Immunity to Pathogens

Question 1

Infection

Answer 1

Harmful relationship between pathogen and host organism

Pathogen must overcome innate immunity and adaptive immunity

Question 2

Innate immunity

Answer 2

Surface/mechanical defences, phagocytic/inflammatory demesnes
Natural resistance that involves pattern recognition receptors not specific for any particular pathogen
Can be through induction of type 1 interferons (IFNalpha and beta) via TLR

Question 3

Pathogenesis

Answer 3

Usually caused by host’s immune response to pathogen rather than direct tissue damage caused by pathogen or its toxins

Question 4

IFNalpha/beta

Answer 4

Made by stimulation of TLR by viral dsRNA
Bind receptor on infected cells and nearby uninfected cells
Induces transcription Mx proteins, Rnase and dsRNA-dependent protein kinase R

Question 5

IFNalpha/beta NK cells

Answer 5

Bind receptor
Inducing lytic activity
Enhanced by IL12 produced by innate immunity dendritic cells
Increase cytotoxic activity of NK cells
(IL12 induces IFNgamma production in NK cells)

Question 6

Mx proteins

Answer 6

Inhibit virus transcription and assembly

Question 7

Rnase L

Answer 7

Degrades vial mRNA

Question 8

dsRNA-dependent protein kinase R

Answer 8

Blocks protein translation

Question 9

Antibodies block spread of viruses by (4)

Answer 9

1. Blocking viral attachment to host cells (secretory IgA)
2. Preventing fusion of viral envelope with host cell membranes
3. Agglutination and opsonization of viral particles for removal by phagocytes
4. Activation of classical complement pathway, causing opsonization of viral particles by C3b and lysis of enveloped virus by membrane attack complex

Question 10

Viral clearance (4)

Answer 10

1. IFNgamma secreted by CD4+ Th1 cells and CD8+ CTL has direct antiviral activity
2. CTL (activated by Th1 cell produced IL2) target and kill virus-infected cells
3. NK cells (activated by IFNgamma and IL2) are directly lytic for infected cells and kill by ADCC
   4) Macrophages (activated by IFNgamma) can kill infected cells by ADCC

Question 11

Viral evasion of immune response (7)

Answer 11

1. Blocking dsRNA-dependent protein kinase R
2. Down regulating class I MHC or TAP molecule for antigen processing
3. Reduce class II MHC expression by APC
4. Alterations in viral antigens by drift/shift
5. Shedding or capping of viral antigen on surface of infected cells following antigen interaction with antibody
6. Interfering with complement function
7. Suppressing antivirus immune responses by activating Treg, altering Th1/Th2 cytokine balance, or destroying lymphoid tissues

Question 12

TAP

Answer 12

Transporter molecule needed for antigen processing

Question 13

Interfering with complement function

Answer 13

Ie. Binding proteins

Question 14

Immunity to extracellular bacteria through antibody (4)

Answer 14

1. Prevent attachment/colonization (IgA)
2. Neutralize bacterial exotoxins /endotoxins
3. Act as opsonin to enhance phagocytosis
4. Activate complement classical pathway

Question 15

Classical pathway

Answer 15

Results in lysis of gram-negative bacteria by MAC
Production of C3b (opsonin)
Production of C3a and C5a (anaphylatoxins) that cause mast cell degranulation
Vasodilation and extravasation of leukocytes into infected tissue
Chemotactic factors produced by mast cells and by complement degradation that are chemotactic for macrophages and neutrophils

Question 16

Bacterial evasion of immune responses (6)

Answer 16

1. Production of pili or adhesion molecules (enhance ability to attach to mucosal epithelium)
2. Secrete proteases that cleave IgA at hinge region to reduce half-life
3. Changes in aa sequence of surface structures
4. Express surface structures such as polysaccharide capsule or M proteins that inhibit phagocytosis
5. Bacterial toxins
6. Interfering with complement system

Question 17

Bacteria interfering with complement system (4)

Answer 17

1. Poor activation of alternative complement pathway due to synthesis of capsules that do not stabilize C3bBb
2. Resistance to MAC due to presence of capsules (gram neg) or peptidoglycan (gram pos) that prevent insertion of terminal complement components
3. Complement activation site deviation by secreted decoy proteins or bacterial surface proteins
4. Acceleration of complement breakdown by secreted enzymes

Question 18

Elastase

Answer 18

Secreted by Pseudonyms aeruginosa

attacks C3a and C5a

Question 19

Immune response to extracellular bacteria increasing pathogenesis by (2)

Answer 19

1. Overproduction of septic shock inducing IL1

2. TNFalpha in repose to cell wall endotoxins of gram neg bacteria

Question 20

Intracellular bacteria colonize phagocytic cells by (3)

Answer 20

1. Inhibiting lysosome fusion (mycobacteria sp)
2. Resisting oxidative/lysosomal attack (mycobacteria sp)
3. Excaping phagosome before fusion with lysosome (listeria)

Question 21

Cell medicated immunity against intracellular bacterial infections

Answer 21

Delayed type hypersensitivity response
Th1 cells (+CTL, NK) release IFNgamma to activate macrophages and enhance class II MHC expression
CTL (activated by IL2 from Th1) ill infected macrophages to release bacteria which is phagocytosed by uninfected macrophages
Chronic cell-mediated immune response if infection persists

Question 22

Granuloma

Answer 22

Isolation of site of infection
Can lead to tissue necrosis due to accumulation of high local concentration of lysosomal enzymes secreted by activated macrophages

Question 23

Protozoa

Answer 23

Unicellular eukaryotic organisms
Often have multistage growth cycles
Some stages are extracellular and others are intracellular
Humoran and cell-mediated immune responses are only effective at certain times

Question 24

Malaria

Answer 24

Caused by Plasmodium species introduced into humans by mosquito bites
Surface antigens change as going through cycle and shed

Question 25

Sporozoites

Answer 25

From mosquito Pass through blood to liver cells Merozoites are produced Only in blood for 30 minutes

Question 26

Merozoites

Answer 26

Leave liver to infect RBC Infected RBC rupture releasing attritional merozoites Become male and female gametocytes that are injected by mosquitos and spread

Question 27

Trypanosome parasite

Answer 27

African sleeping sickness Large repertoire of genes coding for variable glycoprotein Sequential expression allows evasion of antibody responses

Question 28

Helminths

Answer 28

Large, multicellular parasitic worms that are extracellular Protection through humeral and cell-mediated immunity Th2 and IgE synthesis

Question 29

Schistosoma species

Answer 29

Have protective mechanisms that decrease expression of antigens on its outer membrane and antigen masking with host ABO blood group and histocompatibility agents

Question 30

IgE in helminth infection

Answer 30

Worm antigens cause IgE-sensitized mast cells in the gut to degranulate Increased vascular permeability and secretion of eosinophil chemotactic factor

Question 31

Eosinophil chemotactic factor

Answer 31

Calls eosinophils to lumen in gut Eosinophils bind IgG coated work via Fc receptors and release major basic proteins hat kills worm Smooth muscle contraction caused by histamine and other mast cell mediators expels worms

Question 32

Anaphylatoxins in helminthic infections

Answer 32

Induction and maintenance of acute inflammatory responses