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Immuno Year 1 > Exam 1 Spring > Flashcards

Exam 1 Spring Flashcards

1
Q

what is the most effective method for preventing infections?

A

vaccination

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2
Q

what is the 4th modality of ca tx?

A

immunotherapy

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3
Q

what is the reason immune med diseases are rising?

A

unknown

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4
Q

innate immunity definition

A

def in place before infection –> rapidly respond

limit infection before adaptive imm response

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5
Q

adaptive immunity

A

shaped by exposure

incr magnitude and def cap with each successive exposure to partic microbe

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6
Q

features of innate immunity (6)

A
  1. epith barries
  2. present from birth
  3. in place prior to infections –> responds rapidly
  4. activated by structures shared by diff classes of microbes
  5. no memory - not any faster 2nd exposure​​
  6. trigger and amp adaptive imm response
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7
Q

features of adaptive immunity (3)

A
  1. patho-sp
  2. memory! enhanced by repeated exposure
  3. uses cells/mol of innate imm sys to elim microbes
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8
Q

cell meds of innate AND adaptive are derived from….

A

pluripotent hemtopoietic stem cells in bone marrow

  • lymphoid stem = adaptive
  • myeloid stem = innate
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9
Q

neutrophil morphology

A

muiltilobed nuc

small pink granules

short-lived

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10
Q

fx neutrophils

A

phago

activ bac-cidal mech

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11
Q

monocyte morphology

A

bean-shaped nuc

CD14 positive

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12
Q

fx monocyte

A

phago

recruit to sites of inflamm

differn –> tiss macrop

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13
Q

macrophage morph

A

in tissues

ruffled memb

cytop: vacuoles and vesicles

CD14 positive

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14
Q

fx macrophage

A

phago microbes and dead cells

secr cytokines

APC

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15
Q

dendritic cell morph

A

found in epith tissues

long cytop arms

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16
Q

fx dendritic cells

A

antigen

  • capture
  • txp
  • present
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17
Q

mast cell morph

A

found in tissues, mucosa, epith

small nuc

cytop packed with large blue granules

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18
Q

fx of mast cells

A

release granules (histamine) during allergy, anti-helminth

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19
Q

eosinophil morph

A

found in bloodstream, some epith

bilobed nuc

LARGE pink granules

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20
Q

fx eosinophils

A

kill ANTIBODY-COATED parasites

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21
Q

basophil

A

found in bloodstream

biloced nuc

LARGE blue granules

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22
Q

fx basophils

A

nonphago

release active sub during allergy

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23
Q

NK cells morph

A

found in: lymphoid, bloodstream

CD16, 56

LARGE cytop granules

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24
Q

fx NK

A

kill

  • tumor
  • virus
  • ab-coated target cells (ADCC)
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25
Q

lymphocyte morph

A

found in: bloodstream, lymph nodes, submucosa, epith

LARGE dark nuc

small rim of cytop

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26
Q

fx lymphocytes

A

B: CD 19, 20, 21 - produce Ab

TH: CD 3, 4 - reg imm responses

CTL: CD 3, 8 - kill infected, altered cells

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27
Q

plasma cell

A

found in: lymph nodes, spleen, MALT, bone marrow

small dark nuc - intense staining GOLGI

end cell of b-lymphocyte differentiation

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28
Q

fx plasma cell

A

prod Ab

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29
Q

types of adative immunity

A

humoral

  • bloack infections
  • elim extracel microbes

cellular

  • elim phago microbes
  • kill infected cells
  • elim resevoirs of infection
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30
Q

humoral immunity is med by:

A

Ab made by B cells

  • secr –> circ/lumens of mucosal organs –> bind extracel microbes/toxins –> neutralization (prev int-act with host tissues)
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31
Q

cell-med immunity is med by:

A

T cells aga INTRA-cell microbes

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32
Q

A previously health 8 year old boy is infected with an upper respiratory tract virus for the first time. During the first few hours of infection, which one of the following events occurs?

A.A lymphocyte response rapidly controls the infection.

B.An immune response dominated by neutrophils and monocytes keeps the infection under control

C.Killer CD8 T cells destroy infected epithelial cells

D.Antibody neutralizes the virus and prevents the spread of infection

E.Memory B cells quickly become activated to secrete antibody

A

A.An immune response dominated by neutrophils and monocytes keeps the infection under control

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33
Q

foreign sub recog by B and T lympho are called…

A

antigens (epitope recog)

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34
Q

diff b/w how B and T cells recog antigens?

A

T = ONLY protein

B/antibodies: MANY types

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35
Q

what are naive lymphocytes?

A

B and T lympho not yet encountered antigen

“immun” inexperienced - inactivated state

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36
Q

protective imm aga microb induced by…

A

host T and B cell recog AND response to foreign antigen

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37
Q

what kinds of indiv are said to be “immune”

A

when lympho have responded to microbe antigens and protected from subseq exposures of THAT microbe

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38
Q

active immunity is when…

A

protection from prev recog microbe

induced by exposure to foreign antigen

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39
Q

what is passive immunity?

A

immune WITHOUT exposure NOR response to that antigen

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40
Q

how to confer passive immunity?

A

txf serum or lympho of sp-imm indiv

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41
Q

fxs of innate and adaptive immunity are med by…

A

cytokines

  • soluble proteins/peptides
  • concep sim to horm
  • pleiotrophic: may have 2(+) unrelated effects
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42
Q

in normal indiv, primary infection is cleared by…

A

BOTH innate and adaptive immunity

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43
Q

A standard treatment of animal bite victimes, when there is a possibility that the animal was infected with the rabies virus, is administration of human immunoglobulin preparations containing anti-rabies virus antibodies. Which type of immunity would be established by this treatment

A.Active humoral immunity

B.Passive humoral immunity

C.Active cell-mediated immunity

D.Passive cell-mediated immunity

E.Innate immunity

A

Passive humoral immunity

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44
Q

key features of adaptive imm sys (7)

A
  1. specificity
  2. diversity
  3. memory
  4. clonal expansion - inccr # antigen-sp lymphoctytes faced with microbes
  5. specialization - gen repsonse optimal for def aga diff types of microbes
  6. contracftion/homeostasis
  7. nonreactive to self
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45
Q

specificity means

A

only clones of cells with approp receptors to recog a PARTICULAR antigen becomes activated

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46
Q

antigens that adaptive imm sys can recog is…

A

virtually limitless due to extremely diverse repretoire of antigen receptors

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47
Q

what is the downside of having such a diverse repertoire?

A

cells cap of recog 1 antigen fairly small –> clonal expansion of CURRENT infection

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48
Q

effect of clonal expansion after infection clears?

A

adaptive response declines (contracts) but MEMORY cells remain

  • rapid more exhanced response of microbe return
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49
Q

At 15 months of age, a child received a measles-mumps-rubella (MMR) vaccine. At age 22, she is living with a family in Mexico that has not been vaccinated and she is exposed to measles. Despite the exposure, she does not become infected. Which of the following properties of the adaptive immune system is illustrated in this scenario?

A.Self Tolerance

B.Diversity

C.Specialization

D.Memory

E.Specificity

A

Memory

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50
Q

Is it a B cell or a T cell mophologically?

A

NO DIFFERENCE!

All lymphocytes are morphologically similar

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51
Q

How to tell diff lymphocytes apart?

A

CD - detect using antibodies

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52
Q

most common method used to detect presence of bound Ab is

A

flow cytometry

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53
Q

B cell CD expr

A

19

20

21

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54
Q

T cells CD expr

A

2

3

subsets:

  • CD 4
  • CD 8
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55
Q

NK cell CD expr

A

16

56

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56
Q

BCR

A

receptor that recog antigen

memb form of antibody

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57
Q

how to B cells med humoral immunity?

A

prod Ab aga EXTRACELL patho/toxins via recog soluble antigens and antigens pres on microbe surf

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58
Q

antigen recognition and T/B cell activation results in…

A

effector cells

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59
Q

effector cells of B cells =

A

plasma cells –> secr Ab

  • antigen recog induced differen B cell –> plasma –> prod soluble Ab with SAME sp as memb-bound Ag receptor
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60
Q

Ab combat extracel pathogens by…

A

neut –> prev infection

facil destruction –> phago or complement

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61
Q
A

Activated effector B cell (Plasma cell)

notice

  • LOTS of cytop
  • LOTS mito
  • LOTS RER
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62
Q

How do T cells defect antigens?

A

INTRACELL

recog small frag of antigen that have been broken down and presented by APC

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63
Q

Steps to Ag presentation?

A
  1. APC capture Ags
  2. brkdown into small frag
  3. present on MHC
  4. recog by TCR (T-cell antigen receptor) on T cell
  5. activation T cell
  6. cell med immunity
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64
Q

examples of APCs

A

dentritic cells

macrophages

activated B cells

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65
Q

Th cells: antigen recog and effective fx

A

recog microbial antigen on APC –>

  • activate macrophages
  • inflam
  • activ prolif and diffen of T and B cells
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66
Q

cytotoxic T cells: antigen recog and effector fxs

A

recog infected cell expressing microb antigen –> KILL

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67
Q

fx of regulatory T cells

what are their CDs?

A

SUPRESS immune response

CD4 and CD 25

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68
Q

when lymphocytes emerge from bone marrow or thymus….

A

they are mature but first must find antigen recog by their receptors

  • circ from blood –> peripheral organs (1 round a day)
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69
Q

B cell deficiency presentation

A

absent/reduced follicles/germ centers in lymph organs

reduced serum Ig lvls

result:

  • pyogenic bac infections
  • enteric bac/viral infections
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70
Q

T cell deficiency presentation

A

reduced T cell zones in lymophoid organs

reudced DTH rxns to common antigens

defective T cell prolif responses to mitogens IN VITRO

result:

  • viral/intracell infections: p. jiroveci, atyp mycobac, fungi
  • virus-assoc malig: EBV lymphomas
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71
Q

what are the most important APCS? Why?

A

dendritic cells (DCs)

reside in tissues most commonly used as portal of entry of pathos

  • skin
  • muc tissues
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72
Q

A 2 year old boy is evaluated for a immunodeficiency disease. He appears to have a normal number of CD3+ cells, however, there are no CD19+ cells found in the blood or peripheral lymphoid organs (spleen, lymph nodes). Which of the following cell types is this boy deficient in?

