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Flashcards in Chapter 6 Review Deck (79)
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1
Q

Define Innate (natural or native) Immunity

A

Innate Immunity is always present, ready to provide defense against microbes and to eliminate damaged cells

2
Q

What are the stages of innate immunity?

A

1-Recognition of microbes and damaged cells
2-Activation of various mechanisms
3-Elimination of the unwanted substances

3
Q

What are the main components of Innate Immunity?

A

Physical components
-epithelial barriers that block entry of microbes

Cellular Components
-phagocytic cells: mainly neutrophils and macrophages
dendritic cells
natural killer cells

Plasma Components:
-several plasma proteins including the complement system

4
Q

Role of Epithelia in Innate Immunity?

A
  • Mechanical barrier in respiratory and GI.
  • Epithelial cells produce Defensins which are antimicrobial molecules.
  • lymphocytes located in the epithelia fight microbes
5
Q

Role of Monocytes and Neutrophils in Innate Immunity?

A
  • monocytes and macrophages = phagocytes in the blood recruited to site of infection
  • Monocytes that mature at the site of infection are called macrophages
  • all tissue contain resident macrophages that sense and destroy microbes
6
Q

What are the dominate cells of inflammation?

A

macrophages are the dominant cells of inflammation

7
Q

Role of dendritic cells in Innate Immunity?

A
  • located in epithelia, lymphoid organs, and most tissues
  • capture and display antigens for T-lymphocytes
  • also contain receptors sensing microbes and cell damage that when bound release cytokines which is important for anti-viral and inflammation pathways
  • contribute to Innate Immunity but , unlike macrophages, are not main contributors
8
Q

Role of Natural Killer cells in Innate Immunity?

A

-early protection against viruses and INTRAcellular bacteria

9
Q

Role of some soluble proteins and complement system?

A
  • INNATE system response: activated by microbes using the alternative and lectin pathways
  • INNATE system response: circulating mannose-binding lectin and C-reactive proteins
  • ADAPTIVE system response: activated by antigens using classic pathway
10
Q

What two patterns does the Innate Immune System recognize?

A

1- pathogen-associated molecular pattern

2- damage-associated molecular pattern

11
Q

How long does Innate Immunity work with an infection?

A

0-12 hours

again the players are: epithelial barriers, phagocytes, dendritic cells, Complement, and NK cells

12
Q

Receptor locations and functions of Plasma Membrane receptors, Endosomal receptors, and Cytosolic receptors

A
  • Plasma Membrane: detect extracellular microbes (TLR)
  • Endosomal: detect ingested microbes (TLR)
  • Cytoplasmic: detect microbes in cytoplasm (NOD-like)
13
Q

What is the best known of the pattern recognition receptors?

A

-Toll like receptors (TLRs)

14
Q

What receptors contain TLRs?

A
  • Plasma membrane receptors

- Endosomal vesical receptors

15
Q

What pathway happens when you activate TLRs?

A

-activation of two sets of transcription factors
1- NF-kB, which stimulates synthesis and secretion of cytokines and the expression of adhesion molecules which leads to the recruitment & activation of leukocytes
2- Interferon regulatory Factors ( IRFs), which stim production of antiviral cytokines, type I interferons

16
Q

Rare but serious TLR mutation?

A

Germline Loss-of-function mutation

17
Q

Function of NOD like Receptors (NLRs)?

A
  • cytosolic receptors
  • see necrotic products (uric acid, and released ATP), ion disturbances (loss of K+), and some microbial products

-Caspase-1 is inactive–>NLR senses something–>inflammasome forms–>caspase-1 activates–>pro-IL-1B turns into active IL-1B and is secreted–>acute inflammation

18
Q

What are autoinflammatory syndromes?

A
  • AKA periodic fever syndromes
  • Gain of function mutations of NLRs
  • TX = IL-1 antagonists
  • Example #1: Urate crystals being recognized by NLRs leading to the underlying inflammation seen in Gout
  • Example #2: NLRs recognizing lipids and cholesterol crystals abnormally deposited in large amounts may contribute to diabetes type 2 and atherosclerosis
19
Q

Function of C-type lectin receptors (CLRs) ?

Function of RIG-like receptors (RLRs) ?

Function of G protein coupled receptors (GPCRs) ?

Function of Mannose Receptors?

