Macrophages, DCs, and T Cells (Test 1)

neutrophils

-neutropenia

-G-CSFs

erythrocytes

-anemia

-ESAs

eosinophils

-eosinophilic asthma

-IL-5 Mab inhibitors

Cytokines

-low molecular weight (<20 kD)

-Hundreds known

-Regulatory proteins or glycoproteins (interleukins, growth factors)

-Secreted by and utilized by immune cells (neutrophils, macrophage, lymphocytes, etc.) and various other cells (epithelial cells, fibroblasts, etc.) in response to a number of stimuli.

Interleukin (IL-21)

regulates both innate and adaptive immune responses, and has key roles in antitumor and antiviral responses but also exerts major effects on inflammatory responses that promote the development of autoimmune diseases and inflammatory disorders

due to multiple effects

Why is it challenging to develop IL-21 blockers?

Interleukin IL-6

is a proinflammatory cytokine produced by a variety of cell types, including lymphocytes, monocytes, and fibroblasts. Normal levels in blood range from 1- 5 pg/mL.

overproduction

Infection by SARS-CoV2 induces _______________ of IL-6 from bronchial epithelial cells (lung).

IL-6

COVID-19-associated systemic inflammation and respiratory failure can be associated with increased cytokine release, as indicated by elevated blood levels of _____________

Acetemra (tocilizumab)

-IV

-for the treatment of COVID-19 in hospitalized adults who are receiving systemic corticosteroids and require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

-This drug is a biologic-monoclonal antibody that specifically blocks IL-6.

-was initially indicated for rheumatoid arthritis years earlier and for other IL-6 associated inflammatory disorders

repurposed

ACTEMRA is a ____________ therapeutic.

macrophages

-Large, mononuclear cell, derived from monocytes in bone marrow

-are scavenger immune cells that digest bacteria and other cellular debris generated during tissue remodeling and clear cells that have undergone apoptosis (through process of phagocytosis)

T cells

Macrophages function as professional antigen presenting cells (APC) and communicate with what cells?

M1

-classically activated (microbial activity)

-pro-inflammatory (kill-digest bacteria)

M2

-wound-healing (tissue repair)

-Anti-inflammatory

Lipopolysaccharides (LPS)

also known as endotoxins, are complex molecules found in the outer membrane of Gram-negative bacteria. IFN-γ is a cytokine that is produced by T-cells and NK cells

IFN-y release assay (IGRA)

is a blood test used to detect infection with Mycobacterium tuberculosis (MTB), the bacteria that cause tuberculosis (TB)

Kupffer cells (KC)

are liver-resident macrophages. They are the first cells that are in contact with compounds absorbed from the gastrointestinal tract.

osteoclasts

bone

monocytes

bone marrow/blood

microglia

central nervous system

Kupffer cells

Liver

Langerhans cells

skin and mucosa

Dendritic Cells (DC)

-are derived from monocytes, just like macrophages. Bridge innate/adaptive

-Function as a Professional Antigen-Presenting Cells (APC), recognized by T cells. Highly specialized.

-Found in all tissues, higher in those that have contact with the outside environment, such as lung mucosa, epithelial cells of the skin, and the linings of the nose and the gastrointestinal tract.

mature and immature

What are the 2 distinct functional states of dendritic cells?

T cells

-are central regulators of the adaptive immune response

-control antibody responses, activate innate immune cells and lyse target cells

distinguish SELF from NON-SELF

What is the role of T cells?

-CD4+ helper T cells

-CD8+ cytotoxic cells

What are the 2 groups that majority of T cells are grouped into once leaving the thymus?

Cluster of differentiation (CD)

are cell surface proteins expressed on cells of the immune system such as lymphocytes (T-cells, B-cells, and NK-cells), neutrophils, and monocytes/ macrophages

CD molecules

What are the fingerprints of immune cells?

over 300 (wowza)

How many CDs have been identified?

CD4+ T-cells (T helper cells)

HIV infects _______________, with a preference for TH17 and Treg cells.

CD45

is referred to as leukocyte common antigen

CD34

is associated with hematopoietic stem cells

CD44

is a cell surface glycoprotein that is overexpressed in breast cancer and is associated with cancer progression and metastasis (a tumor biomarker)

Antigen presenting cells and T cells

The communication between what cells is fundamental when it comes to T cell activation?

-Dendritic cells

-B cells

-Macrophages/monocytes

The APC family consists of what?

MHC on their surface

What do nucleated cells use to report their cellular contents?

Antigen (Ag) presentation

peptides processed inside the cell that are shuttled to the surface for presentation

T cell receptor (TCR)

T cells use this to sample cells and determine if the antigen present is SELF or NON-SELF

Nonself

peptides derived from pathogens (viruses, bacteria, ect.)

Major histocompatibility complex (MHC)

is a glycoprotein cell surface complex that is located on the surface of cells

peptide fragments

MCH role is to present _____________ of intracellularly digested protein antigens to T cells.

MHC class I (MHC-I)

-Display peptides from self and viral peptides)

-Expressed on surface of all nucleated cells including antigen presenting cells (APC).

-Recognized by T-cell receptor (TCR) of cytotoxic T lymphoctytes (CD8+)

-Peptides displayed are short (8-11 amino acids long).

-Cell mediated response—direct killing of cell containing viral peptides

MHC class II (MHC-II)

-Display peptides from bacterial antigens taken into APCs (macrophages, dendritic cells) by endocytosis or phagocytosis

-Expressed on surface of antigen presenting cells

-Recognized by TCR of helper T cells (CD4+)

-Peptides displayed are 12-20 amino acids long.

-Antibody Response

peptide-MCH complex

T-cell receptors (TCR) are on the cell surface of T cells to recognize what?

The so-called “three-signal model” is usually used to define the APC function required for the activation of T cells

Once peptide is loaded to MHC-what happens next?

signal 1 and 2

APCs need to have at least what signals to have the capacity to stimulate T cells?

kill

CD8+ T-cells can directly _____ cells that are infected with viral pathogens.

Signal I

Sampling- Interaction of APC with T-cell (via class I MHC with TCR)

Signal II

Co-stimulation. Requires additional signals between T-cell and APC

Signal III

CD8+ T-cells release perforin (creates pore in infected cell) and granzymes (pro-apoptotic enzymes) that kill infected cell

CD4 T cells

-T cells that express CD4 glycoprotein on the cell membrane

-also known as helper T cells

-CD4 glycoprotein serves as the T cell receptor

-recognize antigens on the surface of the antigen presenting cells

-recognize antigens presented along with MHC class II molecules

-induce other immune cells to trigger an immune response by secreting cytokines upon recognizing antigens

CD8 T cells

-T cells that express CD8 glycoprotein on the cell membrane

-also known as cytotoxic T cells

-CD8 glycoprotein serves as the T cell receptor

-recognize antigens on the surface of all nucleated cells

-recognize antigens presented along with the MHC class I molecules

-induce cell death of the virus-infected cells or tumor cells either by cell lysis or apoptosis

Major histocompatibility complex (MHC)

is a glycoprotein cell surface complex that is located on the surface of cells