[03.23a] Basic Concepts in Immunity and Hypersensitivity Reactions V2.1.pdf

Immunopathology

What branch of medicine is super dynamic and timely, especially because of the COVID-19 pandemic?

Innate immunity

What type of immunity is always present and ready to provide instant defense against microbes and eliminate damaged cells?

Present before infection

When is innate immunity present?

Epithelium of the skin, Mucosa of the gastrointestinal tract, and respiratory system

What are examples of mechanical barriers that prevent entry of microbes?

Neutrophils and Monocytes

What phagocytic cells are present to phagocytose microbes once the initial line of defense of innate immunity has been breached?

Macrophages

What do monocytes become when they are present in specific tissue?

Mast cells

What innate immunity component plays a key role in allergic reactions and is capable of producing inflammatory mediators?

Innate lymphoid cells (Natural Killer/NK cells)

What cells are components of innate immunity that differ from T-cells in that they do not have T-cell receptors or respond to antigens?

Plasma proteins

What innate immunity component is part of the complement system?

Pathogen Associated Molecular Patterns (PAMPs)

What are the certain structures shared among related microbes that phagocytic cells can recognize?

Damage Associated Molecular Patterns (DAMPs)

What are the molecules released by injured and necrotic cells that can also be recognized by the innate immune system?

Pattern recognition receptors

What are the cellular receptors that recognize PAMPs and DAMPs?

First line of defense

What is innate immunity considered in the body?

Non-specific

Why is inflammation induced by innate immunity considered limited protection?

No memory

Why does the speed of response of innate immunity not increase the second time around?

Adaptive immunity

What does innate immunity prompt to provide robust and better protection?

Toll-Like Receptors (TLRs)

Which class of receptors for innate immunity recognition is the best and most well-known?

Plasma membrane and endosomal vesicles

Where are Toll-Like Receptors (TLRs) present?

Activation of Nuclear Factor kappa B (NF-κB)

What is the culmination of triggering a cytoplasmic TLR?

Transcription factor which stimulates the synthesis and secretion of cytokines and expression of adhesion molecules

What is NF-κB (Nuclear Factor kappa B)?

Recruitment and activation of leukocytes in inflammation

What are cytokines and adhesion molecules needed for?

Antiviral cytokines

What do activated interferon regulatory factors stimulate if an endosomal TLR is initiated?

NOD-Like Receptors (NLRs)

Which cytosolic receptors recognize products released from damaged cells and some microbial products?

Inflammasome

What cytosolic multiprotein complex do NLRs signal via?

Caspase-1

What enzyme does the inflammasome activate?

Cleaves the precursor form of cytokine IL-1

What is the function of activated caspase-1?

Proinflammatory and a pyrogenic interleukin

What is IL-1?

C-Type Lectin Receptor

Which receptor class detects fungal glycans and elicits inflammatory reactions against fungi?

Plasma membrane of macrophages and dendritic cells

Where is the C-Type Lectin Receptor expressed?

RIG-Like Receptors (RLRs)

Which receptors detect nucleic acids of viruses that replicate in the cytoplasm of infected cells?

Production of antiviral cytokines

What do RIG-Like Receptors (RLRs) stimulate?

Lymphocytes and Antibodies

What does adaptive immunity consist of?

Previous exposure to antigen

What does adaptive immunity rely on to provide specific and strong immune defense?

More potent

How is adaptive immunity described in contrast to innate immunity?

Cellular mediated

What adaptive immunity type is directed against intracellular microbes, toxins, and cancers?

T helper cells (CD4+)

Which T lymphocytes help B cells make antibodies and help activate other cells to kill microbes?

T cytotoxic cells or Killer T cells (CD8+)

Which T lymphocytes kill target cells that bear specific antigen while sparing neighboring uninfected cells?

Regulatory T cells

Which T lymphocytes regulate immune response and prevent reaction to autoantigens?

Humoral mediated

What adaptive immunity type is directed against extracellular microbes and their toxins?

B lymphocytes and their products (antibodies or immunoglobulins)

What mediates humoral immunity?

Dendritic cells

Which Antigen Presenting Cells (APCs) link innate and adaptive immunity?

T-cell activation

What is a primary role of dendritic cells related to T cells?

Langerhans cells

Which type of dendritic cell is located on the skin?

Follicular dendritic cells

Which type of dendritic cell is found in the germinal centers of lymphoid follicles of the spleen and lymph nodes?

Presentation of antigens to other cells to initiate T-cell responses

What is the most important role of dendritic cells?

High levels of Major Histocompatibility Complex (MHC)

What molecules do dendritic cells express high levels of, needed for antigen presentation and T-cell activation?

Macrophages

Which important APCs efficiently phagocytose and destroy microbes that are opsonized by IgG or C3b?

T-lymphocytes

Which cells mainly direct adaptive immunity and are thymus-derived?

Thymus

Where are T-lymphocytes developed?

T-Cell Receptor (TCR)

What molecule is responsible for T-cells to recognize antigens?

