Infectious Disease > Week 1: Host-pathogen interactions > Flashcards

Week 1: Host-pathogen interactions Flashcards

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1
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Innate immunity effectors

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  • Macrophages
  • Dendritic cells
  • Granulocytes
  • Antimicrobial peptides
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6
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Adaptive immunity effectors

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  • B cells
  • CD4+ T cells
  • CD8+ T cells
  • Antibodies
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7
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Innate immunity Response/Specificity

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  • Relatively non-specific
  • Recognition of broadly conserved microbial antigens or their effects
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8
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Adaptive immunity specificity

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  • Specific
  • Recognition of microbial peptides in context of MHC I (CD8+ T cells), MHC II (CD4+ T cells) or sepcific antigens (antibodies/B cells
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9
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Innate immunity Response time

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Constitutive and/or rapid (hours to days)

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10
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Adaptive immunity Response time

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Delayed (days to weeks)

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11
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Innate immunity Memory

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*Usually* no memory

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12
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Adaptive immunity memory

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*Usually* has memory

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13
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What protects us from pathogens?

A

Physical barriers

  • skin
  • mucous membranes

pH

Iron hoarding

Innate immune response

Acquired immunity (adaptive)

beneficial bacteria and their products

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14
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Abnormal physiology that can increase risk of infection

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  • Vesicoureteral reflux
  • Auto-splenectomy
  • Atopic dermatitis
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15
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Vesicoureteral reflux role in increased risk of infection

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increased risk of pyelonephritis

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16
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Auto-splenectomy role in increased risk of infection

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  • Splenic necrosis induced by sickle cell anemia, SLE
  • Prone to infections by encapsulated organisms (ie Streptococcus pneumoniae and Haemophilus influenzae)
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17
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Atopic dermatitis role in increased risk of infection

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Increased risk of skin infections (Staph aureus, Strep pyogenes, HSV)

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18
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How does the innate immune system protect us from pathogens?

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  • response is early or constitutive and non-specific
  • Essential for immune cells to go to the site of infection
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19
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How does the acquired immune system protect us from pathogens?

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Delayed because cells and products need to be made - but high specificity and MEMORY! (usually)

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20
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Describe the role/mechanisms of normal flora in protecting us from pathogens

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  • Occupy space
  • Angry neighbors
  • Assist in host function
  • Immunomodulation
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21
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Describe the mechanisms of COST of normal flora in protecting us from pathogens

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  • Opportunistic pathogens
    • Staph infections
    • Dental caries
    • Gastritis
    • Sepsis
  • Nutrient competition
  • Can be passed on to susceptible individuals
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22
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What are the components of the microbiome

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  • Bacteriome
  • Virome
  • Mycobiome
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23
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Adaptive immune cells

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  • CD4+ T cells
  • CD8+ T cells
  • B cells
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24
Q

