IMMUNE RESPONSE TO INFECTIOUS DISEASES

Nonspecific (Innate) and the Specific (Adaptive) Host Defenses

The barrier provided by the epithelial surfaces of the skin and the lining of the gut.

The secretion of the gastric enzymes by specialized epithelial cells lowers the stomach and upper GIT.

The presence of the normal gut flora, which can competitively inhibit the binding of pathogens to gut epithelial cells.

NK cells frequently form the first line of defense against viral infections.

Pathogens Strategies Against the Immune Response

Gram + bacteria contain a peptidoglycan that activate the alternate complement pathway, resulting in the generation of C3b, which opsonizes bacteria and enhance phagocytosis.

Some bacteria (Gram -) produce endotoxins such as LPS, which stimulate the production of cytokines such as TNF, IL-1 and IL-6 by macrophages or endothelial cells. These cytokines can activate macrophages (phagocytosis).

Many viruses induce the production of interferons, which inhibit viral production by inducting an anti-viral response.

barrier

The __________ provided by the epithelial surfaces of the skin and the lining of the gut. (nonspecifc)

secretions of gastric enzymes

The ________________ by specialized epithelial cells lowers the stomach and upper GIT.

normal gut flora

The presence of ____________________, can competitively inhibit the binding of pathogens to gut epithelial cells.

NK cells

___________________ frequently form the first line of defense against viral infections.

Gram +

___________ bacteria contain peptidoglycan that activate the alternate complement pathway, resulting in the generation of C3b, which opsonizes bacteria and enhance phagocytosis.

alternate complement pathway

Gram + bacteria contain peptidoglycan that can activate the ________________________, resulting in the generation of C3b.

Gram -

_________________ bacteria produce endotoxins such as LPS, stimulating the production of cytokines such as TNF, IL-1, and IL-6.

LPS (Lipoproteins)

This is an endotoxin produced by G(-) bacteria to stimulate the production of cytokines

Interferons

Many viruses induce the production of _______________________, which inhibit viral production by inducing an anti-viral response.

Effector molecules or cells in Humoral Response

Antibody (secretory IgA)

IgG

IgM

IgA

Complement activated by IgG or IgM.

(ergo, humoral = antibody mediated)

Effector molecules or cells in Cell-mediated response

IFN-gamma secreted by TH or TC Cells

Cytotoxic T Lymphocytes (CTLs)

NK cells and macrophages

(Emphasis on CELLS)

Type 1 Interferons; NK Cells

The innate immune response to viral infection is primarily through the induction of __________________________ and activation of ___________________________.

Macrophages

Monocytes

Fibroblasts

These are also capable of producing these cytokines.

Interferons alpha and beta

_________________________ can induce an antiviral response or resistance by binding to the IFN alpha and beta receptor. (JAK-STAT Pathway)

JAK-STAT Pathway

Signaling pathway activated by cytokine receptors (IFN-a and b).

induces lytic activity

The binding of interferons alpha and beta to NK cells __________________________.

This makes them very effective in killing virally infected cells.

lysis

In viral neutralization by humoral antibodies, if the induced Ab is of a complement activating isotype, _______ of enveloped virions is ensured.

Viral Neutralization by Humoral Antibody

Operate after viral attachment to host cells (specific host-cell membrane molecules.

May block viral penetration by binding to epitopes that are necessary to mediate fusion of the viral envelope with the viral membrane.

If the induced Ab is of a complement -activating isotype, lysis of enveloped virions is ensured.

Cell-mediated mechanisms are most important in host defense

(CD8+ TC cells and CD4+ TH1 cells, CD4+ TC cells)

Once an infection is established, ________________________________________.

Cells that mediate host defense

CD8+ TC cells and CD4+ TH1 cells, CD4+ TC cells

TH1 Cells

Activated ____________________ produce a number of cytokines (IL-2, IFN-gamma, and TNF that defend against viruses either directly or indirectly).

IFN-gamma

___________________ acts directly by inducing an antiviral state in cells.

IL-2 (Interleukin-2)

___________________ acts indirectly by assisting in the recruitment of CTL (Cytotoxic T Lymphocytes) precursors.

Activate NK cells

Both IL-2 and IFN-gamma activate ______________________, which play an important role during the first days of many viral infections until a specific CTL response develops.

3-4 days after infection, peaks 7-10 days of primary infections

In most viral infections, specific CTL activity rises within _______________________________, _______________, most virions have been eliminated, paralleling the development of CTLs.

by blocking or inhibiting the action of PKR.

