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BIIC > Immunology > Flashcards

Immunology Flashcards

1
Q

Major Histocompatibility Complex (MHC)

A
  1. Fxn: present antigens non-covalently bound to MHC Class I and II to specific T cells
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2
Q

Class I MHC

A
  1. On most uncleared cells
  2. Restricts antigen recognition by CD8 T cells
  3. Antigen binding cleft
    A. Peptides 8-10 aa
    B. Anchor residues: specific AAs needed to bind peptide
    1. Allows for variability if similar AAs at defined positions
      C. Binding cleft closed (baseball glove)
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3
Q

Class II MHC

A
  1. One APCs
  2. Restricts antigen recognition by CD4 T cells
  3. Antigen binding cleft
    A. Peptides 10-13 AAs
    B. Cleft open both ends (hot dog on a bun)
    C. Peptides have internal conserved motifs instead of anchor residues
    D. Generally only APCs
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4
Q

Antigen capture

A
  1. Pathogens enter
  2. Professional APCs in tissues take up and present antigen
  3. APCs migrate -> lymph nodes
  4. Lymph nodes = grand central station
  5. MHC-TCR engagement -> T cells proliferate, activate, and migrate to infection site via efferent vessel
  6. Exception: blood Bourne pathogens filter thru spleen
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5
Q

Dendritic cell migration

A

Cytokines (IL-1, IL-6, TNF-alpha) trigger dendritic cells

  1. Lose adhesiveness for epithelium
  2. Expresses CCR7: chemokine receptor released by lymph node containing presenting APCs
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6
Q

Cells in lymph nodes

A
  1. Dendritic cells: inc MHC class II
  2. Macrophages: must be activated (IFN-gamma) for inc MHC class II
  3. B cells: constitutively express MHC class II
    A. Activated by cytokines for co-stimulatory molecules
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7
Q

MHC structure

A
  1. Peptide binding cleft at amino terminal end
  2. Beta 2-microglobin: MHC class I
  3. MHC class II: alpha and beta chains
  4. Antigen binding cleft
    A. Doesn’t have fine specificity
    B. 2,000 peptides/MHC allele
    C. MHC class I
    D. MHC class II
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8
Q

MHC class I peptides loading

A

Cytosolic/endogenous pathway

  1. Proteins ubinquitinated -> targets for proteosomes
  2. Proteosomes chop proteins -> peptides
  3. TAP (transporter associated w/ antigen processing) uses ATP to translocations peptides -> ER lumen
  4. Tapasin: links empty class I (structure held by chaperones) to TAP for easy access to peptides
  5. Fitting peptide releases chaperones
  6. Stable MHC-peptide complex -> surface via golgi
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9
Q

MHC class II peptide loading

A

Exogenous/endocytic pathway
1. MHC class II synthesis in ER constantly
A. Alpha and beta chains joined by chaperones and invariant chain (Ii)
2. class II w/ Ii thru golgi -> MHC class II compartment (MIIC)
3. EC proteins taken up by APC into endosomes
4. Proteins digested by proteosomes in endosome when pH drops
5. Peptides fuse w/ MIIC
6. Enzymes digest Ii -> CLIP (class II invariant chain peptide)
7. HLA-DM assists replacement of CLIP w/ antigenic peptide
8. Stable MHC II-peptide -> cell surface for TCR to recognize

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10
Q

Proteosomes inhibitors

A 
Lead to protein, P53 accumulation -> apoptosis
1. Used in cancer tx 
  A. Bortezomid
  B. Ixazomid
  C. Carfilzomid
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11
Q

Cross presentation

A 
Peptide from intra or extracellular pathogen -> cytosolic pathway for MHC class I
1. DC digest both to stimulate helper and cytotoxic T cells in close proximity
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12
Q

HLA (human leukocyte antigen)

A
  1. Class I: HLA-A,B, and C

2. Class II: DQ, DR, and DP

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13
Q

MHC genetics

A
  1. Codominant expression
  2. Extremely polymorphic
  3. Family members don’t share unless ID twins
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14
Q

Rheumatoid arthritis HLA allele

A

DR4

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15
Q

Insulin-dependent diabetes mellitus HLA allele

A

DR3/DR4

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16
Q

MS, Goodpasture’s HLA allele

A

DR2

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17
Q

SLE HLA allele

A

DR2/DR3

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18
Q

Psoriasis, ankylosing spondylitis, IBS, reactive arthritis (PAIR) HLA allele

A

B27

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19
Q

Celiac HLA allele

A

(I 8 2 much gluten at DQ)

DQ2 or DQ8

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20
Q

Graves, myasthenia gravis HLA allele

A

B8

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21
Q

B cell surface markers

A

CD19, 20, 21

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22
Q

T cell (all) surface markers

A

CD3

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23
Q

Cytotoxic T cell surface markers

A

CD8

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24
Q

Helper T cell surface marker

A

CD4

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25
Q

NK cell surface marker

A

CD16, 56

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26
Q

Alpha-beta T cells

A
  1. 90% T cells
  2. Secondary lymphoid tissues
  3. Peptide-MHC
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27
Q

Gamma-beta T cells

A
  1. Exception to rule
  2. Can recognize free antigens or processed (lipids or peptides)
  3. <10% T cells
  4. Possible role in pathogenesis of psoriasis and RA
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28
Q

TCR gene rearrangement

A

Allows diversity

1. Beta chain rearranges before alpha chain

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29
Q

T cell maturation

A 
1. Pro-T cell
  A. Proliferation
  B. Initiation somatic recombination of beta chains
2. Pre-T cell
  A. Initiation somatic recombination of alpha chains
3. Immature T cells
  A. Expression TCR
  B. Expression CD4 and CD8 = double (+)
4. Mature T cell
  A. Single (+) = either CD4 or CD8
  B. Released into circulation
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30
Q

T cell selection

A

Goldilocks Principle
1. (+) selection: weak recognition MHC molecule presenting self-peptide -> survival and down regulation either CD4 or CD8
A. Recognize MHC but not self-antigens -> advance
2. (-) selection: too strong/no recognition of self-peptide w/in MHC molecules -> apoptosis

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31
Q

T cell signal transduction

A
  1. CD3, zeta chains, and ITAMS
  2. Activation: CD28 costimulation
  3. Inhibition: CTLA-4 and PD-1
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32
Q

T cell stabilizing adhesions

A
  1. CD4/CD8

2. LFA-1

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33
Q

T cell activation

A
  1. Secondary lymphoid organs
  2. Two activation signals
    A. From interaction naive T cells w/ APCs
    B. 1st = binding TCR or T cell to MHC on APC
    C. 2nd = binding B7 on APC w/ CD28 on T cell
    D. Need both to activate
  3. 2 signals -> 3 transcription factors
    A. NFAT
    B. NF-KB
    C. AP-1
    D. Affect T cell fxn, activation state, and metabolism
  4. Transcription factors -> transcription IL-2 gene
    A. IL-2 necessary for proliferation (activates JAK/STAT pathway)
  5. Inhibiting activation
    A. Drugs prevent NFAT generation and prevents IL-2 transcription
    1. Cyclosporin
    2. Tacrolimus
      B. Immunosuppressive therapies
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34
Q