Basic function of CD4+ T cells

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  • Direct immune responses
  • required for CD8+ T cell memory and Ig class switching
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Basic function of CD8+ T cells
Kill infected cells
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Basic function of B cells
* Make antibody * M-A-D-G-E
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Basic function of macrophages
big cells that eat things and present antigen
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Basic function of monocytes
Like pre-macrophages in the blood
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Basic function of granulocytes
* Eosinophils - (cause allergies and kill worms) * Basophils - (allergies, worms, cytokines) * Neutrophils - (eat bacteria, then die and make pus)
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Basic function of Dendritic cells
* Great at antigen presentation and cytokine production
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Basic function of NK cells
* Kill infected cells and cancer cells * Produce cytokines
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Basic function of cytokines and chemokines
Modulate immune responses
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Pro-inflammatory cytokines and chemokines 4 listed
* IL-6 * TNF-α * IFN-γ * IL-17
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Anti-inflammatory cytokines and chemokines
IL-10
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Cytokines that inhibit intracellular pathogen replication
* IFN-α * IFN-β
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Basic functions of cytokines and chemokines
* Modulate immune response * pro-inflammatory * anti-inflammatory * inhibit intracellular pathogen replication * Recruit immune cells * Activate immune cells
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Describe the mechanisms of innate recognition of pathogens
* Recognition of pathogen products (PAMPS-Pathogen Associated Molecular patternS) by host (PRR-Pathogen Recognition Receptors)
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What are PAMPS?
Recognition of pathogen products (PAMPS-Pathogen Associated Molecular patternS) * Pathogen surface proteins * Pathogen-specific nucleic acid structures
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What are PRRs?
(PRRs-Pathogen Recognition Receptors) * Host receptors (membrane or cytoplasmic) * Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors, RIG-I like receptors (RLRs)
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What is the response of innate recognition of pathogens (PAMPS recognized by PRRs)
* Induce cytokine/chemokine responses to recruit immune cells, limit pathogen replication and modulate the overall immune response
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What are the major types of pathogens?
* Pathogens that require intracellular infection * Pathogens that remain extracellular and can be phagocytosed * Pathogens that are extracellular but are so large they evade phagocytosis
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What are some Intracellular only pathogens?
* Viruses * intracellular bacteria * some fungi
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Responses for Intracellular-only pathogens?
* Th1 responses predominate * IFN-γ * CD8+ T cells * IgG antibody subtypes
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What are some examples of extracellular pathogens that are susceptible to phagocytosis?
* extracellular bacteria * some fungi
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Responses of extracellular pathogens that are susceptible to phagocytosis
* TH17 responses predominate (some overlap with Th1 responses) * IL-17/IFN-γ * Activated macrophages
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Examples of pathogens that are extracellular that are too large for phagocytosis?
* Helminths * Parasites
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Responses pathogens that are extracellular that are too large for phagocytosis?
Th2 responses predominate * IL-4 * IgE antibody * Eosinophils
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Broad categories of immune responses according to pathogen type
* Intracellular (virus and some bacteria) * Extracellular bacteria * Parasites * Fungi * Toxins
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Mechanisms of toxin breakdown
* Cytokine responses * Innate cellular responses * Adaptive responses * Pathogen evasion mechanisms
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Describe the basic mechanism of immune response to intracellular pathogens
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Intracellular pathogen evasion mechanisms: Innate responses
* Block type I IFN * Downregulate MHC I * CMV * Hide PAMPS * Inhibit APC activation * Escape from/survival in phagosome * M. tuberculosis
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Intracellular pathogen evasion mechanisms:Adaptive responses
* Immunodominance * Direct B cell responses to non-protective epitopes (HIV) * Mutation * Antigen shift/drift * influenza * Antibody-dependent enhancement * Dengue virus * Latency * HIV, CMV, EBV
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Describe the basic mechanism of the immune response for extracellular bacteria
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Extracellular bacterial evasion mechanisms of the innate response
* Resist phagocytosis * capsule (Klebsiella pneumoniae) * Escape from/survival in phagosome * Salmonella * Inactivation of complement * S. aureus * Skewing cytokine response * Bordetella
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Extracellular bacterial evasion mechanisms of the adaptive response
* Immunodominance * Direct B cell responses to non-protective epitopes * Mutation * Antigen shift/drift/variation * Neisseria * Antibody neutralization * S. aureus * Antibody degradation * Streptococci
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Describe the basic mechanism of the immune response for extracellular parasites
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Extracellular parasite evasion mechanisms of the innate response
* Too dang big to phagocytose * Tegument * physical barrier * inactivation of complement * Protease inhibitors
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Extracellular parasite evasion mechanisms of the adaptive response
* Neutralization of superoxide radicals * cleavage of antibodies * Antigen shift/drift/variation
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Describe the basic mechanism of the immune response for fungi
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Fungal evasion mechanisms of the adaptive response
* Antigen shedding * Induction of Tregs
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Fungal evasion mechanisms of the innate response
* Escape from/survival in phagosome * Inhibition of complement * Elimination of ROS * Shielding of PAMPS * Size (morphotypes)
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Describe the Immune response to toxins
* Targeting of pathogen doesn't eliminate toxin * superantigen * LPS * Neutralizing antibody blocks toxin activity * need CD4+ T cells to generate potent antibody responses * class switching * Can induce with vaccination with toxoid (inactivated toxin)
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Immune response to Botulinum toxin
Clostridium botulinum * Inhibits acetylcholine release (induces muscle paralysis/weakness) * Passive administration of neutralizing antibody (vaccination with toxoid discontinued in 2011)
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Immune response to Diphtheria toxin
Corynebacterium diptheria * inhibits translation (myocarditis, paralysis) * PAssive administration of neutralizing antibody or vaccination (DTaP, Tdap)
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Immune response to Tetanus toxin
Clostridium tetani * Blocks inhibitory neurotransmitter GABA (muscle rigidity and spasms) * passive adminstration of neutralizing antibody or vaccination
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What are 3 ways a virus can evade the immune response?