Hepatitis C virus which has been shown to overcome the antiviral effect of the interferons _____________________________________.

inhibits antigen presentation of the infected host cells

Herpes simplex viruses (HSV1 and HSV2) _________________________________. (method of viral evasion)

IFN alpha and beta

Some viruses have developed strategies to evade ______________ (host-defense mechanisms)

ICP45

HSV1 and 2 express an immediate early protein called _________________________. (a protein synthesize immediately after viral replication) which effectively inhibits the human transporter molecule needed for antigen processing (TAP).

blocks Ag delivery to class 1 MHC receptors

Inhibition of TAP ___________________________ on HSV-infected cells, thus preventing presentation of viral Ag to CD8+ T cells.

Adenoviruses and CMV

downregulate class 1 MHC expression shortly after infection, using distinct molecular mechanisms and inhibiting Ag presentation to CD8+ T Cells.

CMV, Measles virus, and HIV

reduce the levels of class II MHC molecules, blocking the function of Ag-specific anti-viral helper T cells.

Vaccinia Virus

secretes a protein that binds to the C4b complement component, inhibiting the classical complement pathway.

inhibiting classical and alternative pathways

HSV have glycoprotein component that binds to the C3b complement component

Constantly changing their antigens

A number of viruses escape immune attack ___________________________.

Influenza Viruses

results in the frequent emergence of new infectious strains (repeated epidemics).

Antigenic Variation

___________ among rhinoviruses (common colds) is responsible for our inability to produce an effective vaccine for colds.

Antigenic Variation of HIV

______________ suggest that it accumulates mutations at a rate 65 times faster than that of influenza virus.

Generalized immunosuppresion

Mumps, Measles, EBV, CMV, and HIV evade the immune response by ___________________________.

lymphocytes or macrophages

Generalized immunosuppresion is caused by direct viral infection of _______________________.

Cytokine Imbalance

Alternatively, immunosuppression is a result of _________________________, such as with BCRF1.

BCRF1; suppresses cytokine production by the TH1 subset.

EBV produced a protein called ______________ that is homologous to IL-10, and ________________________________.

IL-2, TNF, IFN-gamma

BCRF1 causes the decline of ______________________________.

A/Hong Kong/1/68

H3N2

A/Hong Kong/1/68 (H3N2 MEANING)

Strain A isolate 1

arose in humans in Hong Kong, 1968.

Antigenic subtypes of 3 HA and 2 NA

Antigenic Drift

accumulation of HA and NA mutations within a single strain of virus in a given geographical area

results in a minor changes in the virus's antigenicity

flu infection occur every 2 years

minor

Antigenic results in a (minor/major) changes in the virus's antigenicity

Antigenic Shift

results from the re-assortment of genomes from different influenza virus strains (from humans and from horse, pigs, and ducks)

occurs every 10 years; Influenza B does not undergo antigenic shift

re-assortment

Antigenic Shift involves ______________________ of genomes, causing the creation of a new strain.

minor changes

Antigenic Drift involves ________________ of genomes, causing changes in the antigenicity.

Humoral antibody; strain-specific

________________ specific for the HA molecule is produced during influenza infection. But its specificity is _____________________ and is readily bypassed by antigenic drift.

Sialic acid binding cleft

________________ necessary for the binding of virions to target cells. Specific Abs specific for these two regions are important in blocking initial viral activity.

Ab titers

In sialic acid binding cleft, this _______________ peak within a few days of infection and then decrease over the next 6 months, the titers then plateau and remain fairly stable for the next several years.

Infection Process of Bacteria

Attachment to Host Cells -> Proliferation -> Invasion of Host Tissues -> Toxin-induced damage to host cells

IgA antibody

blocks the attachment of host cells

N. meningitidis

N. gonorrhea

H. influenzae

bacteria that cleave secretory IgA dimers

This is a bacterial evasion mechanism that avoids IgA antibodies.

Antigenic variation in N. gonnorrhoeae

Phagocytosis

Ab- and C3b- mediated opsonization

Surface structure (polysaccharide capsule, M protein, fibrin coat)

Mechanisms

Induction of apoptosis in macrophages (Shigella flexneri)

How do bacteria prevent phagocytosis?

Generalized resistance of G(+) bacteria

Insertion of membrane-attack complex prevented by long side chain in cell-wall LPS (some G (-) bacteria)

How do bacteria prevent complement-mediated lysis and localized inflammatory response?