T cell proliferation/differentiation

A
  1. 1-2 days after activation
  2. Proliferate -> clone of antigen specific T cell
  3. Differentiate -> 1 of 2 types
    A. Effector T cell: primary immune response, short-lived
    1. Helper
    2. Cytotoxic
      B. Memory T cells: respond subsequent exposures w/ inc sensitivity
    3. Secondary immune response
    4. Long-lived
  4. Inhibition
    A. After several rounds, T cell -> CTLA-4
    B. CTLA-4 binds B7 inhibits proliferation
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35
Q

Effector helper T cells (Th) (CD4)

A
  1. Th1: control cell-mediated rxns
  2. Th2: control humoral rxns
  3. Th17: inflam disorders and some microbial defense
  4. Treg: contraction and inhibition immune response
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36
Q

Th1 cells

A 
Control cell-mediated rxns
1. Intracellular pathogens
2. Bacteria
3. Viruses
4. Fungi
5. Role in chronic inflammation
6. Differentiation
  A. IL-12 and IFN-gamma from intracellular activated dendritic and NK cells activate Th1 cells
7. Cytokines
  A. IFN-gamma
  B. IL-2
  C. TNF-alpha
8. Synapse: CD40/CD20L
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37
Q

Th2 cells

A 
Control humoral rxns
1. Extracellular pathogens
2. Parasites
3. Allergens
4. Encourage inc IgE
5. Differentiation
  A. IL-4 secreted by Th2
    1. Autocrine growth factor in absence of IL-12 from APC
  B. IL-4 also secreted from mast cells and eosinophils w/ parasites and allergens
6. Cytokines
  A. IL-4
  B. IL-5
  C. IL-13
7. Inhibits Mi macrophages and activates M2
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38
Q

Th17 cells

A

Inflammatory disorders and some microbial defense
1. Extracellular pathogens
2. Role in autoimmune disorders
3. Differentiation
A. TGF-beta = immunoregulatory cytokine
B. Cooperation inflammatory and anti-inflammatory cytokines -> T cell production/inc IL-21
C. IL-21 = autocrine cytokine -> Th17 differentiation
4. Cytokines
A. IL-17
B. IL-21
C. IL-22
5. Inc inflammatory processes
A. Inc acute phase proteins
B. Inc chemokines attract WBCs
C. Stimulate inflammatory cytokines from other cells

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39
Q

Effector cytotoxic T cells (CTLs) (CD8)

A 
1. Differentiation
  A. Th1 cells -> cytokines -> naive Tc cells -> CTLs
2. Fxn: kill target cells w/ intracellular pathogens
  A. Requires cell-to-cell contact
  B. Mechanisms
    1. Granzymes/perforin
    2. Fas/FasL
    3. Cytotoxic cytokines
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40
Q

Fas/FasL

A

CTL killing mechanism

  1. Fas expressed by all nucleated cells
  2. Only activated CTLs express FasL
  3. Only binds and -> apoptosis if CTL binds and holds MHC class I
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41
Q

Cytotoxic cytokines

A

CTL killing mechanism

  1. TNF
  2. LT (lymphotoxin)
  3. Produced after binding MHC and TNFR1 on target cell
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42
Q

Superantigens

A

Hold any MHC to any T cells ->

  1. Massive T cell activation and expansion
  2. Cytokine storm: INF-gamma
  3. Kill healthy cells
  4. Staph
  5. Group A strep
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43
Q

CMI response to intracellular bacteria

A
  1. Phagocytes -> IL-12 -> Th1 cell response -> IFN-gamma and CD40L -> activate macrophages to inc ROS
  2. If macrophage can’t kill pathogen after IFN-gamma activation
    A. Pathogen presented on MHC I to CTLs
    B. CTL kills affected cells
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44
Q

CMI response to viruses

A
  1. IFN-alpha and beta initiate rxn
    A. Activate antiviral mechanism in neighboring cells
    1. IFNs land on receptors
    2. Activate RNAse
    3. RNAse chops viral RNA
    4. Viral replication stopped
      B. Inc MHC class I expression -> inc adaptive response
      C. Stimulate NK cells
    5. IL-12 -> NK secrete IFN-gamma and TNF
    6. IL-15 -> NK proliferation and activation
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45
Q

Memory T cells

A
  1. Last years to lifetime
  2. More rapid and amplified response to subsequent exposures
  3. Mediate secondary response
  4. Maintenance: IL-7 blocks apoptosis cascade and supports low-level proliferation
  5. Types
    A. Central memory T cells (Tcm)
    B. Effector memory T cells (Tem)
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46
Q

Central memory T cells

A
  1. Secondary lymphoid tissue

2. Proliferate quickly on secondary exposure

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47
Q

Effector memory T cells

A
  1. Peripheral tissues

2. Secrete cytokines but don’t proliferate as much

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48
Q

Regulatory T cells

A
  1. Suppression CD4+ FoxP3+ cell
  2. Natural or induced
  3. Dec immune response
  4. Active in contraction phase
  5. Inhibit auto-reactive T cell
  6. Mechanism
    A. Express CTLA-4
    B. Anti-inflam cytokines -> healing
    1. IL-10
    2. TGF-beta
      C. Inc IL-2 receptors -> “hog” IL-2 and prevents it from activating other T cells
  7. IPEX syndrome
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49
Q

Allogeneic

A

Genetically dissimilar

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50
Q

Alloimmunization

A

Shows alloantigen to immune system

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51
Q

Blood type H

A

Bombay blood

  1. Super rare
  2. Can only receive H
  3. Can give to others
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52
Q

Whole blood

A
  1. Collected in anti-coagulant
  2. Shelf life: 35 days
  3. At 24 hrs
    A. Granulocytes dysfunctional
    B. Plasma coag factor lose functionality
  4. Indications
    A. Trauma
    B. Massive blood loss
  5. Advantages
    A. Colloid osmotic pressure and coag factors
    B. Doesn’t expose pt to multiple donors
  6. High military use
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53
Q

RBC transfusion

A
  1. “Packed RBCs/RBC concentrates”
  2. Platelet-rich plasma removed
  3. WBCs remain
  4. Shelf life: 42 days w/ preservatives
  5. Type O used in pts w/ unknown blood type and emergent situations
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54
Q

Leukocyte-reduced RBCs (LRRCs)

