Immunology Flashcards

1
Q

Innate immune defenses

A

Epithelial barrier: Skin, respiratory epithelium, enterocytes
Secretions: Mucus, sweat, sebum, cerumen, acid, enzymes, defensins, polyreactive antibodies, surfactant
Endogenous microflora
Resident phagocytes
Pattern recognition receptors (PRR)

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2
Q

cell mediated immune response

A

Mediated by Th1 cells
Most important for intracellular pathogens

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3
Q

humoral immune response

A

Mediated by Th2 cells
Most important for extracellular pathogens

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4
Q

How viruses infect cells

A
  1. Bind to cell receptor (adsorption)
  2. Virions enter cell
  3. Nucleic acid released into cytoplasm
  4. Replication
  5. Protein production
  6. Assembly
  7. Release
  8. Spread
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5
Q

What triggers the innate immune response to viral infection?

A

Recognition of viral patterns by PRRs
RIG-I, MDA5 (cytoplasmic)
**TLR3, 7, 8, 9 **(endosomal)

Cell damage

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6
Q

interferons

A

Glycoproteins, Regulate protein expression
Three types
* Type I
IFNa – dendritic cells
IFNb – any virally infected cell
* Type II
IFNg – activated Th1 cells
* Type III
Various - mucosal epithelial cells

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7
Q

type 1 interferons

A

IFNa – dendritic cells
IFNb – any virally infected cell
Produced upon recognition of TLR7 or TLR9 ligands

Activate JAK/STAT pathways
* Increased production of antiviral and immunoregulatory proteins
* Directly inhibit viral uptake, replication
* Induce apoptosis

Produced within hours (before antibodies), part of innate immune system

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8
Q

humoral immunity in viral infections

A

Antiviral antibodies against viral proteins
Antibody binding prevents viral infection by
* Blocking viral invasion
* Stimulating phagocytosis
* Triggering complement-mediated virolysis
* Promoting viral clumping
* NOT by direct virus destruction

ADCC targets infected cells for destruction
* NK cells and cytotoxic T cells

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9
Q

cell mediated immunity in viral infections

A

Cytotoxic T cells recognize infected cells prior to rupture
* Induce apoptosis
* Recognize peptide-MHC-I complexes and kill cells
* Sensitized by type I interferons

Macrophages are activated by Th1 cells
* Phagocytosis

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10
Q

immune evasion by viruses

A

RNA viruses rely on antigenic variation
DNA viruses – immunoregulatory genes
* Proteins that block IFN signaling
* Proteins that interfere with MHC-I associated antigen presentation
* Evasion of NK cells
* Alterations in humoral immunity: Non-neutralizing or slowly neutralizing antibodies
* Antigenic variation

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11
Q

antigenic variation

A

Point mutations + poor editing
Sporadic recombination of strains
ex: Influenza A
* Express envelope proteins: Hemagglutinins (HA), Neuraminidases (N)
* Gradual variation in amino acid sequence leads to new antigens
* Co-infection leads to new strains
* No longer recognized by adaptive immune system

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12
Q

innate response to bacteria

A

Bacteria are recognized through PRRs (TLR1, 2, 4, 5, 6, 9)

Cytokine release,** complement** activation, inflammation, phagocytosis

Sequestration of nutrients (iron, tryptophan)

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13
Q

PRRs for bacteria

A

TLR1, 2, 4, 5, 6, 9 (9 is both)

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14
Q

adaptive immune response to bacterial infections

A

Extracellular bacteria = humoral immunity
* Neutralization of toxin
* Opsonization by antibodies
* Killing by classical complement pathway
* Phagocytosis by activated macrophages

Intracellular bacteria = cell mediated immunity
* Macrophage activation and killing
* Destruction by cytotoxic T cells

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14
Q

adaptive immune response to bacterial infections

A

Extracellular bacteria = humoral immunity
* Neutralization of toxin
* Opsonization by antibodies
* Killing by classical complement pathway
* Phagocytosis by activated macrophages

Intracellular bacteria = cell mediated immunity
* Macrophage activation and killing
* Destruction by cytotoxic T cells

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15
Q

neutralization

A

Important for toxogenic bacteria

Antibodies generated against toxins:
* Bind
* Prevent interaction with receptor
* Can be IgG or IgA (mucosal surfaces)

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16
Q

opsonization and phagocytosis

A

Opsonization increases efficiency of phagocytosis (natural ketchup)
Antibodies against surface antigens
Bacteria coated in antibodies and complement fragments are primed for phagocytosis
IgM is the most efficient antibody in opsonization

17
Q

destruction by activated macrophages

A

Some bacteria can replicate inside macrophages
Th1 cells activate macrophages by secreting IFNg
Acidification of phagosomes
Intracellular bacterial destruction
NK and cytotoxic T cells can also kill cells infected with intracellular bacteria

18
Q

destruction by activated macrophages

A

Some bacteria can replicate inside macrophages
Th1 cells activate macrophages by secreting IFNg
Acidification of phagosomes
Intracellular bacterial destruction
NK and cytotoxic T cells can also kill cells infected with intracellular bacteria

