1) Penetrate the Epithelial barriers: not easy

  - skin, GI lining, and Respiratory lining

2) Compete w/  Normal flora for Binding Sites

  - Lactobacillus Acidophilous

  - Bifidobacterium Bifidus

3) Evade Innate Immunity

  - Macrophages, Neutrophils and Natural killer cells. 

Innate Immunity

a) What receptors are expressed on Inn. Imm. cells to identify bacterial molecules?

b) What do viruses induce production of?

a) TLR-4: recognize LPS, gram negative bacteria

   TLR- 2: recognize PGN, gram positive bacteria

    TLR-3,7,9: Viral nucleic acids

b) induce production of interferon Alpha, beta and  

    gamma which produce an anti-viral state.

How do pathogens trick to avoid the immune system?

• start living inside cells
• mimic the surface of host cell
• acquire a covering of host membrane molecules
• induce specific type of immunity that allows it to survive
• continuous variation of antigens. ex HIV
• express antigens that resemble our own genes.

Viral Infections

a) How does the innate immune system respond via detection and destruction of viruses?

b) What two components do the adaptive immune system use to respond to viral infections?

a) detection: by Toll-like Receptor (TLRs)

    destruction: by interferons and NK cells

b) cell-mediated and humoral components

Viral Infections

a) Why do viruses need a host?

b) Are infections intracellular or extracellular?

c) How do they survive from host to host?

a) in order to replicate

b) Intracellular

c) long latency periods that can be seen in AIDs

  - infection efficiency (Influenza)

  - use of non-host species vectors (west nile virus)

Viral Infections

a) What genetic information of viruses induces production of IFN?

b) What types of IFN is produced by pDCs?

c) Which TLR respond to dsRNA and ssRNA?

d) What does the anti-viral state inhibit?

a) dsRNA

b) IFNalpha and IFN beta

c) TLR 3 responds to dsRNA and TLR7 responds to ssRNA

d) inhibit replication and infection

Humoral

What activity does the effector molecule antibody (sIgA) under go?

Humoral

What activity does the effector molecule IgG, IgM and IgA antibody do?

Humoral

What activity does effector molecule IgG and IgM antibody do?

Humoral

What does IgM antibody do to respond to viruses?

Humoral

What activity does complement activated by IgG or IgM antibody do?

Cell-mediated Response

What activity does IFN gamma secreted by Th or Tc cells undergo?

Cell-mediated Response

What activity do cytotoxic t lympohocytes have?

Cell-mediated Response

What activity do natural killers and macrophages have?

Explain is viral replication prevented?

[image]

IFN alpha/beta binds to the IFN alpha/beta receptor cause dimerization  cell signal transduction on cytoplasmic tail will produce two pathways

      1) 2,-5 (A) synthase will activate 2-5(A) with ATP   

      then activate RNAse L and degrades poly(A)mRNA

       and get inhibition of protein synthesis

    2)  protein kinase becomes activsted with ATP

        and dsRNA which phosphorylates elF-2 which       

         makes it nonfunctional and get inhibition of

         protein synthesis

a) How do antibodies protect against viruses?

b) Viral entry is mediated through receptors, what receptors do influenza virus and rhinovirus bind to?

a) ab bind to viral surface antigens to 1) protect against re-infection 2) huge amounts of sIgA in lumen block viral attachment

b) influenza virus binds to sialic acid on glycoproteins
    rhinovirus binds to ICAMs

a) When infection occurs, does cell-mediated or humoral immunity (or both) eliminate infected cells?

 b) What cells are the participants? What cytokines are produced and what is the time frame of their peak.

a) Only Cell-mediated immunity

b) Th1: IFN-gamma (induce antiviral state) IL-2 (Expands CTL-P) and TNF-alpha. IL2 and IFN gamma activate nk cells

CTL : peaks 7-10 days post infection

   - elimate virally infected cells

• virion is 90-100 nm
• surrounded by plasma membrane of host
• 2 glycoproteins on surface; hemagglutinin (HA; viral attachment to sialic acid on glycoproteins) and Neurominidase (NA; detach from sialic acid aka budding)
• matrix protein beneath lipid bi-layer
• nucleocaspid contains 8 ssRNA which associated w/ RNA polymerase and protein. Each ssRNA encode for one or more proteins.