A
  • CLRs: on plasma membrane of dendritic cells and macrophages. They detect fungal glycans and are elicit inflammatory reactions to fungi
  • RLRs: in cytoplasm of most cells. detect nucleic acids of viruses replicating in cytoplasm of infected cells. Stimulate the production of antiviral cytokines
  • GPCRs: on neutrophils. macrophages, and most other leukocytes recognize bacterial peptide N-formylmethionyl residues. stimulated chemotactic response
  • Mannose: see microbial sugars (contain terminal mannose sugars unlike mammals) and induce phagocytosis of the microbes
20
Q

What are the two main reactions of the Innate Immune System?

A
  • Inflammation: recruited leukocytes destroy microbes and ingest and eliminate damaged cells
  • Antiviral defense: Type ! interferons act on infected and uninfected cells. Activate enzymes degrading viral nucleic acids and inhibit viral replication–> this moment is called the antiviral state
21
Q

Receptors used by Innate Immune System vs Receptors used by the Adaptive system?

A
  • Innate: 100s of receptors to see 1,000 molecular patterns

- Adaptive: two receptors (antibodies and T-cell receptors) with millions of variations to see millions of antigens

22
Q

Define Adaptive (acquired or specific) Immunity

A
  • Lymphocyte and their products, including antibodies
  • Humoral Immunity
  • Cell-mediated Immunity
23
Q

What is humoral Immunity?

What is Cell-mediated Immunity?

A
  • Humoral: protects against extracellular microbes and their toxins. Mediated by B-lymphocytes and their secreted products, Antibodies (also called immunoglobulins, Ig)
  • Cell: host defense against intracellular microbes. mediated by T (thymus derived) lymphocytes which express highly specific receptors for antigens
24
Q

Function of B lymphocytes?

A
  • B lymphocyte + microbe = antibodies =

- Neutralization of microbe, phagocytosis, complement activation

25
Q

Function of Helper T lymphocytes?

A
  • T lymphocyte receptor + microbial antigen presented by antigen presenting cells =
  • activation of macrophages
  • inflammation
  • activation (proliferation and differentiation) of T and B lymphocytes
26
Q

Function of Cytotoxic T lymphocytes?

A
  • T cell + infected cell presenting antigen on its surface =
  • killing infected cell
27
Q

Function of regulatory T lymphocytes?

A

-Suppression of immune response

28
Q

Function of natural killer (NK) cells?

A

-Killing of infected Cell

29
Q

What are naive lymphocytes?

A
  • lymphocytes that have yet to come in contact with an antigen
  • once activated they differentiate into effector cells which eliminate the microbes (mature lymphocytes) and memory cells (which remain ready to act if the microbe returns)
30
Q

What is clonal selection?

A

-lymphocytes specific for a large number of antigens exist before exposure to antigen, and when antigen enters it selectively activates the antigen-specific cells

31
Q

How is antigen receptor diversity achieved?

A

somatic recombination of the genes that encode receptor proteins

32
Q

What do B lymphocytes make and activate?

A
  • B lymphocytes make antibodies and activate other leukocytes to destroy microbes
  • B lymphocytes are the only cell in the body capable of producing antibody molecules, the mediators of humoral immunity
  • make up 10-20% of circulating lymphocytes
  • Develop form precursors in the bone marrow
33
Q

What do cytotoxic T lymphocytes (CTLs) do?

A

Cytotoxic T lymphocytes (CTLs) kill infected cells

34
Q

What do regulatory T lymphocytes do?

A

Regulatory T lymphocytes limit immune responses and prevent reactions against self antigens

35
Q

T lymphocyte precursors come from where and develop where?

A

T lymphocyte precursors come from hematopoietic stem cells and mature in the thymus

36
Q

Majority of mature T lymphocytes are found where?

A

60-70% of T lymphocytes in the blood are mature T lymphocytes.

37
Q

T cell recognizes antigens by means of what?

A

by means of a T cell receptor (TCR)

38
Q

What is a TCR made of?

A

TCRs are made up of a disulfide linked heterodimer between an alpha and beta polypeptide chain

39
Q

How does a TCR function?

A

TCR recognizes peptide antigens that are presented by the major histocompatibility complex (MHC) molecules on the surfaces of antigen presenting cells

40
Q

What transduces the signal from the TCR to the inner T cell?

