Immunity to Infection

Course of a typical acute infection

1. Establishment of infection

2. Induction of adaptive response

3. Adaptive immune response

4. Immunological memory

Humoral immunity is mediated by…

antibodies

Humoral immunity can be transferred by _____ via _______

antibodies; immune serum

Humoral immunity is effective against…

extracellular stage of pathogens

Humoral immunity is best at…

inhibiting infection and reducing pathogen spread

Cell-mediated immunity is mediated by…

T lymphocytes

Cell-mediated immunity can be transferred by…

T cells

Cell-mediated immunity can only be transferred to…

MHC-matched recipient

Cell-mediated immunity is effective against…

intracellular stage of pathogens

Cell-mediated immunity is best at…

clearing an established infection

Humoral immunity is a ___ immune response

Th2

Cell-mediated immunity is a ___ immune response

Th1

Protective immune response to local infection or penetration of the epithelium

Wound healing induced

Antimicrobial proteins and peptides, phagocytes, and complement destroy invading microorganisms

Protective immune response to local infection of tissue

• Complement activation

• Dendritic cells migrate to lymph nodes

• Phagocyte activation

• NK cells activated

• Cytokines and chemokines produced

Protective immune response to lymphatic spread

• Pathogens trapped and phagocytosed in lymphoid tissue

• Adaptive immunity initiated by migrating dendritic cells

Protective immune response via adaptive immunity

Infection cleared by specific antibody, T cell dependent macrophage activation, and cytotoxic T cells

Extracellular sites of infection

Interstitial spaces, blood, lymph, epithelial surfaces

Intracellular sites of infection

Cytoplasmic, vesicular

Extracellular organisms

viruses, bacteria, fungi, protozoa, worms

Intracellular organisms

Viruses, specific bacteria, protozoa

Extracellular protective immunity mechanisms

• Antibodies

• Complement

• Phagocytosis

• Neutralization

• Antimicrobial peptides

Intracellular protective immunity mechanisms

• Cytotoxic T cells

• NK cells

• T cell & NK cell dependent macrophage activation

Direct mechanisms of tissue damage by pathogens

• Exotoxin production

• Endotoxin

• Direct cytopathic effect

Indirect mechanisms of tissue damage by pathogens

• Immune complexes

• Anti-host antibody

• Cell-mediated immunity

Innate responses to viral infection

• INF-alpha & INF-beta production (type I INFs)

• NK cell activation

Anti-viral effects of INF-alpha & INF-beta

• Induce resistance to viral replication in all cells

• Increase MHC class I expression and antigen presentation in all cells

• Activate NK cells to kill virus-infected cells

NK cells are activated by ___ in response to viral infection

INF-alpha & beta

Actions of activated NK cells in viral infection

• Secrete INF-gamma

• Kill virus-infected cells

Mechanisms of antibody responses to viruses

• Blocks binding of virus to cells (neutralization)

• Blocks fusion of viral envelope with host plasma membrane (neutralization)

• Opsonization

• Complement activation & lysis of enveloped viral particles

• Agglutinates viral particles

Which antibodies blocks binding of virus to cells?

IgA & IgG

Which antibodies block fusion of viral envelope with host plasma membrane?

IgG, IgM, & IgA

Which antibodies cause opsonization and complement activation?

IgG & IgM

Which antibodies agglutinate viral particles?

IgM

Mechanisms of CMI responses to viruses

• IFN-gamma secreting Th1 cells & NK cells - Direct antiviral effect

• CTLs - kill virus infected cells

• NK cells - kill virus-infected cells by ADCC

Viral mechanisms of evasion

• Antigenic variation (drift & shift)

• Immunosuppression

• Interference with antigen presentation

What viruses use antigenic variation?

Influenza viruses

What viruses use immunosuppression?

FIV, HIV, SIV, FeLV

What viruses use interference with antigen presentation?

Herpes viruses and adenoviruses

Effect of interference with antigen presentation

Decrease MHC I presentation in virus-infected cells

Antigenic drift

Caused by point mutations resulting in a gradual change of the antigens involved in the virus binding to the host cell receptors

Antigenic drift is responsible for…

annual changes in circulating strains of the influenza virus

Antigenic shift

Results in sudden large changes in th antigen structure, which occurs when 2 vastly different strains of influenza viruses exchange their viral genomes, resulting in the generation of a unique viral strain

Antigenic shrift is responsible for…

pandemics

Immune responses to extracellular bacteria

• Antibodies

• Th17 cells

Antibody immune responses to extracellular bacteria

• Blocking adhesion to host cells (IgA, IgM, IgG)

• Opsonization

• Complement activation

• Toxin neutralization

Th17 cell responses to extracellular bacteria

Neutrophil recruitment

Immune responses to intracellular bacteria

• Th1 immune response

• NK cell activation

Th1 immune responses

CD4+ T cells secreting IFN-gamma

CTLs killing infected cells & secreting IFN-gamma

Granulomatous inflammation

Partial activation of macrophage leads to granuloma formation

Bacteria use several ______ to subvert immune defense

virulence mechanisms

Virulence mechanisms/factors

Bacterial enzymes and other molecules that make the bacteria pathogens and cause disease

Serotype/strain

Different versions of a bacteria with different capsular polysaccharides

Superantigen

Disable immune system by nonspecifically activating several CD4+ T cells

Superantigen action

Binds to MHC II, CD4 TCR, & CD28 and clamps down on them, causing indiscriminate activation & proliferation of CD4+ T cells

Do superantigens require antigen processing for activity?

No

What does binding by superantigens cause?

Massive cytokine release through activation of many CD4+ T cells, causing disease

Examples of superantigens

• Staphylococcal enterotoxins

• Toxic shock syndrome toxin-1 (TSST-1)

Protozoal parasites

Unicellular parasites which can be intracellular or extracellular

Example of intracellular protozoal parasite

Toxoplasma

What type of response do intracellular protozoal parasites elicit?

Th1 responses (protective)

Example of extracellular protozoal parasite

Trypanosomes

What type of response do extracellular protozoal parasites elicit?

Antibody response

Helminths

Multicellular worm parasites

What type of response do helminth parasites elicit?

Th2 type response with IgE antibody

What happens if a helminth invades tissue?

IgE antibody responds & binds to helminth

How do parasites evade the immune system?

• Antigenic variation

• Poor antigenicity

Methods of using poor antigenicity to evade the immune system

• Coating with host proteins

• Molecular mimicry (resembling host antigens)

Example of antigenic variation

Variant surface glycoproteins (VSGs) in trypanosomes