Alpha (α) and beta (β) polypeptide chains

What components make up the disulfide linked heterodimer of most T-cell receptors?

Variable (antigen-binding) region and a constant region

What two regions does each polypeptide chain of the TCR have?

Peptide antigens that are bound to and presented by MHC molecules

What specific type of antigens does the TCR recognize?

CD3 Complex and ζ (zeta) Chain Dimer

What complex, made up of 6 polypeptide chains, is non-covalently linked to each TCR?

Transduction or the spread of signals into the T-cell

What is the function of the CD3 Complex and ζ Chain Dimer?

Gamma-Delta TCR Complex

Which T-cell complex recognizes peptides, lipids, and small molecules without a display by MHC proteins?

Epithelial surfaces (such as skin, gastrointestinal and urogenital tracts)

Where are cells expressing the Gamma-Delta TCR Complex primarily located?

Alpha-Beta Complex

What TCR complex is expressed by around 95% of T lymphocytes?

CD4 and CD8

What proteins serve as co-receptors in T-cell activation?

Co-stimulation (e.g., via CD28)

What is needed to promote dynamic and robust T-cell activation, in addition to antigen recognition via MHC?

CD4 T-cells

Which T-cells function as cytokine secreting helper cells that assist macrophages and B lymphocytes?

Class II MHC molecules

What type of MHC molecule does CD4 bind only to?

CD8 T-cells

Which T-cells function as cytotoxic T-lymphocytes that destroy host cells containing microbes?

Class I MHC molecules

What type of MHC molecule does CD8 bind only to?

B-lymphocytes

What cells are the only ones in the body capable of producing antibodies?

Bone marrow

Where do B-cells develop?

Membrane immunoglobulin (IgM or IgD) and Associated Signaling proteins (Igα or Igβ)

What is the B-cell antigen receptor complex composed of?

Igα and Igβ

What associated signaling proteins help propagate the signal (signal transduction) in the B-cell receptor complex?

CD21

Which B-cell co-receptor recognizes complement products generated during innate immune response?

CD40

Which B-cell receptor receives signals from helper T-cells?

Plasma cells

What do activated mature B cells develop into, capable of producing antibodies?

Eccentric nucleus with a checkerboard appearance

What is a distinguishing histological feature of a plasma cell's nucleus?

Natural Killer (NK) cells

What type of cells are large granular lymphocytes that are part of the innate immune system?

Does not express T-cell receptors (TCR) or Immunoglobulins (Ig)

What does a Natural Killer (NK) cell not express?

Virus-infected cells and tumor cells

What are two examples of damaged or abnormal cells that NK cells recognize and destroy as a first line of defense?

CD16 receptors

What receptors do NK cells express that confer Antibody-Dependent Cellular Cytotoxicity (ADCC)?

Antibody-Dependent Cellular Cytotoxicity (ADCC)

What is the ability to lyse IgG-coated target cells called?

Interferon-𝝲 (IFN-𝝲)

What cytokine do NK cells secrete that activates macrophages to destroy ingested microbes?

IL-12

Which cytokine regulates NK cell activity by activating killing of target cells and secretion of IFN-𝝲?

Neural cell adhesion molecule (NCAM)

What is CD56, expressed by NK Cells, also called?

Molecules that display peptide fragments of protein antigen for recognition by antigen-specific T cells

What is the function of the Major Histocompatibility Complex (MHC)?

Human Leukocyte Antigens (HLA)

What is the alternate name for MHC, due to its initial detection in human leukocytes?

Rejection of transplanted organs

What do MHC/HLA genetic products induce?

Chromosome 6

Where are the genes encoding MHC/HLA clustered?

Highly polymorphic

How are HLA haplotypes described?

Identical twins

Who are the only individuals who express the same MHC molecules?

All nucleated cells and platelets

Where is Class I MHC expressed?

Peptides derived from cytoplasmic proteins (e.g., virus-specific antigens, tumor-specific antigens)

What kind of peptides does Class I MHC display?

CD8+ T cells

Which T cells recognize antigens bound to Class I MHC molecules?

Class I MHC-restricted

How are CD8 T-cells described in their recognition of antigens?

CD8 molecule

What acts as a co-receptor that binds to the Class I MHC heavy chain on the T-cell?

Eliminate virus and kill tumor cells

What are the important functions of CD8 (cytotoxic) T-lymphocytes?

HLA-D

In what region is Class II MHC encoded?

B-lymphocytes, macrophages, dendritic cells

Where is Class II MHC expressed?

Antigens derived from extracellular microbes and soluble proteins

What kind of antigens does Class II MHC present?

CD4 T-helper cells

Which T-cells are Class II MHC restricted?

Intracellular messengers

What are cytokines in the context of immune cell communication?

Interleukins, Chemokines, Interferons, Lymphokines

What categories are encompassed by cytokines?

Control the harmful effects of inflammation or tissue damage

What is the therapeutic relevance of controlling cytokine synthesis and release?

TNF, IL-1, IL-12, type 1 IFNs, IFN-γ, and chemokines

What are the predominant cytokines released during the activation of the innate immune system?