immunity

Immune System

Introduction to the Immune System
The human body must defend itself against unwelcome inviders. It must also deal with abnormal body cells, which, in some cases, may develop into cancer. Two major kinds of defense have evolved to counter such threats. Innate Defenses Acquired Defenses

Overview of the Immune System

External Barriers:
intact skin epidermis Acid mantle of skin Keratin Intact mucous membranes Mucus Nasal hairs Cilia Gastric juice Acid mantle of vagina Lacrimal secretion Urine normal flora ..compete other m.o. .. Production of antibacterial sub.

White blood cells (WBCs)

Macrophages
B-lymphocytes
T-lymphocytes
Natural killer(NK) cells
Mast cells

Internal Cellular Defenses:

1\Phagocytic cells Neutrophils Monocytes Eosinophils Dendritic cells 2\ NKC

How do neutrophils eat and digest microbes ?

Granules

Internal Cellular Defenses:

Natural Killer Cells Non-specific Perforins Apoptosis


Natural Killer (NK) Cells (Cytotoxic lymphocyte) Promote cells lysis by direct cell attack against virus-infected or cancerous body cells Release cytolytic chemicals (perforins) that attack a targets cell's cell membrane and bore hole. Granzymes are released and cellular enzymes disrupted. Present in spleen, lymph nodes, red bone marrow, and blood

How does the killer kill ?

Kills both host cells and microbes
Release of granules with perforins and proteases

Inflammatory Response

Inflammatory Response
Cardinal signs of inflammation redness, pain, heat and swelling Local versus systemic inflammation Septic shock

Cytokines

Small proteins – secreted by cells of the immune systemAffect the behaviour of other cellssignalling moleculesKey players in innate and acquired immunity

Which cells release cytokines ?

Cells of the immune system:Neutrophils – when they encounter a pathogen Macrophages – when they encounter a pathogenNK cells – on encountering a microbe infected cell /tumour cellLymphocytes – when they are activated

Examples of cytokines

Interferons Interleukins Tumour necrosis factor (TNF)

Interferons –Interferon is one of a growing class of cytokines, proteins that deliver instructions from cell to cell. Normally, interferon, and the similar interleukins, mediate a continual conversation between cells about growth and defenses. Interferons are named after their ability to "interfere" with viral replication within host cells. Interferon was identified more than 50 years ago by Isaacs and Lindenmann during their studies of the phenomenon of viral interference, the ability of an active or inactivated virus to interfere with the growth of an unrelated virus.Gamma interferon - produced by lymphocytes, mobilizes and activates macrophages and NK cells, stimulates synthesis and expression of more class I and II MHC, and enhances activity of B cells and cytotoxic T cells

Alpha interferon - produced by most leukocytes, mobilizes and activates macrophages and NK cells. Beta interferon - produced by fibroblasts, mobilizes and activates macrophages and acts to reduce inflammation

Interferons (IFN)

Signalling proteins produced by by virus infected monocytes and lymphocytesSecreted proteins – Key anti-viral proteins“Interfere” with virus replication Warn the neighbouring cells that a virus is around... If we did not have IFNs – most of us may die of influenza virus infection

Complement - twenty plasma proteins that amplify the inflammatory response, lyses microorganisms and enhances phagocytosis by opsonization. Two pathways: classic and alternative. Pyrogens - secreted by macrophages and signal the body to increase temperature; high body temperature inhibits microbial multiplication and enhances body repair processes.

Interleukins

Interleukins – 1-37Not stored inside cellsQuickly synthesized and secreted in response to infectionKey modulators of behaviour of immune cellsMostly secreted by T-lymphocytes & macrophages

What to interleukins do ?

Interleukins
Proliferation of immune cells
Activation of immune cells
Increase antibody production
Inflammation

Antigen (Ags)

Antigens are substances that can mobilize immune system and provoke a response Types: 1\ Complete antigen - functional properties: immunogenecity - stimulate B and T cell formation and antibody production reactivity - react with B and T cells

2\Small antigens (peptide, nucleotide, hormones) - may bind to body's own biological molecules (proteins); antigen when bound to body's own molecules may cause an immune response, this is called an allergy. Small antigens are called haptens (incomplete antigen) and alone are not immunogenic. Reactivity (immune response) is dependent upon antigen structure; localized regions, antigenic determinants are where antibodies or B and T lymphocytes can bind. 3\. Self Antigens Are not foreign or antigenic to us, but are strongly antigenic to other individuals egs. blood transfusions and organ transplants

Intra cellular … extra cellular microbes

Major Histocompatibility Complex (MHC) antigens Found on all cells except RBCs Involved in tissue recognition (aids in transplantation recognition) Two types of MHC antigens: MHC class I found on all body cells MHC class II found on antigen present cells Antigen Presentation Ingestion of the antigen Digestion of antigen into peptide fragments Fusion of vesicles (peptide fragments with MHC-II molecules) Binding of peptide fragments to MHC-II molecules Insertion of antigen-MHC-II complex into plasma membrane


