Immunity Flashcards
What is pathology?
Study of the causes and effects of diseases
What is aetiology?
The cause, set of cause, or manner of causation of a disease of a condition
What is pathogenesis?
Progressive changes as disease develops
What is the surgical sieve?
Is an approach to differential diagnosis.
Differential diagnosis is distinguishing of a particular disease or condition from others that present with similar clinical feature.
Can use mnemonic:
Vitamin CDEF
vascular infective trauma autoimmune metabolic iatrogenic neoplastic congenital degenerative endocrine functional
Differential diagnosis informs which pathological investigations may be required
What are the key organs of the immune system
1) Thymus Where T-cells mature 2) Bone Marrow Yellow tissue in centre of bones responsible for making white blood cells which later become lymphocytes 3) Lymph nodes Produce and store cells that fight infection and disease 4) Spleen Largest lymphatic organ in the body contains white blood cells helps control amount of blood in body
What is the lymphatic system
“the motorway” - linking key organs e.g adenoid tonsils, thymus, spleen, bone marrow
transports clean fluids back to the blood
Drains excess fluid from tissue
removed “debris” from cells of body
Transports fat from digestive system
What type of immunities are there?
1) Innate
2) adaptive
What is innate immunity?
First line of non-specific defense
What is adaptive immunity?
Specific and acquired - second line of defence
What occur in innate immunity
1) Physical barrier to infection e.g. Epithelium/ epithelial layers of skin and mucosal/ glandular tissue
or. Chemical barrier to infection e.g Acidic pH + anti-microbial proteins and peptides
- cytokines/chemokines
2) Cellular responses to infection using innate cell subsets and complement
- phagocytic cells (macrophages, neutrophils)
- antigen-presenting cells (dendritic cells)
3) Chemokines/cytokines
- Chemokine - cells recruitment
- Cytokine - cell activation/ proliferation -> inflammation response
How long does does innate immunity take?
1 - 3 days
-> regular contact with potential pathogens which are destroyed within minutes or hours - only rarely causing disease
What occurs in adaptive immunity
1) B cells (humoral response) (long term immunity)
- production of antibodies -> block infections and eliminate extracellular microbes
2) T cells (cell-mediated response) (communicate with innate cells)
- cell - cell communication
e.g. phagocytosed microbes in macrophages
responded to by - helper T lymph.
Activate macrophages to kill phagocytosed microbe
intracellular microbes e.g. virus replicating withun infected cells
responded to by - Cytolytic T lymp.
kill infected cells and eliminate reservoir of infection
How long does adaptive immunity take?
4 - 10 days
repeated infections met immediately with strong and specific response
What can cause inflammation?
1) Invading micro-organism
2) particular materials (dust, join prostheses)
3) Altered self cells
4) transformed malignant cells (cancer)
What is inflammation?
1) Initiation - response to harmful agent
2) Progression - containment of harmful agent
3) Amplification - modulation of immune response
4) Resolution - healing (acute inflammation) e.g. mild/severe gingivitis
acute - appropriate response to a threat, resolution when no longer required
5) Failure to resolve (chronic inflammation) e.g periodontitis
chronic - unresolved, failure in control mechanism self damage
What is periodontitis and what causes it?
- Chronic inflammatory disease
- Destruction of soft and hard tissues which support teetj
- Plaque build up - microbial dysbiosis (microbial imbalance/maladaption)
- immune dysregulation (ie. removal of plaque not always enough)
name the innate cell subset/ immune cells
- Cells of myeloid origin:
Mast cells Monocytes ->Macrophages Neutrophils Basophil Eosinophil
- Cells of lymphoid origin:
Natural killer cells
Origin?
