17 - Infectious diseases and vaccines

Question 1

intermediate host

Answer 1

vector. Carries infection from one organism to another

ticks, fleas, flies, mosquitoes

Question 2

vector-borne infection

Answer 2

infection carried by an intermediate host, which helps the pathogen get past the physical barriers of defence (epithelial sufaces on skin, f.ex)

Question 3

lipopolysaccharide

Answer 3

endotoxin produced by some bacteria.

stimulates macrophages or endothelial cells to produce cytokines (IL-1, IL-6 and TNF-alpha (tumor necrosis factor))

Question 4

peptidoglycan

Answer 4

in cell wall of many bacteria

activates the alternative complement pathway, leading to oponization and phagocytosis or lysis

Question 5

what do viruses typically induce the production of?

Answer 5

interferons, which can inhibit viral replication by inducing an antiviral respose in neigbouring cells

NK cells also kill virus infected cells (and others)

Question 6

sepsis

Answer 6

infections entering the bloodstresm

Question 7

septic shock

Answer 7

if sepsis occurs, the pathogen spreads all over the body, and the subsequent immune response can do more damage than the pathogen itself

Question 8

what determines which immune tools are availible and best suited for pathogen detection and elemination?

Answer 8

(type of pathogen), entry site and ultimate location

Question 9

mucosal or barrier infections are typically controlled by…

Answer 9

Th2-Type responses

Question 10

most infectious agents enter though …

Answer 10

mucosal routes (mouth, eyes, nose, urogenical tract). Tricky, as the mouth has to be in contact iwth food, commensal microbes (expected and essential). Can’t kill them all, has to have some tolerance, but can’t let other bad microbes penetrate the epithelial cell lining of the body either; must limit the amount of bad microbes that enter.

Question 11

MALT

Answer 11

mucosal-associated lumphoid tissue

se chap 13

Question 12

what does a Th2 type response mean?

Answer 12

• activation of ILC2
• Th2 specific cytokines (IL-4 and -13)
• IgE capable of recognizing surface epitopes of the pathogen
• cells expressing IgE receptor (mast cells, basophils, eosinophils)
• dimeric IgA (dIgA), found most abundantly at mucosal surfaces, serves important role in neutralizing pathogens and maintaining barrier integrity. Binding of IgA to pathogens can block them from attaching to epithelial cells (neutralization), and thus aid passively in the elimination of the infectious organism (without inducing inflammation)

Question 13

what does Th2 type response work against

Answer 13

particularly helminths (worms)

Question 14

What two main types of infection can happen once the pathogen has breached the barrers?

Answer 14

intra- and extracellular

Question 15

extracellular infections

Answer 15

intestinal fluis or bloodstream. Can remain local or spread (via circulatory or lymph).

immune mediators vary, but can include PRRs on phagocytic cells, complement, antimicrobial compounds, cytokines (activate immune cells), and antibody (IgG, mIgA, IgM). Often Tfh, Th17 and/or Th2

Question 16

Intracellular infections

Answer 16

most diffucult for IS to find and destroy

not recognized by Ab (antibodies) once inside the cell (but can be before entry)

eradication of infectious organisms that occupy endosomal spaces inside ost cells requires a strong Th1 pathway response.

DTH = delayed type hypersensitivity relies on cytokines secreted by Th1 cells (like IFN-gamma) to activate macrophages that can digest these vesicle-bound agents and overcome common pathogen-induced immune evasion of phagosome-lysosome fusion.

PRRs

Eradication of cytosolic infections requires strondg and comprehensive cell-mediated immunity; activated pAPCs (frequently DCs), CD4+ T cells that can licence DCs for cross-presentation (often Th1 type) and CD8+ T cells.

Question 17

DTH

Answer 17

DTH = delayed type hypersensitivity relies on cytokines secreted by Th1 cells (like IFN-gamma) to activate macrophages that can digest these vesicle-bound agents and overcome common pathogen-induced immune evasion of phagosome-lysosome fusion.