A.B cells

B.CD4 T cells

C.CD8 T cells

D.NK cells

E.Neutrophils

A

B cells

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73
Q

Consider the 2 year old boy in the previous case found to be deficient in CD19+ cells. Which of the following capabilities would this child’s immune system lack?

A.The presentation of antigen by MHC molecules

B.The recognition of antigen derived from an intracellular pathogen

C.The mobilization of neutrophils during the first few hours of an infection

D.The production of antibody against extracellular pathogens

E.The maintenance of the epithelial barrier

A

production of antibody against extracellular pathogens

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74
Q

1st line of defense of the immune sys

A
  1. skin
  2. muc memb/secr
  3. normal flora
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75
Q

2nd line of defense

A
  1. innate immune cells
  2. inflam
  3. complement
  4. antimicobe substances
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76
Q

3rd line of defence

A

adative immunity: lymphocytes

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77
Q

intraepith T cells

A

final protective cmpt of epith

non-classical T cells – expr only limited range of antigen receptors

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78
Q

cell mediators of innate immune sys (6)

A

NENEMI

neutrophils

epith

NK cells

eosinophils

monocytes/macrop

ILC (innate lymphoid cells)

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79
Q

soluble mediators of innate immune sys (4)

A
  1. complement
  2. cytokines
  3. acute phase reactants
  4. coag factors
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80
Q

biological barriers of innate immune sys

A

normal flora

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81
Q

most patho gain entry to tissues via

A

skin

respir tract

GIT

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82
Q

fx of normal flora of epith

A

competes for nut and oclonization

sstim secr antimicrobial sub

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83
Q

epith mechanical barriers

A

tight jxns

mucus (goblet cells) - prevent adherence

mucociliary elevator

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84
Q

epith chem barriers and mechanism

A

skin

  • sweat - anti-microbe FA

muc memb

  • HCl (parietal cells) - low pH
  • tears/saliva - enz dig
  • defensins/cathelicidins - direct toxicity
  • surfantant - opsonin
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85
Q

PAMPS

A

limited # of microbial products recog by innate immune sys that are shared among broad groups of microbes

  • structures essential for surv and infectiveness of microbes

NOT pres on host cells

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86
Q

PAMP of influenza/mumps/parainfluenze/measles

A

ssRNA

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87
Q

types of receptors of innate immunity

A

TLR

N-formyl peptide

mannose

scavenger

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88
Q

recog of PAMPS med by…

A

PRR (pattern recog receptors)

  • TLR = major family
  • NLR (nod-like) = nicrobial prod, dmg tissues
  • RIG-like = viral RNA
  • c-type lectin = recog mannose residues
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89
Q

types of TLRs

A
  1. bac lipopep
  2. bac pipopep/peptidoglycan
  3. dsRNA
  4. LPS
  5. bac flagellin
  6. bac lipopeptides
  7. ssRNA
  8. ssRNA
  9. CpG DNA
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90
Q

PAMP/DAMP of NOD-like receptors

A

bac cell wall pep-glycans

intracel crystals

changes in ATP/ion conc

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91
Q

cytosolic DNA sensors recog what kinds of PAMP/DAMP

A

AIM2

  • bac and viral DNA
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92
Q

c-type lectin receptors recog

A

mannose

  • microbial mannose and fructose residues

dectin

  • fungal cell wall glucans
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93
Q

scavenger receptors recog

A

CD36

  • microbial diacylglycerides
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94
Q

innate immune receptors med

A
  1. prod of effector molecules/cytokines –> induce innate and adaptive immunity
  2. stim phago
  3. chemotactic –> guide phago to infection site
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95
Q

NLRP-3 engagement results in…

A

combine with caspase 1 –> activates IL-1 –> fever, inflammation

complex = inflammasome (NLRP-3 + caspase 1)

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96
Q

sterile (non-infectious) inflam NLRP3 activators

A

gout: monosodium urate
alz: beta-amyloid plaq

DM2: free FA, islet amyloid polypep

atherosclerosis: ox-LDL, cholesterol

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97
Q

MyD88 deficiency

A

recurr, severse pus-forming/pyogenic bac infection

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98
Q

IRAK4 deficiency

A

recurr severe bac infections

  • cellulitis
  • arthritis
  • meningitis
  • osteomyelitis
  • organ abscesses
  • sepsis
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99
Q

UNC93B deficiency and TLR3 mutations

A

incr suscep to encephalitis caused by HSV

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100
Q

IKK/NEMO deficiency

A

ectodermal dysplasia

  • conical/absent teeth
  • sparse hair
  • hypohidrosis (decreased sweat glands)

immunodefic

  • recurr sinopulm infections
  • mycobac
  • opportunisitic org
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101
Q

Carl is a 1 month old healthy child who has not, as yet, received any childhood vaccines. He presents with his first episode of otitis media that is successfully treated with antibiotics. Which of the following immune components contributed the most to the clearing of the infectious agent during the first few days of the infection?

●

A.Antigen receptors on B lymphocytes

B.Toll like receptors on macrophages

C.Cytokines that promote antibody production

D.T cell responses to bacterial antigens

E.Memory B cells

A

TLRs on macrophages

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102
Q

what cells are sentinels for infectious org?

A

resident DCs and tissue macrophages

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103
Q

recog of PAMPS/DAMPS by resident tissues macrophages results in…

A

release of inflam cytokines: IL-1, TNF-alpha

  • stim P and E selectin
  • rolling of neutrophils due to shear forces and weak bonding
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104
Q

after rolling, what happens to neutrophils?

A

activated macrophages prod chemokines (IL-8/CXCL8) –> induce HIGH AFFINITY integrins (ICAM-1, VCAM-1)

  • neutrophil recog IL-8 receptor via their CXCR 1 & 2
  • neutrophils bind to integrins via their Mac-1, LFA-1, VLA-4
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105
Q

how to neutrophils extravasate?

A

b/w endothelial cells: increased basc perm via histamine, PG, LT

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106
Q

G-CSF

A

granulocyte CSF

  • prod @ site of infection
  • incrs prod of neutrophils by bone marrow
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107
Q

inflammation is …

A

accum leukocytes @ infection site

assoc vasc dila

incr leakage of fl/proteins into tissue

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108
Q

hallmark of acute inflamm

A

neutrophils

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109
Q

temporally distinct patterns of expr of adhesion mol/chemokines typ result in…

A

early neutrophil recruit

  • LFA1/MAC-1 : ICAM-1
  • CXCR1/2 : IL-8

later monocyte recruit

  • VLA-4 : VCAM-1
  • CCL2 : CCR2
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110
Q

leukocyte adhesion deficiency

A

auto recessive - decr mvmt leukocytes to inflam

  • delated sep of umbilical cord
  • recurr bac/fung infections: skin, lungs, GIT, perirectal

absent/deficient

  • β2 integrins, LFA-1 and Mac-1: heterodimers of CD18 & 11

result:

  • prev tigh adhesions
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111
Q

dx and tx of leukocyte adhesion deficiency

A

dx: CD18 flow cytometry
tx: BMT/SCT

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112
Q

It is generally thought that a limited amount of inflammation at the site of vaccination helps to stimulate a strong adaptive immune response to the vaccine antigens. Which of the following substances, if introduced with the vaccine, would best serve the purpose of attracting a neutrophil infiltrate into the area?

A.G-CSF

B.IL-8

C.Prostaglandin

D.E selectin

E.TNFalpha

A

IL-8

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113
Q

what are the most abundant leukocyte in blood?

A

neutrophils

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114
Q

neutrophil granules

A

specific: lysozyme, collagenase, elastase - degrade bacterial
azurophillic: defensins/cathelicidins - microbicidal

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115
Q

NETs

A

DNA chromatin networks –> trap bac/fungi –> kill via its granules

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116
Q

what is the prominent emch by which inflammation can dmg host tissue?

A

neutrophil granule enz and ROS

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117
Q

prod and storage of neutrophils

lifespan?

A

prod: G-CSF

reserve pool in bone marrow

lifespan = 6 hours : major cmpt of pus

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118
Q

macrophages orgin from

A

fetal hematopoietic organs (yolk, sac, liver)

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119
Q

fx macrophages (4)

A
  1. ingest/kill microbes and apop host cells
  2. secr cytokines –> onto endothelial cells –> recruit leukocytes
  3. APC –> (+) T cells
  4. prom repair of dmg tiss
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120
Q

once a microbe has be engulfed by a macrophage…

A

killed by phagolysosome

  • ROS: NADPH oxidase/MPO
  • iNOS
  • proteolytic enz (lysozyme)
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121
Q

CGD

A

mutation in NADPH phagocyte oxidase

effect:

  • recurr infection with catalase –> bac/fungi infections
  • granulomas: inab to kill/phago bac
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122
Q

M1

A

classically activated macrophages - inflam/kill via innate inflam response

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123
Q

cytokines secr by M1

A

IL-1beta: vasc-endo & lymphocytes, local tiss destruction, effector cells –> fever, prod IL-6

IL-6: fever, acute-phase proteins by hepatocytes

IL-12: activ NK cells

TNF-alpha: increase vasc perm, incr lymph drainage –> fever, shock

CXCL8: recruit neutrophils, basophils

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124
Q

M2

A

activated by IL-4 & IL-13 in absence of strong TLR signals –> reduce inflammation & med tissue repair

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125
Q

what are the link b/w innate and adaptive immunity?

A

DCs: capture antigen –> bring to draining lymph nodes –> present to naive T cells

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126
Q

types of dendritic cells

A

cDC (conventional) - capture antigen in perip –> present to adaptive imm in draining lymph nodes

pDC (plasmacytoid) - circ in blood –> recruit to inflamm sites –> activated –> prod IF-1 (interferon 1)

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127
Q

mast cell released things and timing: (3)

A

degranulation - seconds

eicosanoids - minutes

cytokines/chemokines/ GFs - hours

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128
Q

mast cell degranulations and fx

A

histamine - vasodil, increase perm

TNF-alpha

tryptase/chymase - proteolytic –> kill bac & inactiv toxins

amines

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129
Q

mast cell eicosanoids

A

LT

PG

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130
Q

cytokines/chemokines/GFs of mast cells

A

TNF-alpha, IL-4/5/6/13/17, VEGF

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131
Q

true or false: NK cells express antigen receptors

A

FALSE - no antigen receptors like T and B cells

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132
Q

how do NK cells recog target cells?