Dendritic cell
Innate immune cells
Describe the character of monocytes/macrophages
Monocytes - in blood macrophages - in tissue early responder Phagocytose + present antigens bactericidal mechanism
Stimulates response of other immune cells
Describe the character of Mast cells
Granulocytes (contain histamines) Early responders Blood -> tissue Function: protect again pathogens - parasitic worms \+Allergy - histamines -> inflammation
Describe the character of neutrophils
Phagocytic granulocytes most numerous Blood - tissue contain granules bactericidal mechanism Neutrophil extracellular traps -> microbes
Describe the character of basophils and eosinophils
Granulocytes -> degrade enzymes and antimicrobials
large -> defense against parasites (b: anti-parasitic immunity. E: killing of antibody-coated parasites)
allergy -> basophil histamine -> inflammation
Where are defence cells derived from?
Common precursors in bone marrow
Give example of innate and adaptive like immune cells ie the inbetweeners
Natural killer cells
dendritic cells
innate lymphoid cells
Describe the character of dendritic cells
Derived from myeloid + lymphoid lineage several types e.g langerhans cells antigen presenting cell (APC) move tissue -> lymph nodes passing on info activate T cells and B cells (directly) star shaped degrade pathogens (not main function) bridge between innate and adaptive immune responses
How do dendritic cells present antigens?
1) Pathogen or extracellular antigen phagocytized by antigen-presenting cell (e.g dendritic cell)
- placed into a vesicle.
- lysosomes to extract antigens
2) antigens bins with MHC protein that enter vesicle
3) MHC (carrying antigen) released from vesicle and travel to outer surface of cell membrane
4) dendritic cell is now presenting antigens -> activate t-cells that bind with MHC proteins
What is the role of dendritic cells in memory generation?
Immature dendritic cells take up bacterial antigens in the skin.
-> migrate to lymph node + differentiate
-> mature dendritic cells can
: prime naive t-cells (co-stimulatory activity) +
transfer antigen to other dendritic cells in lymph node
Describe the character of natural killer cells
considered part of innate immunity
large
granules - lytic (kills some virus infected cells)
recognise and kill abnormal cells/tumours/viral infected cells
holds back virus before adaptive immunity
Describe the character of Innate Lymphoid Cells (ILC)s)
Non cytotoxic (NK cell family members)
link adaptive and innate
3 subsets ILC1, ILC2, ILC3
produce cytokines similar to T cell: TH1, TH2 and TH17
ILC1: bacteria + protozoa in cells. Chronic inflammation
ILC2: helminths, asthma, allergic diseases. Metabolic homestasis
ILC3: Bacteria in cells. Chronic inflam. also Lymphoid tissue development. Intestinal homeostasis.
Where do T-cells derive from and mature?
Derive in bone marrow
mature in thymus
Where do T-cells travels
Circulate through blood and lymph.
Found in large numbers in lymphoid organ
What type of immunity do T-cells have
cellular immunity
What to T-cells protect against
Intracellular microbes
How do T- cells recognise antigen presenting cells
T Cell Receptor (TCR)
What is the T cell repertoire?
The diversity in t cells receptors = can respond to numerous antigens
How do t cells avoid responding to self peptides?
checkpoints - so t cells only respond to foreign pathogens
What types of T cells are there?
1) T helper cells (CD4+) - support immune cells to fight threat
2) Cytotoxic T cells (CD8+) - destroy our infected cells (virus)
3) Regulatory T cells (Tregs) - regulate or suppress other cells in the immune system
How do T cell start out?
As naive cells +
have receptor for very specific proteins (e.g antigencs via DC presentation)
How do cytotoxic CD8+ T cells destroy infected self cells
1) cytotoxic T cells interacts with the MHC 1-epitope complex on infected cell -> granzymes and perforins
2) perforins form pores in the plasma membrane.
Granzymes enter the cells and break down protein - lysing the cell
How are T cells activated + their fate determined?