Question 18

Antiviral innate response

Answer 18

• complement activation via innate pathways
• PRR recognize PAMPs
• PRR signaling induces IFN-alpha and -beta (type I interferons) and NK activation
• IFN alpha/beta binding tor eceptors -> antiviral activiry + resistance to viral replicatoin. Through JAK-STAT (leads to production of new transcripts, one of which encodes an enzyme for viral RNA degradation). IFN binding also induces dsRNA-dependent protein kinase (PRK) (leads to inactivation of protein synthesis. binding also induces lytic activoty in NK cells, enhanced by IL-12 (produces by DCs early in response to viral infection)
• triggering of adaptive IS

Question 19

viruses neutralized by Ab

Answer 19

Ab crucial for blocking spread and secondary infection

exposure ideally leads to production of Ab, especially those who localize to areas with viruses; surface or mucosal IgA and circulating IgG are often most protective.

during secondary response, Ab most effective if located by the viral entry, and bind to virus so it struggels with binding to and entering host cells (neutralizing Ab). oral polio vaccine = example

can also happen after viral attachment. Ab bind to epitopes necessary for fusion of viral envelope and cell membrane, thus blocking entry. If Ab is of a complemet-activating isotype, lysis of enveloped virions may ensue.

Ab or complement may also agglutinate viral particles and function as an opsonizing agent to facilitate Fc or C3b receptor-mediated phagocytosis of the free virions

Some isotypes of Ab bound to infected target cells can trigger ADCC by NK

Question 20

How are IgG and IgA generated=

Answer 20

during primary response when viruses or virions are recognized in extracellular spaces (as virus spreads from dcell to cell/infected cells burst).

Question 21

Neutralizing Ab

Answer 21

bind to viruses to prevent them from binding to and entering cells

Question 22

humoral immune responses to viruses

Answer 22

• Antibody (esp IgA) blocks binding of virus to host cells, thus preventing infection or reinfection
• IgG, IgM and IgA Ab block fusion of viral envelope with host cells plasma membrane
• IgG and IgM Ab enhance phagocytosis of viral particles (opsonization)
• IgM Ab agglutinates viral particles
• complement activated by IgG or IgM Ab mediates opsonization by C3b and lysis of enveloped viral particles by membrane-attack complex

Question 23

cell mediated immune responses to viruses

Answer 23

IFN-gamma secreted by Th or Tc cells has direct antiviral activity (induces antiviral state in nearby cells)

cytotoxic T lymphocytes kill virus-infected self cells

NK (activated by IFN-y and IL-2) and macrophages kill virus-infected cells by Ab-dependent cell mediated cytotoxicity (ADCC)

Question 24

cell mediated virus clearance

Answer 24

Ab important in acute phases of infection, but can’t eliminate established infection.

Both CD8+ and CD4+ are needed

activated Th1 produce cytokines (IL-2, IFN-gamma, TNF-alpha).

IFN-gamma induces antiviral state in nearby cells

IL-2 help activate cytotoxic T lymph precursors, generating effector population of cytotoxic cells.

both IFN-gamma and IL-2 activate NK cells

Th1 cells directed against the same pathogen (though not always the same epitopes) are required in order to licence pAPCs for cross-presentation, allowing activation of naïve CD8+ T cells

Question 25

How do viruses evade immune response?

Answer 25

blocking or inhibiting PKR (important for inhibition of translation + essential to signal transduction in IFNalpha/beta actions)

Herpes simplex virus (HSV) inhibits antigen presentation by infecteed host cells (inhibits TAP, fig 7-14). This blocks antigen delivery to MCHI.

mutate to change surface antigens (need new vaccine every year)

general or specific immunesupression (EBV or HIV). HIV infects lymphocytes or macrophages (destroys cell or alters function)

Question 25

How do viruses evade immune response?

Answer 25

blocking or inhibiting PKR (important for inhibition of translation + essential to signal transduction in IFNalpha/beta actions)

Herpes simplex virus (HSV) inhibits antigen presentation by infecteed host cells (inhibits TAP, fig 7-14). This blocks antigen delivery to MCHI.

mutate to change surface antigens (need new vaccine every year)

general or specific immunesupression (EBV or HIV). HIV infects lymphocytes or macrophages (destroys cell or alters function)

Question 26

Original antigenic sin

Answer 26

teh tendency to focus an immune attack on those antigens that were present during the original/primaty encounter with a pathogen and for which we have established memory.