A

absence of MHC I

“stress signals”

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133
Q

how do NK cells induce apop of target cells?

A

perforin/granzyme

Fas/FasL

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134
Q

NK cell receptors: inhib v activating

A

inhib:

  • KIR: bind MHC I
  • KLRG-1
  • NKG2/CD94

activating:

  • CD16 (FcR) - ADCC (Ab-dep cell-med cytotoxicity): kill Ab-coated cell
  • NKG2D
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135
Q

NK cell cytokines

A

IL-12: prod INF-gammy

IL-15: dev/mat

IF-1: enhance killing fx

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136
Q

what fxs together to kill intracell microbes?

A

activated macrophages prod IL-12 –> activ NK to –> IFN-gamma –> activ macrophages

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137
Q

viruses and the immune sys

A
  1. Virus infects host cells
  2. CD8 T cells recognize viral antigen:MHC complex. Kill host cell
  3. Viruses evolve to evade the CD8 T cell response by suppressing MHC class I expression
  4. Natural killer cells develop to recognize cells that have decreased MHC class I expression
  5. Viruses encode decoy MHC class I molecules that cannot present Ag, but suppress NK cell activation!
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138
Q

Lymphocytes with Limited Antigen Receptor Diversity

A

features of both innate and adaptive immune sys: considered part of innate sys

  1. gamma-delta T cells: somatically rearrange Ag recept
  2. NK-T cells: T-cell antigen receptors (TCRs)
  3. B-1 cells: expr Ag receptors, secr Ab (usually prod natural Ab that recog carbs on cell walls of bac)
  4. marginal zone B cells: Ag receptors
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139
Q

main functions of complement

A
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140
Q

3 pathways of complement activation

A

classic: IgG/IgM Ab - humoral adaptive immunity
alt: microbal surf proteins - innate
lectin: lectin mannose binding - innate, but requires time gain strength

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141
Q

C3 cleavage

A

central to all C’ pathways:

  • later in classic/lectin
  • activates alt

a - chemoattractant: mast cells –> vasoactive

b - opsonin (coval binding)

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142
Q

activation of alt C’ pathway

A

C3 spont hydrolyzed in plasma in low lvls –> iC3 (C3 tickover)

fac B (serine protease, active enq of C3/C5 convertases) + iC3 –> C3b –> readily bind to microbe surf

  • cleavge of fac B by fac D
  • stby by properdin

–> activation alt path

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143
Q

C’ lectin pathway

A

MBL - acute phase reactant (liver) during periods of inflamm

  • innate immunity: bc init by microbial prod

bind MBL to microbe –> bkdwn C4 & C2 –>

  • C4b + C2a –> complex –> C3 convertase
    • C3b binds complex –> C5 convertase
      • init late steps of C’
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144
Q

C’ classic pathway

A

init by bindning Ab to Ag: adaptive

  • C1 bind to Fc portions of 2 IgG or IgM –> cleave C4 & C2 –> C4b2b complex = C3 convertase
    • C3b binds to complex –> C5 convertase
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145
Q

all 3 C’ pathways lead to…

A

coat of convalently attached C3b = opsonin

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146
Q

last steps of C’

A

C5 convertase cleaves C5

remaining C6-C9 bind seq to C5b

C9 polymerizes –> MAC –> pokes hole

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147
Q

C’ deficiencies

A

C3: recurr severe bac infections –> usually fatal

C5-C9: incr suscept to Neisseria (thin cell wall - esp suscep to MAC)

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148
Q

regulation of C’

A

mammal cells can reg, microbes cannot

  • overwhelming C’ –> coat with antibody –> C’ target
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149
Q

Factor I

A

proteolytically cleaves C3b and C4b

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150
Q

Factor H

A

dissoc alt pathway C3 convertase

co-fac for Fac I med cleavage of C3b

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151
Q

C4BP

A

dissoc classic C3 convertase

co-fac for Fac I med cleavage of C4b

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152
Q

DAF

A

dissoc c3 convertase

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153
Q

CD59

A

blocks C9 binding –> inhib MAC

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154
Q

MCP

A

membrane cofactor protein

cofac for Fac I for proteolysis of C3b into inactive frag

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155
Q

C1 INH

A

stops activation of classic path: interferes with C1q cmpt

  • prev C1 r2s2 from activating
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156
Q

hereditary angioedema

A

inherited: deficiency in C1 INH
* excessive C1 activation –> subseq activation of kinin sys (C2b)

unpredictable/recurr episodes of periodic swell in subQ/submuc

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157
Q

in the innate immune response, the principal sources of cytokines are…

A

macrophages

mast cells

dendritic cells

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158
Q

major proinflamm cytokines

A

TNF

IL-1

IL-6

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159
Q

local effects of proinflam cytokines

A

vaso-dil: marginalization of leukocytes

activates endothelium - adhesion mol

incr vasc perm - diapedesis/extravasation

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160
Q

sys effects of inflam cytokines

A

liver: acute-phase proteins –> C’, opsonin

bone marrow, endothelium: neutrophil mob –> phago

hypoT: incr body temp –> decr microbe replication

fat/M: get more E –> decr microbe replication

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161
Q

pyrogens

A

ab to induce fever: IL-1, IL-6, TNF-alpha

elev temp

  • slows patho growth: most grow & replic optimally @ temps below human body
  • actively seques iron –> lim bac growth
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162
Q

acute-phase proteins

A

IL-6

  • MBL –< incr phago, trigger lectin C’
  • CRP - binds PL-choline –> incr phago, trigger classic C’
  • SAA
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163
Q

early clinicla and patho manifestations of septic shock are caused by…

A

very high levels TNF-alpha due to systemic bac infection

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164
Q

IL-8

A

recruits neutrophils

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165
Q

IL-12

A

prod by activated macrophages and DCs –> NK & CD4 T cells –> IFN-gama –> bidirectional activation

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166
Q

major innate cytokine prod in response to viral infection is…

A

IFN-I

  • host cells recog via viral PAMPS (dsRNA) by PRRs (Rig-1)

secr by virally infected cells and leukocytes to protect surr cells from infection

  • activ JAK-STAT sig pathway
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167
Q

fnal role of innate immune response

A

alert adaptive immune response

  • signal 1: antigen recog by lymphocytes
  • signal 2: moles induced during innate imm response
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168
Q

evasion of innate imm: pneumococci

A

cap polysacc –> inhib phago

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169
Q

evasion of innate immunity: staphylococci

A

produces catalase –> resists ROS

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170
Q

evasion of innate immunity: neisseria meningitidis, streptococci

A

sialic acid –> inhib C3/C5 convertase

M protein –> blocks C3 fx

resists alt C’

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171
Q

evasion of innate immunity: pseudomonas

A

synth mod LPS –> resists antimicrobial peptides

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172
Q

bone marrow

A

common lymphoid progen cell

  • precursor: T, B, NK
    • most steps B cell mat in BM –> finals events @ 2ndary lymphoid organs, particularly spleen

common myeloid progen cell

  • RBCs, platelets, granulocytes (N, E, B), monocytes (most DCs)
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173
Q

thymus

A

3rd parayngeal pouch

  • flat, bilobed
  • 2 compartments:
    • outer cortex = thymocytes
    • inner medulla = T cell maturation
      • DCs and macrophages help with mat
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174
Q

thymic cortical epith cells

A

secr IL-7: GF req for early T cell dev

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175
Q

thymic medullary epith cells

A

remove self-reactive T cells

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176
Q

thymus through time

A

enlarges during childhood

involutes after puberty

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177
Q

DiGeorge syndrome

A

mutations in genes for thymus dev

  • T cell deficiency

also effects parathyroid & heart dev due to 3rd pharyngeal pouch origin

  • hypocalcemia
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178
Q

•A 52 year old man who receives radiation therapy and cytotoxic drugs for treatment of cancer sustains significant damage to his bone marrow. Which of the following changes will most likely occur?

•

A.Decreased production of monocytes but not B lymphocytes

B.Decreased production of B lymphocytes but not T lymphocytes

C.Decreased production of neutrophils and monocytes but not B lymphocytes

D.Decreased production of B and T lymphocytes, monocytes, neutrophils, and red blood cells

E.Normal production of all red blood cells due to compensatory extra medullary hematopoiesi

A

A.Decreased production of B and T lymphocytes, monocytes, neutrophils, and red blood cells

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179
Q

•In DiGeorge syndrome, the thymus fails to develop. Which of the following characterizes the immunodeficiency state in this syndrome?

A.Low numbers of neutrophils and monocytes in the blood.

B.Deficiency in antibody production in response to bacteria polysaccharides

C.Deficiency in cell mediated immunity in response to an intracellular infection

D.Normal T cell numbers, however, defective T cell activation

E.Deficiency in B cell maturation

A

A.Deficiency in cell mediated immunity in response to an intracellular infection

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180
Q

peripheral lymphoid organs fx

A

collect/cencentrate antigens –> gives oppor for naive lymphocytes to recog

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181
Q

lymph contains (3)

A

debris from dying cells

antigens

DCs with captured antigen

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182
Q

celephantiasis

A

interstitial fluid collected by not drained by lymph

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183
Q

paracortical area of lymph node

A

DCs present captured Ags to T cell

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184
Q

primary lymphoid follical

A

B cell zone

contains FDCs

  • forms meshwork to present antigens to B cells
185
Q

secondary follicle of lymph nodes

A

with germinal center –> intense B cell prolif

186
Q

medullary cords of lymph nodes

A

macrophage and plasma cells

187
Q
A
188
Q

how do lymphocytes wind up in the correct regions of lymph nodes?

