Innate Immune System
What is the first barrier to the immune system?
Physical/ Physiological Barrier
Ex: Epithelium, Mucus, Tears, Mucociliary Apparatus, Commensal Flora
What is the definition of a hypersensitivity?
An exaggerated or inappropriate immune response to an antigen that leads to discomfort, tissue damage, and disease
What are the cardinal signs of inflammation (5)
Heat, redness, swelling, pain, loss of function
Calor, Rubor, tumor, dolor, functio laeso
Where do naive T-cells encounter antigens presented on MHCs?
Secondary lymphoid organs(tonsils, xALT, lymph nodes, spleen) and circulation
What are sentinel cells and name 3 examples?
Specialized cells that monitor the local environment for pathogens
Dendritic cells, macrophages, and mast cells
What are the primary and secondary lymphoid organs of the body?
Hint: There are 2 primary and 4 Secondary
Primary- Bone marrow/ Bursa of Fabricius
Secondary- Spleen, lymph nodes, tonsils, xALT(Peyers patch, etc)
Antibodies against intrinsic or extrinsic antigens results in what type of hypersensitivity?
Type 2- result of cross-reactive antibodies direct toward an extrinsic agent that binds to normal tissue or antibodies against self-antigens
A predominance of which leukocyte type signals an ACUTE infection?
Bonus question- An OVERWHELMING infection
Neutrophils
Banded Neutrophil(Left shift)
What initiates naive T-cell differentiation into effector T-cells?
What are the 5 CD4 T-cell subsets and what is their main function?
Antigen Presenting Cells (DC, Macrophages, B cells)
Th1- intracellular pathogen
Th2- Parasites
Th17- Extracellular
Tfh- B-cell stimulation
Treg- Immune regulation
What are exogenous and endogenous antigens?
What MHC-type is each typically presented on?
Exogenous antigens are antigens not made within the host (bacteria, allergens, etc)- MHC-2
Endogenous antigens are synthesized within infected cells (viral peptides, etc)- MHC-1
Name 3 innate immune cells and what lineage they belong to (myeloid or lymphoid)
Basophil, Neutrophil, Eosinophil, Monocyte, macrophage- Myeloid
Natural Killer Cell- Lymphoid
Anaphylaxis is an example of what type of Hypersensitivity? What antibody is associated with this?
Type 1- due to release of histamine from degranulating mast cells in response to IgE
Name 2 positive Acute-Phase Proteins and 1 Negative Acute Phase Protein
C-reactive Protein, Serum Amyloid A
Albumin
What are the steps in T-cell homing?
Rolling(L-selectin), activation (CCL21), Adhesion (LFA-1), Diapedesis (CCL21, CXL12)
What Immunoglobulin(Ig) is associated with mucosal immunity?
What Immunoglobulin(Ig) is associated with early antibody production/ rises first during infection?
What Immunoglobulin(Ig) is associated with later antibody production/ rises later in infection?
IgA
IgM
IgG
Name 2 cytosolic receptors and what they recognize during cellular infection
NOD-like receptors- recognize peptidoglycan of intracellular bacteria
RIG-1-like receptors- recognize dsRNA and ssRNA (virus)
Type-3 Hypersensitivity immune complexes can be deposited where in the body?
Kidneys(Membrano-Proliferative Glomerulo-Nephritis), joints(Immune-mediated Polyarthritis (IMPA), Arteries (arteritis)
What are the 3 major steps of acute inflammation?
Vasodilation/Dilation of local small vessels- redness/heat
Increased vascular permeability- allows exit of fluid, plasma, proteins, and leukocytes- swelling, pain
Migration and accumulation of leukocytes- pain, loss of function
What are the 3 signals that APC deliver to naive T-cells?
MHC-TCR- Activation
CD28- Survival
Cytokines (IL-6, 12, 23, 4, etc)- Differentiation
Name 3 immune-privileged sites and explain why immune-privileged sites are more prone to autoimmune attack
Brain, eyes, testis, uterus
Shielded from the active immune system (barriers), lack lymphatic drainage, high levels of anti-inflammatory molecules (TGF-B, IL-10)
Name the 3 complement pathways and what activates each pathway
Classical Pathway- antibody bound to a pathogen
Alternative Pathway- binding of complement directly to pathogen surface
MBLectin Pathway- Lectin binds to mannose on pathogen
Type 4 Hypersensitivity is caused by what cell type in response to what?
(Must provide cell type AND what causes the response)
T-cell mediated response to antigen presentation (MHC, foreign peptide antigens)
What are the major pro-inflammatory cytokines?
IL-1, IL-6, and TNF-alpha
Describe the 2 ways that B-cells can be activated
T-cell independent- BCR Type 1 responds to specific types of antigens with highly repetitive structure. TLR Type 2 happens in response to PAMPS such as LPS
T-cell dependent- Requires T-cell to BCR interaction. B-cell presents processed antigen to T-cell and is then activated
What is positive and negative selection of T-cells and where does it occur?
Occurs in the Thymus
Positive selection- learning to recognize self-MHC. If they bind and recognize, they are allowed to continue
Negative selection- T-cells that bind too strongly to self-MHC are eliminated to establish self tolerance