Innate + Adaptive Immunity + MHCs Flashcards
First line of defense
Innate immunity
What are two major roles of the innate immune system?
- Recognize microbes based on the chemical structures they express that are NOT FOUDN on human tissues
- To stimulate the adaptive immune system
What is the difference in the nature of receptor in innate and adaptive immunity?
Innate=pattern recognition receptor
Adaptive=specific receptors
Pre-programmed
adaptive immune response. antigen does not instruct the adaptive immune system
Adaptive immunity is organized into what two defense systems?
Humoral and cell-mediated
Humoral immunity
antibodies and complement-mediated responses
Cellular immunity
T cell and NK (natural killer) cell mediated immune response
What are the three hallmarks of adaptive immunity?
Specificity, Inducibility, Memory (SIM)
4 major components of innate immune system and their importance
- Epithelial Barriers
- Phagocytes
- Natural Killer cells
- Compliment system
They have unique properties to serve as early warning system of microbial invasion, react by destruction of pathogen
2 roles of epithelial barriers in innate immune system
physical barrier against infection, epithelial cells make defensins (antibiotics/ host defense peptides)
3 main phagocytes
Macrophage, neutrophils, dendritic cells
What’s a dendritic cell found in skin?
langerhan cell
What phagocyte can’t communicate with adaptive cells?
neutrophils
How do macrophages interact with bacteria?
PRRs (pattern recognition receptors)
What are two examples of pattern recognition receptors? (PRRs)
- TLR (toll like receptors)
- NOD (nucleotide binding oligomerization domain)
TLR4
recognize lipopolysaccharides (LPS) produced by bacteria
TLR5
recognizes flagellan (allows bacteria to move)
TLR3
recognizes double stranded RNA (found on membrane of phagosomes, we don’t make this!)
These cytosolic proteins picks up bacterial products/stress proteins and trigger gene activation steps
NODs
This lectin carbohydrate binding protein is present on phagocytes and can recognize carbohydrates on membrane of bacteria
Mannose receptor
These are similar to cytoxic T cells (same killing mechanism) but are activated when MHC1 is absent
Natural Killer cells
All of our nucleated cells express
MHC1
Two receptors on NK cells
KAR and KIR (killer activating and killer inhibiting receptors)
Receptor on NK that engage MHC1
killer inhibiting cells
Receptor on NK that recognizes stress responses made by cell when undergoing viral infection
Killer activating cells
NKs are part of innate immune system, but why might you think they’re adaptive?
They are lymphocytes
What are two examples of Killer activating receptors (KARs) on natural killer cells?
NKG2D, CD16
Describe how a receptor like CD16 on NK cells works in a typical antibody dependent cellular cytotoxicity (ADCC)
An NK cell expressed CD16, which recognizes and binds portion of antibody (Igg) which is bound to pathogen-infected target cells. Once bound, NK cell releases cytokines.
What makes up the compliment system?
family of proteins circulating in body fluids, promote elimination of infected organisms
What are the three pathways of the compliment system?
- Classical pathway-uses elements of adaptive immunity
- Alternative pathway
- Mannose binding lectin pathway
Intracellular pathogens
cell-mediated immunity
extracellular pathogens
humoral immunity (b-cells and plasma cells, antibodies)
What is the cross talk between innate and adaptive immunity?
Antigen presenting cell (APC)
Professional APCs (3)
Macrophages, Dendritic cells, B-cells (not actively phagocytic, but produce antibodies)
Which phagocytic cells is not an APC and why?
Neutrophil, they do not express MHCII and so do not “cross-talk” / engage in adaptive immunity.
Bacteria are ingested by
phagocytic cells inside APC
bacteria-ingested phagosome are referred to as
endosome/phagosome
The endosome can fuse with lysosome to form?
Phagolysosome
What happens as the endosome migrates to interior of APC? What induces this?
Bacterial protein get broken down due to decrease in pH
What acid proteases breakdown bacterial protein?
Cathepsins
Where is MHCII complex made?
endoplasmic reticulum in APC
definition of antigen
a molecule that reacts with an immune receptor (antibody or T cell receptor)
The important marker on T helper cells (Th)
CD4+
The important marker on cytotoxic T cells
CD8+
Pattern recognition receptors (PRRs) recognize and react against?
Pathogen-associated molecular patterns (PAMPs) expressed by microbes such as bacteria, viruses, and fungi
What are unique about antigen processing cells?
Cells that express MHCII (major histocompatibility complex class II)
Every mammal has an MHC, what is the term designated for human MHC?
HLA = human leukocyte antigen (a subset of genes that form a multigene family)
What are the three loci that encode MHCII?
DP, DQ, DR
What gene do you have at each loci in MHCII?