A

chemokines

189
Q

spleen basic fxs

A

drains bloodborne antigens

removes aging and dmged blood cells/particles (immune complexes and opsonized microbes)

190
Q

red pulp of spleen

A

macrophages remove microbes and old/dmged RBS

blood –> central splenic A –> vasc sinusoids (open circulation) –> splenic sinus –> vein –> portal circ

191
Q

indiv lacking spleen…

A

highly suscep to infections with encap bac norm cleared by opsonization and phgo of splenic macrophages

192
Q

white pulp of spleen

A

lymphocyte rich

org around central arteries: sep from red pulp via marginal zone

  • contain marginal zone B cells
  • site of immune response targ bloodborne antigens
193
Q

segregation in the spleen

A

T cells

  • PALS (around central arteries)

B cells

  • follicles

sim to LNs

194
Q

SALT AND MALT

A

sp-L tissues found inder skin and epith of GIT, RT, UGT

  • lymphocytes
  • macrophages
  • DCs

site of immune responses to antigens that breach epith

195
Q

examples of MALT

A

pharyngeal tonsils

peyer’s patches

196
Q

cells of SALT

A

keratinocytes

Langerhan’s cells - immature DCs

  • forms con’t epith mesh –> capture Ag –> mig to draining LNs –> APC

intraepithelial T cells

melanocytes

197
Q

•A 5 year old boy with recurrent infections is discovered to have a genetic defect that impairs B cell development. Which of the following abnormalities is most likely to be found in this patient?

•

A.Small thymus

B.Absence of follicles in lymph nodes and spleen

C.Enlarged tonsils

D.Diminished parafollicular zones in the lymph nodes

E.Hypocellular bone marrow

A

Absence of follicles in lymph nodes and spleen

198
Q

trafficking requirements for adaptive immune response

what is actually first (innate immune response)

A

recruit neutrophils & monocytes (innate)

Ag “carried” to perip L organs

naive lymphocytes circ through

activated lymph go to site of infection

199
Q

Ag presentation by DCs to T cells takes place

A

paracortical area of LN

200
Q

Major DCs

A

surface markers: CD11c, CD1C, dectin 1/2

TLRs: varios

Ts: IRF4

maj cytokine prod: IL-12

fx:

  • innate immunity - souce of inflam cytokines
  • adative imm: APC mostly to CD4 T cells
201
Q

Cross-Presenting DCs

A

surf markers: CD11C, CD141, CLEC9A, XCR1

TLRs: various

Ts: IRF8

maj cytokines prod: IL-23

fx:

  • adaptive imm: APC to CD8 T cells
202
Q

plasmacytoid DCs

A

surf markers: BDCA 2/4, CD123

TLRs: 7/9

Ts: E2-2

maj cytokines prod: IFN-1

fx:

  • antiviral: early innate response
  • prime antiviral T cells
203
Q

how are immature DCs activated?

A

DC TLRs bind to microbe cmpts

DC stim by inflamm cytokines induced by microbe

204
Q

how to ag-bearing DCs leave perip tissue –> LNs?

A
  1. activation: TLRs or inflamm cytokines
  2. change cell type form ag uptake –> APC
    • incr MHC/antigen complexes: provides 1st signal of T cell activation
    • incr costimulatory mol: prov 2nd signal for T cell activation
205
Q

activated DCs incr expression of…

A

CCR7 (chemokine for T cell zone of LN)

  • binds CCL19 & 21 (T cell zones of LN)
  • also expr by naive T cells
206
Q

how do B cells get to LNs?

A

naive B cells expr CXCR5 –> binds CXCL13

  • produced only in follicles by FDCs
207
Q
A
208
Q

lymphocyte homing

A

activated effector lymphocytes selectively enter LNs (reverses previously just recirc)

209
Q

naive T lymphocytes delivered to 2ndary lymph tissues via _______ and leave circulation and migrate into the stroma of LNs via __________

A

arterial blood flow

HEV (postcap venules) - lined by plump endothelial cells

  • rich adhesion mol & chemokines for naive T cells
210
Q

T cell homing

A

naive T cells: L-selectin (CD62L) —> PNAd (endothelial cells of HEV) = rolling

T cell zones of LN (CCL19 & 21) bind CCR7 –> allows expr of high affinity integrins (LFA-1/VLA-4) –> allow naive T cells bind ICAM-1 –> firm adhesion –> migration to T zone

211
Q

true or false: T cell homing is similar to B cell migration (homing)

A

TRUE

212
Q

egress (leaving) from a LN is controlled by…

A

expr of receptors for S1P

213
Q

what happens after naive T cell activation?

A

must reduce expr of adhesion mol that init targeted it to the LN

  • L-selectin, CCR7: no longer directed to LN

upreg adhesion mol & chemokine receptors

  • typ present on endothelial cells @ perip inflam sites
    • activated by inflam med
      • recruitment no Ag specific: but only T cells that see their cognate Ag @ infection site become reactivated
        • held @ site
        • contrib to killling
  • ex: skin = E-selectin, CLA-1
214
Q

engineered Abs aga integrins or endothelial adhesion mol do…

A

block migration of effector T cells to tissue in diseases like MS and inflam bowel

215
Q

Fingolimod is a drug used to treat autoimmune diseases, which blocks the function of sphingosine-1 phosphate (S1P), by binding to its receptor S1PR1 and downregulating it’s expression. Patients treated with this drug become lymphopenic, ie, they have low number of lymphocytes in the blood. Why?

A

S1P binding to S1PR1 on lymphocytes is required for exit of lymphocytes from lymphoid tissues

216
Q

A group of researchers is studying the effects of the CXCL13 gene by knockout mice experiments. Which of the following might you expect to see upon examination of the animal’s lymph nodes?

A.Hypocellular paracortex

B.Hypercellular paracortex

C.Hypocellular follicles

D.Hypercellular follicles

A

Hypocellular follicles

217
Q

compare and contract innate and adaptive immunity: receptors

A

innate:

  • germline encoded
  • limited diversity
  • <100 different types of invarient receptors

Ig/TCR:

  • somatic recombin of gene segments
  • greater diversity
  • only Ig and TCR with millions of variations of each
218
Q

compare and contrast innate v adaptive immunity: distribution of receptors

A

innate = nonclonal - identical receptors on all cells of same lineage

adaptive = clonal - clones of lymphocytes with distinct specificites expr different receptors

219
Q

Ab-mediated effector fxs (5)

A
  1. neutralization of microbes/toxins
  2. activate classic C’
  3. opsonizattion
  4. cell-med cytotoxicity
  5. mast cell activation
220
Q

antigen definition

A

any structure bound by Ag or TCR

  • binding portion = determinant/epitope
  • typ larger than the region

multivalent: multiple DIFFERENT epitopes
polyvalent: multiple IDENTICAL epitopes

221
Q

compare and contrast B v T cell antigen recognition: antigen-binding site

A

b = 3 CDRs in VH & VL

t = 3 CDRs in V-alpha and V-beta

222
Q

B cell vs T cell antigen recognition: nature of bound antigen

A

B = macromol & small chemicals

T = peptide-MHC complexes

223
Q

immunogen definition

A

substance that acitvates lymphoytes & stim immune respnose

antigen is not necessarily an immunogen

224
Q

T-independent antigen

A

polysacc cross-link multiple B cell antigen receptors –> strong activation signal –> activate B cell indep of Th cell

225
Q

T-dependent antigen

A

protein antigen allow B cell to elicit help from activated CD4 T cells

  • conformational epitope –> endocytosis –> digest and present the protein part of the antigen that was previously “hidden”
226
Q

T cells can only recognize

A

linear peptide epitode in context of MHC

227
Q

haptens versus carriers

A

hapten = binding onto B cell

carrier = what a T cell can bind

binding on hapten on B cell causes endocytosis and presenting of carrier which binds T cell

228
Q

DNP and pcn in relation to haptens and carriers

A

antigenic but NOT immunogenic –> must fuse with protein to work

  • does not have correct linear seq to stimulate T cell initially
229
Q

antibodies may be directed again…

A

hapten

carrier

or the conjugate

230
Q

pcn MOA

A
  1. pcn (hapten) binds to RBC –> creates new antigens on surface
  2. forms Ab specific for conjuguate of drug (hapten) and cell surf protein (carrier)
  3. binding of pcn-mod RBCs –> C’ lysis or phago by macrophages in spleen
    • via IgG
  4. immune mediated hemolytic anemia
231
Q

newborn vaccines

A

newborns = poor response to bac capsule polysacc T-indep antigens

soln: improve vaccine by fusing polysacc (hapten) to protein (carrier)
* bind to B cell –> present protein on MHC II –> recog by T cell –> mount STRONGER Abs (versus weak IgM)

232
Q

adjuvants definition

A

substances that themslves are not immunogenic but can enhance the immunogenicity of other substances

233
Q

how to adjuvants work?

A

create antigen depot –> slowly release antigen

induce Ag aggregation –> eaiser to phago, proc, present to T cells

induce inflammation –> induce expr costimul mol

234
Q

Alum

A

alum-salt adjuvants:strong responses to Ag

235
Q

vaccines that contain alum (7)

A

DTP/DTaP (diphtheria-tetanus-(acell)-pertussis)

HiB (hemophilus influenzae type b)

pneumococcal

hep A & B

HPV

anthrax

rabies

236
Q

cross-reactivity

A

Ab or TCR can recog 2 sim but non-identical Ag

  • share 1 or more epitopes: tetanus toxoid & tetanus toxin
  • structurally sim: bac & auto Ags
237
Q

rheumatic fever

A

streptococcus pyogenes antigen similar to self-antigens of heart valves - jones criteria

  • fever
  • rash
  • carditis
  • arthritis
  • subQ nodules
  • syndeham chorea
238
Q

•A 3 year old male who is small for his age presents with a history of pyogenic infections. A culture of purulent discharge from an abscess grows out Staphylococcus aureus. Protective immunity against this organism requires an immune response which targets the polysaccharide chains of the bacterial capsule. Which of the following cell types is most important for the adaptive immune response to this type of antigen?

A.CD4 T cells

B.B cells

C.CD8 T cells

D.Antigen presenting cells

E.Natural killer cell

A

b cells

239
Q

•A patient treated with penicillin presents with fever associated with kidney damage from complement-mediated hemolysis of red blood cells (RBC). What is the role of penicillin in this disorder?

•

A.Carrier

B.Hapten

C.Polyvalent antigen

D.Autoantigen

E.Immunogen

A

hapten

240
Q

•A 41 year old patient visits a physician for a physical. She recalls to her physician that in childhood, she experienced two bouts of fever, headache and sore joints following severe sore throats. Although she appears to be well at the present, which of the following sequelae of her childhood illness is most likely to present as a chronic disease in her later years?

