Immunology Flashcards
Signal One:
T cells are generated in the Thymus and are programmed to be specific for one particular antigen. Once they leave the thymus, they circulate throughout the body until they recognise their antigen on the surface of antigen presenting cells (APCs). The T cell receptor (TCR) on both CD4+ helper T cells and CD8+ cytotoxic T cells binds to the antigen as it is held in a structure called the MHC complex, on the surface of the APC. This triggers initial activation of the T cells. The CD4 and CD8 molecules then bind to the MHC molecule, stabilising the whole structure. This initial binding between a T cell specific for one antigen and the antigen-MHC it matches sets the whole response in motion. This normally takes place in the secondary lymphoid organs.
Signal Two:
In addition to TCR binding to antigen-loaded MHC, both helper T cells and cytotoxic T cells require a number of secondary signals to become activated and respond to the threat. In the case of helper T cells, the first of these is provided by CD28. This molecule on the T cell binds to one of two molecules on the APC - B7.1 (CD80) or B7.2 (CD86) - and initiates T-cell proliferation. This process leads to the production of many millions of T cells that recognise the antigen. In order to control the response, stimulation of CD28 by B7 induces the production of CTLA-4 (CD152). This molecule competes with CD28 for B7 and so reduces activation signals to the T cell and winds down the immune response. Cytotoxic T cells are less reliant on CD28 for activation but do require signals from other co-stimulatory molecules such as CD70 and 4-1BB (CD137).
Signal Three:
Once the T cell has received a specific antigen signal and a general signal two, it receives more instructions in the form of cytokines. These determine which type of responder the cell will become - in the case of helper T cells, it will push them into Th1 type (cells exposed to the cytokine IL-12), Th2 (IL-4), or IL-17 (IL-6, IL-23). Each one of these cells performs a specific task in the tissue and in developing further immune responses.
The correct answer is: Interaction between CD28 on T cells and CD80/86 on antigen presenting cells
What is CVID?
defect in B-cell differentiation into plasma cells and impaired secretion of Ig
Erythema nodosum
- form of panniculitis with features of a delayed-type hypersensitivity reaction
- erythematous, tender nodules on the shins
- septal panniculitis without vasculitis
- resolves spontaneously within a few weeks
- Leg elevation, rest, and compression aid in reducing symptoms.
lceration should be absent
Erythema nodosum
- form of panniculitis with features of a delayed-type hypersensitivity reaction
- erythematous, tender nodules on the shins
- septal panniculitis without vasculitis
- resolves spontaneously within a few weeks
- Leg elevation, rest, and compression aid in reducing symptoms.
lceration should be absent
What is the strogest predictive marker of disease progression in all stages of HIV?
CD38 expression on CD8
Chronic granulomatous diseae
Defect in PHOX enzymes
which has 4 subunits
>400 known defects
Inability to produce superoxide radical to kill engulfed bacteria
Lipid and protease inhibitors
lipdystrophy
Which CD molecules do memory T cells express?
CD45Ro
Roles of
IL2, IL3, IL4, IL5, IL6, IL8, IL11:
IL2: T-cell proliferation
IL3: hematopoietic lymphoid growth and proliferation
IL4: acts on B cells to promote IgE class switch
IL5: regulates esinophil growth and activation
IL6: differentiation of activated B –> plasma cells
IL8: Neutrophil chemotaxis
IL11: stimulate megakaryocytopoiesis –> produce platelets
PAMPs
Gram +ve bacteria: Peptidoglycan bacterial DNA lipoteichoic acids
Gram -ve: LPS
RNA virus: dsRNA
Yeast: Mannans
Which TLR bind to LPS?
TLR-4
Responsible for toxic shock syndrome in G-ve bacterial sepsis
ILC cells
part of the innate immunity
mirror Th1, Th2, Th17 and CD8 T-cell actions
Rapid produceer sof effector cytokines
Fucntion in fetal development (LTI) - involved in the development of secondary lymphoid organs
**PLZF **is important in developedment of ILC
ILC 1
NK and non-NK cells
Produe IFNg, TNF
intracellular pathogens
May drive IBD and RA
ILC 1
NK and non-NK cells
Express TF-Tbet
Produe IFNg, TNF
intracellular pathogens
May drive IBD and RA
Toxo, lupus, MS, alzheimers
- ILC precursor influenced by IL15,IL7 produce ILC1
- IL12, 15, 18 activates ILC to produce IFN-g and TNF
- *defence against viruses
*NK cells are activated by IL15
ILC 2
express GATA3
Produce IL4,5,9, 13
heminths/protozoa
Drive allery and atopy
Asthma, Schistosoma
ILC precursor –> IL7 –> ILC2
L25, 33,TSLP activates ILC2 –> IL5, IL13
ILC3
Express RORgt
Produce IL17, IL22
**extracellular organism
**
implicated in IBD and MS
Associated with obesity
ILC3 is activated by IL-1beta, IL23 to produce IL17, IL22
iNK T cells
Rapid responders
Distince T-cell population express invariant** alpha, beta TCR,** as well as surface proteins common for NK cells (CD16, 56, granzyme production)
REcognise glycolipid antigen on CD1d, and express R for IL12, IL18 (which are innate cytokines)
positively selected from DP thymocytes by mild affinity binding to self antigen when presented on CD1d R and co stimulated by SLAM
MAIT cells
Innate-like T cells
Semi invariant alpha/beta TCR
lack diversity
**Recognise riboflavin synthesis derivatives **via MR1
- common in gut bacteria and fungus
they do have a memory phenotype
abundant in** liver** and lungs
Gamma delta T-cells
TYpe 1: in thymus and peripheral tissue: recognise stress-related antigents
Type 2: peripheral blood, mainly recognise phosphoantigens
Roles:
- Cytokines: produce IFN-g in the presence of IL2, IL15
> IL17+ gamma delta TC differentiation in the presence of IL7
- Cytotoxicity: induce cell death by apoptosis or antibody dependent cellular toxicity
- Antigen presentation: to CD4/CD8 cells, and induce **DC maturation via TNF alpha **
Other roles in infection:
- neutrophil mobilisation and clearance
- Antimicrobial peptides, maintain barrier, kill infected cells
- neutrophil recruitmetn and granuloma formation
Associated with IBD, inflammatory arthropathy etc
Neutrophils
NETOSIS:
- sheets of DNA and histones with granules contents (lysozyme, elastase, defensins)
- TRAP bacteria and fungi –> death of organism
Implicated:
- sepsis
- thrombosis
- gout
- SLE, RA
- Athrosclerosis
IF type 1
IFNa(13-14 subtypes) with INF-beta
- dependent on phosphyralation of IRF3 and NFkB
antiviral response
Associated with SLE, other autoimmune disease
inadequate/defect: severe or prolonged viral infections:
- TLR3 defect –> HSV encephalitis
- worse covid infection(Esp in men)
IF type 3
similar in structure to IL-10
STAT1-STAT2 dimerisation
NFkB
widerange of role
Classical - canonical:
- response to various immune receptors (PAMPs,DAMPs, TLR ligands, IL1R, TCR, TNFR1)
- rapid and transient
- activation of p50, RELA and cREL
important for inflammation, cell proliferation, differentiation and survival
Alternative:
- induced by ligands of TNF-receptor superfamily, and can also be induced by viruses and some bacteria –> negative regulator and dampner of virus induced Type1 IF response
- Activation of p100
- required for lymphoid development, B-cell maturation, regulation of innate and adaptive immune response
Defect is associated with primary immunodeficiency (i.e. CVID)
Relopathies
Overactivation NFkB which regulates B-cell survival, and generate inflammation