A

The TCR complex which is made up of the following:

  • the alpha and beta chain (class II MHC) with the antigen attached to
  • the CD3 proteins (epsilon/gamma on the left and delta/epsilon on the right) and zeta proteins (zeta proteins are identical in all T cells)

The linked CD3 complex and zeta chains initiate the activating signals

41
Q

What is the role of CD4 in the T cell activation?

A
  • signal 1 = CD4 and CD 28 are also involved in T cell activation
  • some cells use CD8 instead of CD4 but the function is the same
  • signal 2 = costimulators (the hook that hooks to CD28) are CD80 and CD86)
42
Q

Difference between CD4 helper T cells and CD8 cytotoxic T cell recognition?

A
  • CD4 helper T cells only recognize type II MHC

- CD8 cytotoxic T cells only recognize type I MHC

43
Q

What do integrins do?

A

-promote the binding between adhesion molecules and Antigen presenting cells (APCs)

44
Q

How do B-cells recognize antigens?

A
  • They recognize via the B-cell receptor complex which is made of Membrane-bound IgM and IgD isotypes, present on the surface of all mature and naive B cells
  • B cells also have CR2 and CD21 which recognize complement products generated during innate immune responses to microbes and CD40
45
Q

B cells develop into what after what?

A

-B cells develop into plasma cells after stimulation by antigens

46
Q

How does the Epstein-Barr Virus (EBV) infect cells?

A

EBV uses CR2 as a receptor to enter and infect B cells

47
Q

What is the most important antigen-presenting cells initiating T-cell responses against protein antigens?

A

Dendritic cells

48
Q

What are Langerhans cells?

A

Langerhans cells are immature dendritic cells within the epidermis

49
Q

Dendritic cells are recruited where to do what?

A

dendritic cells are recruited to the T cell zones of lymphoid organs, where they are ideally located to present antigens to T cells

50
Q

What are some functions of macrophages?

A
  • function as antigen presenting cells
  • T-cells enhance macrophage ability to kill ingested microbes
  • participate in effector phase of humoral immunity
51
Q

What are the functions of NK cells?

A

-destroy irreversibly stressed cells
destroy abnormal cells (virus infected cells)
-Virus infected or neoplastic cells express LESS MHC I molecules = target for NK cells

52
Q

What two cell surface molecules are commonly used to identify NK cells?

A
  • CD-16 and CD56

- CD16 used to lyse IgG coated cells which process is called antibody-dependent cell-mediated cytotoxicity (ADCC)

53
Q

What is the common activating receptor family of NK cells?

A

-NKG2D receptors recognize surface molecules that are induced via damage

54
Q

What do NK cells secrete? What proliferates NK cells? What promotes killing and secretion of IFN-y?

A
  • IFN-y which activates macrophages to destroy ingested microbes
  • proliferation–>IL-2 IL-15
  • kill/secretion of IFN-Y–> IL-12
55
Q

Innate Lymphoid Cells are what?

A

populations of lymphocytes that lack TCRs but produce cytokines similar to those that are made by T cells

56
Q

Generative Lymphoid organs are what?

A
  • the thymus (where T cells develop)

- the bone marrow (site of production of all RBCs and where B cells mature)

57
Q

Peripheral lymphoid organs are what?

A

lymph nodes, spleen, and mucosal and cutaneous lymphoid organs

58
Q

What is lymphocyte recirculation?

A

Lymphocytes constantly recirculate between tissues and home to particular sites; naive lymphocytes traverse the peripheral lymphoid organs where immune responses are initiated, and effector lymphocytes migrate to sites of infection and inflammation

59
Q

What do MHC class 1’s do?

A
  • expressed on all nucleated cells and platelets
  • display peptides that are derived from proteins, such as viral and tumor antigens, that are located in the cytoplasm and usually produced in the cell and class 1-associated peptides are recognized by CD8+ T lymphocytes
60
Q

What do MHC class 2’s do?

A
  • expressed on cells that present ingested antigens (i.e. macrophages, B lymphocytes, and dendritic cells)
  • present antigens that are internalized into vesicles, and are typically derived from extracellular microbes and soluble proteins
61
Q

Cytokines of the innate immune system are?

A
  • made by macrophages, dendritic cells, NK cells, endothelial/epithelial cells
  • TNF, IL-1, IL-12, type I IFNs, IFN-y
62
Q

Cytokines of the adaptive immune system are?

