Immune system and innate immunity Flashcards
The 2 types of immunity
Innate-common set of responses activated by most microbes
Adaptive-individual response to specific antigen exposure. Can change during response through adaptation
Components of innate system:
Physical
Epithelial surfaces (eg skin, GI tract etc) can secrete antimicrobial substances such as defensins
Cytokines such as IL-1 and TNFalpha can increase such secretions
Epithelia also have lymphocytes and mast cells that can create antibodies against LPS (lipopolysaccharide)
Components of innate system:
Cellular-Neutrophils
Medium sized and has a large multilobed nucleus with many organelles
Main functions include phagocytosis, producing antimicrobial peptides and reactive nitrogen and oxygen species
Components of innate system:
Cellular- Macrophages
Large and has a large rounded nucleus with many organelles
Many functions including: Phagocytosis, antigen presentation, complement proteins, cytokines, inflammatory mediators and N/O reactive species.
Components of innate system:
Cellular- Dendritic cells
Large cells with a small nucleus:cytoplasm ratio and has membrane protusion
functions include: antigen inflammatory, interferon, cytokines, co simulatory signals and reactive O species
Structures on microbes not present on mammalian cells
Mannose receptors
Opsonin receptors
Toll like receptors
7TM alpha helical receptors
What happens when innate cells bind to pathogens?
Phagocytosis by macrohages or neutrophils
Killing of infected cells by NK cells
Presentation to t-cells by APC (dendritic) cells
Toll like receptors
Similar to drosophila toll receptors-has 10 mammalian forms
Found in most cells of innate immune system and respond to many microbial markers eg. LPS, ds RNA, and bacterial peptidoglycans
Increased expression of inflammatory genes: TNFalpha, IL-1, IL-12, E-selectin, iNOS
Lipopolysaccharide (LPS)
Endotoxin produced by gram negative cell walls that stimulate the immune system and induces local and systemic inflammation
Potent activator of macrophages inducing cytokine and reactive O species release
Systemic inflammatory response syndrome (SIRS): Fever, neutrophilia, septic shock
Phagocytosis
Done by neutrophils and macrophages though neutrophils are more common
Microbes taken in through endocytosis and fused with lysosome with degrading enzymes (lysozyme, elastase and collagenase)
Reactive O species: super oxide, H202, NO
Stages of phagocytosis
- Bacteria attach to pseudopodia
- Bacterium ingested forming phagosome
- Phagosome fuses with lysosome
- Enzymes digest captured material
- Digestion products released from cell
Complement system
A cascade of plasma protein activated by microbes and has three pathways; lectin, classical and alternative
All of these result in cleavage of C3 into C3A and C3B
This leads to opsonisation and phagocytosis
Zymogens gain activity by cleavage
Cytokines
Mediate many effector functions of the innate system
2 major groups:
TNF/ IL-1- Mostly produced by LPS challenged macrophages and are proinflammatory
stims neutrophil migration to the site
IL-12- produced by macrophages/dendritic cells and promotes NK cytolysis as well as stiming IFN production in t cells and NK cells. IFN stimulates macrophage killing of microbes
Overall innate system
Same response for every pathogen
The cells involved are effector cells that aid in the removal of the pathogen
Cells are recruited to site of action by inflammatory mediators
Types of hypersensitivity
type 1- immediate hypersensitivity
type 2-autoanitbodies
type 3-deposition of immune complexes
type 4- t cell mediated tissue injury
types 2-4 are types of autoimmunity
Type 1- hypersensitivity
mast cells stimulated by crosslinking of fcr bound IgE
very rapid after exposure to antigen
requires repeated exposure before immune response is generated
no innate response
IL-4 promotes TH2 development and class switching to IgE
Type 2- Autoantibodies
activates complement and stimulates phagocytosis
recruits neutrophils that cause tissue damage
can bind to receptors which can stimulate/inhibit function
eg.graves disease
type 3- Immune complex deposition
Occurs after multiple injections of antigens
Deposition occurs in small vascular beds, joints and renal glomeruli
Leads to complement activation and Fcr mediated responses
Eg Systemic disease such as Lupus
type 4- t cell mediated tissue injury
Caused by TH1 and CD8 cells that release IFNalpha to activate macrophages and TNF to induce inflammation
Damage caused by hydrolytic enzymes, ROI’s and cytokines
eg. type 1 diabetes
Autoimmunity
Failure or breakdown in maintaining autoimmunity
Main causes are genetic susceptibility (polygenic) and environmental triggers
Transplantation
Donor MHC recognised as foreign
CtL cells, TH cells and antibodies will damage donor tissue
Graft vs host disease may occur
Blood types
Classified into ABO depending on antigen presented upon RBC’s
All people have basic glycolipid (O) but some have attached carbohydrates (A or B)
People have antibodies against antigens we don’t have
E.g. A type A person would have anti B antibodies
Tumours
Have only a few non self antigens (oncoproteins) that are usually hidden
Mostly targetted by CTL or NK cells
Treated with anitbodies, vaccines and costimulation
Immunodeficiency
Genetic-X linked agammaglobulinemia or severe combined immunodeficiency (SCID)
Acquired- HIV/AIDS
From infections, drugs or cancer treatment
HIV/AIDS
Infects dendritic cells initially
CTL’s and antibody production occurs and partially suppresses the infection
The virus then infects T cells via CD4 and chemokine receptors and causes lymphopenia
