Immune Response To Infectious Agents

Front 1

Type 1 INF

Back 1

a. IFNα and INFβ
b. Act as first line of defense against viral antigens
c. Production induced by dsRNA

Front 2

Type 1 INF functions

Back 2

a. Upregulate expression of class I HLA molecules
b. Inhibition of protein translation
i. Induces a kinase that phosphorylates and inhibits elongation initiation factor-2 (eIF-2)
c. Destruction of viral mRNA
i. Induces 2’,5’ oligoadenylate synthetase→ activates latent endonuclease RNAseL

Front 3

Leukocyte INF/fibroblast INF

Back 3

a. Leukocyte (α)
b. Fibroblast (β)

Front 4

NK cells

Back 4

a. Recognize virus-infected cells that have down-regulated their display of class I MHC molecules in an attempt to evade Tc cells
b. Use KIRs to survey the surface ofhost cell for MHC molecules
d. Recognize MICA and MICB on cell surface
e. ADCC

Front 5

No KIR molecules on host cell

Back 5

i. Host cell is spared from destruction
ii. If viral infection has downregulated Class I MHC, KIRs will not find sufficient ligands and infected cell will be killed

Front 6

ADCC

Back 6

i. Nk cell recognizes antibody-coated (IgG)targets via CD16 (Fcγ receptor)

Front 7

NK cells and INFγ

Back 7

i. INFγ→ type 2, or immune interferon
ii. Weakly antiviral
iii. Upregulates MHC molecule expression
iv. Stimulates cell-mediated immunity by activating macrophages, Tc cells, and NK cells
v. Produces perforin and granzymes

Front 8

NK cells and FasL

Back 8

i. NK cells use FasL to kill infected or neoplastic host cells

Front 9

Complement and virolysis

Back 9

i. Complement can induce virolysis when it binds to the viral envelope

Front 10

Components of adaptive immunity effective against viruses

Back 10

a. Adaptive immune response→ 2 weeks
b. T cells and B cells with TCR and sIG molecules specific for virus become activated and undergo clonal expansion in lymph nodes, spleen, and MALT
c. Pre-existing circulating antibodies may be able to immediately quell viral infection (2°)

Front 11

T cell vs. humoral immunity

Back 11

a. T cell immunity is more important than humoral immunity
b. Persons with Ab deficiency seldom suffer from more frequent or more sever viral infections than normal people
c. T cell deficiencies result in profound susceptibility to viruses

Front 12

TH cell responses to viruses

Back 12

a. Tc cells become activated by interacting with the infected cell via TCR/antigen, CD8/class I MHC, CD40/CD40L, CD28/B7 interactions
b. Activation also stimulated by INFγ and IL-2 and type 1 INF
c. Kill host cell by perforin, granzymes, granulysin, INFγ, and FasL

Front 13

Ab-mediated immunity to viruses

Back 13

a. Neutralization of virus infectivity by binding to viral components needed for attachment
b. Inactivation of viral enzymes needed for host cell invasion
c. Activation of classical complement→ lysis of virions and infected host cells
d. Opsonization of virions for phagocytosis
e. Facilitation of ADCC against virus-infected cells

Front 14

Gram (-)

Back 14

i. Thin peptidoglycan layer
ii. LPS in outer membrane
iii. LPS differs among serotypes of bacterial species→ Ab for one serotype ineffective against other serotypes
iv. Lipid A moiety→ activates alternative complement, stimulates release of IL-1, IL-6, and TNFα through CD14/TLR4

Front 15

Gram (+)

Back 15

i. Thick peptidoglycan layer
ii. C3b/C4b effective as opsonins→ phagocytes
iii. Contain lipoteichoic acid in cell walls
iv. TLR2/CD14+LTA=release of pro-inflammatory cytokines from phagocyte
v. Superantigens produced by gram (+) bacteria participate in gram (+) septic shock

Front 16

Septic shock

Back 16

i. Can be gram (+) or gram (-)
ii. Implies presence of an infection somewhere in the body
iii. Bacteria cannot be recovered from bloodstream
iv. 70% of cases due to gram (-) infections

Front 17

Physical and chemical barriers to bacteria

Back 17

i. Found on skin and mucosal surfaces
ii. Lysozyme enzyme in tears, sweat, and saliva→ breaks down peptidoglycan

Front 18

Commensal microorganisms (normal flora)

Back 18

i. Prevent colonization by pathogenic species
ii. Prolonged antibiotic usage can dirupt the normal flora and lead ot infection by Candida albicans (yeast) or Clostridium difficile (+)
iii. Albicans→ thrush
iv. Difficile→ diarrhea or pseudomembranous colitis