•

A.Anemia

B.Myocarditis

C.Glomerulonephritis

D.Mitral valve disease

E.Neurological disease

•

•

A

Mitral valve disease

rheu-MITRAL fever

241
Q

how do the majority of T cells recog peptide antigens?

A

bound and displayed by MHC

  • TCR recog residues of peptide Ag AND of the particular MHC that is displaying it
242
Q

MHC restriction

A

TCR can only recog peptide antigens when displayed on OWN MHC molecules

243
Q

why do most T cells only respond to protein antigens?

A

MHC Ag can only bind peptides from PROTEIN antigens

  • can display peptides from foreign proteins AND self proteins
244
Q

human v mouse MHCs

A

human = HLA: human leukocyte antigens

mouse: H-2 antigens

245
Q

MHC I

A

present ag to CD8+ (CTL)

all nucleated cells expr this

246
Q

MHC class II

A

present antigen to CD4+ (Th)

expressed by APCs

  • macrophages
  • DC
  • B cells
247
Q

MHC class III

A

complement

TNF

lymphotoxin

248
Q

which MHC classes are structually similar to txmemb proteins?

A

I & II

249
Q

MHC I structure

A

alpha chain (of 3 domains) noncovalently attached to b2-microglobulin (b2-M)

amino term alpha 1 & 2 form peptide binding cleft: peptides 8-11 aa in length

250
Q

MHC II structure

A

2 chains: alpha and beta

  • cleft = peptides 10-30aa in length
251
Q

HLA are encoded…

A

multiple loci on short arm of chr 6

class III = genes for C’ and some cytokines

252
Q

MHC I loci encodes

A

MHC class 1 alpha chains:

  • HLA-A & -b & -C

beta-2-M is encoded on chr 15

253
Q

MHC II loci encodes

A

MHC class II alpha and beta chains

  • HLA-DP & -DQ & -DR
254
Q

MHC haplotype

A

complete set of MHC alleles inherited on each chr

  • each individual has 2
255
Q

MHC genes are the most ___________ genes in the genome

A

highly polymorphic: different alleles for each MHC gene are present among different individuals in population

  • so great that any 2 people are EXTREMELY unlikely to have exactly same MHC genes and molecules
  • accom a different complement of peptides presented to T cells
256
Q

alleles of MHC mol are ________ expressed

A

co-dom: from both chr

  • max diversity –> allows wider array of peptide ag presented to T cells
257
Q

multiple MHC alleles benefits to indiv and gen pop?

A

indiv: greater diveristy of patho-derived peptides presentduring infection –> improves strength of immune response by incr # of patho-specific T cells

gen pop: always someone able to present any particular microbial protein ag –> will not succumb to newly encountered mutated microbe

258
Q

structure of MHC I receptor domains and binding

A

peptide binding cleft: alpha 1 & 2

  • floor = peptide antigen
  • walls = TCR

T-cell CD8 co-receptor: alpha 3

  • does not interact with CD4

CD8 T cells can only respond to antigen presented by MHC I

259
Q

structure of MHC II receptor domains and binding

A

peptide binding cleft: alpha 1 and beta 1

  • floor - peptide antigen
  • walls = TCR

T-cell CD4 co-receptor: alpha 2 and beta 2

CD4 can only respond to antigen presented by MHC II

260
Q

successful antigen recognition involves

A

binding of TCR to peptide-MHC complex

binding of CD8 OR CD4 co-receptor to MHC I or II

261
Q

what kind of specificity do MHC mol have?

A

broad - many diff peptides can bind to same MHC mol

262
Q

how many peptides can each MHC mol display at one time?

A

ONE - each T cell responds to single peptide

263
Q

MHC molecules can bind ONLY _______

A

peptides: protein ag

no other chemicals

264
Q

how to MHC molecules acquire peptides?

A

intracell assembly

265
Q

stable surf expr of MHC mol requires…

A

bound peptide: empty MHC is disassembled

266
Q

lenght of time of MHC presentation

A

very slow off-rate: display long enough to be located by T cell

can be days

267
Q

autosomal MHC I deficiencies

A

decreased CD 8 T cell numbers and fx

necrotizing granulomatous skin lesions & RT infections

not viral infections - b/c virus is intracel

268
Q

bare lymphocyte syndrome

A

defective expr of MHC II –> decr CD4 T #s and fx

impaired: cell-med immunity & B cell response to T-dep antigens

lethal unless BMT

269
Q

what is the most important genetic factor in detm suscep to autoimmune disease

A

MHC - but not the only factor

  • vast maj of people with HLA disease associated allele never dev disease
    • still not completely known why
270
Q

how can particular MHC alleles contribute to dev of autoimmune diseases?

A
  1. ineffective @ displaying self antigens in thymus –> defective removal of autoreactive T cells
  2. peptide antigens presented by these MHCs fail to stim immunosuppressive reg T cells
  3. VERY efficient at presenting self-peptide in periphery –> incr likelihood of activating autoreactive patho T cells
271
Q

CD1

A

surface glycoprotein that can present lipids/glycolipids to T cells

  • expressed in associated with beta-2 microglobulin

non-classical ag presentation

  • non-MHC endcoded
  • non-polymorphic
272
Q

how does CD1 work?

A

binds hydrophobic regions of lipids –> expose polar region for alpha-beta or gamma-delta T cells & NK cells

273
Q

what is the key presenter of ag to naive T cells?

A

DC cells –> migrate to T-cell zone of LN to present

274
Q

how do APCs display antigens that are recognized by specific lymphocytes?

A

T cells:

  • MHC-associated peptides: cytosolic for I, vesicular for II

B cells:

  • native antigens
  • APCs = macrophages, FDC in germinal centers
275
Q

how do APCs activate T cells?

A

costim & cytokines induced by microbes act as “second signals”

ensure that T cells respond BEST

276
Q

why are DCs most efficient APCs for initating immune responses?

A
  1. location
  • @ sites of microbe entry
  • receptors that recog inflamm cytokines
  1. receptors for capturing microbes
  • PRRs with very active endocytosis
    • mannose, c-type lectin, TLRs
  1. migration
  • CCR7
  • co-localize in peripheral L tissues with naive T cells
  1. mature while migrating
  • incr lvls of MHC: induce costim & decr endocytosis
    • convert from ag capture –> APC and T cell activation
277
Q

immature DCs are activated when:

A

DC TLRs bind microbal cmpts

stim via inflam cytokines from microbe

278
Q

what are the signals that DCs provide to activate T cells?

A
  1. increase MHC/antigen complexes
  2. increase costim molecules

programmed change that DC undergoes upon activation in peripheral tissues

279
Q

fxs of different APCs: DCs

A

naive T cell activation

clonal expansion

differentiation into effector T cells

280
Q

fxs of different APCs: macrophage

A

effecgtor T cell activation

activation of macrophages: cell-med immunity

281
Q

fxs of different APCs: B cells

A

effector T activation

B cell activation

antibody production

humoral immunity

282
Q

Which of the following cell types is best equipped for the activation of naïve T cells?

A.B cells

B.Macrophages

C.Eosinophils

D.Neutrophils

E.Dendritic cells

A

DCs

283
Q

antigen processing and presentation means:

A

how APCs and normal cells break down larger proteins –> small polypeptide epitodes –> present to T cells on MHC I or II

284
Q

sources of protein antigen for APC?

A

extracell: internalized by specialized APCs
intracell: cytosolic proteins (microbial or self) from cell’s OWN protein prod machinery

285
Q

difference b/w extracell and intracell antigen presentation?

A

extracell = MHC II

intracell (cytosolic) = MHC I

286
Q

antigen processing

A

conversion of native antigen (globular protein) into peptides cap of binding to MHC

  • loaded in same cell compartments where MHC are synth and assembled
287
Q

MHC II processing of protein antigens

A
  1. endocytose extracell protein
  2. biosynth MHC: with invarient chain Ii
  3. association
  4. present on surf for CD4 cell
288
Q

MHC I processing of protein antigens

A
  1. cytosolic protein –> proteasome
  2. enter ER via TAP
  3. attachment to MHC
  4. presentation on surf for CD8 CTL
289
Q

before an ag can be processed via MHC II pathway….

A

exogenous ag must be bound & internalized

different APCs bind protein ag

  • DC & macrophages recog structures shared by board groups of microbes: TLF, MBR
  • macrophages - Fc & C3b –> opsonizing ab and C’
  • B cells: specific! = high affinity
290
Q

Class II MHC pathway of processing and presentation of peptide ags

A
  1. extracel protein ingested into endosomes/lysosomes
  2. brkdown –> peptides
  3. MHC II mol constantly produced in ER with Ii to block ER loading
  4. MHC/Ii complex targeted to late endosome/lysosome vesicles
  5. CLIP removed by HLA-DM and extracel peptide Ag takes its place
  6. presentation
  7. recog by CD4
291
Q

The class I MHC pathway of processing of endogenous cytosolic protein antigens

A
  1. cytosolic proteins ubiquitin tagged –> proteosome
    • most = endogenous derived (self, virus, tumor)
    • some = proteins of phago microbes that enter cytosol
  2. peptides –> ER via TAP
  3. load onto empty tapasin-anchored MHC I complexes
    • holds MHC in place
  4. complex stab & released from TAP
  5. txp to cell surf
  6. recog by CD8 T cells
  7. activates CTL that destroy cells infected with intracell microbes & eradicate reservoirs of infection
292
Q

what is the problem for CD8 cells?

A

only ag presented by activated DCs can activate naive T cells

soln: some DCs can capture infected cells –> txp ag to cytosol –> enter class I pathway
* explains how non-prof APCs can lead to init of CD8 cell response

293
Q

what is the significance of segregating class I and class II MHC pathways?

A

respond in diff ways –> find BEST way to combat microbes

294
Q

protein antigens of microbes that live in cytoplasm of infected cells enter what pathway?

A

MHC I –> cells recog by CD8 –> kills infected cell

295
Q

protein antigens of microbes endocytosed from extracel environment enter what pathway?

A

MHC II –> recog by CD4 Th cells –> activate macrophages to destroy phago microbes & activate B cells to prod antibodies aga extracell microbes

296
Q

what does immunodominance of peptide epitopes mean?