An alpha and beta gene
Why is MHC a “complex?”
multigenic
multiallelic
codominant expressed genes
What covers MHCII in ER to prevent binding to peptides in ER?
Invariant Chain
Little vesicles derived from ER find way to endosome pathway. What is the part of invariant chain still on MHCII?
CLIP (CLass II associated Invariant Peptide)
What removes CLIP from MHCII?
HLA-DM
What binds to MHCII on surface of APC?
T-helper cells
MHCII genes map to what chromosome in humans?
6th chromosome
When are MHCII directed to cell surface?
When peptide binding site on MHCII interacts with broken up bacterial peptide (10-16 amino acids long)
Increases number of antigen-specific lymphocytes to keep pace with microbes
Clonal expansion
B cells undergo final differentiation stage to form
plasma cell
makes and secretes immunoglobulin
plasma cell
Where to B lymphocytes mature?
Bone marrow
Where do T lymphocytes mature?
Thymus
IL-12
cytokine in innate immunity that activates NK cells
interferon-gamma
cytokine of innate immunity that NK cell produces
In measuring immune response, what are two ways the secondary exposure differs from the first?
Kinetics and magnification.
Test used to measure immune activation
(antibody) titer test
How does HIV affect immune response?
HIV binds to CD4 on Th cell. Knocks out Th-CD4, destroys downstream and upstream response.
This pathway of the compliment system uses elements of adaptive immunity to take place
classic pathway
-antibody dependent (products of V cells, which are adaptive immunity
Which antibodies activate classical pathway of complement system?
IgM, IgG
The chemical species that elicits the antibody response
immunogen
What is an example of certain antigens that are not good immunogens? (ie not good at eliciting an antibody response)
haptens
In order, list the 5 most effective immunogens
Macromolecular proteins, smaller proteins, carbohydrates, lipids, nucleic acid
Three important properties of immunogens that influence effectiveness of immune response
foreignness, molecular size, and chemical complexity
definition of antigen
substances produced by microbes as well as noninfectious molecules
what is the difference in recognition between T cells (cell-mediated) and antibodies (humeral)?
T cells recognize only antigens, antibodies can recognize many types of molecules (proteins, carbs, lipids)
Ensures that distinct antigens elicit specific response in adaptive immunity
specificity
leads to enhanced responses to repeated exposures to the same antigens in adaptive immunity
memory
which complex class is associated with the endocytic pathway?
MHCII (bacteria ingested by endosome)
when antigen found outside cell
MHCII
which complex class is associated with the exocytic pathway?
MHCI (brings peptide from cytosol to ER lumen)
when antigen found inside cell
MHCI (virus infects cell and produces viral proteins INSIDE the cell)
major pathway for breakdown of viral proteins
ubiquitination
scaffolding protein, made by all of our cells, binds to viral proteins and tags them for destruction
ubiquitin
where viral proteins get broken down inside cell
proteosome
2 important properties of proteosome
1) tube-like structure
2) contains proteolytic enzymes that point interior of tube
Where are MHCI molecules synthesized and found?
In lumen of ER
MHCII and peptide (on APC) interact with which cell?
T helper cell
MHCI and peptide (on target cell) interact with which cell?
Cytotoxic C cell
What protein brings viral proteins from cytosol into the ER?
TAP (Transporter-associated Antigen Presentation
TAP (function and 3 important properties)
- heterodimer
- embedded in ER membrane
- ATP dependent transporter
- brings peptides from cytosol into lumen
Loci involved with MHCI
B C A
Schematic representation of MHCII
alpha 1 beta 1
alpha 2 beta 2
Schematic representation of MHCI
alpha 1 alpha 2
B2m alpha 3
The 3 loci B C A on MHCI encode for what parts of the molecule?
ONLY encodes the alpha chain (alpha 1, 2, 3)
B2m isn’t encoded by the loci on MHCI but has a very critical function? What is B2m responsible for? How is it different than the alpha genes?
required for folding of class I molecule and transport to membrane surface. It is not polymorphic (encoded by beta-2microglobulin gene)
superdomain that peptide forms with in MHCI is?
alpha 1 and alpha 2
superdomain that peptide forms with MHCII is?
alpha 1 and beta 1
Superdomain of MHCI can hold about how many amino acids in peptide?
9 amino acids
The superdomain of MHCII can hold a peptide of about how many amino acids?
10-30 (floor sides are kind of open, so peptide can fall outside of actually site and accommodate a larger peptide)
Each loci in MCHII encodes for
an alpha and a beta polypeptides
N-terminal domain of MHCII
alpha or beta 1
membrane proximal domain of MHCII
alpha or beta 2
A _____ is inherited from each parent
haplotype (one set of the gene on the chromosome)