Front 19

Reversal of loss of flora

Back 19

1. Yogurt
2. Sweet acidophilus milk
3. Probiotic tablets with Lactobacillus or Bifidobacterium

Front 20

Neutrophils and macrophages

Back 20

i. PAMP/TLR interactions
ii. IgG, CRP, complement
iii. Phagocytes kill bacteria using lysosomal enzymes or respiratory burst

Front 21

Lectin and alternative pathways

Back 21

i. Activated by MBL and LPS
ii. Activation causes lysis of gram (-) bacteria and opsonization of (+) and (-) bacteria
iii. C5-C9 deficiency→ infection by Neisseria (-)

Front 22

γδ cells and NKT cells

Back 22

i. Act as sentires to prevent bacterial invasion of epithelial and MALT by recognizing acterial ipid antigens in association with CD1 molecule

Front 23

TH cells

Back 23

i. Activated by macrophages/MHC II
ii. Can differentiate into TH1, TH2, TH17

Front 24

B cells

Back 24

i. Produces antibodies that:
1. Perform a WIDE VARIETY OF FUNCTIONS

Front 25

Immune response to fungi

Back 25

a. Cause serious disease only in individuals whose immune systems are compromised by long-term corticosteroid use, congenital or acquired immunodeficiencies, chemotherapy, or immunosuppressive therapy
b. Neutrophils or macrophages with glucan receptors can kill fungi with defensins and ROS

Front 26

TH1/TH17 and fungi

Back 26

i. Most important subsets in fighting fungi
ii. High correlation between T cell deficiency and enhances susceptibility to infections
iii. TH2 responses to fungi detrimental to human host

Front 27

Immune response to protozoans

Back 27

a. Eliminated by Ab-mediated mechanisms (extracellular)
b. Intracellular protozoa induce TH1-derived cytokines (INFγ) to activate macrophages and Tc cells for elimination of infected host cells

Front 28

Immune response to helminths

Back 28

a. Typically macrophages and neutrophils

Front 29

Frustrated phagocytosis

Back 29

i. Neutrophils
ii. Release hydrolytic enzymes extracellularly
iii. Damage worms that are too large to engulf
iv. Antigens released by dead or dying worms taken up by macrophages, present antigens to TH2 cells
v. TH2→ IL-4/IL-13→ IgE by B cells
vi. TH2→ IL-5→ eosinophil recruitment

Front 30

IgE and helminths

Back 30

i. IgE coats worms and cross-links with high affinity Fce receptors on mast cells and basophils
ii. Cross-linkage leads to degranulation and release of histamine and SRS-A
1. Smooth muscle contraction and increased vascular permeability→ worm expulsion and increased extravasation of eosinophils from bloodstream into tissue

Front 31

Eosinophil arrival at helminth infection site

Back 31

i. Esoinophilic Fce receptors cross-linked by IgE on worm
ii. Eosinophil degranulates, releases major basic protein and eosinophil cationic protein

Front 32

Major basic protein

Back 32

a. Damages worm integument

Front 33

Eosinophil and ROS

Back 33

1. Eosinophils can produce ROS and NO species
2. Eosinophils inhibit mast cell-derived histamine by producing histaminase
3. Inhibits SRS-A by arylsulfatase
4. Help to eliminate worm and turn off inflammatory reactions

Front 34

Bacterial capsules

Back 34

i. Antiphagocytic, neutralized by antibody

Front 35

Antigenic variation

Back 35

i. Allows microbe to doge the immune system by changing antigens displayed on microbe surface
Shift/drift

Front 36

Antigenic drift

Back 36

a. Point mutations in viral genome result in minor antigenic changes to viral hemagglutinin and/or neuraminidase molecules over time

Front 37

Antigenic shift

Back 37

a. Major, abrupt change in hemagglutinin and/or neuraminidase molecules that results from reassortment of the segmented influenza genome when more than one viral subtype infect the same host cell

Front 38

Multiple serotypes

Back 38

i. Infection with one serotype does not confer protection against other serotypes

Front 39

Immune suppression

Back 39

i. Epstein-Barr virus encodes a protein similar to IL-109 that interferes with TH1 maturation and function
ii. HIV kills CD4+ cells

Front 40

Blocking of IgG Fc-mediated effector functions

Back 40

i. Protein A from staphylococci
ii. Protein G from streptococci
iii. Bind to Fc fragment of IgG so that IgG cannot fix complement, interfere with opsonization, or facilitate ADCC