A

not all peptide epitopes presented equally

“determinant selection”

  • unique set of MHC alleles select best MHC-binding peptides –> select immunogenicity of individual = immunodominat!
297
Q

MHC I v II: composition of stable peptide-MHC complex

A

I: polymorphic alpha chain of MHC, beta-2-microglobin

II: polymorphic alpha and beta chains of MHC

298
Q

MHC I v II: cells that express MHC

A

I: all nucleated cells

II: DC, mononuc phagocytes, B lymphocytes, endothelium, thymic epithelium

299
Q

MHC I v II: responsive T cells

A

I: CD8

II: CD4

300
Q

MHC I v II: source of protein antigens

A

I: cytosolic proteins - mostly synth in cell (can have ones that are phagoed)

II: endosomal/lysosomal proteins - internalized from extracell environ

301
Q

MHC I v II: enz responsible for peptide generation

A

I: cytoplasmic proteasome

II: endosome/lysosome proteases (cathepsins)

302
Q

MHC I v II: site of loading of MHC

A

I: ER

II: specialized vesicles

303
Q

MHC I v II: molecules invovled in txp and loading of peptides onto MHC

A

I: TAP

II: Ii & DM

304
Q

causes of MHC I deficiencies

A

mutations

  • TAP
  • tapasin

absense –> failure to produce stable MHC I mol –> expr fewer

305
Q

what kinds of viruses evade CD8 T ecll response and how?

A

inhib proteasomal activity:L EBV, human CMV

block TAP txp: HSV

block MHC synth and/or ER retention: adenovirus, human CMV

removal of MHC I from ER: CMV

interfere with CTL recog with “decoy” viral class I-like mol: murine CMV

306
Q

Ag displayed by FDCs are…

A

coated by ab and complement (C3b, C3d) –> target for activated B cells

  • selects B cells that bind ag with high affinity
307
Q

Cytomegalovirus (CMV) is a common infection that often produces no clinical symptoms, however, can be quite dangerous in immunocompromised patients. CMV has a number of mechanisms by which it evades the immune response. One mechanism involves blockade of the TAP molecular complex. Which of the following is the most likely outcome of this blockade?

A.Reduced humaral immunity

B.Impaired neutrophil recruitment

C.Reduced activation of helper T cells

D.Impaired cytolytic destruction of infected cells

E.Reduced expression of costimulatory molecules by infected cells.

A

impaired cytolytic destruction of infected cells: CD8

308
Q

BCR v ab

A

basic structure is similar aside from transmemb region in cell-bound form

  • soluble Ig produced by effector B cells
309
Q

different stages of B cells

A

will express ag either as cell surf receptor or secreted as ab

310
Q

what class of glycoproteins are Ab?

A

gamma-globulin

311
Q

composition of ab

A

4 polypep chais: 2 heavy and 2 light

held together by disulfide bonds

312
Q

secreted IgG versus membrane IgM

A

IgM has extra Ch4 portion close to PM of B cells with transmemb tails

313
Q

what makes up the antigen binding pocket

fx?

A

variable regions of light and heavy chain - 2 indentical

determines antigen specificity

314
Q

fx of constant region of ab?

A

detms isotype: IgG, IgM, IgD, IgE

C’ deposition

Fc receptor binding

transcytosis

315
Q

regions of antibody are classified by….

A

proteolytic frag

  • papain –> 2 Fab frag and 1 Fc frag
  • pepsin –> 1 F(ab)2 frag: digestion occurs below hinge region = 2 arms are attached
316
Q

CDRs

A

antigen-binding site: aa seq variably concentrated in short, hypervariable stretches

  • each region = 3 CDRs
317
Q

isotypic v allotypic v idiotypic differences in Ab

A

isotypic: constant regions due to usage of diff c-region genes
allotypic: different allesles of SAME C GENE (polymorphic)
idotypic: variable portion differences

318
Q

IgA isotype

A

mainly dimer

fx: mucosal immunity

319
Q

IgD

A

trace amts in serum

monomer

fx: naive B cell antigen receptor

320
Q

IgE isotype

A

monomer

fx: helminth parasite def, immediate hypersense

321
Q

IgG isotype

A

most abundant in serum

monomer

fx:

  • opsonization
  • C’ activation
  • antibody-dep cell-med cytotoxicity (ADCC)
  • neonatal immunity
  • feedback inhib of B cells
322
Q

IgM isotype

A

pentamer

fx: native B cell antigen receptor (monomeric form), C’ activation

323
Q

relationship b/w valency of interaction and avidity of interaction of Ab on cells

A

higher valency = high avidity of interaction

324
Q

fx of hinge region of ab

A

loc b/w Fab and Fc portions –> allow indep mvmt

325
Q

what is affinity

A

strength of binding b/w single antigen binding surf on ab and one epitope of ag

326
Q

what is antibody avidity?

A

total strength of binding b/w compelx antigen (multi-epitope) and dimer/pentamer ab complex

327
Q

change in ab affinity and avidity over course of immune response

A

IgM (pentamer) early when ab affinity low

as immune response con’t –> antibody affinity improves

    • class switching = uses smaller molecules (G, E, A)

increased affinity compensates for decreased in # of binding sites for maintaining overall avidity for antigen

328
Q

Changes in Antibody Structure During the Humoral Immune Response

A
329
Q

clone

A

population of lymphocytes with identical antigen receptors

330
Q

monoclonal

A

derived from single cell clone –> will be specific for SAME epitope on SAME antigen

331
Q

polyclonal

A

derived from multiple clones –> specific for MULTIPLE epitopes or ag

332
Q

how to produce a monoclonal ab?

A
  1. immunize mouth with ag X
  2. boost days later to incr # of ag-sp B cells
  3. remove spleen –> isolate B cells
  4. fuse B cells with immortalized myeloma cell line
  5. culture in medium that allows only fused cells to grow
  6. isolate SINGLE clones of ab-prod immortal B cell
  7. you’ve made a hybridoma
333
Q

so what’s the point of mAb’s (monoclonal antibodies)

A
  1. ID pheno markers on particular cell types
  2. imm-dx
  3. tumor ID
  4. therapy
  5. fx analysis cell surf and secr mol
334
Q

TCR structure

A

surf ag receptor on T cell that recog MHC ag-present

similar to Ig

2 types:

  • α β: predominant in lymphoid tissues
  • γ δ: predominantly at mucosal surfaces
335
Q

Features of the TCR (αβ)

A

memb-bound heterodimer

  • anchored: not prod in secreted form (like ab)

each variable region contains 3 CDRs with CDR3 being MOST variable

short cytoplasmic tail: no transduction of activation signal - requires CD3 complex which can transmit some signals

no class switching –> no effector fx

336
Q

each T cell has TCR for how many specificities?

A

ONE - αβ TCR recog ag only in context of MHC

  • low affinity –> str by addn cell surf adhesion mol: LFA-1 to ICAM-1
337
Q

how to compensate for short cytoplasmic tails of TCRs?

A

T cell co-receptors (CD4 and CD8) recog nonpolymorphic regions of MHC –> transmit activating signals

338
Q

non-traditional T cells

A

recog wide variety of ag: many are non-protein

  • NOT MHC restricted
339
Q

Comparison of antigen-recognizing molecules of the adaptive immune system: chart

A
340
Q

flow cytometry findings of different CDs

A
341
Q

most diverse CDR

A

CDR3 –> key for determining ag specificity

  • spans jxn of V and C regions
342
Q

how is enormous diversity of ag receptors created?

A

somatic recombination

formation of antigen receptors take place during B and T cell dev: random rearragement of antigen receptor gene seg

343
Q

IL-7

A

critical for init prolif and survival or earliest lymphocyte precursors

rearragement process is random & error prone –> high lvls of precursor cell death

344
Q

somatic recombination

A

randomly joining of gene seg

345
Q

Steps of Ig heavy chain somatic recombination

A
  1. D pairs with J
  2. V joins DJ
  3. Ig heavy chain Ts
  4. VDJ RNA spliced into 1st heavy chain C RNA (mu)
  5. RNA T(L) to produce M heavy chain
  6. if heavy chain recomb successful, light chain gene recombined next
346
Q

germline configuration of T cell antigen receptor loci

A

D gene seg not part of TCR-alpha chain locus

during som-recomb:

  • 1 V + one of many D and J and one of C regions
347
Q

The germline configuration of B cell antigen receptor loci

A

many different C region gene segments - extracellular and transmembrance/cytoplasmic domains

348
Q

when does Ig som-recomb happen? What does that mean?

A

during lymphocyte dev: B in bone marrow, T in thymus

  • indep of antigen

each lymphocyte will be DIFFERENT from seg combining in neighboring cell

349
Q

VDJ recombinase

A

lymphoid sp-enz: combosed of RAG1 and RAG2 proteins (same name genes)

fx:

  • recog DNA signal seq that flank all V, D, and J gene seg –> brings those together –> cleaves –> ligased to be V-J or V-D-J exon without intervening DNA seg
350
Q

where odes the diveristy of hte B and T cell antigen receptor repertoire come from?

A

combinatorial diversity: diff combos of V, D, J seg

junctional diversity: addn/removal of nt seq @ jxns

351
Q

mechanism of diversity in ag receptors

A

exonucleases removed nts from VDJ seg during recomb –> TdT adds random nts to the region –> overhanging DNA seg created and filled on (P nts)

352
Q

what is the price paid for tremendous B and T cell antigen receptor diversity?

A

recomb can prod seq that do not recog antigen

soln: multple pts of regulation to select for fx ag recep

353
Q

SCID

A

severe combined immunodeficiency

defects in both T cel land B cell arms of adaptive immune response

  • IL-7R
  • ADA
  • RAG
354
Q

IL-7R mutation –>

A

blocks T cell maturation

B cell mat intact b/c they CAN use other GFs

355
Q

ADA mutation –>

A

ADA = salvage pathway of purine synth

loss –> accumulate toxic purine metabolities –> kill lymphcyte prolif during maturation –> decreased B, T, NK cells

356
Q

RAG mutation –>

A

RAG1/2 mutation –> blocks VDJ recomb –> absence of T and B cells

357
Q

processes invovled in maturation of lymphocytes from BM precursors

A
  1. prolif immature cells
  2. expr of ag receptor genes
  3. selection that expr useful receptors
358
Q

what chain gene is 1st to be expr which results in the expression of IgM?