A
  1. WBCs removed
  2. Indications
    A. Prevent febrile nonhemolytic transfusion rxn
    B. Mitigate rxn to MHC/HLA antigens
    C. Prevent transfusion-transmitted CMV infection
    D. Prevent transfusion-related immunomodulation (TRIM)
  3. Very expensive to make
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55
Q

Washed RBCs

A
  1. Plasma proteins removed
  2. Indications
    A. Pt has had allergic rxn to transfusion
    B. IgA deficient pts
    1. Exposure to IgA -> anaphylaxis
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56
Q

Irradiated RBCs

A
  1. Very expensive
  2. Indications
    A. Prevent transfusion-associated GVHD
    1. Rare, but fatal
    2. Neonates
    3. Pts w/ blood cancers
    4. Stem-cell transplant pts
    5. Immunodeficiency pts
  3. Can’t replicate
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57
Q

Frozen RBCs

A 
1. Destroys most constituents 
  A. RBCs and few WBCs saved
2. Frozen storage up to 10 yrs
3. Use w/in 24 hrs after thawing
4. Stock pile of rare donor types
5. Autologous donations for later use
6. Expensive
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58
Q

Nucleic acid amplification testing

A
  1. MP-NAT: minipool NAT - pooled samples from up to 16 donors
  2. Multiplex NAT: tests for multiple pathogens
  3. ID-NAT: individual donor NAT
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59
Q

Pathogen reduction technology for transfusion

A
  1. Filters
  2. UV light
  3. Culturing tech
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60
Q

Blood cell subsititutes

A
  1. Nothing can replace whole blood
  2. RBC substitutes
    A. Perfluorcarbons
    B. Hemoglobin-based O2 carriers
    C. Stem cell derived
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61
Q

B1 cells

A
  1. Super rare
  2. Dev in fetal liver
  3. Self-renewing
  4. Body cavities
  5. Respond carb antigens on bacteria
  6. Secrete IgM
  7. Limited V-region repertoire (innate-like receptor)
  8. Membrane IgM+IgD-
  9. Thymus-independent response
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62
Q

Conventional B2 cells

A
  1. Develop in bone marrow
  2. Respond protein antigens
  3. Secretes IgM first, then switches
  4. Diverse V-region repertoire
  5. Membrane IgM+IgD+ (IgMlow, IgDhigh)
  6. Thymus dependent response
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63
Q

B2 cell development

A 
1. CLP proliferates -> Pro-B/T cells 
  A. Failure to express CD19 -> apoptosis 
  B. Germline DNA
  C. Ig expression: none 
2. Pre-B cells
  A. Recombined H chain gene 
  B. Ig expression: Pre-BCR and cytoplasmic u 
  C. Failure to express antigen receptor -> apoptosis 
3. Immature B cells 
  A. Recombined H chain
  B. Ig expression: IgM
  C. Weak antigen recognition -> muture
  D. Strong antigen recognition -> apoptosis 
  E. Functional
4. Mature B cells 
  A. Ig expression: IgM and IgD
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64
Q

B cell rearrangements

A

*T cells don’t do this
1. Pro-B cell
A. H-chain rearrangement
2. Pre-B cell
A. L-chain rearrangement
3. Immature B cells
A. Rearrangement stops

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65
Q

Self-reactive B cells

A
  1. Random generation B and T cell receptors -> receptors specific for self
  2. Clonal deletion
    A. Both B and T cells go thru (-) selection -> eliminate self-reactive receptors
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66
Q

Anergy

A
  1. B cells w/ weaker rxn to self-antigens -> Anergic (unresponsive)
  2. Dec IgM expression
  3. Can’t respond to antigen
  4. Don’t know why maintained in blood
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67
Q

BCR editing

A
  1. “do over” option for B cells that react to self
  2. More light chain rearrangement
  3. Retest (-) selection
  4. Need RAG
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68
Q

Clonal ignorance

A 
Self-reactive but do’t respond during development
1. Not “taught” which antigen to target
  A. Antigen not encountered
  B. Low concentration
  C. Binds too weakly
2. Not anergic
3. Exist w/ low app invite for antigen
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69
Q

Mature B cell CD markers

A
  1. IgM+, IgD+
  2. CD19+, CD20+: used to ID B cells
  3. CD21-: present when activated by signal from spleen
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70
Q

B cell (+) selection

A
  1. If don’t enter follicle -> die (~3 days)
  2. Survival signal in follicle -> CD21 expression in mature cells
  3. Competition to enter follicles
    A. Memory and mature cells favored
  4. B cells leave follicle if no antigen encounter
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71
Q

Marginal zone B cells (MZ B cells)

A
  1. Develop in bone marrow
  2. Resident in spleen - don’t recirculate
  3. Respond carb antigens on bacteria
  4. Limited V-region repertoire (innate-like receptor)
  5. Membrane IgM+IgD-
  6. Thymus-independent response
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72
Q

Mature B cell outcomes

A
  1. Antibody secretion (IgM first)
  2. Isotype switching
  3. Affinity maturation
  4. Memory B cell
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73
Q

B cell antigen recognition in periphery

A
  1. Recognition -> lymphocyte activation and differentiation
    A. Includes plasma and memory cells
  2. Peripheral tolerance: mechanism to eliminate self-reactive lymphocytes in periphery
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74
Q

B cell activation

A
  1. Secrete Ab
  2. IgM always first
  3. Cytokines -> isotype switching
    A. From macrophages and Th cells
  4. With T cell help
    A. Strong response cytokine production
    B. Class switching
    C. Induction of memory cells
    D. Affinity maturation
    E. Conventional B cells
    F. Protein antigens
    G. Thymus-dependent antigens (TD)
  5. W/o T cell help
    A. Limited response
    B. Limited class switching
    C. Limited memory
    D. Less affinity maturation
    E. B-1/MZ B cells
    F. Antigens not usually proteins
    G. Thymus-independent antigens (TI)
  6. 2 signals
75
Q

B cell activation signals

A
  1. Antigens bind BCR (> or = 2)
    A. Crosslinking BCRs
    1. Cross linked BCR
    2. Signal from transmembrane signaling molecules
      A. Ig alpha and Ig beta : take place of T cell CD3
    3. Signal -> transcription factors
    4. Cell proliferation and differentiation
    5. Consequences
      A. Class II MHC inc
      B. Inc B7 -> T cell activation
      C. Antigen presentation
      D. Adhesion molecules: stop B cells
      E. Inc CCR7: chemokine receptor
      F. Migrate to edge of follicle and interact w/ T cells
  2. Engagement w/ helper T cells (T dependent Ab response)
    A. (MHC:TCR) + (CD40:CD40L) = proliferation
    B. Inc cytokines (IL-4) -> proliferation and differentiation
  3. Signal #2 for T-independent antigens
    A. No T cell help
    B. MZ and B-1 cells play greater role
    C. Non-protein antigens
    D. Cells shorter-lived
    E. Ab less affinity
    F. Doesn’t generate memory
76
Q