Question 27

Bacterial infections

Answer 27

IR to extra- and intracellular differ.
Extrac: humoral. Intrac: Th1-mediated immune responses

Extracellular induces Ab-production. Extrac bacteria typically induce local imflammatory response. could be triggered by immunogeinc toxins. Endotoxins = part of bacterial cell wall, exotoxins = secreted.

intracellular (vesicular) activate TLRs and NK mediated killing. the IR requires Th1 mediated IRs, such as DTH (chap 15). cytokines secreted by CD4+ (most importantly IFN-y) are crucial for activating macrophages to phagocytose the bacteria.

Question 28

Host immune response against bacteria attaching to host cells

Answer 28

blockage of attachment by secretory IgA Ab.

Bacterial response:
secretion of proteases that cleave secretory IgA dimers)
Antigenic variation in attachment structures

Question 29

Host immune response against bacterial proliferation

Answer 29

Phagocytosis (Ab- and C3b-mediated opsonization)

Bacterial response: production of surface structures (like polysaccharide capsule) that inhibit phagocytic cells AND mechanisms for surviving within phagocytic cells AND induction of apoptosis in macrophages

Complement-mediated lysis and localizes inflammatory response

Bacterial evasion mechanisms:
generalized resistance of gram-positive bacteria to complement-mediated lysis AND insertion of membrane-attack complex prevented by long side chain in cell-wall-LPS (some gram negative bacteria)

Question 30

Host immune response against bacterial invasion of host tissues

Answer 30

Ab-mediated agglutination

Bacterial evasion: secretion of elastase that inactivates C3a and C5a

Question 31

Host immune response against bacterial toxin-induced damage to host cells

Answer 31

Neutralization of toxin by Ab

Bacterial evasion:
secretion og hyluronidase, which enhances bacterial invasiveness

Question 32

Protozoan parasites (not finished - not relevant? p 655).

Answer 32

diverse, but all are unicellular euks, many motile, some pathogenic.

Not 1 common protozoan parasitic infection cycle.

The term parasite is a broad category, including unicellular protozoan euks that live inside host cells to macroscopic worms. Thus, the mode of immune detection and alimination will depend on the parasite stage and the location of the infection.

Question 33

Parasitic worms

Answer 33

typically generate weak immune responses, although Th2-type responses (including ILC2s and IL-4 and IgE production) are associated with the most protective immunity against this type of pathogen.

Question 34

Fungal infections

Answer 34

Few fungi (400) are disease for humans. others help us (bread, wine, etc).

Fungal disease = MYCOSES. classified on three criteria; site of infection, route of acquisition, and level of virulence.

Innate immunity controls most fungal infections (physical barriers and agents. Too much antibiotics can also induce fungal infection, as it kills commensial organisms in the body. Resolution of infection is rapid, initiated bt PRRs.

Fungi evade immune system f. ex. by production of a capsule (blocks PRR binding).

Both humoral and cellular pathways are engaged against fungel infections, as evidenced by memory responses and increased susceptibility in immune-compromised individuals, where the primary modes of clearance of mycoses appear to bemmediated by Th1 and possibli Th17.

Question 35

immunogens

Answer 35

epitopes on a pathogen that can be recognized by T and B cells

Question 36

Live attenuated vaccines

Answer 36

weakened forms of the infectious agent used to trigger a robust adaptive immune response. Advantages include effector cell types well matched with natural infection (including CTLs) and strong, long-lived, protective memory even after one single exposure. An important disadvantage is the potential for reversion to more virulent forms that can cause disease

Question 37

“killed” vaccines

Answer 37

an infectious organism can be killed or chemically inactivated, and then administered as a means to trigger protective adaptive immune responses. Advantages include the low risk of reversion and disease, plus rapid production times. Disadvantages include lower immunogenicity, poor cell-mediated immune responses (esp. CTLs) and a weaker protection that can necessitate booster shots

Question 38

Subunit vaccines

Answer 38

Use just a part of an inactivated or killed infectious agent; thus they share many of the same advantages and disadvantages, with the added advantage of simpler, safer and more rapid production time