Lecture 6 Part 2 Bacterial Mechanisms Flashcards
- What is a cytokine?
- What are chemokines and what do they do?
- Cytokines: Protein messenger molecules which are produced by stimulated cells (ie. sentinel cells)
- Chemokines: Messenger molecules with attract immune cells (esp. PMNs and M0s)
List the areas which bacteria can alter/derain proinflammatory cytokines
- Bacteria can produce molecules which are unrecognizable at TLR
- Bacteria can blockade signal transduction of the TLR to the desired location
- Bacteria can accellerate the destruction of signal intermediates of the TLR signal
- Bacteria can redirect inflammatory cytokine production to antiinflammatory cytokine production
List the ways bacteria evade killing by innate defenses
- Can inhibit PRR signaling
- Evade action of defensins
- Protecting their membrane by adding capsules
- Prevent phagolysosmal killing
- Some bacteria can block the attachment of the lysosome to the phagosome
- Blocking of phagocytosis
- Use of a bacterial capsule or bacterial biofilms
- Can produce antioxidants which destroy the neutralizing oxidants
- The use of bacterial toxins (ie. leukotoxins)
- Kill the phagocytic cells before they can kill them
- What is the function of factor H in extracellular bacteral evasion of PMNs?
- What is the purpose of Protein A as it relates to binding of Ab?
- Bind factor H and then factor I
- Causes inactivation of C3b and therefore complement
- Use of Protein A
- Binding of antibody at the Fc portion enabling opsonization
What is the Type 3 secretion system?
- Type 3 secretion system
- Secretions by extracellular bacteria which occur after phagocytosis acting as a needle releasing bacteria from phagosomes
Listeria evades killing from phagocytic cells by escaping into the cytoplasm soon after phagocytosis. What are some other mechanisms intracellular bacteria evade destruction?
- They can inhibit M1 macrophage production by initiating M2 macrophage class switch.
- Prevention of phagosome lysosome fusion once phagocytized
- Contain such things as lipid capsules to have a resistance to lysosomal enzymes
What mechanism does Brucella abortus use to survive phagocytosis? What about M**icobacterium tuberculosis and Salmonella enterica?
-
Brucella abortus
- Prevents phagosome maturation
-
Micobacterium tuberculosis
- Prevents phagosome maturation
- Detoxifies antioxidants
-
Salmonella enterica
- Prevents phagosome maturation
- Modifies endosomal trafficking
- Detoxifies antioxidants
- What are the humoral immunity defense mechanisms?
- What are the cell mediated immunity defense mechanisms?
Humoral immunity defense mechanisms:
- B cells/plasma cells
- Ab IgM, IgG, IgA, IgE, and IgD
Cell mediated immunity defense mechanisms:
- T cells - alpha/beta TCRs
- CD4+
- CD8+
- T cells - gamma/delta TCRs
To develop a vaccine against these bacteria it is important to understand what?
Bacteria’s virulence factors
- How they are beating the immune system
- How vaccines can be designed to defeat these mechanisms
- What are Exotoxins?
- What are Endotoxins?
Exotoxins
- Protein toxins which are secreted by the bacteria which cause some sort of pathogenesis
Endotoxin
- Lipopolysaccharide in outer layer of G (-) bacteria which cause some sort of pathogenesis
Why are antibodies against pathogenic cell wall antigens relatively ineffective?
Pathogenic bacteria generally contain a capsule which conceal the bacterias cell wall. This protectant of the cell wall blocks the antibody from getting inside to attach to the antigen presented
What is the site of action and effector function of IgM?
IgM
Site of action: Intravascular
Effector function: Complement and Agglutination
What is the site of action and effector function of IgG?
IgG
Site of action: Intravascular, Interstitial space, and Transplacental/colostral
Effector function: Complement, Agglutination, Neutralization, Opsonization, Systemic immunity in neonate, and ADCC
What is the site of action and effector function of IgA?
IgA
Site of action: Mucosal surfaces and Mothers milk
Effector function: Neutralization at body surfaces, Block attachment at body surfaces, and Intestinal Immunity in neonates
What is the site of action and effector function of IgE?