Affinity maturation

A

Abs w/ varying affinity for same antigen

  1. Germinal centers
  2. Rapid B cell proliferation
  3. Somatic hypermutation of specific areas of variable regions
  4. Selects for Abs w/ highest affinities for antigens
77
Q

Isotype switching

A

Same specificity, different fxn

  1. Depends on cytokines present
  2. Switch out heavy chains
78
Q

Clonal proliferation

A
  1. 4 postulates
    A. B and T cells express single type of receptor w/ unique specificity
    B. B/T cell activated when antigen encountered
    C. B/T cells proliferate and differentiate w/ same specificity = clonal proliferation
    D. Self-reactive B/T cells should be deleted = clonal deletion
79
Q

Autoimmunity

A

Loss of tolerance by B/T cells

80
Q

Tolerance

A

State of unresponsive lymphocytes to antigen after encounter w/ it

  1. Central
  2. Peripheral
81
Q

Central tolerance

A 
1. T cells 
  A. Goldilocks principle 
  B. AIRE: autoimmune regulator
    1. Self-antigens from other areas presented in thymus -I autoimmunity when released
2. B cells
  A. Deletion
  B. Receptor editing
82
Q

Peripheral tolerance

A 
1. T cells 
  A. Anergy
    1. Don’t inc B7 or CD40 by presenting B cells 
  B. Suppression (Treg)
  C. Deletion
     1. No 2nd signal or expressing CTLA-4
2. B cells 
  A. Anergy
    1. No 2nd signal 
  B. Deletion
    1. No 2nd signal
  C. Regulation by inhibitory receptors
83
Q

Immune privilege

A 
Lymphocytes kept out so they don’t notice antigens 
1. Sites have backup systems Incase they get in
  A. Dec MHC
  B. Inc Fas/FasL
  C. Inc Treg
2. Locations 
  A. Brain
  B. Eye 
  C. Uterus
  D. Testis
84
Q

Tolerance failure

A 
1. Central in primary lymphoid tissue
  A. (-) selection
2. Peripheral tolerance in secondary lymphoid tissue
  A. T/B cells not anergic, suppressed, or deleted
3. Genetics 
  A. Mutations in immune genes
  B. MHC alleles
4. Infection and inflammation
  A. Poor contraction or regulation
  B. Molecular mimicry
85
Q

Molecular mimicry

A 
Microbe has epitope that looks like self-antigen
1. Cross-reactive T cells
2. Cross-reactive Abs 
3. Adaptive immune cells attack self
4. Group A strep
  A. Strep pyogenes 
    1. Scarlet fever
    2. Rheumatic fever: Abs cross-react w/ cardiac myosin
    3. Necrotizing fasciitis
86
Q

Bacteremia

A
  1. Septic shock #1 COD in ICUs
  2. Gram (-) bacteria expressing LPS -> macrophages spleen and liver
  3. Bacteremia
    A. Bacteria in blood stream
    B. Leads to septicemia
  4. Septicemia
    A. Bacteria and toxins in blood
    B. Acute inflammatory response
  5. Toxic shock
87
Q

Toxic shock- extracellular bacteria

A
  1. Causes
    A. Inflammation mediated tissue destruction
    B. Toxins
    1. Exotoxins: heat labile (Cytotoxins and neurotoxins)
    2. Enterotoxin: exotoxins in GI
    3. Endotoxins: in cell wall (Heat stable)
88
Q

High concentrations TNF-alpha

A
  1. Endogenous pyrogen: reg hypothalamus -> fever
  2. Macrophages -> IL-1, IL-6
  3. Activates coag system from liver
  4. Dec marrow stem cell division
  5. Cachexia
  6. DIC and vascular collapse = hallmark septic shock
    A. Irreversible and fatal
89
Q

Humoral immune repose

A

Fight extracellular bacteria

  1. Bacteria protein taken up by APCs -> processed and presented by exogenous pathway
  2. Presentation Class II MHC -> CD4 T cells
  3. CD4 -> cytokines -> B cells
  4. B cells -> Abs
90
Q

Antibody fxns

A
  1. IgG inc phagocytosis by macrophages and neutrophils
  2. Opsonization -I motility and invasion
  3. IgG and IgM neutralize toxins
  4. IgA neutralize GI and resp toxins
  5. IgG and IgM -> complement -> MAC
91
Q

Innate immunity against extracellular pathogens

A
  1. Phagocytosis by macrophages and neutrophils
  2. Complement activation
    A. Gun+ peptidoglycan- and Gm-LPS -> lectin complement cascade
    B. Cb3 opsonized bacteria-> inc phagocytosis
    C. MAC lysis
92
Q

Innate immunity against intracellular pathogens

A
  1. First line of defense
  2. Phagocytosis
  3. Initially neutrophils, NK cells
  4. IFN-gamma -> macrophages
93
Q

Cell-mediated immune (CMI) response

A
  1. Designed to fight intracellular pathogens and tumor cells
  2. Tailored depending on pathogen
  3. Steps
    A. Macrophages ingest pathogen but need help -> IL-12 -> NK cells
    B. NK cells -> IFN-gamma -> inc ROS in macrophages
    C. Pathogens processed and presented on MHC by endogenous pathway
    D. Presentation Class I MHC -> CD8 T cells
    E. CD8 T cells kill infected cells via granzymes/perforin, Fas/FasL, or cytotoxic cytokine TNF
    F. Infected cells -> lots of IFN-gamma -> inc CD8 T cell activation
94
Q

Granulomatous inflammation

A
  1. Granuloma = lesion dev as result of prolonged chemotactic stimulation
    A. Epitheloid cells: enlarged macrophages
    B. Multinucleated giant cells
    C. Fibroblasts
    D. T cells
    E. Can become necrotic in center
    F. Fxn: wall off pathogen if can’t be eliminated
  2. Valley fever: fungal organism
  3. TB: bacteria
  4. Macrophages release enzymes -> surrounding tissue damage
95
Q

Innate immunity against fungi

A
  1. APCs usually ineffective bc too big for phagocytosis
  2. Alternative and lectin complement cascade triggered by cell wall components
  3. Complement mediated degranulation -> inflammation
96
Q

Adaptive immunity against fungi

A
  1. IL-17 from Th17 cells -> inc neutrophils -> inc inflammation
  2. Inflammation -> antimicrobial substances
    A. Defensins: hydrophobic peptides inserted into mem and disrupt it
    1. Produced by
      A. Epithelial cells mucosal layers
      B. Neutrophils
      C. NK cells
      D. CTLs
    2. Directly toxic to
      A. Fungi
      B. Bacteria
      C. Enveloped viruses
97
Q