A

μ (Mu) heavy chain gene

359
Q

significance of rearragement of 2nd chr?

A

successful –> VDJ recomb will move forward

unsuccessful –> cell = apop

2 alleles allows for multiple chances for successful rearrangement

360
Q

what is the surrogate light chainn

A

placeholder to stabilize expr of pre-B cell receptor

  • inhib futher heavy chain rearrangement
    • if both alleles used, then no problem
    • if 1st allele was successful –> prevent using 2nd allele to redo recomb
  • further prolif of pre-B cells
    • lost a bunch of cells during failed recomb so need to replace
  • stim of K light chain recomb
    • indep of heavy chain recobin
361
Q

allelic exclusion

A

produtivec rearrag on one chr –> turns off further rearrag

  • Ts RAG stopped & RAG proteins degraded

ensures that all ag receptors expressed will have SAME ag specificity

362
Q

light chain rearragement of pre-B cell

A

cells with light chain success combine with heavy chain –> selecgted to surviv e nad prolif

363
Q

XLA

A

x-linked agammaglobulinemia

  • def in B cell dev: BTK gene
  • males over 6mo

result:

  • low to absenb B cells
    • low serum Ig
    • underdev L tissues - no germinal centers
    • absent plasma cells
  • recurr RT infections by extracel bac & viruses norm neut by Ab
    • bac: strep, h.influenzae
    • virus: polio, coxsackievirus
364
Q

BTK

A

enq that signals for light chain rearrag

req for B cells to dev beyound pre-B cell stage in bone marrow

365
Q

selection of B lymphocytes is _____ selection

A

negative - screen via binding of self antigen with high affinity

if binding occurs:

  • reactivate RAG to gen 2nd light chain –> change specificity (receptor editing)
  • apop
366
Q

receptor editing

A

gen new light chain - ONLY if there is an allele yet to be rearranged

ONLY IN B CELLS

367
Q

final step of B cell dev

A

in periphery - spleen: expr IgM and IgD

368
Q

chart of steps in maturation of T cells

A
369
Q

allelic exclusion in T cell development

A

2 attempts to rearragement for both beta and alpha gene

  • success @ 1st attempt turns off any further attempts for other allele
    • success of beta signals rearragemetn of alpha gene
370
Q

selection for T cells

A

positive

  • recog of self-MHC
    • class I –> retains CD8, loses CD4
    • class II –> retains CD4, loses CD8

negative

  • del double-positive T cells that strongely recog MHC-self peptide complexes
371
Q

what does the process of negative selection in the thymus require?

A

presentation of self ag/MHC complexes in thumus

Ts AIRE - allow expr 100s of different tissue specific genes to be presented

  • so T cells can recognize self and not react
  • rxn –> apop
372
Q

APS-1

A

autoimmune polyendocrine syndrome type 1

  • monogenic disorder caused by AIRE mut
  • triad
    • mucocutaneous candidiasis
    • autoimm addison’s
    • autoimm hypoparathyroidism
373
Q

Congenital immunodeficiencies caused by defects in lymphocyte development chart

A
374
Q

A B cell tumor is isolated from a patient. If two separate DNA probes with different sequences (Probe 1 and Probe 2) show that the immunoglobulin genes of one B cell tumor are in the conformations shown below, at what stage did the B cell become a tumor?

A.A pro B cell

B.A pre B cell

C.An immature B cell

D.A mature B cell

E.A memory B cell

A

A pre B cell

375
Q
A
376
Q

T cell activation and accessory molecules

A

molecules other an ag receptors involved in T cell response

ligang-receptor int-act:

  • ag-recog
  • adhesion
  • signal (activate, supress)

invarient amoung ALL T cells

377
Q

factors that impact T cell activation

A

TCRs engaged by Ag/MHC - requires 2 or more TCRs

  • low affinity!

length of engagement: req several min to gen enough signals to activate

378
Q

fx of adhesion molecules for T cell activation

A

productive activation requires stabilization

  • integrins: LFA-1 (bind to ICAM-1)

naive T cells have low affinity integrins –> high affinity integrins

  • via Ag recog
  • cause clustering –> allows strong binding to APCs
379
Q

best defined costim for T cells

A

B7-1(CD80) & B7-2 (CD86) –> recog by CD28 (on virtually all T cells)

  • essen for activation of naive T cells

​ICOS: CD28-like molecule expressed by CD4 cells

  • provide help to B cells in follicles (follicular Th cells)
380
Q

significance of costim requirement

A

ensures naive T cells only activ FULLY by microbial ag

  • NOT by harmless self or foreign ags
381
Q

vaccines and B7

A

vaccines = only pure microbial proteins

require adjuvant to induce B7 expr by APCs to offer sufficient co-stim to T cells specific for vacccine Ags

382
Q

anergy

A

T cells that get Ag receptor stim but NOT costim signal

  • need BOTH signals to proceed

makes cell unresponsive/quiescent –> death

383
Q

other fx of CD28 constim receptor?

A

can be inhib and limit or terminate an immune response

  • CTLA-4 can also bind B7 but it’s singal = suppression
    • like PD-1: inhib receptor that recog idfferent but related ligands on many cell types
384
Q

CTLA-4 and PD-1 engaged on their ligands –>

A

inhib T cell activation/effector fx:

  • supress response to self antigens
  • term responses upon clearance of ag
385
Q

CTLA-4 blockage

A

tumor regression via enhancing of tumor-sp immune responses

autoimune inflam

386
Q

what is the TCR-CD3 complex for?

A

intraacyto region of TCR is too short to transduce activation signal

  • requires CD3 chains!
    • ITAMS regions that require (P) to signal
387
Q

activation steps of T cell signalling

A
  1. TCR bind to MHC-peptide complex and CD4/8 binds to nonpolymorphic regions of MHC I/II
  2. binding of CD4/8 brings Lck (tyrosine kinase) to ITAMS
  3. activate Lck –> (P) tyr residues in ITAMS
  4. docking site for Zap-70 –> getts (P) by Lck –> activates
  5. several signally pathways
388
Q

Zap-70 activation via _____ activates….

A

(P)

Nuclear factor of activated T cells (NFAT) pathway

PKC-NF-kB pathway

Ras/Rac-MAP Kinase pathway

PI-3 Kinase pathway

389
Q

Calcium-NFAT pathway

A

ZAP-70 –> (+) PLC (phospholipase C) –> IP3 –> ER –> release Ca2+ –> (+) calcineurin (phospatase) –> (+) NFAT –> nuc –> (+) expr for IL-2 & IL-2 receptor

390
Q

Protein Kinase C (PKC)-NFkB

A

PLC –> IP3 + DAG

DAG –> PKC –> recreuit to TCR –> (P) IkB-NFkB (bound together ) –> IkB + NFkB

  • (P) causes IkB to be destroyed
  • NFkB –> nuc
391
Q

RAS/Rac MAP Kinase pathway:

A

ZA-70 (P) adaptor proteins in PM –> recruit RAS & RAC inter-med –> activate via GDP-GTP exchange –> enz cascade –> MAP kinase ERK/JNK –> induce expr c-Fos & (P) c-Jun –> dimer –> AP-1 –> activates T cell genes

392
Q

Phosphatidylinositol-3 (PI-3) kinase pathway

A

trigger TCR, CD28, IL-2 receptor –> PI3 kinase –> (P) PIP2 –> PIP3 –> Akt/PkB (ser-thr kinase) –> anti-apop proteins –> surv ag-stim T cells

393
Q

mTOR

A

kinase similar to Akt

promotes cell surv & growth

target for rapamycin - used to tx graft rejection

394
Q

Ts factors activated due to T cell stim drive expr of genes for…

A

T cell prolif

cytokine production

effector mech

395
Q

clonal expansion of T cells is due to

A

IL-2:

  • induced within 1-2 hours after T cell activation
  • alongisde high affinity form of IL-2 receptor
396
Q

IL-2 is produced by… and then fxs to?

A

ag-stim T cells

acts on same T cell

induces prolif and surv

INDUCED BY ACTIVATION OF NFAT

397
Q

cyclosporin

A

blocks IL-2 via inhib of NFAT

398
Q

which cells prolif the most?

A

CD8

most during anti-viral response

399
Q

superantigens

A

bac/viral toxins –> (+) T cells in antigen-nonspecific way

  • bind simultaneously to MCH II & TCRs (particular beta chain variable region)

binds to wide array from TCR –> EXCESSIVE polyclonal response –> can invovle CD4 T cells

massive release of inflam cytokines (IL-1/2, TNF-alpha) –> septic shock

400
Q

staph aureus enterotoxins

A

exotoxins prod by gram positive

most common cuase of food poisoning in humans

401
Q

TSST

A

toxin related to stap enterotoxin –> causes toxic shock synd

  • mass of activated T cells –> TNF –> fever, disseminated intravasc coag –> CV shock

assoc with tampon use and sx wounds

402
Q
A
403
Q

most important cell surf protein involved in T cell effector fx of CD4 cells is…

A

CD40L

404
Q

during mycobacterium infectons, what does CD4 T cells do/

A

req to activate macrophages –> destroy intraell bac (cell-med immunity)

405
Q

anti-helminth and CD4 cells

A

involves CD4 T cells

BUT

dominated by B cell prod of IgE –> (+) eosinophils & mast cells

406
Q

different T cell subsets defied by capa to…

A

produce different sets of cytokines

  • Th 1, 2, 17

dev in response to types of microbes BEST at eradicating - influenced by innate immune response

407
Q

Th1 cells critical for

A

stim phago-med killing of intracell microbe: IFN-gamma

408
Q

effects of IFN-gamma

A
  1. activate macrophages
  2. amp CD4 response: expr of MHC II & B7 on macrophages and DCs
  3. production of opsonizing IgG ab from B cells
  4. differen CD4 –> Th1 subset –> inhib dev of Th2 and Th17
409
Q

differentiation of Th1 cell is driven by…

A

IL-12 - DC & macrophages via stim through TLR & other PRRs

INFgamma - NK (in combo with IL-12) –> (+) Ts –> INF-gamma by Th1 CD4 T cells

usually prod during innate immune response to bac

410
Q

what is an example of cell-med immunity directed by Th1 CD4 T cells?