a) What is the type of influenza dependent on?

b) What are the types?

c) Which type is responsible for major pandemics in humans?

d) how many variants are in HA and NA?

a) matrix composition and nucleoprotein composition

b) A,B,C

c) A

d) Ha- 13 and NA- 9

a) Are antibodies necessary for recovery?

b) is reinfection possible?

a) No, recovery occured in mice that had antibodies suppressed.

b)Re-infection is possible.

• opsonization of bacteria
• neutralization of toxins (exotoxins eg. diptheria and endotoxins e.g LPS)
• lysis of bacteria through complement pathway
• complement activation through mast cell activation results in localized inflammation
     - vasodiation and extravasation (neutrophil 
       accumulation)

1. bacteria will evade
2. ab will neutralize bacterial toxins
3. complement-mediated lysis of bacteria
4. ab and complement split profuct c3b bind to the bacteria serving as opsonins to increase phagocytosis
5. c3a and c5a induce local mast degranulation, releasing substances that mediate vasodilation and extravasation of lymphocytes and neutrophils.
6. other complement products are chemotactic for neutrophils and macrophages.

1. attachment
2. proliferation
3. invasion of host tissue
4. toxin induced damage to host cells

• pili
• adhesion molecules (Bordetella Pertussis)

• prevent attachment of bacteria
• some bacteria can overcome via protease decreasing 1/2 life of IgA eg. Heamophilus Influenzae

Overzealous immune system can be pathogenic

  - bacterial septic shock
        - predominant cytokines involved: IL 1 and TNF-a

        - Source: Macrophages

  - intracellular bacteria cause granulomas
        - extensive tissue damage 
        - eg. tuberculosis

a) What bacteria causes tuberculosis?

b) What happens after macrophage Ingest?

c) What cells are granulomatous lesion formed from? What do the lesions do?
d) What cytokines eliminate the pathogen?

a) Mycobacterium Tuberculosis

b) Cannot digest pathogen, the pathogen will eventually replicate itself and burst releasing bacilli

c) Macrophage and TH1 cells produce the lesions which are containment and destruction of healthy tissue

d) IL-12 and IFN gamma

Immune Response contributing to disease

a) What is septic shock induced by?

b) What cytokines are responsible?

a) endotoxins

b) IL-1 and TNF alpha

Immune Response contributing to disease

a) What is shock induced by?

b) what is an example of a pathogen?

a) superantigen exotoxins

b) Staphylococcus

Immune Response contributing to disease

Granulomas are chronic activation of what cells?

Immune Response contributing to disease

What disease do antibodies to flagella contribute to WHAT TYPE of hypersensitivity?

Evasion of immune system

How does Gonorrhea evade the immune system?

• enhanced attachment to host cells
• proteases that cleave IgA
• changing surface antigens

Parasitic Diseases

a) What are some examples of the diseases that are caused by protozoans??

b) What immunity is active during the location of the blood born-stages?

c) What immunity is necessary during the location of infection of host cells?

a) Malaria and African sleeping sickness (Trypanosoma)

b) humoral antibody

c) cell-mediated immunity

a) What type of species does the disease malaria come from?

b) How many people are affected world wide?

c) What is the life cycle?

d) How does it evade the immune system?

a) Plasmodium

b) 600 million

c) Blood --> liver --> RBCs

d) Change antigens during maturation, intracellular proliferation, sporozite in blood only 30 minutes and can slough off antigen coat.

Fungal diseases (Mycosis)

a) What are some examples of cutaneous infections?

b) Where are subcutaneous infections? How?

c) how is in controlled?

a) athletes foot, jock itch, and ringworm

b) secondary infections of lungs, CNS, bones and abdomen by ingestion, inhalation or innoculation into the blood stream.

c) phagocytosis via neutrophils, controlled by innate barriers, activation of complement