Immunodiagnositic Assays

A
  1. Detect presence (and often amt) of Ab/Ag
    A. Titer = relative concentration Ab/Ag in sample
  2. Agglutination rxns
  3. Labeling
98
Q

Agglutination Rxns

A
  1. Ab cross-link w/ Ag-coated particles -> agglutinate
  2. IgM best because pentamer
  3. Hemagglutination: involves RBCs
  4. Soluble attaches insoluble -> precip
  5. Coomb’s test
  6. Slide agglutination
  7. Agglutination inhibition
99
Q

Coomb’s test

A 
1. Direct: detect hemolytic anemia 
  A. Blood sample has Ab
  B. Coomb’s reagent has Ag
  C. Agglutination = cross-linking
2. Indirect: used to test blood type
  A. Pt serum has Ab
  B. Donor blood added
  C. Pt Abs bind donor RBCs
  D. Add Coombs reagent binds pt Ab on donor RBCs
  E. Agglutination
100
Q

Slide agglutination

A
  1. Cheap, easy
  2. Hemagglutingation
  3. Used military
  4. Bacterial agglutination
  5. Latex agglutination
101
Q

Bacterial agglutination

A

Agglutinate when mixed w/ pt serum w/ Ab in it

102
Q

Latex agglutination

A

Latex beads w/ Ag/Ab

103
Q

Agglutination inhibition

A

Absence of agglutination = (+)

  1. Ab and Ag-coated beads in kit => agglutination just kit reacting w/ self (-)
  2. Pt sample w/ Ag competes w/ Ag-coated beads and takes up binding sites on Ab instead => no agglutination (+)
104
Q

Hemagglutination

A
  1. Type RBCs
  2. (+)= spread out in well
  3. (-) = small “button” RBCs
105
Q

Labeling

A 
Visualization and/or quantification
1. Fluorophores
  A. Flow cytometry 
  B. Immunofluorescence microscopy
  C. Western blot
2. Enzymes or substrates
  A. ELISA
106
Q

Flow cytometry

A

Abs to cell-specific surface markers labeled w/ different dyes
1. Machine counts them based on color and graphs it

107
Q

Immunofluorescence microscopy

A
  1. Direct (DFA)
    A. Labeled primary Ab directly binds cells/tissue -> Ag present
  2. Indirect (IFA)
    A. Labeled secondary Ab binds to and indicates presence of primary Ab specific for tissue antigen
    B. Boosts signal to make it brighter
108
Q

ELISA

A 
Enzyme-linked Immunosorbent Assays
1. Enzyme conjugated to Ab reacts w/ colorless substrate -> colored product
2. Detect and quant Ag and Ab in pt sample
3. Common enzymes
  A. Horseradish peroxidase
  B. Alkaline phosphate 
4. Methods
  A. Direct
  B. Indirect
  C. Sandwich: ID Ag instead of Ab to inc signal 
5. Uses
  A. HIV testing
  B. Drugs
  C. Infections 
  D. Hormone levels
109
Q

Blood sporazoa

A
  1. Plasmodium species

2. Babesia microti

110
Q

Blood flagellates

A
  1. Trypanosoma species

2. Leishmania species

111
Q

Blood flukes

A

Schistosoma species

112
Q

Malaria

A
  1. One child dies every 30 sec
  2. Distribution: 2,000 cases/yr in US
  3. Transmission
    A. Transplacental
    B. Anopheles mosquitoes
  4. Plasmodium species
    A. P. Falciparum - most common and pathogenic
    B. P. Vivax - common
    C. P. Malariae
    D. P. Ovale
    E. P. Knowlesi (zoonotic)
113
Q

P. Falciparum

A
  1. Unique gametocytes
  2. Most common cause of jaundice in endemic areas
  3. Most pathogenic
    A. Parasitized RBCs stick to vessel endothelium
    1. Obstruction
    2. Thrombosis
    3. Local ischemia
  4. High rate fatal complications
    A. Cerebral malaria
    1. Neurological dysfunction
    2. Encephalitis
      B. Malarial hyperpyrexia
      C. Algid malaria (circ shock)
      D. Black water fever: dark urine from hemolysis -> kidney failure
114
Q

Malaria paroxysms

A

Closely related to event in blood stream
1. Chills, nausea, vomiting, and headache: schizonts burst and parasites enter bloodstream
A. Lasts 15-60 min
2. Febrile stage (>40C): invade new RBCs
A. Last several hrs
3. Sweating stage: dec temp, fatigue/sleep

115
Q

Malaria Dx

A
  1. Blood smear: Giemsa stain
  2. Rapid antigen test (RAT)/rapid diagnostic test
    A. Stick test
    B. Low specificity
    C. PCR
116
Q

Malaria control challenges

A
  1. Vector insecticide resistance
  2. Parasite gene deletions -> false (-) on dx tests
  3. Parasite drug efficacy and resistance
117
Q

Malaria vaccines

A
  1. PfSPZ: cryopreserved irradiated P. Falciparum sporozoites

2. RTS, S/AS01: recombinant circumsporozoite of P. Falciparum

118
Q

Trypanosomes

A
  1. T. Brucei species vary glycoprotein coat => hard to dx
  2. African sleeping sickness
  3. Chaga’s disease
119
Q

African sleeping sickness

A
  1. Tsetse flies
  2. T. Brucei rhodesiense (Eastern)
    A. Worse- quickly fatal
  3. T. Brucei gambiense (Western)
  4. Presentation
    A. Swelling at bite site
    B. CNS: lassitude
    C. Anorexia
    D. Tissue wasting
    E. Unconsciousness
    F. Eventual death
  5. Dx:
    A. Blood smear
    B. LN aspirate
    C. CSF
  6. Control
    A. Isolation
    B. Fly control measures
120
Q

Chaga’s disease

A 
American type African sleeping sickness
1. Kissing bugs (triatoma)
2. Trypanosoma cruzi
3. Blood forms in early acute stage and at intervals later
  A. Trypomastigotes: extracellular
4. Tissue forms in heart muscle, liver, and brain
  A. Amastigotes: intracellular colonies (dot/dash) 
5. No effective tx
6. Dx: blood smear
7. Control: insecticides 
8. Usually self-limiting
9. Mostly in S. America
121
Q

Chaga’s disease presentation

A
  1. Romana’s sign: periorbital swelling and conjunctivitis
  2. Fever
  3. Regional lymphadenitis
  4. Interstitial myocarditis
  5. Megaesophagus
  6. Megacolon
122
Q

Leishmania

A
  1. Sandfly transmission
  2. Cutaneous
    A. Names vary w/ geographical location
    B. Wet or dry
  3. Mucocutaneous
  4. Visceral
  5. Dx: RDT
  6. Control: vector management
123
Q