19
Q

bacterial evasion of innate defenses

A

Interfere with TLR signaling
* Modify PAMPs (molecular patterns)
* Interfere with intracellular signaling

**Resistance to antibacterial peptides **
**Block phagocytosis **

Intracellular bacteria
* Interfere with phagosomal maturation
* Escape phagosome

20
Q

bacterial evasion of adaptive defenses

A

Antigenic variation
Secrete proteases to destroy antibodies or cytokines
Survival within macrophages
Interference with macrophage polarization

21
Q

TLRs that recognize viruses

A

3, 7, 8, 9 (9 is both)

22
Q

parasites

A

Organism that lives in/on host and gets nutrients from the host or at the expense of the host
Three categories of eukaryotic parasites
* Protozoa – single-celled, intra- or extracellular
* Helminths – multicellular, extracellular
* Arthropods – multicellular, extracellular

23
Q

Immune response to protozoa

A

Innate mechanisms similar to bacteria and viruses
Mutual adaptation and species-specific infection is important
* Toxoplasma in cats vs. other mammals

Stimulate both cell mediated and humoral response
* Humoral – antibodies opsonize parasites in blood and tissue
* Cell mediated is important for intracellular protozoa

24
Q

extracellular protoza immune response

A

Similar response to bacteria
* Complement activation
* Activation of macrophages for phagocytosis

Th22 responses are important
* Macrophages produce IL-22

Recruitment of neutrophils
* Oxidative damage to pathogen

25
Q

intracellular protozoa immune response

A

Intracellular location protects organisms from immune detection
Some actively penetrate cells
* Toxoplasma sp., Cryptosporidium sp.

Th1 responses are important
* Recruitment of cytotoxic T cells

26
Q

immune evasion by protozoa

A

Parasite-induced immunosuppression
* Secondary infections and sepsis

Reduced antigenicity of encysted protozoan

Antigenic variation

Infections more common in immunosuppressed hosts

27
Q

adverse consequences of immune reponse to protozoa

A

Immune response to protozoa may result in hypersensitivity
Type I: Trichomoniasis infection causes local irritation of genital tract
Type II: Parasite antigens bind to host erythrocytes
Type III: Immune complex formation in visceral leishmaniasis

28
Q

immune reponse to helminths

A

Larvae and adults trigger Th2 adaptive response
* Attacked by eosinophils and basophils

Adult worms are expelled from mucosal surface by IgE binding
* Cell mediated immunity less important
* Innate immune cells and Th2 cells secrete IL-4, IL-5 and IL-13
* Increased production and recruitment of eosinophils
* Eosinophils have Fc receptors and bind to opsonized worms

Thick cuticles or tegument
* Complement and perforin (cytotoxic T cells) will not penetrate
* If outer covering is damaged, they can grow a new one

Eosinophils and macrophages release Th2 cytokines – cuticle damage
* important in destroying migrating larvae

Similar clinical signs to type I hypersensitivity: (Eosinophilia, Edema, Asthma, Urticaria)

29
Q

helminth immune evasion

A

Migrating larvae are very good at immune evasion
Innate immunity
* Neutrophil inhibitors
* Surface antioxidants
* Interfere with complement

Adaptive immunity
* Reduced antigenicity over time
* Antigenic variation
* Interference with antigen processing

30
Q

immunosuppression by parasites

A

Common feature of parasitized animals
Parasites produce immunosuppressive molecules
* ex: Fasciola hepatica proteases can destroy antibodies

Redirection of T cell response
* Produce IL-10 which is immunosuppressive

31
Q

immune response to arthropods

A

Fleas, ticks, mosquitos, mites, lice
Inject saliva
* Digestive enzymes
* Immunomodulatory substances

Three types of response
* Th1 response
* Th2 response
* Cutaneous hypersensitivity

32
Q

immune response to fungi

A

Innate immune response
* PRRs recognize fungal PAMPs
* Neutrophil recruitment – moderately effective
* Small spores may be ingested by macrophages

Adaptive response
* Th1 most important
* Activated macrophages
* Neutrophils

33
Q

Enzyme Linked Immunosorbant Assay (ELISA)

A
  1. add serum that has antigen, binds to captured antibodies
  2. add labeled/detection antibodies
  3. add substrate
  4. signal detection
34
Q

monoclonal antibodies

A

react to one antigen

35
Q

polyclonal antibodies

A

Reacts to many antigens expressed by a certain pathogen

36
Q

snap tests

A
  1. precoated capture antibodies on matrix
  2. add serum/conjugate, antigen binds to capture antibodies
  3. wash antibodies that are not bound
  4. substrate moves across matrix making color
37
Q

immunohisochemistry

A
  1. primary antibody targets protein
  2. direct: enzyme on primary antibody
  3. indirect: secondary antibody binds to primary antibody
  4. gives off a color
38
Q

agar gel diffusion assay

A

Test for antigen-specific antibody in test serum
Wells in a gelatinous matrix
Known antigen in middle well
Serum from control and possibly infected animals in peripheral wells
Look for lines of precipitation

39
Q

COVID 19 rapid antigen test

A

Antigen binds to detection antibody
The complex migrates and is captured by antibody coated in the test band area
Control antibody only recognizes the detection antibody (not antigen)