Lectures 1 and 2: introduction Flashcards
What is the immune system
Combination of cells and proteins that fight foreign invaders
The cellular and molecular immune mechanisms allow the effector mechanisms to do what
Distinguish between self and non-self and eliminate non-self
When the immune self loses ability to distinguish between self and non-self what is the result
Autoimmunity
What is the microbiota made up
Bacteria, Arachae and fungi that are normally inhabiting the body
Where is microbiota located in body
Present on skin and mucosal surfaces
What are some functions of the microbiota
Occupies site that could be colonized by a pathogen, competes with pathogen for nutrients, produce toxins that kill pathogens, aid in host digestion of food products
Self
Normal body constituents expressed by healthy cells, marked with MHC
Non-self
Cells/molecules to which the immune system has no prior exposure during maturation or does not normally encounter, foreign cells/substances
No MHC marker
Pathogen
Causes disease
Opportunistic pathogen
Pathogens that don’t typically causes disease but can under the right conditions
Ex: patient on antibiotics and develops C-diff
What are the characteristics of the innate immune system
Rapid response to non-self in a non-specific manner
Does the innate immune system protect us against pathogens or non-pathogens
Non-pathogens
What recognizes a pathogen in the innate immune system
Pattern recognition receptors
What is included in the cellular mediate innate immune response
Neutrophils, macrophages, mast cells, lymphoid cells, basophils, eosinophils
What is included in the humoral mediated innate immune response
Complement, natural antibodies, acute phase proteins, antimicrobial peptides, soluble lectins
What are some characteristics of adaptive immunity
Acquired immunity, antigen specific response that are adapted to the specific pathogen. Slow, enhanced by repeated exposure
What are the barrier defenses of the innate immune system
Ski, mucosal epithelium with tight junctions, goblet cells, mucociliary escalator
Why is the skin an effective defense barrier
Acidic, dry, sloughing off cells, lyzozymes, normal microbiota
What is the function of goblet cells in defense of pathogens
Secrete mucous and prevent bacteria from reaching epithelial cell surface
How does mucociliary blanket prevent bacteria from breaching epithelial layer
Ciliated epithelial cells that line the airways, coated with mucous that traps pathogens and moves up and out of lungs
If microbes breach the epithelial layer what is the 2nd line of defense
White blood cells- phagocytic cells like macrophages and DC’s, neutrophils, NK,
Complement system
Cytokines
What is the complement system
Serum proteins that trigger inflammatory response and initiate phagocytosis
What are cytokines
Proteins made by immune cells to coordinate attack on invading pathogen
PAMP
Pathogen associated molecular patternw
What are examples of PAMPS
LTA, LPS, TA, CpG, viral RNA, flagellin
What is CpG DNA
C followed by G in sequence, methylated in mammals, unmethylated in bacteria
TLR4 binding to LPS
LPS (-) binds to LBP which then binds CD14 and then TLR4 with MD-2. Acts on transcription factors and initiates an immune response with inflammatory cytokines
What does Imiquimod
Medication that binds and stimulates TLR7/8 that enhances the immune response against equine sarcoids and aural plaques
What cells have oxidative burst
Neutrophils and macrophages
What is oxidative burst
Neutrophils and macrophages can create hydrogen peroxide and superoxide that damage iron containing enzymes which is common to bacteria. Fenton reaction with iron creates hydroxyl radical that attacks DNA
Why are pro-inflammatory cytokines induced by and what are some examples
C3a, C5a, macrophages, dendritic cells, ex:TNF, IL-1, IL-6
Septicemia
Bacterial infection throughout blood stream
What are the downstream signaling consequences of septicemia
Cytokine production recruits neutrophils, leave blood vessels and cause leakage, this results in decreased BP and organ failure
What are natural killer cells
Killer cells that induce apoptosis of infected host cell. Store toxic granules and release when recognize non-self
Where are the complement proteins produced
Liver
What are the three complement pathways
Mannose binding lectin, classical, alternative
what is the goal of all three complement pathways
Create C3 convertase to make C3a and C3b, C3b is opsonin that can mark for phagocytosis
Antigen
Foreign substance which binds BCR’s and TCR’s, antibody generator
What creates antibodies
B cells
Antibodies
Attack specific antigens, bind epitopes on antigens
Epitope
4-16 amino acid recognized by antigen binding site on antibody
Monovalent
Antigen with 1 epitope
Multivalent
Antigen with multiple of the same epitope
Polyvalent
Antigen with multiple different epitopes
Haptens
Antigens that bind to antigen receptor but can’t induce immune response alone, need to be conjugated to carrier
What is a clinical application for haptens
Conjugated vaccines- allow immune system to recognize some antigens that may alone be haptens- induce weak immune response
How is variability on BCR’s and TCR’s created
Recombination
What are BCR’s
Membrane bound antibodies on B cell surface, bind antigens of varying shapes and sizes
What are TCR’s
Expressed on surface of T cell, bind linear peptides displayed by MHC
What is humoral immunity in adaptive immunity
Antibody immunity produced by effector B cells (immunoglobulins)
Critical role in defense against extracellular pathogens
What is cell mediated immunity in adaptive immunity
Mediated by effector T cells that produce their effect by direct contact with target cells
Describe lymphocyte activation
Upon recognition of antigen, B and T cells become activated and result in clonal proliferation and differentiation into effector and memory cells.
Effector cells eliminate antigen via antibody secretion or cell mediated killing
Memory cells provide protect against same antigen during next encounter
What make MHC I
All uncleared cells
Where do MHC I’s present
CD8 Tc cells
What do MHC I present
Antigen fragments from viruses and intracellular bacteria
What is the result of MHC I presentation
Apoptosis of presenting cell
What makes MHC II
Antigen presenting cells
Where do MHC II present
CD4 Th cells
What do MHC II present
Fragments from extracellular sources
How do TC cells function
MHC I presents antigen which binds TCR that then releases toxic granules to infected cell
How do Th cells function
MHC II presents and activate macrophages, B, cells, and other responses
What does Th1 activate
Macrophages
What does Th2 activate
Responds to extracellular bacteria and fungi, generates inflammatory responser
What does Th17 do
Stimulate neutrophil response to extracellular bacteria and fungi
what does Tfh do
Stimulate antibody production from B cells
What does Treg do
Regulates immune responee
Describe B cell activation by helper T cells
Activation of B cell leads to clonal proliferation and differentiation and then BCR binds, processes and displays antigen to Th cell
Describe T cell independent B cell activation
BCR binds antigen with repeated structural components, crosslinking of BCR’s to repeat structures signal to proliferate and activate, produce low affinity IgM
What are some examples of cross talk between adaptive and innate immunity
Dendritic cells present to T cells
Antibodies enhance phagocytosis, mast cell degranulation and complement activation
T cell cytokines stimulate macrophage activity