Mucocutaneous Leishmania

A 
Espundia
1. Leishmania braziliensis 
2. Locations
  A. Amazonian basin
  B. Peru
  C. Mexico
  D. Guatemala
3. Slow growing and large ulcers 
4. Rarely progress
  A. Asphyxiation 
  B. Starvation
  C. Stable resp infection
5. Cultural stigma => may avoid finding help
124
Q

Visceral Leishmania

A
  1. Leishmania donovani
  2. Usually fatal w/o tx
  3. Presentation
    A. +/- dermal symptoms
    B. Fever
    C. Hepatosplenomegaly
    D. Wt loss
    E. Swollen lymph nodes
    F. Anemias
    1. Low RBCs
    2. Low WBCs
    3. Low platelets
  4. Can by epidemic
  5. Kala-azar (black fever)
    A. Often fatal
    B. Post-kala-azar dermal Leishmaniasis (PKDL) if recover
    1. Nodules and rash (look like cutaneous)
125
Q

Schistosoma

A 
Valentine parasite
1. Long worms
2. Live 10-20 yrs in venous system
3. Schistosoma mansoni: inf mesenteric veins large intestine 
4. S. Japonicum: inf and sup mesenteric veins small intestine 
5. S. Haematolbium: veins urinary bladder
6. 200 million people globally 
7. DX: O and P: fecal sample detects eggs
8. Females lay 100s-1000s eggs/day
  A. Swept thru veins
    1. Lodge in liver -> granulomatosis 
       A. Fibrosis
       B. Portal HTN
       C. Hepatosplenomegaly
    2. Excreted w/ urine/feces
9. Control: none
126
Q

Schistosoma presentation

A
  1. Itchy rash w/in 1 hr
  2. 2-12 wks after exposure
    A. Fever
    B. Headache
    C. Chills
    D. Diarrhea
    E. Aka: katayama fever/snail fever
  3. Inc eosinophils
127
Q

Helminths

A
  1. Physical size = challenge for immune system
  2. Most eat mucosal tissue or blood
  3. Secrete pathogenic proteins
    A. Immune system can usually respond to proteins
    B. Excretory-secretory (ES) proteins
    1. Unique to helminths
    2. Ligate TLRs -I innate immune response
  4. Innate immunity not critical - no defined PAMPs
  5. Humoral and CMI very imp
    A. Skewed toward Th2 response -> B cells -> IgE
    B. Helminths can molt surface antigens
128
Q

Paragonimiasis

A

Worm in crawfish that can cause lung infections

129
Q

Adaptive immunity against helminths

A
  1. Parasites trigger IgE class switching
  2. Mast cells degranulation and tissue inflam
  3. Eosinophils called in -> Type 1 hypersensitivity response
  4. Inflammation -> parasites detach from mucosa
  5. T cells trigger B cells -> IgE -> coats parasite -> pathogen expelled
130
Q

Protozoa

A
  1. Often many life stages
  2. Th1 CMI response = critical
  3. Adaptive immunity
    A. Parasitized cells present antigen to CD8 cells
    B. CD8 -> IFN-gamma
    C. IFN-gamma -> inc killing ability infected cells
    D. CD4 T cells -> B cells -> IgE after class switching
    1. Can bind and neutralized extracellular parasites
    2. IL-4 -> IgE
131
Q

Evasion of immune response

A
  1. Viral mutation rate
  2. Helminths molting
  3. Protozoan induction Th2 response
132
Q

Select agents

A

Have potential to pose severe threat to public animal, or plant health or to animal/plant products
1. Healthcare workers should be most concerned

133
Q

Tier 1/Category A agents

A

Most dangerous select agents

  1. Anthrax
  2. Burkholderia mallei and pseudomallei
  3. Clostridium (botulism)
  4. Ebola
  5. Francisella tularensis
  6. Marburg
  7. Smallpox, variola major virus
  8. Plague, yersinia pestis
134
Q

Bacillus anthracis

A
  1. Anthrax
  2. Polypeptide capsule - unique
  3. Spores can last 40 yrs in environment
  4. Infection
    A. Inhalation = woolsorter’s disease
    1. Worst
      B. Cutaneous
    2. Best
      C. GI and injection
  5. Gram (+)
  6. Medusa head colonies
  7. Toxins: now used to target cancer cells
    A. PA: protective antigen
    1. Pore forming
      B. LF: lethal factor
    2. Immune suppression and cell death
      C. EF: edema factor
    3. Cell and tissue swelling
135
Q

Inhalation anthrax Pathogenesis

A
  1. Spores inhaled
  2. Phagocytosed in lungs
  3. Transported mediastinal LN -> bleed
  4. Germination and toxin production in mediastinal LN
  5. Hemorrhagic mediastinitis and sepsis
  6. Death
136
Q

Inhalation anthrax presentation

A
  1. No person to person transmission
  2. Initially
    A. Fever
    B. Headache
  3. Then
    A. Chest discomfort
    B. SOB
  4. Rapid progression -> pulm hemorrhage and shock
  5. Meningitis can complicate
  6. Imaging
    A. Widening mediastinum
    B. Bloody fluid around lungs
    C. Enlarged LNs
137
Q

Inhalation anthrax tx

A 
1. Post-exposure prophylaxis immediately
  A. Antibiotics
  B. 60 day course
2. 3-dose post-exposure vaccine regimen 
  A. 0 wks
  B. 2 wks
  C. 4 wks
3. Antitoxins - when symptoms appear
  A. Not very effective 
  B. Anthrax immune globulin = anti-PA
  C. Raxibacumab (ABthrax) = anti-PA
138
Q

Cutaneous anthrax

A 
“Environmental anthrax”
1. Untreated fatality 20%
2. Treated fatality rate <1%
3. Localized infection
4. Antibiotics
  A. 60 days
139
Q

Yersinia pestis

A
  1. Black Death
  2. Bubonic plague and pneumonic plague
  3. Vectored by fleas on rodents
  4. Gram (-) rod
    A. Facultative intracellular
    B. Bipolar staining, closed safety pin staining
    C. Oxidase (-)
    D. Doesn’t ferment lactose
  5. Bubonic form
    A. Less severe
    B. Localized to LN
    C. Buboes
  6. Pneumonic form
    A. Most severe and infectious
    B. Mortality almost 100%
  7. Septicemia form
    A. Necrotic digits common if survive
140
Q

Tularemia

A 
1. Franciscella tularensis
  A. Fastidious, gram (-), aerobic coccobacillus
  B. Facultative intracellular pathogen
  C. Prefer macrophages 
  D. Extended survival
    1. Water
    2. Mud
    3. Animal carcasses 
2. Mostly N. Hemisphere
3. Multiple forms of disease related to route of infection
141
Q

