  • T cell independent antigens: no additional stimulation needed with strong enough cross-linking
81
Q

dynamic processes that occur after a B cell contacts antigen

A
  • capture and display intact antigens by CR2 expressed on follicular dendritic subcapsular sinus macrophages
  • T cell helps drives B cell proliferation and differentiation
  • Naive B cells search for specific antigens presented by dendritic cells in B cell area, naive T cells search for specific antigen presented by dendritic cells in T cell area
    • activated T proliferate/differentiate
    • activated B cells move to boundary region
    • activated B cells present antigen to effector TFH cells, forming cognate interactions
    • T cell cytokines drive B cell diversitification→antibody isotype switching
  • medullary cords are primary focus for expansion of antigen activated B cells
82
Q

memory B cells

A
  • Long-lived cells that don’t divide, exist in periphery until they interact with antigens
  • Secondary response is stronger, faster, more IgG, antibody affinities increase as they go through germinal center reactions
83
Q

what are the mechanisms by which self-tolerance is generated?

A
  • deletion of reactive cells (central tolerance)
    • negative selection of B cells in bone marrow
    • negative selection of T cells in thymus through tissue-specific proteins
    • functional deletion through deletion of helper cells
  • inactivation of reactive cells (peripheral tolerance)
    • ​anergy in autoreactive B/T cells that reach circulation
    • blocking of presentation or activation
84
Q

what are the ways in which antigen regulates self-tolerance?

A
  • chemical nature of antigen stimulates different types of response
    • protein antigens→humoral immunity and CMI
    • polysaccharides and lipids cannot induce CMI
    • proteins induce class switching, affinity maturation, generation of memory
  • amount of antigen determins magnitude and type of response
  • portal of entry
  • packaging of antigen
  • presentation of antigen
85
Q

what are the ways in which antibody regulates self-tolerance?

A
  • *antibody can sequester antigen, *preventing it from being recognized by other antigen recognizing cells
    • e.g., RH disease prevented by utilizing principle of preventing immune response by using dose of antiRh antibody
  • *antibody can contribute to inhibition of antibody production *by cross-linking Ig and TCRs on same B cell
  • immune complexes (antibody+antigen) can regulate either by inhibiting or augmenting B cell response
86
Q

what are the ways in which T cells can regulate self-tolerance?

A

suppression of autoimmune respones by Treg(CD4, CD25 T cells with FoxP3 TF); produce IL-10, TGF-ß suppresses effector T cells to help regulate immune system

87
Q

how does the immune system compensate for pathogen avoidance of host?

A
  • Bacteria: primary adaptive immune response is antibody response
  • Parasites: T cells activate macrophages; CTLs kill infected cells
  • Viruses: T cells activate macrophages; CTLs kill infected cells; NKs; interferons; antibody prevents infection by neutralizing virus
88
Q

immune responses to listeria monocytogenes

A

activated macrophages at site of infection: short term enhancing of macrophages by TH1 for non-specific killing

  • long term immunity is specific and can be transferred with CD4 T cells
89
Q

immune responses to mycobacterium TB

A

T cell response determines outcome of disease

  • TB leprosy through activated TH1 (normal)→organism present at low/undetectable levels, low infectivity, normal T cell responsiveness
  • Lepromatous leprosy through activated TH2 (abnormal)→organisms show florid growth in macrophage, high infectivity, low/absent T cell responsiveness
90
Q

when should you consider immunodeficiency in your differential?

A
  • 2 or more invasive bacterial infections
  • persistant or recurraent sinopulmonary infections
  • unusual agents or unusual severity of common infections
91
Q

severe combined immunodeficiency (SCID)

A
  • x-linked recessive
  • most common: IL2 ychain defect; cytokines that signal through this chain are lost→lymphopenia (no B or T cell production)
  • treat: early death without bone marrow transplant, aggressive antibiotics/virals/fungals antibody while waiting for transplant
  • diagosis: analysis of lymphocyte proliferation in response to mitogens, non-self HLA, specific antigens
92
Q

humoral immunodeficiency

A
  • most common: Bruton’s tyrosine kinase mutation→absence of B cells
  • diagnosis: B cell count and quantitative imunoglobulins (IgA usually most deficient; shows up after birth because you still have mom’s IgA)
  • treat: IgG shots
  • lifelong risk lymphoma and encapsulated bacterial pathogens (e.g., strep. pneumonia)
93
Q

complement immunodeficiency

A
  • CD8 deficiency
  • risk of N. meningitides
  • treat: vaccine, antibiotic prophylaxia for any febrile illness
94
Q

phagocyte deficiency

A
  • most common: chronic granulomatous disease
  • diagnosis: assay of neutrophil NADPH oxidase (normal=blue dye reduction on active neutrophils)
  • highest risk of infections with catalase positive bacteria (produce enough ROS to have itself killed, break down peroxide)
  • treat: antibiotic prophylaxis, IFNy
95
Q

