lecture 9 : immunity, disease, and vaccines objectives: understand how the body fights infections...

Lecture 9: Immunity, Disease, and Vaccines Objectives:•Understand how the body fights infections

•Defense strategies•Components of the defense

•Understand how pathogens fight the defense•Understand how a vaccine works

Objectives:•Understand how the body fights infections

•Defense strategies•Components of the defense

•Understand how pathogens fight the defense•Understand how a vaccine works

Background Reading: Chapter 35

Three Lines of DefenseBarriers at Body Surfaces• Physical barriers• Chemical barriers• Normal flora• Disposable surfacesNonspecific Responses (Innate Immunity)• Inflammation

– Fast acting cell types (self vs. non-self)– Cells that remove debris– Proteins: hole plugging, hole making, and cutting tools

Specific Immune Responses (Cellular Immunity)• B and T cells• Communication• Antibodies and perforins

Barriers at Body Surface• Intact skin and mucous membranes• Lysozyme • Normal bacterial flora• Flushing and Sheading

Three Lines of DefenseBarriers at Body Surfaces

Nonspecific Responses (Innate Immunity)• Inflammation

– Fast acting cell types (self vs. non-self)– Cells that remove debris– Proteins: hole plugging, hole making, and cutting tools

Specific Immune Responses (Cellular Immunity)

Nonspecific Responses

• Lymph nodes trap and kill pathogens

• Natural killer cells attack a range of targets

• Inflammation

InflammationFast acting cell types (self vs. non-self)Cells that remove debrisProteins: hole plugging, hole making, and cutting tools

Complement System

• Plasma proteins that take part in both specific and nonspecific response

• Activation of one triggers cascade of reactions that activate others

CASCADE REACTION

FORMATION OFATTACK COMPLEXES

LYSIS OFTARGET

Acute Inflammation

• Nonspecific response to foreign invasion,

tissue damage, or both

• Destroys invaders, removes debris, and

prepares area for healing

• Characterized by redness, swelling,

warmth, and pain

Inflammation

• Mast cells release histamine• Capillaries dilate and leak• Complement proteins attack bacteria• White cells attack invaders and clean up

Inflammation

• Redness- vessel dilation• Warmth- increased blood flow• Swelling- edema, leaking• Pain- pressure on free nerve endings

Three Lines of DefenseBarriers at Body Surfaces

Nonspecific Responses (Innate Immunity)

Specific Immune Responses (Cellular Immunity)• B and T cells• Communication• Antibodies and perforins

Immune Responses

• Directed against specific invaders

• Carried out by T cells, B cells, and

macrophages

• Communication signals such as

interleukins play a vital role

Definitions: B cells, T Cells, and Macrophage

• B cell– Covered with antibody (one type)– Don’t recognize MHC presented antibody, only free

antigens

• T Cell (Thymus)

– Ignore free antigen– recognize only antigen presented by MHC

• Macrophage– Clears particles– Presents MHC antigens

Definitions

Antibody Structure• Antibody consists of

four polypeptide chains

• Certain parts of each chain are variable; impart antigen specificity

variable regionof heavy chain

antigen-binding site antigen-binding site

hinge region(flexible)

variable region of light chain

constant region of light chain

Definitions

Antigen:

Any substance that stimulates the production of antibodies

Usually a protein or large molecule

Little 3-D shapes that antibodies can recognize.

RecognitionRecognition

Self and Non-selfSelf and Non-self

antigen framents

MHC molecule

antigen-MHC complex

MHC

Recognition

Displaying non-self

Features of Immune System

• Immunological specificity– B and T cells zero in on certain kinds of

pathogens; response is pathogen specific

• Immunological memory– Immune system recognizes and reacts

swiftly to a pathogen it has “seen”

Memory and Effector Cells

• When a B or T cell is stimulated to divide,

it produces more than one cell type

• Memory cells are set aside for future use;

they are the basis for immune memory

• Effector cells engage and destroy the

current threat

Key Component of Immune Response

Key Component of Immune Response

• MHC markers• Antigen-presenting cells• Helper T cells• Effector cytoxic T cells• Natural killer cells• B cells

Overview of an Immune Response

Naive helper T cell

Naive B cell

Antigen-presenting cell

Activated helper T cell

Effector B cell

Naive cytotoxic T cell

Effector cytotoxic T cell

Antibody - mediated response

Cell - mediated responseKey Components of

Immune Response• MHC markers• Antigen-presenting

cells• Helper T cells• Effector cytoxic T cells• Natural killer cells• B cells

Lymphocyte Battlegrounds

• Lymph nodes filter antigens from body fluids

• Macrophages, dendritic cells, B cell and T cells in nodes and spleen mount a defense

Antibody-Mediated Response

• Carried out by B cells

• Targets are intracellular pathogens and

toxins

• Antibodies bind to target and mark it for

destruction by phagocytes and

complement

Antibody- Mediated Response

Naive B cell

Antigen-presentingB cell

Helper T cell

Interleukins

Memory B cell

Effector B cellsecretes antibodies

• Virgin B cell becomes antigen-presenting B cell

• Helper T cell binds to antigen-MHC complex on the B cell

• Interleukins stimulate B cell division and differentiation

• Effector cells secrete antibodies

5 Classes of Immunoglobulins

• IgM are secreted first; trigger complement reactions, agglutination

• IgD function is not understood

• IgG activates complement; can cross placenta

• IgA associates with mucus-coated surfaces

• IgE triggers inflammation

Cell-Mediated Response

One macrophage

Another macrophage

interleukins

interleukins Helper T cell

Cytotoxic T cell

Infected body cell

• Carried out by T cells

• Stimulated by antigen-

presenting macrophages

• Main target is antigen-

presenting body cells

(cells with intracellular

pathogens) or tumor cells

Organ Rejection

• Cytotoxic T cells can contribute to rejection of transplanted tissue

• They recognize a portion of the donor cell’s MHC complex as self, view a portion as foreign

• Treat the combination as an antigen-MHC complex and attack donor cells

Allergies• Immune reaction to a harmless substance

• Genetic predisposition

• IgE responds to antigen by binding to mast cells and basophils

• These cells secrete the substances that cause symptoms

Anaphylactic Shock

• A life-threatening allergic reaction

• Caused by the release of histamine by

many mast cells and basophils

• Airways constrict and blood pressure

drops as capillary permeability soars

Autoimmune Disorders

• Immune system makes

antibodies against self

antigens

• Grave’s disease

• Myasthenia gravis

• Rheumatoid arthritis

Bacterial Pathogen

Category A Threats:

• Defined by the CDC as high-priority agents include organisms that pose a risk to national security because they:

– Can be easily disseminated or transmitted from person to person

– Result in high mortality rates and have the potential for major public health impact

– Might cause public panic and social disruption

– Require special action for public health preparedness.

Infection type Mortality (untreated)

Cutaneous 20%

Intestinal 80-90%

Inhalation 90*-99%

*with treatment

Bacillus anthracis

Major Symptoms

• Skin- – characteristic sores

• Intestinal- – fever, intestinal discomfort,

intestinal ulceration.

• Inhalation- – fever, cough, malaise (flu-like)– Sever respiratory distress,

chills, edema

Pathophysiology

Immunization

• Process that promotes immunity

• Active immunization - – Antigen-containing material is injected

– Confers long lasting immunity

• Passive - – Purified antibody is injected

– Protection is short lived

first exposureto antigen

subsequent exposureto the same antigen

Immunization

HIV Picture

All you need to know

• Chapter 35

• Table 35.1

• Table 35.1 figure 35.5

• Figure 35.6

• Figure 35.7