Tularemia epidemiology

A
  1. 500,000 cases/yr worldwide
  2. 100-300 cases/yr US
    A. Mostly summer (ticks) and winter (rabbits)
  3. ID50 = 1 bacillus
  4. Routes of infection
    A. Arthropod bite
    B. Direst animal contact
    C. Inhalation of aerosol
    D. Eating contaminated H2O or poorly cooked meat
    E. Small mammal bite
  5. No person to person transmission
142
Q

Ulceroglandular Tularemia

A
  1. Most common form
  2. Rarely fatal
  3. Bacteria thru skin -> macrophages -I phagosome-lysosome fusion and survives intracellularly
    A. Inhibits pH drop
    B. No inc ROS
  4. After 3-5 days a painful papule dev
  5. Ulceration after 96 hrs
  6. Painful lymphadenopathy
  7. Abrupt onset
    A. Fever
    B. Chills
    C. Malaise
    D. Myalgia
  8. Spread other organs -> abscess and granulomatous formation
143
Q

Pneumonic Tularemia

A
  1. 30% mortality rate
  2. Bacteria inhaled
  3. Necrotizing granulomas
  4. Bronchopneumonia, bronchitis, or tracheitis
    A. Patchy infliltrates in lobes -> lobular pneumonia
    B. Hilar LN enlargement
    C. Non-productive cough
    D. Retrosternal pain
  5. Bacteremia can occur
    A. Macrophages -> hilar lymphatics
144
Q

Oropharyngeal Tularemia

A
  1. 30% mortality rate
  2. Bacteria ingested (large dose) -> bloodstream
    A. Bacterial cell lysis -> endotoxemia
  3. Presentation
    A. Fever
    B. Sore throat
    C. Abdominal pain
    D. Nausea
    E. Vomiting
    F. Diarrhea
    G. Splenomegaly
145
Q

Oculoglandular Tularemia

A
  1. Rare form
  2. Rub eyes after contact
  3. Involve conjunctival sac and nearby LN
  4. Presentation
    A. Pain and itching
    B. Photophobia
    C. Intense ocular congestion
    D. Lacrimation
    E. Edema of conjunctiva and mucopurulent discharge
  5. Very localized => low mortality rate
146
Q

Typhoidal Tularemia

A
  1. 30% mortality rate
  2. Hallmarks
    A. Systemic bloodstream involvement
    B. Sepsis
  3. Presentation
    A. Often pneumonia
    B. Fever
    C. Chills
    D. Myalgia
    E. Malaise
    F. Wt loss
  4. Difficult to dx because lack ulcers and lymphadenopathy
  5. Usually from bite and bacteria -> directly to blood stream
147
Q

Tularemia dx

A

Difficult and dangerous
1. Hx helpful
2. Culture aspirate of PN, sputum, and/or sinus drainage
A. (+) cultures in 3+ days
B. Required special agar
3. 4-fold inc IgG titer or single titer >160
A. Ab cross-react w/ Brucella and others

148
Q

Tularemia prevention

A
  1. Untreated mortality rates 5-30%
  2. CDC guidelines
    A. Insect repellent
    B. Wear gloves when handling sick/dead animals
    C. Avoid mowing over dead animals
  3. Avoid reservoirs and vectors
  4. Process specimens in biohazard hood
  5. Live, attenuated vaccine
    A. Only dec severity
149
Q

Brucellosis

A 
1. Strains cause human diseases 
  A. B. Abortus-cattle
  B. B. Canis-dogs
  C. B. Suis-swine
  D. B. Melitensis- goats and sheep
2. Worldwide distribution
3. Mild/asymptomatic in reservoir host
4. Disease severity varies 
5. Bacteria characteristics
  A. Fastidious, gram (-) aerobic coccobacillus 
  B. Phagocytosed -> LN
  C. Facultative intracellular pathogen
  D. Disease dev depends on dose, virulence, species and breed + humoral and cellular response
  E. Range presentations 
    1. Cure
    2. Abscesses
    3. Granulomata
150
Q

Brucellosis epidemiology

A
  1. Worldwide, uncommon in US
  2. Onehealth: vaccinate animals -> infection control for humans
  3. Highest risk
    A. Consume unpasteurized milk products
    B. Direct contact infected animals (vets)
    C. Lab techs and researchers
151
Q

Brucellosis presentation

A
  1. Dietary and employment Hx
  2. Ingestion or animal contact -> blood
  3. Spreads lymphatically
  4. Multiplies in macrophages
  5. Becomes systemic
  6. Undulating fever
152
Q

Brucellosis disease

A
  1. Incubation: few days -> several wks or months
  2. Polymorphism in clinical symptoms = typical
  3. Nonspecific, generalized symptoms
  4. Abscesses and granulomas if infection persists
  5. Advanced disease
    A. GI symptoms
    B. Arthritis
    C. Resp symptoms
    D. CV probs
    E. Cutaneous probs
    F. Neurological probs
  6. Symptoms last months to years
  7. 3% mortality rates
153
Q

Brucellosis bacteria characteristics

A
  1. Small, gram (-) coccobacillus
  2. Obligate aerobe
    A. Some require more CO2
  3. Weak LPS => immune system doesn’t respond
  4. No motility
  5. Catalase, oxidase, and urease (+)
  6. Prefers macrophages
    A. Inhibits phagolysosomes fusion -> survives in endosomes
    B. Immune system
    1. CMI most imp
    2. Ab produced but not effective
  7. Can survive wks to months
    A. Milk products
    B. Animal after-birth
    C. Aborted fetuses
    D. Soil
    E. Paper
154
Q

Brucellosis tx and prevention

A
  1. Tx lasts 6+ wks
  2. Prevention
    A. Animal immunization- live, attenuated
    B. Eliminate infected animals
    C. Avoid unpasteurized dairy products
155
Q

Coxiella burnetii

A
  1. Obligate intracellular pathogen
  2. Zoonosis: Q fever
    A. Vets, farm workers, lab workers
    B. ID50 = 1
    C. Symptoms similar to severe flu - high fever
  3. Select agent
    A. Endospore-like forms survive environment 5 months
  4. Ticks might be vectors
156
Q

Coxiella burnetii pathogenesis

A
  1. Enjoys acidified phagolysosomes
  2. T4SS
  3. Localizes genital tract and mammary glands
157
Q

Coxiella burnetii dx

A
  1. Handle suspect samples w/ care
  2. Notify lab
  3. MZN-method
    A. Modified Ziehl-Neelsen stain
  4. MAF: modified acid stain
  5. PCR
  6. Yolk-sac culture
158
Q

Coxiella burnetii prevention and tx

A
  1. Isolation
  2. Antibiotics not effective
    A. Tetracyclines given
  3. Vaccine for animals and humans
    A. Not available in US
159
Q

Immune processes use for energy

A
  1. Inducible hematopoiesis
  2. Clonal expansion of B and T cells
  3. Cell migration and phagocytosis
  4. Cytokine synthesis and release
160
Q