A

mycobacterium Tb

primary Tb = early, uncontrolled prolifand spread of bac in the pulm alveoplar macrophages (lasts 3 wks)

@ 3 wks: CD4 response aga Tb mounted via high lvls IL-12 –> Th1 differen & IFN-gamma prod –> (+) infected macrophages to better kill Tb

  • form intracell phagolysosome
  • NO/ROS
  • granulomas
411
Q

activation of macrophages by Th1 CD4 effect T cells requires…

A
  1. Th1 specific for ag presented by macrophage @ infection site
  2. prod IFN-gamma by Th1 –> bind to IFN-gamma of macrophage
  3. int-act b/w CD40L b/w Th1 and macrophage
  4. macrophage activated = classically activated

bidirectional int-act b/w cells of innate & adaptive immune sys

412
Q

Th1 effector fx

A

activate macrophages

secr TNF-alpha –> (+) adhesion of endothelium & (+) chemokines –> inflam

CD4 –>

  • CD8 –> CTL
  • helper B –> plasma cells
413
Q

cytokines of Th2

A

IL4: (from Th2 & Tfh) –> class switch to IgE –> opson helminth & bind Fc of mast cells and eosinophils

IL5: (+) eosinophiles –> MBP & major catonic protein –> kil helminth

IL13: (+) mucus secr & intestinal peristalsis

414
Q

how do cytokines from Th2 differ in their effect on macs than Th1?

A

Th1 –> INF-gamma –> (+) classic mac –> kill, cytokine secr

Th2 –> IL-4, IL-13 –> inhib mi-cidal of macs & (+) fibrosis via incr collagen synth

415
Q

what are M2?

A

alt-activated macs via IL4 anad IL13 in absence of strong TLR signals

reduce inflamm & prom tissue repair

416
Q

how do ______ cells differentiate into Th2 cells?

A

CD4 (in presence of IL-4 and absence of IL12) –> Th2

source:

  • (+) CD4 prod small amts of IL4 when (+) in absence of IL-12
  • (mast cells)
  • (basophils)
417
Q

Th17 cells

A

prod only:

  • IL-17
    • recruit neutrophils and monocytes
    • defensins
  • IL-22
    • maint integrity of epith barriers
418
Q

Th17 cells destroy…

but can be implicated in..

A

destroy: extracel bac & fungi

implicated in: inflam disease –> MS, IBD, RA

419
Q

dev req for Th17

A

IL-1, 6, 23 + TGF-beta

TGF-beta = usually inhib immune response but prom dev of Th17 in PRESENCE of IL-6 or IL-1

420
Q

CD4 effector subsets on themselves and other subsets

A

amp themselves and INHIBT others

421
Q

mycobacterium lepra

A

bac in macs –> leprosy

2 clinical forms:

  • tuberculoid
    • dom Th1 response –> poor growth in macs
      • low infectiveness
      • loc infection
      • normal serum Ig
  • lepromatous
    • dom Th2 response –> florid growth
      • mac killing inhib by Th2 response
      • high infectivity
      • disseminated
      • hypergammaglobinulinaemia
422
Q

A major function of ____ cells is to activate macrophages. Which CD4 T cell subset activates macrophages and what molecules are essential for this function?

A.Neutrophils, IL-1 and TNFa

B.Th17, IL-17 and IL-22

C.Th2, IL-4 and CD28

D.CD8, IL-2 and IL-12

E.Th1, IFNg and CD40L

A

Th1, IFNg and CD40L

423
Q

Activated macrophages (classical or alternative) perform all of the following functions except:

A.Inhibition of fibroblast proliferation and angiogenesis within damaged tissues

B.Production of lysosomal enzymes and reactive oxygen species that kill phogocytosed microbes

C.Presentation of antigen to helper T cells

D.Secretion of inflammatory cytokines such as TNFa and IL-1

E.Production of NO

A

Inhibition of fibroblast proliferation and angiogenesis within damaged tissues

424
Q

Which type of T cell is most likely to promote acute neutrophilic inflammatory responses that defend against extracellular bacteria and fungi?

A.Th1

B.Th2

C.Th17

D.CD8+ CTL

E.T follicular helper cell

A

A.Th17

425
Q

naive CD8 cell activation depends on…

A

cross presentation of ag by DCs

virus-infected cell destroyed –> frags endycyto up by host DC (has MHC II) –> present on MHC I alongside costim B7 –> activates virus-sp CD8 –> prolif –> kills infected cells

426
Q

how do CD4 cells “help” (+) naive CD8 cells?

A

DC can present ag to CD4 and CD8

DC with high levels of B7 –> (+) naive CD8 –> IL-2 –> self prolif and differentiation

APC –> (+) CD4 –> (+) APC (DC) –> expr B7 –> co-stim naive CD8

APC –> (+) CD4 (to make IL-2) & CD8 to expresss IL-2 receptors –> IL-2 sec by activated CD4 will (+) CD8 IL-2 receptor –> (+) CD8

427
Q

co-stim of CD8 T cell

A

required during stim

CD8 can self-prolif and differentiate but secr IL-2 that self acts

effector phase does not need co-stim –> allows targeting of non-APCs –> kill

428
Q

CTLs kill target cells via

A

apoptosis

  • perforin/granzyme
  • Fas/FasL
429
Q

All of the following are associated with immune responses to intracellular bacteria except:

A.Interferon gamma production by bacterial-antigen specific CD4 T cells

B.Opsonization of infected cells by complement

C.IL-12 production by macrophages

D.Granuloma formation

E.Cytotoxic T cell killing of infected macrophages

A

Opsonization of infected cells by complement

430
Q

how can mycobac evade cell immunity?

A

inhib phagolysosome fusion –> survs in phagosome

431
Q

how does HSV evade cell immunity?

A

inhib TAP txper (into ER) –> no ag presentation

432
Q

how does CMV evade immunity?

A

inhib proteosome activity

remove MHC I from ER

–> no ag presentation

433
Q

how does EBV evade immunity?

A

inhib proteosome activity –> no ag presentation

prod IL-10 –> inhib mac and DC activation

434
Q

how does the pox virus inhib immunity

A

prod soluble cytokine receptors –> bind extrcel cytokines –> decreased cytokine binding onto effector cells –> decreases activation

435
Q

T cell exhausion

A

virus –> (+) inib receptors like PD-1 (sim to CTLA-4) –> (-) CD8 –> prematurally terminated response to virus –> chronic infection – T cell exhausion

436
Q

which cells contritube to hypersense?

A

CD4

  • Th1: RA
  • Th2: asthma - IL4 + IL13 –> (+) IgE, IL-5 –> (+) eos –> chronic asthma
  • Th17: crohns - neutrophil recruit to gut –> lyso enz + ROS

CD8

  • DM I –> beta cell lysis
437
Q

general properties of cytokines (4)

A

prod transient response to ag: TCR signal and costim

autocrine/paracrine - T cell activation induces expr of cytokines and high-affinity receptors for this cytokines

pleiotropism - each cytokine has mult actions

redundancy - mult cytokines share same/sim actions

438
Q

compare and contrast innate v adaptive immunity: cytokines

A

innate: TNF, IL-1, 12, IFN-gamma
adaptive: IL-2, 4, 5, IFN-gamma

439
Q

compare and contrast innate v adaptive immunity: major cell source

A

innate: macs, NK
adaptive: T cells

440
Q

compare and contrast innate v adaptive immunity: prinicple physio fxs

A

innate: med inflam (local and sys)
adaptive: reg T ells growth and diffen, (+) effector cells (mac, eos, mast)

441
Q

compare and contrast innate v adaptive immunity: stimuli

A

innate: LPS (endotoxin), bac pep-glyc, viral RNA, T cell derived cytokines (IFN-gamma)
adaptive: protein ag

442
Q

compare and contrast innate v adaptive immunity: amounts produced

A

innate: high - detectable in serum
adaptive: low - usulaly undetectable in serum

443
Q

compare and contrast innate v adaptive immunity: local or stim effects, roles in disease

A

innate: both –> septive shock (sys diseases)
adaptive: usually local only –> local issue injury (granulomatous inflam)

444
Q

compare and contrast innate v adaptive immunity: inhibitors

A

innate: corticosteroids
adaptive: cyclosporine, FK-506

445
Q

TNF effects (6)

A
  1. endothelium - inflam, coag
  2. neutrophil - activ
  3. hypoT - fever
  4. liver - synth acutep phase
  5. M/fat - catabolism (cachexia)
  6. apop
446
Q

IL-1

A

endothelium - inflam, coag

hypoT - fever

liver - acute phase prot

447
Q

IL-12

A

T cells –> Th1 diffen

NK/T cells –> IFN-gamma, incr cytotoxic activity

448
Q

chemokines are most important for…

A

leukocyte: chemotaxis, activation, migration to tissues

449
Q

IL-12

produced by…

effect?

A

prod: macs, DC

effect:

  • stim NK & CD4 –> INF-gamma –> bidirectional stim and incr cytotoxic activity
  • Th1 differen
450
Q

IFN-1

A

prod:

  • alpha - mac
  • beta - fibroblasts

effect:

  • (+) anti-viral state
  • incr MHC I
  • activates NK
451
Q

IL-10

A

main prod by reg T cells

inhib –>

  • IL-12 production
  • expr costim
  • MHC II
452
Q

IL-15

A

prolif NK

prod memory CD8 cells

453
Q

IL-18

A

stim INF-gamma prod from NK & T cells

454
Q

IL-23

A

(+) Th17 cells –> Th17 production

455
Q

TGF-beta

A

inhib T & B cells and mac

(+) IgA

angiogenic

(+) fibroblastss –> (+) collagen synth

456
Q

IL-13

A

isotype switch B cells –> IgE

increase musuc prod in epithelium

increase collagen synth in fibroloasts and M2

457
Q

lymphotoxin

A

prod by T cells –> recruit neutrophils & lymphoid organogenesis

458
Q

IL-4

A

B cell isotype swithc to IgE

(+) Th2

inhib IFN-gamma med activation of macrophages –> (+) M2

mast cell prolif

Immuno Year 1 (4 decks)

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