T cell immunodeficiencies

A
  • DiGeorge Syndrome
    • congenital thymic hypoplasia/aplasia (variable T cell numbers and function)
  • HIV/AIDS
    • loss of CD4 cells
96
Q

passive immunization

A

use of immune serum to give an immediate resistance to an infection

97
Q

active immunization

A

act of immunizing with antigens to induce immune response to a pathogen

98
Q

live attenuated vaccine

A

a weakened virus that can replicate to a limited extent

  • delay giving them until after materal antibodies are gone
99
Q

herd immunity

A

when enough individuals are immunized such that spread of an infection is slowed or halted

100
Q

DPT vaccine

A

older vaccine with whole killed pertussis (good adjuvant with strong innate immune responses but often lead to fever)

101
Q

DTaP

A

acellular vaccine (pertussis toxois and other purified components, Al salts); may not work as well

102
Q

IPV

A
  • inactived polio vaccine
  • world is not almost polio-free
  • OPV (rarely causes polio in immunodeficient individuals–no longer used)
    *
103
Q

MMR

A
  • 3 live attenuated virus
  • given at 12-15 mo because infants have maternal antibodies that prevent virus from growing
  • wakefield: autism-MMR link
104
Q

HPV

A
  • protects against types 16, 18 (gardasil also 6 and 11), prevents 70% of cervical cancer
  • recommended for all girls 11-12
105
Q

rabies vaccination

A

post exposure prophylaxis with RIG locally, HDCV and PCECV

106
Q

NK cells

A
  • innate lymphocyte critical for humans; susceptible to frequency herpetic infection (e.g., CMV) without it
  • 2 types: cytolytic and cytokine producing
  • made in bone marrow; can leave blood and traffic into sites of infection in response to inflammation
  • pathogen detected by ILa/ß, TNFa, IL12→proliferation and differentiation of NK which then produces IFNy→activates T cells
  • NKs spare healthy cells that express MHC class I and low amounts of stress induced self molecules
107
Q

what are the “safety features” of NK cells

A
  • can only kill 1 target cell at a time and in close proximity; actived locally
  • sense density of various cell surface molecules, integration of signals dictates how the NK responds
  • default is to remain inhibited: inhibitory receptors trump single activating receptor signal; education in bone marrow sets threshold of inhibitory signaling that NK activating receptors must overcome
108
Q

how does NK fight against CMV?

A
  • CMV down-regulates MHC class 1 and interferes with peptide presentation by MLA to avoid CD8 T cell response but this makes them susceptible to NK killing
  • NK subset epands upon infection and stays elevated throughout life→NK memory
109
Q

how do uterine NK control invasion of fetal trophoblast cells in developing placenta?

A
  • too little invasion: insufficient arterial blood→preeclampsia
  • too much blood supply→obstructed labor due to large fetus
110
Q

what are the mechanisms by which NK cells work?

A
  • macrophages (producing IL12, 15) activate NKs which in turn activate macrophages through secretion of IFNy
  • NKs can limit number of dendritic cells when innate immunty has infection under control OR promote differentiation and migration to lymph node to start up adaptive immune response
  • Nks have TLRs 3,7,8: sense viral infection through binding to ss or dsRNA
111
Q

killer inhibitory receptors (KIRs)

A
  • no direct recognition of HLA-A, B, or C (no peptide recognition involved)
  • CD94:NKG2A receptor turned on in development before KIRs and keep NK cells tolerant until KIRs are acquired, then CD94:NKG2A receptor down-regulated
  • KIRs mediate education of developing NK cell but also actively suppresses killing of healthy cells
112
Q

yd T cells

A
  • plentiful in tissues (especially in gut)
  • involved in tissue homeostasis, repair and protection
  • no MHC restricted
  • recognizes phosphoantigens and lipid antigens
113
Q

ab T cells

A
  • restricted by nonpolymorphic MHC class 1-like molecules (CD1 restricted)
  • CD1 presents myobacterial lipids because they replicated in endosomes and intracellular vesicles, important for control of leprosy and TB
114
Q

NKT cells

A
  • express NK recepors
  • bind glycolipids
  • requires signal from TCR and cytokine for activation
  • do not recirculate between blood and lymph
115
Q

Mucosa Associated Invariant T cells (MAIT)

A
  • effector ab T cells that live in mucosa, liver, blood
  • recognize riboflavin molecules (human cells don’t make these molecules, presented by MR1)

GER Unit 6 (5 decks)

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