Infections inc RMR

A
  1. Fever inc RMR 7%/degree above 100F
  2. Requires extra fuel for protein synthesis
    A. Macronutrients
    B. Acute phase proteins, complement, cytokines, Abs
    C. Sepsis -> dec 20% total body protein
  3. Micronutrients reg and control metabolic processes
161
Q

Malnutrition and obesity

A
  1. Inflam cytokines -> dec appetite
  2. Obesity
    A. Inc infections
    B. Inc inflam
    C. Dysregulate immune system
  3. Animals w/ infection force fed -> inc mortality
162
Q

Moderate caloric dec beneficial for immune system

A
  1. Dec iron available for bacteria

2. Inc T cell fxn

163
Q

Nutritionally acquired immune deficiency syndrome (NAIDS)

A
  1. Malnourishment ->
    A. Inc severity disease
    B. Inc complications
    C. Inc illness duration
164
Q

Malnutrition and infection

A
  1. Inc risk death from mild infection
  2. Infections inc severity of malnutrition
  3. Viscous cycle
  4. Infections
    A. Net protein loss
    B. Hyperglycemia
    C. Inc RMR and nutritional needs
165
Q

Glutamine immune fxn

A

Predominant a.a. In blood
1. Supplies 35% energy to immune cells
A. B cell transformation -> plasma cells
B. Inc phagocytes ability and killing capacity macrophages
C. Reg T cell proliferation
2. Conditionally essential a.a. In illness/injury
3. Glutamine-rich diet dec hospital infection rates

166
Q

Iron immune fxn

A 
1. Deficiency -> dec inflam response 
  A. Dec resp burst
  B. Dec PMN killing
  C. Dec lymphocyte response
  D. Dec NK cell activity
2. Don’t correct deficiency during infection - feed bacteria 
3. High Fe promotes HIV progression
4. Deficiency protects against malaria
167
Q

Zinc immune fxn

A
  1. Humans can’t store it
  2. Required by enzymes
  3. Deficiency impairs
    A. Clonal expansion T and B cells
    B. NK cell cytotoxicity
    C. Phagocytosis
    D. Complement activity
    E. Wound healing
  4. Supplements
    A. Dec/shorten disease
    B. Zinc toxicity dec immune fxn (massive amt)
  5. Cold remedies
    A. Taken early may -I rhinovirus binding and replication
  6. Side effects
    A. Nausea
    B. Bad taste
    C. Loss smell/taste
168
Q

Selenium immune fxn

A
  1. Glutathione peroxidase: helps remove H2O2
  2. Deficiency ->
    A. Dec glutathione peroxidase activity
    B. Inc ROS levels -> damage PMNs and macrophages
    C. Dec lymphocyte activation
    D. Dec cytokine production
169
Q

Vitamin A immune fxn

A

Maintain epidermal and mucosal integrity
1. Inc recovery, doesn’t prevent infection
2. Deficiency ->
A. Loss cilia, micro villa, mucus
B. Dec # and fxn PMNs, macrophages, and NK cells
C. Dec lymphocyte fxns and dec homing to gut

170
Q

Vitamin D immune fxn

A 
Enhance innate but -I adaptive immunity
1. Deficiency role in disease 
  A. SLE
  B. MS
  C. TB
  D. Periodontal
  E. Impaired wound healing
171
Q

Vitamin E immune fxn

A
  1. Antioxidant
  2. Inc IL-2
  3. Supplementation
    A. Inc Ab titers to some vaccine Ag
    B. May reverse age-related decline in immune fxn
    C. Downside: may inc risk prostate cancer
172
Q

Vitamin C immune fxn

A
  1. Concentrated in macrophages and neutrophils
  2. Antioxidant
    A. Neutralize ROS that escape phagolysosome
  3. Don’t inhibit bactericidal activity
  4. Doesn’t prevent against common cold
173
Q

Stress and immunity

A
  1. Acute stress inc immune response
  2. Chronic stress dec immune response
    A. Cortisol: anti-inflam/immunosuppressive effects
174
Q

Acute sleep deprivation and immunity

A
  1. Dec adaptive immunity (Th1)
  2. Dec lymphocytes
  3. Dec vaccine Ab response
175
Q

Chronic sleep deprivation and immunity

A
  1. Dec adaptive immunity (Th1)
  2. Dec lymphocytes
  3. Dec vaccine Ab response
  4. Inc innate immunity/inflam
  5. Inc IL-6, IL-1, TNF
  6. Inc leukocyte trafficking
176
Q

Infectious/inflam condition and sleep

A
  1. Inc sleepiness
  2. Inc NREM sleep
  3. Dec REM sleep
177
Q

Drugs affecting immune response

A
  1. Glucocorticoids
  2. Calcineurin inhibitors
  3. Mycophenolate mofetil: blocks G nucleotide synthesis -> dec DNA synthesis
  4. Antimetabolites -I folic acid synthesis -> dec DNA synthesis
  5. Alkylating agents -> DNA breakage -> apoptosis
178
Q

Radioimmunoassay (RIA)

A
  1. Ag-Ab complex detected w/ secondary Abs
    A. Primary Abs from pt serum
    B. Ag and radiolabeled secondary Ab in test kit
  2. Used to detect and quantify Ab titer
  3. RAST: radioallergosorbent test
179
Q

RAST

A

Radioallergosorbent test

1. Used to test for specific IgE in pt serum when can’t use dermal allergy testing

180
Q

Immunoblotting

A

Western blot

  1. ID and determine relative quantity Ag/Ab (proteins) in pt serum
  2. Clinical use: confirms ELISA for Lyme disease
  3. Like ELISA but on membrane
181
Q

Nephelometry

A
  1. Measure immmune complex in liquid phase
  2. Determine [Ab] in sample
  3. Common uses
    A. Measure IgM, IgG, and IgA
    B. Useful for B cell cancers
    1. Serum FLCs (light chains) - for severity/progression
182
Q

Precipitation rxns

A
  1. Soluble Ag + soluble Ab -> insoluble complex (lattice formation) -> precip
  2. Polyclonal > monoclonal Abs
  3. Zone of equivalence: optimal [Ag] and [Ab] for max precip
  4. Radial immunodiffusion
  5. Double immunodiffusion
183
Q

Radial immunodiffusion

A
  1. Precipitin ring forms if Ag in pt serum at equivalence zone
  2. Ring diameter proportional to Ag in serum
  3. Occasionally used dx hemolytic anemia and complement disorders
184
Q

Double immunodiffusion

A
  1. Detect and quantify Ab/Ag
  2. Precipitin line forms between wells in equivalence zone if Ab in serum
  3. Replaced by ELISA
  4. Still used to ID coccidioidomycosis

BIIC (7 decks)

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