A
  • produced by CD4 T lymphocytes

- IL-2, IL-4, IL-5, IL-17, and IFN-y

63
Q

What is the job of TGF-B and IL-10?

A

-they terminate the immune response

64
Q

What are hematopoiesis (colony-stimulating-factors)?

A
  • formation of blood cell colonies from bone marrow progenitors
  • increase leukocyte numbers during infections
  • produced by marrow stromal cells, t lymphocytes, macrophages and others
  • i.e. GM-CSF and IL-17
65
Q

Upon activation what do B lymphocytes proliferate and differentiate to?

A

Plasma cells that secrete different classes of antibodies with distinct functions

66
Q

Ploysaccharides and lipids stimulate secretion of mainly _____ antibody

A

IgM

67
Q

Isotype switching among the Igs is achieved by what?

A

IFN-y and IL-4

68
Q

What Ig antibody coats (opsonizes) microbes and targets them for phagocytosis during the humoral response?

A

IgG

69
Q

Th2 stimulates the secretion of what Ig?

A

IgE

70
Q

Which Ig is actively transported across the placenta and protects the newborn?

A

IgG

71
Q

IgM and IgG activate the complement system via what pathway?

A

Classical pathway

72
Q

Key Concept:
The innate immune system uses several families of receptors, notably the toll-like receptors, to recognize molecules present in various types of microbes and produced by damaged cells

A

Key Concept:
The innate immune system uses several families of receptors, notably the toll-like receptors, to recognize molecules present in various types of microbes and produced by damaged cells

73
Q

Key Concept:
Lymphocytes are the mediators of adaptive immunity and the only cells that produce specific and diverse receptors for antigens

A

Key Concept:
Lymphocytes are the mediators of adaptive immunity and the only cells that produce specific and diverse receptors for antigens

74
Q

Key Concept:
T (Thymus-derived) lymphocytes express antigen receptors called T cell receptors (TCRs) that recognizes peptide fragments of protein antigens that are displayed by MHC molecules on the surface of antigen-presenting cells.

A

Key Concept:
T (Thymus-derived) lymphocytes express antigen receptors called T cell receptors (TCRs) that recognizes peptide fragments of protein antigens that are displayed by MHC molecules on the surface of antigen-presenting cells.

75
Q

Key Concept:
B (bone-marrow-derived) lymphocytes express membrane-bound antibodies that recognize a wide variety of antigens. B cells are activated to become plasma cells, which secrete antibodies

A

Key Concept:
B (bone-marrow-derived) lymphocytes express membrane-bound antibodies that recognize a wide variety of antigens. B cells are activated to become plasma cells, which secrete antibodies

76
Q
Key Concept:
Natural Killer (NK) cells kill cells that are infected by some microbes, or are stressed and damaged beyond repair. NK cells express inhibitory receptors that recognize MHC molecules that are normally expressed on healthy cells, and are thus prevented from killing normal cells
A
Key Concept:
Natural Killer (NK) cells kill cells that are infected by some microbes, or are stressed and damaged beyond repair. NK cells express inhibitory receptors that recognize MHC molecules that are normally expressed on healthy cells, and are thus prevented from killing normal cells
77
Q

Key Concept:
Antigen-presenting cells (APCs) capture microbes and other antigens, transport them to beyond organs and display them for recognition by lymphocytes. The most efficient APCs are dendritic cells, which live in epithelia and most tissues

A

Key Concept:
Antigen-presenting cells (APCs) capture microbes and other antigens, transport them to beyond organs and display them for recognition by lymphocytes. The most efficient APCs are dendritic cells, which live in epithelia and most tissues

78
Q

Key Concept:
CD4+ helper T cells help B cells make antibodies, activate macrophages to destroy ingested microbes, stimulate recruitment of leukocytes and regulate all immune responses to protein antigens

A

Key Concept:
CD4+ helper T cells help B cells make antibodies, activate macrophages to destroy ingested microbes, stimulate recruitment of leukocytes and regulate all immune responses to protein antigens

79
Q

Key Concept:
Antibodies secreted by plasma cells neutralize microbes and block their infectivity, and promote the phagocytosis and destruction of pathogens. Antibodies also confer passive immunity to neonates.

A

Key Concept:
Antibodies secreted by plasma cells neutralize microbes and block their infectivity, and promote the phagocytosis and destruction of pathogens. Antibodies also confer passive immunity to neonates.