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What are 3 ways extracellular bacteria can evade the immune response?
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What evasion mechanisms allow influenza virus to re-infect the population every year?
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List a cytokine and one cell type that plays a major role in immune responses to infection with
* Virus * Extracellular bacteria * Nematode
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Summary of host-pathogen interactions
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Intracellular infection response cytokines
* Type I IFN * IFN-α (13 subtypes) * IFN-β * IFN-γ * Drives TH1 response (generation of CD8+ T cells)
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Type I IFN mechanism
* IFN-α (13 subtypes), IFN-β * Induce antiviral state in self and neighboring cells via interferon- stimulated genes (ISG) * inhibition of mRNA transcription and translation * Inhibit viral replication by binding to viral proteins * Dampen over-inflammatory responses * Activate APCs * Help induce CD4 and CD8 T cell responses
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IFN-γ mechanism against intracellular infection
* drives Th1 response (generation of CD8+ T cells) * Macrophage activation for killing intracellular pathogens
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Macrophage mechanism against intracellular infection
* Destruction of ingested pathogen * IFN-γ makes them really good at this * Oxidative/respiratory burst, lysozymes
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Macrophage and Dendritic cells mechanism against intracellular infection
* Antigen processing/presentation * MHCI (presentation to CD8+ T cells) * MHCII (cross-presentation to CD4+ T cells) * Cytokines * Type I IFN * IFN-gamma * Inflammatory cytokines
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Natural killer (NK) cells mechanism against intracellular infection
* Type I IFN * IFN-γ * Cytotoxicity (recognizes low/funky MHC I) * ADCC
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Infected non-immune cells mechanism against intracellular infection
* Type I IFN * MHC I presentation
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CD8+ T cells mechanism in the adaptive immune response
* Cytotoxicity * kills infected cells by inducing apoptosis * Cytokines
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CD4+ T cells mechanism in the adaptive immune response
* Generation of CD8+ T cell memory * Induction of B cell antibody class switching (CD40/CD40L) * Direction of Th1 response through cytokine production IFN-gamma)
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B cells mechanism in the adaptive immune response
* IgM * early response * IgG * Complement, opsonization, neutralization, ADCC * IgA * mucosal infections * ADCC, neutralization, immune exclusion
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Cytokines for Extracellular Bacterial Infection
* IL-17 * Type I IFN
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Mechanism of IL-17 against extracellular bacterial infection
* Drives Th17 response (antibody) * Neutrophil, macrophage recruitment
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Mechanism of Type I IFN against extracellular bacterial infection
* Activates phagocytes * Helps induce CD4 T cell responses * Can help, can hurt
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Mechanism of Macrophages against extracellular bacterial infection
* Phagocytosis, killing * IFN-γ * Antigen processing for T cells * MHC II * Cytokines
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Mechanism of neutrophils against extracellular bacterial infection
* Phagocytosis * Cytokines * Nets
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Mechanism of Dendritic cells against extracellular bacterial infection
* Antigen processing for T cells * MHC II * Cytokines
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Mechanism of NK cells against extracellular bacterial infection
Cytokines
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Mechanism of Antimicrobial peptides against extracellular bacterial infection
AMPs
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Mechanism of B cells against extracellular bacterial infection
* IgM * early response; polysaccharides; opsonization * IgG * complement * opsonization * IgA * induction of B cell antibody class switching (CD40/CD40L) * Direction of Th17 response through cytokine production (IL-17)
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Features and Functions of IgM
* Early response * Polysaccharides * Opsonization
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Features and functions of IgG
* Complement * Opsonization
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Features and functions of IgA
* Mucosal infections * Neutralization
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CD4+ T cells
* Induction of B cell antibody class switching (CD40/CD40L) * Direction of Th17 response through cytokine production (IL-17)
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Cytokine response for Extracellular parasite infection
IL-4 (from CD4+ T cells) results in * IgE production * Alternatively activated macrophage activation
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Functions of alternatively activated macrophages
* Anti-inflammatory * wound healing * Targeting of parastie, glucose transport, eosinophil recruitment * Antigen processing for t cells * MHC II * Cytokines
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Functions of eosinophils in an extracellular parasite infection
Parasite killing by * granule release * directed by IgE binding to parasites
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Functions of dendritic cells in an extracellular parasite infection
* Antigen processing for T cells (from MHC II) * Cytokines
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Functions of NK cells in an extracellular parasite infection
IL-4
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B cell function for an extracellular parasite infection
IgE from B cells allows for * Targeted degranulation by eosinophils
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CD4+ T cells function in an extracellular parasite infection
* Induction of B cell antibody class switching (CD40/CD40L) * Direction of Th2 response through cytokine production (IL-4, 5, 13)
101
Describe the cytokine response in a fungal infection
IFN-γ, IL-17 * Drives Th1 and Th17 response * Neutrophil, macrophage recruitment * Acvtivation of CD8+ T cells * Activation of macrophages to kill phagocytized fungi * Release of anti-microbial peptides (AMPs)
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Macrophage function in a fungal infection
* Phagocytosis/killing * Antigen processing for T cells * MHC II * Cytokines
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Neutrophils function in a fungal infection
* Phagocytosis/killing * Cytokines * NET formation
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Dendritic cells function in a fungal infection
* Antigen processing for T cells * MHC II * Cytokines
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Innate cellular immune response function in a fungal infection
* Macrophages * Neutrophils * Dendritic cells * Iron and Zinc sequestration * γδ T cells making IL-17 * Antimicrobial peptides
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Adaptive immune response in fungal infection
B cells CD4+ T cells
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B cells in fungal infection
* IgM * early response; polysaccharides; opsonization * IgG * Complement * IgA * Mucosal infections * Neutralization
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CD4+ T cells function in fungal infection
Induction of B cell antibody class switching (CD40/CD40L) Direction of Th1 or Th17 response through cytokine production (IL-17, IFN-γ)
109
Bacteria that can degrade antibodies
Streptococci
110
Bacteria that can neutralize antibodies
S. aureus
111
Bacteria that utilizes antigenic shift/drift
Neisseria
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