Concepts of Immunity

Which enzymes are activated within the phagolysosome by binding of a microbe?

1. phagocyte oxidase 2. Inducible nitric oxide synthase 3. Lysosomal proteases

Which cells are abundant in chronic inflammation?

Macrophages

Secreted PRRs

Secreted by macrophages, epithelial cells, liver cells Active complement and opsonize micromial cells

What are the three epithelial barriers in the innate immune system?

Skin, GI tract and respiritory tract Lined by contiuous epilelia that physically prevent the entry of microbes

What non infectious agents may also be antigenic?

Tissues and cells from transplants Cancer cells Substances that cause an allergic reaction, E.g. Pollen

How is oxygen independent killing carried out?

Using lysosomal enzymes such as lysozyme

How does the innate immune system identify microbes?

Using pattern recognition receptors (PRR)

What does inducible nitric oxide synthase do?

catalyses the conversion of arginine to nitric oxide (NO). NO is a microcidal substance

What does phagocyte oxidase do?

converts molecular oxygen to superoxide anion and free radicals which are toxic to the ingested microbe

PRRs that signal infection

examples: Toll-like receptors Engagement of receptors activates pro-inflammatory signalling pathways

How doe the GI tract prevent infection?

flushing of saliva low gastric pH Motility Lactoferrin Commensal bacteria defensins

Which cells are part of the innate response?

- Neutrophils (phagocytes) - Monocytes (phagocytes) - Eosinophils - Basophils - Natural Killer Cells

What are some of the second line defenses of the innate immune response?

- Phagocytic white blood cells - Inflammatory response - Antimicrobial proteins

What are the first line responses of the innate response?

- Skin - mucous membranes - Other secretions E.g. acidic pH of the stomach/ vagina and lysozymes in tears - Rapid inhalation over nose bones and flushing in urinary tract - pH changes

What are the functions of the immune system?

1. Defense against infections 2. Defense against tumours 3. Recogises and responds to tissue grafts and newly introduced proteins 4. Contains antibodies which are highly specific reagents and detect any class of molecule

What are the moponents of the innate immune system?

1. Epithelial barriers 2. Cellular components

What are the implcations of having defense against infectious diseases?

1. deficiency = increased susceptability to infection. E.g. AIDS 2. Vaccination boosts immune defenses and protects against infection

What are the main features of the innate response?

1. It is a NON SPECIFIC IMMEDIATE response - works within hours 2. Occurs in vertebrates and invertebrates 3. Non antigenic specific 4. Consists of a "first line" and "second line" 5. Always present 6. Recognise and respond to microbes but do not act against non microbial agents 7. Instructs the adaptive response

What are the main features of the adaptive immune response?

1. It is specific!! 2. Primarily restricted to vertebrates 3. Lag phase to the response - slower response which takes 12+hours 4. Antigen specific 5. Introduction of memory cells

Where are the two mechanisms of killing microbes that phagocytosis allows for?

1. Oxygen dependant mechanisms - more important 2. Oxygen independent mechanisms

What are the classifications of PRRs?

1. PRRs that signal infection 2. PRRs that are phagocytic 3. secreted PRRs

Describe the process of phagocytosis

1. Phagocyte extends plasma membrane around a recognised microbe (membrane evaginations = pseudopodia) 2. Membrane closes up and pinches off forming a membrane bound vesicle called a phagosome 3. phagosome fuses with lysosomes = phagolysosome 4. Lysosomal proteases break down microbial proteins 5. Digestion products are released from the cell

Describe the oxygen dependent mechanism of phagocytosis

1. phagocytes (neutrophils and macrophages) bind to constant regions on anibodies using Fc receptors 2. This binding triggers an increase in oxygen uptake - A RESPIRATORY BURST 3. Powerful bactericidal agents (superoxide anion and singlet oxygen) are formed from the extra oxygen

What is an antigen?

A cell or molecule that can stimulate an immune response

What is the life span of a neutrophil?

A few hours. When they die their content spills out as puss and can cause additionaly damage to host tissue (immune athology)

What is chronic granulomatous disease?

An inherited immunodeficiency where there is a deficiency of the phagocyte oxidase enzyme.

What are antigens?

Agents/substances that stimulate an immune response

Name some classes of infectious antigens

Bacteria, viruses, parasites and fungi

Which classes of microbes do PRR

Bacterial carbohydrates (LPS) Nucleic acids e.g. viral dsRNA LTA peptidoglycan lipoarabinomannan Mannans B-glycans

What are the implications of recognising tissue grafts and newly introduced proteins?

Barrier to transplatation and gene therapy

What does the immune system consist of?

Cells, tissues and molecule that mediate resistance to infection

What is the immune response? What is the physiological function of the immune system?

Co ordination and reaction of cells to infectious microbes Prevent infections and eradicate existing infections

How does the repiratory tract prevent infection?

Cough reflex Luminal macrophages Collectins mucoculliary surfactant

What do pattern recognition receptors do?

Encoded for in the germline (contrast with gene recombination in adaptive immunity). They recognise patterns on microbes called PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs) which are not present on host cells. They identify a "class of microbe"

Phagocytic PRR

Expressed on the surface of phagocytic cells (macrophages, PMNs and DCs) Promote uptake (attachment, engulfing and destruction) of pathogens by phagocytes through phagocytosis

How does the urinary tract prevent infections?

Flushes urine and vagina has a low pH

What are the implication of haing defense against tumours?

Immunological approaches for lab testing are widely used in clinical medicine and research

Why does inflammation sometimes casue tissue damage?

In strong reactions during phagocytosis the enzymes are released into the extracellular space which leads to tissue injury

How does the skin prevent infection?

Lined by contiuous epilelia that physically prevent the entry of microbes Contain (intraepithilial) lymphocytes which act but have limited diversity

What agents are involved in the (third line) adaptive immune response?

Lymphocytes Antibodies

Which cells are capable of phagocytosis?

Macrophages, neutrophils and dendritic cells

Give some examples of phagocytic PRRs

Monnose receptors of macrophages Glucan receptors of phagocytes Scavenger recceptors

What does polymorphonuclear mean and which cells belong in the category

Multi-lobed nucleus Neutrophils

Which cells are abundant in acute inflammation?

Neutrophils

Which are the most abundant Leucocyte in the blood?

Neutrophils and numbers double rapidly in response to infection

Why does chronic granulomatous disease cause granuloma?

Phagocytes are unable to eradicate intracellular microbes and the host attempts to contain the infection by calling more macrophages and lymphocytes --> granuloma

What is immunity?

Resistance to infectious diseases

What is an EPITOPE?

The specific region on an sntigen tha an antibody binds to. It is a portion of a polypeptide that binds to the MHC molecule for presentation to a T-Cell. The immune response generates different antibodies depending on the epitope.

What does antigen mean?

anti= antibody gen=generating

What is the basis for PRR classification?

profile localisation function