Secretion of elastase that inactivates C3a and C5a (such as Pseudomonas)

How do bacteria prevent Ab-mediated agglutination

Secretion of hyaluronidase, which enhances bacterial invasiveness.

How do bacteria prevent neutralization of toxin by antibody?

Elastase

inactivates C3a and C5a (like Pseudomonas) that prevents agglutination

Hyaluronidase

enhances bacterial invasiveness

Corynebacterium diphtheriae

found in plants, animals, and in humans V-shapes and palisade arrangements

colonized the skin, respiratory, gastrointestinal, urinary, and genital tracts.

Pathogenicity of C. diphtheriae

Diphtheria toxin is responsible for the rapid signs and symptoms such as sore throat, localized pain, fever, pharyngitis, and an oozing fluid.

Pseudomembrane (of C. diphtheriae)

a thickened fluid; adheres tightly to the tonsils, uvula, palate, pharynx, and larynx that cannot be dislodged without causing bleeding in the underlying tissue

Suffocation

In severe cases, occlude respiratory passages can cause __________________.

Cutaneous diphtheria

also causes cell death and the formation of Pseudomembrane on the skin.

heart and nerve cells

Cutaneous and Respiratory infections can kill _________________, causing arrythmia and coma-death.

Penicillin and Erythromycin

DPT Vaccine

Treatment of Corynebacterium diphtheriae

Mycobacterium tuberculosis

Agent of Tuberculosis

Primary Tuberculosis

typically occurs in children; involves the formation of tubercules-small, hard, nodules in the lungs

First Stage of Tuberculosis

Inhalation of respiratory droplets

(5 micrometers in size; ID: 1-3 bacilli) MID: 10 cells.

Second Stage of Tuberculosis

phagocytosis by macrophages

Third Stage of Tuberculosis

Replication of M. tb, inside the macrophage (few weeks); mild fever

Fourth Stage of Tuberculosis

Tubercle formation (T-lymphocytes produce lymphokines-triggers inflammation).

Fifth Stage of Tuberculosis

Production of caseous necrosis (cheese-like consistency) from dead lung cells.

Tuberculous Cavity

center becomes liquefied and filled with air

Ghon complexes

calcium deposits around the tubercle (dormant stage)

Secondary or Reactivated Tuberculosis

occurs among immunosuppressed TB infected individuals

results when M. tb breaks the stalemate, ruptures the tubercle, and reestablishes an active infection.

Disseminated Tuberculosis

results when macrophages carry the M. tb via blood and lymph to various sites such as bone marrow, spleen, kidneys, spinal cord, and brain

Borrelia burgdorferi

vectors are hard ticks of the genus Ixodes

Bull's Eye Rashes

expanding rashes

Bull's Eye Rashes

rashes, headaches, and arthritis; in some cases severe neurologic complications develop including excruciating headaches, meningitis, loss of memory, and mood swings

it's the deposition of the complexes (Ag-Ab complexes can activate the complement system)

IL-1 and LPS are involved in the pathogenesis of Lyme Disease

IL-1

LPS

involved in the pathogenesis of Lyme Disease

Depends in part on the location

The type of immune response that develops to protozoan infection and the effectiveness of the response ___________________________ of the parasite within the host.

Maturational Changes

The __________________________ from sporozoite to merozoite to gametocyte allow the organism to keep changing its surface molecules.

Intracellular Phases of the Life Cycle

The __________________________________ in liver cells and red blood cells allow the organism (Plasmodium, the agent of Malaria) to multiply while it is shielded from attack

Design of Malaria Vaccine

focus largely on the sporozoite stage

little

(Little/A lot) is known about the humoral and cell-mediated responses in the protective immunity to protozoan disease.

Variant Surface Glycoprotein (VSG)

An effective humoral antibody response ___________________ that covers the trypanosomal surface and allows the elimination of these parasites from the blood stream both by opsonization and subsequent phagocytosis.

antigenic shifts

occur by duplication of gene segments encoding variant VSG molecules and their translocation. (in protozoans)

not strongly

In helminths, the immune system is (strongly/ not strongly) engaged. Thus, the level of immunity generated to helminths is often very poor.

Adult schistosome worms; host

__________________ decrease the expression of Ag and also enclose itself in a glycolipid and glycoprotein coat derived from the ___________, masking the presence of its own Ag.

Cercariae; schistosomules

Antigens present on the membrane of ____________ and young __________________ are promising vaccine components because these stages appear to be most susceptible to immune attack.

IgE / Eosinophils

Antibodies present in mast cells, WBC that is responsible in parasitic infections.