* Complement fixation is the main mechanism used against cellular antigens Antibodies bound to cells change shape and expose complement binding sites This triggers complement fixation and cell lysis Complement activation: Enhances the inflammatory response Uses a positive feedback cycle to promote phagocytosis Enlists more and more defensive elements
Complement Fixation and Activation

Chapter 21, Immune System

* Neutralization – antibodies bind to and block specific sites on viruses or exotoxins, thus preventing these antigens from binding to receptors on tissue cells Other Mechanisms of Antibody Action

Chapter 21, Immune System

* Agglutination – antibodies bind the same determinant on more than one antigen Makes antigen-antibody complexes that are cross-linked into large latticesCell-bound antigens are cross-linked, causing clumping (agglutination) Precipitation – soluble molecules are cross-linked into large insoluble complexes Other Mechanisms of Antibody Action

ACQUIRED IMMUNITY

All cells have cell surface macromolecules Adaptive immunity is sensitive to specific infections Antigens distinguish self versus non-self

ACQUIRED IMMUNITY

* Two types of lymphocytesB lymphocytes – oversee humoral immunityT lymphocytes – non-antibody-producing cells that constitute the cell-mediated arm of immunityAntigen-presenting cells (APCs):Play essential auxiliary roles in immunity Cells of the Adaptive Immune System

Chapter 21, Immune System

* Immature lymphocytes released from bone marrow are essentially identical Whether a lymphocyte matures into a B cell or a T cell depends on where in the body it becomes immunocompetent B cells mature in the bone marrow T cells mature in the thymus
Lymphocytes

ACQUIRED IMMUNITY

Humoral Immunity
Also known as antibody-mediated immunity Utilizes B-lymphocytes Recognizes antigen directly Made in the bone marrow


Humoral immunity or humoural immunity is the aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is so named because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Its aspects involving antibodies are often called antibody-mediated immunity.

What is an antibody?

Produced by Plasma cell (B-lymphocytes producing Ab) Essential part of adaptive immunity Specifically bind a unique antigenic epitope (also called an antigenic determinant) Possesses antigen binding sites Members of the class of proteins called immunoglobulins

Antibody Structure

What does an antibody look like ?

2 identical heavy chains 2 identical light chainsEach heavy chain – has a constant and a variable regionEach light chain has a constant and a variable region H
H
L
L
Constant region
Variable region

Antibody: structure and function

Fab – fragment antigen bindingFc- Fragment constant

Antibody: Fab

Fab region Variable region of the antibody Tip of the antibody Binds the antigen Specificity of antigen binding determined by VH and VL

Antibody: Fc

Fc region Constant region Base of the antibody Can bind cell receptors and complement proteins

Antibody Classes

Antibody Classes

Chapter 21, Immune System
* Major roles in immunity are: To engulf foreign particles To present fragments of antigens on their own surfaces, to be recognized by T cells Major APCs are dendritic cells (DCs), macrophages, and activated B cells
Antigen-Presenting Cells (APCs)

Cell-Mediated Immunity

Utilizes T-lymphocytes T-cells are made in the bone marrow but mature in the thymus gland. Cannot recognize antigens directly.

Chapter 21, Immune System

* Since antibodies are useless against intracellular antigens, cell-mediated immunity is needed Two major populations of T cells mediate cellular immunity CD4 cells (T4 cells) are primarily helper T cells (TH) CD8 cells (T8 cells) are cytotoxic T cells (TC) that destroy cells harboring foreign antigens Other types of T cells are: Suppressor T cells (TS) Memory T cells
Cell-Mediated Immune Response


* Regulatory cells that play a central role in the adaptive immune response Once primed by APC presentation of antigen, they: Chemically or directly stimulate proliferation of other T cells Stimulate B cells that have already become bound to antigen Without TH, there is no immune response
Helper T Cells (TH)

Chapter 21, Immune System

* TH cells interact directly with B cells that have antigen fragments on their surfaces bound to MHC II receptorsTH cells stimulate B cells to divide more rapidly and begin antibody formationB cells may be activated without TH cells by binding to T cell–independent antigensMost antigens, however, require TH co-stimulation to activate B cells Helper T Cell

Helper T-cells stimulate B-cells

* TC cells, or killer T cells, are the only T cells that can directly attack and kill other cells They circulate throughout the body in search of body cells that display the antigen to which they have been sensitized Their targets include: Virus-infected cells Cells with intracellular bacteria or parasites Cancer cells Foreign cells from blood transfusions or transplants
Cytotoxic T Cell (Tc)

Cytotoxic T-Lymphocyte Stimulation

Chapter 21, Immune System
* Suppressor T cells (TS) – regulatory cells that release cytokines, which suppress the activity of both T cells and B cells Other T Cells

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