IgE
Site of action: Subcutaneous and Submucosal
Effector function: Mast-cell sensitization (most IgE is found bound to mast cells) and Eosinophil activation
What is the function of IgA at mucosal surfaces?
- In the mucus can bind to toxins and bacteria dragging it out of the intestinal mucosa and into the intestinal lumen
- The diametric IgA binds to the polyimmunoglobulin receptor to get transported across in a vesicle. The IgA can capture the invading pathogen which is in a vesicle and re-secrete it out
- If the pathogen/toxin has made it across the epithelium they can carry them back through the epithelium in vesicles and into the intestinal lumen
Extracellular bacteria tend to have polysaccharide capsules that are hydrophilic. How does this help them evade phagocytosis by neutrophils?
- The membrane of the neutrophil is hydrophobic. So the hydrophilic polysaccharides causes the neutrophil to repel the bacteria.
- If hydrophobic membrane however, much like macrophobic bacteria have.
- Bacteria will tend to get phagocytized
- These walls are common in intracellular bacteria
Describe the endogenous pathway of antigen presentation?
Intracellular bacteria or viral proteins attach to ubiquitin–> this leads them to proteasomes which they are broken down in to small AA peptides–> these then head to the RER and golgi where they are broken down into small ~9 AA strips–> these will then leave the RER and are in vesicles containing a MHC I receptor –> peptide is then attached to the receptor and be presented on the cell surface
Describe the exogenous pathway of antigen presentation?
Bacteria/Ag is phagocytosed–> lysomes containing MHC 2 receptors attach to the phagocytized bacteria/Ag breaking it down. A peptide will attached to the MHC 2 receptor and be transported to the cell wall for presentation
- How is class switching initiated?
- What cell type initiates this?
- Initiated when a specific Ag is presented to a T helper cell form a B cell. The T helper cell will secrete cytokines when attached initiating class switching to preferred Ab
- T helper cells
What are the main ways bacteria evade killing by the adaptive immune response?
- Antigenic variation
- Capsules!
- Secrete proteases to destroy antibody
- Stimulation of immunosuppressive cytokines
- Stimulation of IL-10 –> M2 macrophages
- Superantigens
- Stimulates death of a lg. number of T cells
What are superantigens and what do they cause?
Superantigens
- Ag which are produced from a bacteria whichcrosslink MHC II and the T cell receptor (V-beta-3+ which many T cells possess) results in cytokine storm –> T cell destruction
- Stimulate an increased pathogenic T cell response to Ag
Example Staphylococcus Enterotoxin B
- Responsible for toxic shock syndrome
- Also causes food poisoning
List the three types of fungal infections
Three basic types
- Surface infections (ringworm)
- Infections on mucosal surfaces (candidal yeast)
- Pulmonary infections (histomycosis, blastomycosis, coccidioidomycosis)
- What are bacterins?
- What are toxoids?
Bacterins
- Are inactivated or killed bacteria which are used in a vaccine
Toxoid
- Are the inactivated toxins which are used in a vaccine
- Treated by some mechanism to induce a immune response but not be pathogenic
- Example Clostridial vaccines
What type of bacteria are type of bacteria are clostridial organisms?
Clostridial infections (G+, anaerobes, and produce toxins)
Why are Clostridium tetani antibodies ineffective, but antibodies against their toxin effective?
Infection process of Clostridium tentani:
- Puncture wound –> organism grows in tissue damaged necrotic tissue–> produces toxin inside which causes signs
Ab cannot get in to this necrotic tissue, Ab against the organism therefore. However, Ab are useful against the toxin because the toxin is leaked out of the necrotic tissue where Ab can attach.
What is the pathogenesis of enterotoxemia in calfs caused by Clostridium perfringens?
Problem when calf takes a big feeding Lg. clot of milk (normal amounts of C. perfringens become large amounts)–> lg. amount of toxins–> causes enterotoxemia
Management practices to avoid:
- Manage how much calf feeds at one time and how often a calf suckles
What are the advantages of introducing adaptive immunity at body surfaces?
- NO needles
- You are introducing the immunity where the pathogen enters
What are multifactorial diseases?
Multifactorial diseases
- Are combinations of: distress, viral infection, bacterial infection, nutrition, etc… which result in disease
- (eg. Bovine respiratory disease)