CD4+ T cells begins are naive t cells
three signals activate + determine fate of cells
1) Activation of T cell: MHC + TCR (t cell receptor) - signal delivered by antigen presenting cell
2) Survival and clonal expansion of T cell: Co stimulation molecule interactions (CD80/86/40 on DC + CD40L/28 on T cells)
Signal 1 but no signal 2 called anergy
3) Differentiation into subset of effector T cell (specifically for CD4+ helper T cells) : cytokines/ potential signal for interleukins - signal dictates which T helper cell the naive cell becomes
For CD8+ T cells signal 3 leads to effector function e.g. production of enzymes for degradation
T cell priming also results in the generation of memory T cells
What are the CD4+ T cell subsets and their functions
1) TH1 - support macrophages -> to destroy intracellular microbes
2) TH2 - produce cytokines -> recruit + activate mast cells, eosinophils + promote barrier immunity at mucosal surfaces
3) TH17 - secret IL-17 family cytokines -> induce local non-professional immune cells to release cytokine and chemokines.
4) TFH - induce specific B cell responses (promote opsonising antibody response)
5) Treg cell - suppress T cell activity to prevent autoimmunity
What occurs when a naive t cells are presented with antigens?
it undergoes:
expansion + differentiation into effector cells
- most effector cells are short lived
How do T cells become memory cells?
only a small % become memory t cells (> 20 year life span)
Activated -> expansion -> contraction -> memory
In B cells, what does clonal expansion lead to?
2 subsets:
1) Plasma cells - antibody factories
2) Memory B cells - quick antibody response
Memory generation - B cells
Interaction between T cell and B cell
Cytokine signals released from T helper cell
induce B cell proliferation
1) generates plasma cells which produce antibodies
Initally produce IgM
Switch to IgG
2) Generated memory B cells
What cells are phagocytic cells?
Neutrophils
Macrophages
TissueDCs
Mast cells
What cells are professional antigen presenting cells
Macrophages
dendritic cells
B cells
What cells fight parasite infection
Eosinophils
Basophils
What cells are involved in allergic reactions
Basophils
Mast Cells
What cells are innate and adaptive inbetweeners
Dendritic Cells
Natural Killer Cells
Innate Lymphoid Cells
Which cells direct and control magnitude of immune reaction?
T cells
How are defence cells relevant in oral pathology?
Immune dysregulation plays a role
gingivitis -> periodontitis = differences in gum structure.
increase in the number of immune cells in the tissue
tissue is destroyed in the process.
The majority of these cells are lymphocytes.
The balance between protective and destructive immune responses is essential
Describe the response to infection
1)Innate immune response: immediate 0- hours
infection
recognised by pre-formed, non specific and broadly specific effectors
removal of infectious agents
2) Early induced innate response: early 4-96 hours
infection
recruitment of effector cells
recognition of PAMPS (pathogen associated molecular pattern) + activation of effector cells and inflammation
removal of infectious agents
3)Adaptive immune response: late > 96 hours
infection
transport of antigens to lymphoid organs
recognition by naive B and T cells
clonal expansion and differentiation to effector cells
removal of infectious agents
Name the microorganisms
bacteria virus fungi protozoa helminths
What is the innate immune response?
First line of defence (1 to 4 days)
no memory or lasting immunity
Present from birth
Effective: regular contact with pathogens, destroyed in mins/hours, rarely cause disease
responses: broad/nonspecific
contribution of non professional immune cells: epithelial/endothelial cells + fibroblasts
recruit immune cells to site of infection
What are the components of of innate immunity
1) Physical/ anatomical barrier - epithelial tissue/ mucosal barrier/ oral gingival
2) cellular mechanism
3) Plasma factors
What compounds does the epithelial barrier produce in the oral cavity?
1) Antimicrobial peptides -
1) directly kill microbes /2) module host immunity
2) Immunoglobulins (Secretory IgA) - coat microbes for host recognition
3) Lactoferrins - transport or iron ions + antimicrobial activity
4) Lysozymes - target cell walls of bacteria
5) Cystatins - anti protease activities + supports minerlization of teeth
